Eligibility Criteria and Representativeness of Randomized Clinical Trials That Include Infants Born Extremely Premature: A Systematic Review

Leeann R Pavlek; Brian K Rivera; Charles V Smith; Joanie Randle; Cory Hanlon; Kristi Small; Edward F Bell; Matthew A Rysavy; Sara Conroy; Carl H Backes

doi:10.1016/j.jpeds.2021.04.028

. Author manuscript; available in PMC: 2022 Aug 3.

Published in final edited form as: J Pediatr. 2021 Apr 21;235:63–74.e12. doi: 10.1016/j.jpeds.2021.04.028

Eligibility Criteria and Representativeness of Randomized Clinical Trials That Include Infants Born Extremely Premature: A Systematic Review

Leeann R Pavlek ^1,^2,^*, Brian K Rivera ^1,^*, Charles V Smith ³, Joanie Randle ⁴, Cory Hanlon ⁴, Kristi Small ⁴, Edward F Bell ⁵, Matthew A Rysavy ⁵, Sara Conroy ^6,⁷, Carl H Backes ^1,^2,^4,^8,⁹

PMCID: PMC9348995 NIHMSID: NIHMS1823121 PMID: 33894262

Abstract

Objective

To assess the eligibility criteria and trial characteristics among contemporary (2010-2019) randomized clinical trials (RCTs) that included infants born extremely preterm (<28 weeks of gestation) and to evaluate whether eligibility criteria result in underrepresentation of high-risk subgroups (eg, infants born at <24 weeks of gestation).

Study design

PubMed and Scopus were searched January 1, 2010, to December 31, 2019, with no language restrictions. RCTs with mean or median gestational ages at birth of <28 weeks of gestation were included. The study followed the PRISMA guidelines; outcomes were registered prospectively. Data extraction was performed independently by multiple observers. Study quality was evaluated using a modified Jadad scale.

Results

Among RCTs (n = 201), 32 552 infants were included. Study participant characteristics, interventions, and outcomes were highly variable. A total of 1603 eligibility criteria were identified; rationales were provided for 18.8% (n = 301) of criteria. Fifty-five RCTs (27.4%) included infants <24 weeks of gestation; 454 (1.4%) infants were identified as <24 weeks of gestation.

Conclusions

The present study identifies sources of variability across RCTs that included infants born extremely preterm and reinforces the critical need for consistent and transparent policies governing eligibility criteria.

Infants born extremely preterm (<28 weeks of gestation) constitute <10% of preterm births but contribute disproportionately to the burden of adverse outcomes.¹ Despite evidence of improved clinical outcomes over the past decade, the strength of available data in the treatment of infants born extremely preterm has been called into question.^2–5 In the absence of sufficient evidence, healthcare providers may deliver suboptimal treatments to infants born extremely preterm or expose these infants to unrecognized harms.⁶

Randomized clinical trials (RCTs) are considered the gold standard for evaluating the therapeutic efficacy of a drug or intervention.^7,8 In the design of RCTs, investigators must reconcile strategies that provide internal (eg, treatment efficacy) and external (eg, treatment effectiveness relevant to the population of interest) validity. Strict eligibility criteria limit generalizability and preclude understanding of the risk–benefit profile germane to the populations likely to receive an intervention.^8–11 Although previous investigators have characterized RCTs in adult and older pediatric patients,^12–14 the eligibility criteria of RCTs including infants born extremely preterm have not been well characterized.

The primary objective of the present study was to assess the nature and extent of eligibility criteria and trial characteristics among contemporary (2010-2019) RCTs that included infants born extremely preterm. In view of the differences in treatment practices for infants born at <24 weeks of gestation,^4,15 a secondary objective was to evaluate whether eligibility criteria result in under-representation of infants born at <24 weeks of gestation.

Methods

Data Sources

This study was registered with the PROSPERO database, the international prospective registry of systematic reviews¹⁶ (http://www.crd.york.ac.uk/NIHR_PROSPERO, identifier # CRD42020196141) and performed according to the PRISMA guidelines.¹⁷ With assistance from research librarians at Nationwide Children’s Hospital Library, the authors performed a comprehensive search of PubMed and Scopus (Appendix; available at www.jpeds.com), including trials published in peer-reviewed journals from January 1, 2010, to December 31, 2019, with no language restrictions.

Data Abstraction and Study Definitions

Eligibility for trial inclusion in this systematic review was formulated according to the PICOT framework¹⁸ (ie, Participants, Interventions, Comparator, Outcomes, Timeframe).

Participants: Infants born extremely preterm, defined as reported mean (or median) gestational age <28 weeks of gestation for either individual treatment arms or overall study cohort.
Intervention: Any therapeutic intervention.
Comparator: Any placebo or nonplacebo control intervention.
Outcomes: Classification of eligibility criteria (see definitions to follow). Both inclusion and exclusion criteria were considered as “eligibility criteria.”
Timing: Published between January 1, 2010, and December 31, 2019.

RCTs in which infants were allocated randomly to receive a specific intervention or a placebo (or nonplacebo control) were included. Trials in which the treatment allocations were not assigned randomly (eg, patient-choice trials) were excluded. All included clinical studies were published in peer-reviewed journals. When follow-up data of previously reported trials were identified, only the original reports were used. Foreign-language articles were translated to English using Google Translate.¹⁹ When possible, alternative sources (eg, ClinicalTrials.gov) were used to collect and/or confirm or eligibility data. All citations were imported into an electronic reference database (EndNote X8; Clarivate Analytics).

Data Extraction

Two authors independently assessed the eligibility of identified studies and extracted data using standardized forms. Differences were resolved by reviewing with a third author, and the final determinations were agreed on by consensus. Decisions on study eligibility criteria were made independently of the data extraction and before data analyses. The following were abstracted from each trial: publication year; source(s) of financial support; location(s) and affiliated university; single or multicenter study with local, national, or international enrollment; numbers and characteristics of eligibility criteria; demographics; primary outcomes; and general focus. Consistent with previous reports, rationales for the eligibility criteria were recorded when provided.¹¹

For trials not reporting infant race/ethnicity, maternal data were used. Race/ethnicity were categorized as (1) Black non-Hispanic (referred to as Black); (2) White non-Hispanic (referred to as White); (3) Hispanic (including Black or White Hispanic); (4) Asian; and (5) other or unknown. Mothers identifying with more than 1 race or who could not be categorized were considered “other or unknown.” Paternal race/ethnicity was not recorded.²⁰ Each study was categorized by the number of randomized infants: (1) <50; (2) 50-99; (3) 100-199; (4) ≥200. Consistent with previous reports among adults and older children,¹¹ studies in greater-impact factor journals (≥5.0) were compared with those in lower-impact journals (<5.0); impact factors were determined based on year of publication.²¹

To investigate whether changes in eligibility criteria were observed following a 2014 joint statement on the care of infants born extremely premature,²² RCTs were divided into 2 epochs by year of publication (Epoch 1: 2010-2014; Epoch 2: 2015-2019). In view of efforts by the US Food and Drug Administration to increase justification of eligibility criteria, rationales provided by authors for their criteria were recorded.²³ When data were unclear or additional information was necessary, 2 attempts were made to contact the corresponding authors for clarification.

Study Quality

The methodologic quality of each trial was assessed using a modified version of the Jadad scale, in which greater scores indicate greater quality ratings.^24–26 The maximum score that could be attained was 8, with high-quality trials receiving a score of ≥6.²⁶ This was applied independently by 2 investigators, differences were adjudicated by a third investigator.

Data Synthesis

Categorical variables are presented as counts and percentages, and continuous variables are presented as means (SD) or medians (range). Basic analyses consisted of 2-sided t-tests or Mann–Whitney U tests for continuous variables and χ² tests or Fisher exact tests for categorical variables. Associations between trial characteristics and number of eligibility criteria were evaluated with linear regression models. Residual plots were tested for violations of the assumptions of heteroscedasticity and normality of the errors. The estimated means and 95% CIs for each trial characteristic were calculated. The independent associations between trial characteristics with the presence of age-based exclusions were evaluated with Fisher exact tests. All tests were 2-tailed. Stata 16 (StataCorp LLC) and GraphPad Prism (GraphPad Software) were used.

Results

The flow diagram (Figure 1) summarizes the identified, screened, eligible, and included clinical trials (N = 201). Study characteristics are briefly summarized in Table I, with a list of included clinical trials in Table II (available at www.jpeds.com).^27–228 Information on journal impact factor was available for 96.0% (n = 193) of included manuscripts; 54 (26.9%) were published in high-impact journals. Most clinical trials (73.1%, 147/201) were identified as high quality; no disagreements existed between reviewers that impacted categorization of trials as being high quality vs low/moderate quality. The most common area of focus was respiratory (n = 97, 48.3%), followed by feeds/nutrition (n = 38, 18.9%; Table III [available at www.jpeds.com]). The most common primary outcome measures included bronchopulmonary dysplasia or a composite of bronchopulmonary dysplasia or death (n = 17 trials, 8.5%), time in target peripheral capillary oxygen saturation range (12 trials, 6.0%), time to full feeds (n = 8 trials, 4.0%), and patent ductus arteriosus management and/or treatment (n = 8 trials, 4.0%). Sixteen clinical trials (8.0%) had diagnostic elements (eg, near-infrared spectroscopy) that differentiated thresholds for various treatment modalities. Outcomes beyond initial hospitalization were reported in 17 clinical trials (8.5%).

Table I.

Summary data from trial manuscripts

Data	All trials (N = 201)
Publication year
2010-2014	109 (54.2)
2015-2019	92 (45.8)
Study location(s)
Multiple centers
Single country	47 (23.4)
International	27 (13.4)
Single centers
US	42 (20.9)
Europe	37 (18.4)
Australia	19 (9.5)
Canada	9 (4.5)
Turkey	8 (4.0)
Other	12 (6.0)
Study funding source(s)^*
Government	90 (44.8)
Institution	50 (24.9)
Private foundation	41 (20.4)
Industry	27 (13.4)
Unknown	58 (28.9)
Number of trial participants
<50	82 (40.6)
50-99	48 (23.8)
100-199	34 (16.8)
200 or more	38 (18.8)

Open in a new tab

Data shown as number/count (% of trials).

Some clinical trials cited multiple funding sources (N = 69, 34.3%).

Table II.

Manuscripts included in the review (N = 201)

Authors	Year	General area of focus	Study groups (n)	Group means ± SD, medians (ranges), or medians (IQRs), wk	N, infants <24 weeks of gestation
Abounahia et al⁵²	2019	Respiratory	1: Sildenafil (20) 2: Placebo (20)	1: 26.9 ± 1.55 2: 26.7 ± 1.84	0
Arsenault et al⁵¹	2019	Feeds/nutrition	1: No supplementation (6) 2: Medium-chain triglyceride oil supplementation (11)	1: 27.8 (range 23-32) 2: 25.5 (range 23-28)	2
Balasubramanian et al⁵⁰	2019	Hematologic	1: Cord blood sampling (40) 2: Admission blood sampling (40)	1: 26.5 ± 1.25 2: 26.4 ± 1.39	2
Chuang et al⁴⁹,^*	2019	Sedation/pain	1: Developmental care (initial) (7) 2: Standard care (initial) (7)	26.8 ± 2.0	–
Claassen et al⁴⁸	2019	Respiratory	1: BabiPlus (23) 2: B&B Bubbler (19)	1: 26.0 ± 2.0 2: 25.4 ± 1.4	–
Clyman et al⁴⁷	2019	PDA	1: Conservative treatment (98) 2: Early, routine treatment (104)	1: 25.9 ± 1.1 2: 25.7 ± 1.2	25
Curley et al⁴⁶	2019	Hematologic	1: Low threshold (331) 2: High threshold (329)	1: 26.7 (IQR 24.9-28.7) 2: 26.6 (IQR 24.9-28.9)	69
de Vries et al⁴⁵	2019	Other (IVH interventions)	1: Early intervention (64) 2: Later intervention (62)	1: 27.4 ± 3.3 2: 27.4 ± 3.2	2
El-Naggar et al⁴⁴	2019	Placental transfusion	1: Cord milking (37) 2: Immediate cord clamping (36)	1: 27.6 ± 1.8 2: 27.2 ± 2.0	0
Fischer et al⁴³	2019	Respiratory	1: Nasal HFOV (4) 2: Nasal CPAP (2)	1: 25^0/7 (range 23^4/7-26^3/7) 2: 24^0/7 (range 23^6/7-24^6/7)	–
Gajdos et al⁴²,^*	2019	Respiratory	1: Manual control (initial) (6) 2: Automated control (initial) (6)	25.3 (range 23-26)	–
Hunt et al⁴¹,^*	2019	Respiratory	1: Volume of 4 mL/kg ventilation (18) 2: Volume of 5 mL/kg ventilation (18) 3: Volume of 6 mL/kg ventilation (18) 4: Volume of 7 mL/kg ventilation (18)	26 (range 24-30)	0
Kirpalani et al⁴⁰,^*	2019	Respiratory	1: Sustained inflations (215) 2: Standard resuscitation (211)	25.30 ± 0.97	–
Kluckow et al³⁹	2019	PDA	1: Paracetamol (29) 2: Placebo (28)	1: 27 (mean) 2: 27.1 (mean)	–
Kochan et al³⁸	2019	Other (IVH/PVL)	1: Flat head position (90) 2: Elevated head position (90)	1: 25.39 ± 1.64 2: 25.89 ± 1.74	0
Latremouille et al³⁷,^*	2019	Respiratory	1: HFNC/CPAP 2: CPAP/HFNC	27.0 (range 24.1-29.3)	0
Ley et al³⁶	2019	ROP	1: rhIGF-1/rhIGFBP-3 (61) 2: Standard care (60)	1: 25^4/7 wk ± 8 d 2: 25^4/7 wk ± 10 d	–
Marr et al³⁵	2019	Respiratory	1: 42-d dexamethasone tapering course (30) 2: 9-d dexamethasone tapering course (29)	1: 25.2 ± 1.2 2: 25.2 ± 1.1	0
O’Currain et al³⁴	2019	Respiratory	1: Standard mask (65) 2: Fitted mask (66)	1: 27 ± 2.2 2: 27 ± 2.1	0
Onland et al³³	2019	Respiratory	1: Hydrocortisone (182) 2: Placebo (190)	1: 25.4 (IQR 24.9-26.4) 2: 25.6 (IQR 24.7-26.4)	0
Parker et al³²	2019	Feeds/nutrition	1: Gastric residual evaluation (74) 2: No gastric residual evaluation (69)	1: 27.1 ± 2.4 2: 27.0 ± 1.2	3
Pereira et al³¹	2019	Hematologic	1: Active support (19) 2: Moderate support (42) 3: Permissive (21)	1: 25.7 (range 23.4-28.9) 2: 25.8 (range 23.3-28.7) 3: 25.6 (range 23.7-28.7)	8
Rath et al³⁰	2019	Other (PICC placement)	1: Contrast (20) 2: No contrast (21)	1: 26 (median) 2: 27 (median)	–
Reynolds et al²⁹,^*	2019	Respiratory	1: Automated control (30) 2: Manual control (30)	26 (IQR 24-27)	4
Thomson et al²⁸	2019	Other (glucose control)	1: Standard care/control (10) 2: Real-time continuous glucose monitoring (10)	1: 27.96 ± 2.1 2: 27.5 ± 2.8	–
Wejryd et al²⁷	2019	Feeds/nutrition	1: L reuteri receiving (68) 2: Placebo (66)	1: 25.5 ± 1.2 2: 25.5 ± 1.3	22
Amaro et al⁶⁹	2018	Respiratory	1: Early caffeine (41) 2: Control (42)	1: 25.7 (IQR 24.3-27.0) 2:26.1 (IQR 24.2-28.4)	10
Bottino et al^68,^*	2018	Respiratory	1: Nasal CPAP treatment mode (initial) (30) 2: Nasal HFOV treatment mode (initial) (30)	26.4 ± 1.8	–
Eze et al⁶⁷	2018	Respiratory	1: Sprinting, wean (40) 2: Nonsprinting, wean (40)	1: Mean 26.5 (range 23.6-30.6) 2: Mean 27.4 (range 23.9-30.7)	–
Gerges et al⁶⁶	2018	Feeds/nutrition	1: Oral feedings at 30 wk (34) 2: Oral feedings at 33 wk (31)	1: 27.4 ± 1.1 2: 27.5 ± 1.2	–
Hochwald et al⁶⁵	2018	PDA	1: Ibuprofen + paracetamol (12) 2: Ibuprofen + placebo (12)	1: 27.7 ± 1.3 2: 27.2 ± 1.4	0
Imbulana et al⁶⁴	2018	Respiratory	1: Barrier (31) 2: No barrier (30)	1: 27.4 ± 1.7 2: 27.5 ± 1.9	–
Kieran et al⁶³	2018	Infection/sepsis	1: Chlorhexidine (148) 2: Povidone–iodine (156)	1: 27 ± 2 2: 27 ± 2	–
Klotz et al⁶²	2018	Respiratory	1: Noninvasive HFOV–noninvasive CPAP (13) 2: Noninvasive CPAP–noninvasive HFOV (13)	1: 26 (range 23-29) 2: 27 (range 25-31)	–
McGrory et al⁶¹	2018	Respiratory	1: Heated-humidified (132) 2: Unconditioned (141)	1: 27 ± 1.8 2: 27 ± 1.8	–
Phelps et al⁶⁰	2018	ROP	1: Myo-inositol (317) 2: Placebo (321)	1: 25.6 ± 1.4 2: 25.7 ± 1.3	–
Rosterman et al^59,^*	2018	Respiratory	1: SIMV (initial) (22) 2: NAVA (initial) (22)	26^4/7 (range 23^0/7-39^0/7)	–
Rüegger et al⁵⁸,^*	2018	Respiratory	1: Noninvasive HFOV (40) 2: Nasal CPAP (40)	26.5 ± 1.5	–
Salas et al⁵⁷	2018	Feeds/nutrition	1: Early feeding (30) 2: Late feeding (30)	1: 26 (IQR 24-28) 2: 26 (IQR 24-27)	9
Spittle et al⁵⁶	2018	Other (social outcomes)	1: Higher risk, intervention (21) 2: Higher risk, control (26) 3: Lower risk, intervention (40) 4: Lower risk, control (33)	1: 27.0 ± 1.6 2: 27.5 ± 1.4 3: 27.4 ± 26.8^† 4: 27.4 ± 1.6	0
Strunk et al⁵⁵	2018	Infection/sepsis	1: Coconut oil (36) 2: Control (36)	1: 27.9 (IQR 26.3-29.3) 2: 27.9 (IQR 25.4-29.1)	4
Travers et al⁵⁴,^*	2018	Respiratory	1: Oxygen environment (initial) (12) 2: Nasal cannula (initial) (13)	27 ± 2	6
van den Heuvel et al⁵³,^*	2018	Respiratory	1: Oxygen saturation target 86%-94% (41) 2: Oxygen saturation target 88%-92% (41) 3: Oxygen saturation target 89%-91 % (41)	26 (IQR 25-27)	0
Alkan Ozdemir et al⁸⁵	2017	Respiratory	1: SIMV + volume guarantee (19) 2: PSV + volume guarantee (15)	1: 26.7 ± 1.5 2: 26.9 ± 2.2	–
Beker et al⁸⁴	2017	Feeds/nutrition	1: Smell/taste before feeds (28) 2: Control feeds (23)	1: 26.7 ± 1.5 2: 27.2 ± 1.4	–
Ben Jmaa et al⁸³	2017	Other (immunization)	1: Placebo (28) 2: Ibuprofen (28)	1: 27.2 ± 2 2: 27.8 ± 1.8	–
Brandon et al⁸²	2017	Other (Circadian rhythm)	1: Early cycled light, inpatient (61) 2: Late cycled light, inpatient (57) 3: Early cycled light, outpatient (40) 4: Late cycled light, outpatient (43)	1: 26.3 ± 1.4 2: 26.3 ± 1.5 3: 26.0 ± 1.3 4: 26.2 ± 1.5	–
Collins et al⁸¹	2017	Respiratory	1: Docosahexaenoic acid (631) 2: Control (642)	1: 26.7 ± 1.5 2: 26.7 ± 1.5	46
El-Mashad et al⁸⁰	2017	PDA	1: Paracetamol (100) 2: Ibuprofen (100) 3: Indomethacin (100)	1: 26 ± 1.9 2: 25 ± 2.1 3: 26 ± 2.1	–
Glackin et al⁷⁹	2017	Respiratory	1: HFNC (22) 2: Nasal CPAP (22)	1: 26.9 ± 1.5 2: 27.3 ± 1.5	0
Hansen-Pupp et al⁷⁸	2017	ROP	1: rhIGF-1/rhIGFBP-3 (9) 2: Standard care (10)	1: 26^1/7 (range 24^3/7-27^4/7) 2: 25^6/7 (range 23^3/7-27^2/7)	–
Hasan et al⁷⁷	2017	Respiratory	1: Placebo (222) 2: iN0 (229)	1: 25.6 ± 1.5 2: 25.6 ± 1.4	–
Jiravisitkul et al⁷⁶	2017	Respiratory	1: Sustained lung inflation (17) 2: No sustained lung inflation (16)	25-28 (lower strata)	0
Kugelman et al⁷⁵	2017	Respiratory	1: QVAR/beclomethasone (18) 2: Placebo (20)	1: 26.4 ± 2.1 2: 26.9 ± 1.9	–
Lemyre et al⁷⁴	2017	Respiratory	1: Poractant alfa (42) 2: Bovine lipid extract surfactant (45)	1: 26.5 ± 1.5 2: 26.9 ± 2.1	–
Mukerji et al⁷³	2017	Respiratory	1: Noninvasive high-frequency ventilation (16) 2: Biphasic CPAP (23)	1: 26.1 ± 1.3 2: 26.5 ± 1.6	1
Najm et al⁷²	2017	Feeds/Nutrition	1: Clinoleic (37) 2: SMOFlipid (41)	1: 25.6 ± 1.6 2: 25.5 ± 1.3	15
Shetty et al^71,^*	2017	Respiratory	1: NAVA (initial) (9) 2: Assist control ventilation (initial) (9)	25 (range 22-27)	–
Williams et al⁷⁰	2017	Feeds/nutrition	1: Iodide (631) 2: Placebo (628)	1: 27.4 ± 2.0 2: 27.4 ± 2.0	–
Backes et al¹⁰⁵	2016	Placental transfusion	1: Immediate cord clamping (22) 2: Delayed cord clamping (18)	1: 24.6 ± 1.1 2: 24.4 ± 1.2	8
Ballard et al¹⁰⁴	2016	Respiratory	1: Late surfactant (252) 2: Control (259)	1: 25.2 ± 1.2 2: 25.2 ± 1.2	“Very very few”
Baud et al¹⁰³	2016	Respiratory	1: Hydrocortisone (255) 2: Placebo (266)	1: 26.4 (IQR 25.1-27.4) 2: 26.5 (IQR 24.9-27.4)	0
Bellagamba et al¹⁰²	2016	Feeds/nutrition	1: Standard protein (82) 2: High protein (82)	1: 27 (IQR 26-29) 2: 27 (IQR 26-28)	–
Costeloe et al^101,^*	2016	Feeds/nutrition	1: Bifidobacterium breve (BBG-001) (315) 2: Placebo (319)	<28 subgroups	38
Fort et al¹⁰⁰	2016	Feeds/nutrition	1: Placebo (36) 2: 200 IU/d Vitamin D (34) 3: 800 IU/d Vitamin D (30)	1: 25.5 ± 1.4 2: 25.3 ± 1.4 3: 25.1 ± 1.6	15
Greze et al⁹⁹	2016	Respiratory	1: GrW (46) 2: GrA (39)	1: 27.7 ± 1.9 2: 27.9 ± 1.4	–
Hascoët et al⁹⁸	2016	Respiratory	1: Poractant alfa (59) 2: Control (59)	1: 26.2 ± 1.5 (range 24-31) 2: 26.6 ± 1.3 (range 23-30)	1
Ishihara et al⁹⁷	2016	Respiratory	1: Biphasic nasal CPAP (66) 2: Regular nasal CPAP (66)	1: 27.6 (range 26.2-28.7) 2: 27.3 (range 25.7-28.1)	–
Jain et al^96,^*		Respiratory	1: Pressure control (PC) (24) 2: Volume guarantee (VG) (24)	25 ± 1.5	–
Levit et al⁹⁵	2016	Feeds/nutrition	1: Low dose (69) 2: Control (67)	1: 27 ± 2 2: 26 ± 2	–
Ng et al⁹⁴,^*	2016	Feeds/nutrition	1: Bolus feeds (initial) (10) 2: Slow infusion feeds (initial) (10)	27.5 (range 25-30)	0
Phelps et al⁹³	2016	ROP	1: 0 mg/kg/d (placebo) (35) 2: 10 mg/kg/d (29) 3: 40 mg/kg/d (30) 4: 80 mg/kg/d (28)	1: 26.5 ± 1.6 2: 26.6 ± 1.8 3: 26.7 ± 1.8 4: 26.7 ± 1.9	–
Robinson et al⁹²	2016	Feeds/nutrition	1: Placebo (10) 2: Low dose (9) 3: High dose (9)	1: 26.5 (IQR 25-28) 2: 26 (IQR 26-27) 3: 25 (IQR 25-25)^†	–
Shetty et al⁹¹,^*	2016	Respiratory	1: PAV/ACV (20) 2: ACV/PAV (20)	25.7 (range 24.4-33.5)	0
Shetty et al⁹⁰	2016	Respiratory	1: CPAP (initial) (20) 2: HHFNC (initial) (20)	27.6 (range 24.6-31.9)	0
Sohn et al⁸⁹	2016	Other (oral microbiota)	1: Intervention (6) 2: Control (6)	1: 27 (range 25-30) 2: 27 (range 25-28)	0
Vesoulis et al⁸⁸	2016	Respiratory	1: Standard-dose caffeine (30) 2: High-dose caffeine (29)	1: 26.5 ± 1.9 2: 25.8 ± 2.0	0
Victor et al⁸⁷	2016	Respiratory	1: <28 wk, nasal BiPAP (157) 2: <28 wk, nasal CPAP (147)	1: 26 (range 25-27) 2: 26 (range 25-27)	–
Yeh et al⁸⁶	2016	Respiratory	1: Intervention (131) 2: Control (134)	1: 26.5 ± 2.2 2: 26.8 ± 2.2	–
Anell-Olofsson et al¹³⁵	2015	Sedation/pain	1: Bolus and early intermittent infusion (9) 2: Delayed intermittent infusion (9)	1: 24^6/7 (range 24^0/7-26^4/7) 2: 26^0/7 (range 24^3/7-29^3/7)	0
Bassler et al¹³⁴	2015	Respiratory	1: Budesonide (437) 2: Placebo (419)	1: 26.1 ± 1.3 2: 26.1 ± 1.3	–
Beker et al¹³³,^*	2015	Respiratory	1: 4 cm H₂O nasal CPAP (30) 2: 6 cm H₂O nasal CPAP (30) 3: 8 cm H₂O nasal CPAP (30)	25.9 (IQR 24.6-26.8)	0
Bhat et al¹³²,^*	2015	Respiratory	1: Proportional assist (initial) (12) 2: Assist control (initial) (12)	25 (range 24-26)	0
Bozdağ et al¹³¹	2015	Respiratory	1: Poractant alfa (21) 2: Beractant (21)	1: 27.9 ± 2.3 2: 27.2 ± 2.3	–
Bravo et al¹³⁰	2015	Hematologic	1: Low SVC flow, dobutamine (9) 2: Low SVC flow placebo (9)	1: 27 ± 2 2: 26.4 ± 2	2
Clarke et al¹²⁹,^*	2015	Respiratory	1: Routine control (Initial) (16) 2: Algorithm-based control (Initial) (16)	26.7 ± 1.3	–
Hyttel-Sorenson et al¹²⁸	2015	Other (hemodynamics/monitoring)	1: NIRS (86) 2: Control/blinded NIRS (80)	1: 26.6 (IQR 25.7-27.4) 2: 26.8 (IQR 25.5-27.6)	0
Katheria et al¹²⁷	2015	Respiratory	1: Early caffeine (11) 2: Routine caffeine (10)	1: 27 ± 0.9 2: 27 ± 0.9	0
Kong et al¹²⁶	2015	ROP	1: Laser (7) 2: IVB, 0.625 mg (7)	1: 24.6 ± 1.5 2: 24.2 ± 1.5	–
Kribs et al¹²⁵	2015	Respiratory	1: LISA (107) 2: Conventional (104)	1: 25.3 ± 1.1 2: 25.2 ± 0.9	–
Laborie et al¹²⁴	2015	Feeds/nutrition	1: Light protected (293) 2: Light exposed (294)	1: 27.6 ± 1.5 2: 27.7 ± 1.5	0
Lal et al¹²³,^*	2015	Respiratory	1: Automated (27) 2: Routine (27)	25 (IQR 24-27)	–
Lee et al¹²²	2015	Feeds/nutrition	1: Placebo (24) 2: Colostrum (24)	1: 26^5/7 (IQR 24^3/7-27^1/7) 2: 26^5/7 (IQR 24^2/7-27^4/7)	–
Lee et al¹²¹,^*	2015	Respiratory	1: NAVA (initial) (15) 2: PS (initial) (15)	27^1/7 (IQR 26^0/7-28^2/7)	–
Lista et al¹²⁰	2015	Respiratory	1: Nasal CPAP alone (control) (143) 2: Sustained lung inflation + nasal CPAP (148)	1: 26.8 ± 1.2 2: 26.8 ± 1.1	0
McPherson et al¹¹⁹	2015	Respiratory	1: High-dose caffeine (37) 2: Standard-dose caffeine (37)	1: 26.3 ± 1.9 2: 26.8 ± 1.8	0
Nair et al¹¹⁸	2015	Respiratory	1: Nasal CPAP cycling (13) 2: Nasal CPAP continuous (17)	1: 27 (IQR 26-28) 2: 27 (IQR 26-27)	0
Nasef et al¹¹⁷	2015	Respiratory	1: CPAP (initial) (5) 2: HFNC (initial) (5)	1: 26.5 ± 1.4 2: 26.7 ± 1.4	–
Newnam et al¹¹⁶	2015	Respiratory	1: CPAP, continuous, mask (35) 2: CPAP, continuous, prongs (21) 3: Alternating mask/prongs (22)	1: Mean 26.7 (range 23.3-31.1) 2: Mean 27.3 (range 24.0-32.0) 3: Mean 26.5 (range 23.0-30.1)	–
Okulu et al¹¹⁵	2015	Respiratory	1: Early prophylactic INSURE (40) 2: Late prophylactic INSURE (40)	1: 26.9 ± 1.9 2: 27 ± 2.2	–
Omarsdottir et al¹¹⁴	2015	Feeds/nutrition	1: FTMM (69) 2: FMM + FTMM (71)	1: 25.9 ± 1.2 2: 26.0 ± 1.3	–
Reilly et al¹¹³	2015	Thermoregulation	1: Occlusive wrap (411) 2: No wrap (402)	1: Mean 25.6 2: Mean 26	0
Rios and Kaiser¹¹²	2015	Hematologic	1: Hypotensive, vasopressin (10) 2: Hypotensive, dopamine (10) 3. Nonhypotensive (50)	1: 25.7 ± 2 2: 25.1 ± 1 3: 25.6 ± 1	8
Salas et al¹¹¹	2015	Feeds/nutrition	1: Re-feed residuals (36) 2: Fresh feed, no residuals (36)	1: 26 (IQR 25-27) 2: 26 (IQR 25-27)	–
Schultzke et al¹¹⁰	2015	Respiratory	1: Pentoxifylline (41) 2: Placebo (40)	1: 25.2 ± 1.2 2: 25.3 ± 1.4	–
Tang et al¹⁰⁹	2015	Respiratory	1: Abrupt wean with HFNC (15) 2: Abrupt wean without HFNC (15) 3: Gradual wean with HFNC (15) 4: Gradual wean without HFNC (15)	1: 27.7 ± 1.5 2: 27.1 ± 1.8 3: 27.5 ± 1.3 4: 27.7 ± 1.1	0
Thome et al¹⁰⁸	2015	Respiratory	1: High pCO₂ target (179) 2: Standard pCO₂ target (180)	1: 25.6 ± 1.4 2: 25.7 ± 1.3	26
van Kaam et al¹⁰⁷,^*	2015	Respiratory	1: Automatic FiO₂ control (80) 2: Manual FiO₂ control (80)	26 (IQR 25-28)	5
Waitz et al¹⁰⁶,^*	2015	Respiratory	1: Manual phase (initial) (15) 2: Automated phase (initial) (15)	25 (range 23-28)	–
AlKharfy et al¹⁵⁷	2014	Infection/sepsis	1: Twice-daily topical petroleum jelly (35) 2: No topical petroleum jelly (39)	1: 27 ± 2 2: 27 ± 2	–
Benjamin et al¹⁵⁶	2014	Infection/sepsis	1: Fluconazole prophylaxis (188) 2: Placebo (173)	1: 25 (IQR 24-26) 2: 25 (IQR 24-26)	–
Bravo et al¹⁵⁵	2014	PDA	1: EchoG (28) 2: ST (21)	1: 27.2 ± 2.2 2: 27.3 ± 3	–
Buzzella et al¹⁵⁴	2014	Respiratory	1: Nasal CPAP 4-6 cm H₂O (47) 2: Nasal CPAP 7-9 cm H₂O (46)	1: 25.6 ± 1.2 2: 25.5 ± 1.3	–
Deshpande et al¹⁵³	2014	Feeds/nutrition	1: Clinoleic (17) 2: SMOFlipid (17)	1: 26.45 ± 1.92 2: 26.73 ± 1.62	–
Doglioni et al¹⁵²	2014	Normothermic regulation	1: Total body wrap (50) 2: Control (50)	1: 25.7 ± 1.7 2: 25.8 ± 1.7	–
Hair et al¹⁵¹	2014	Feeds/nutrition	1: Control (39) 2: Human milk cream (39)	1: 27.7 ± 2.1 2: 27.6 ± 1.6	0
Hallenberger et al¹⁵⁰,^*	2014	Respiratory	1: Manual control (initial) (34) 2: Manual control + closed-loop automatic control (initial) (34)	26.4 (range 23.0-35.3)	–
Hochwald et al¹⁴⁹	2014	Hematologic	1: Hydrocortisone (11) 2: Placebo (11)	1: 26.1 ± 1.5 2: 25.6 ± 1.37	–
Kaufman et al¹⁴⁸	2014	Infection/sepsis	1: Hand hygiene + gloves (60) 2: Hand hygiene alone (60)	1: 25.7 ± 1.8 2: 25.9 ± 1.7	–
Kinsella et al¹⁴⁷	2014	Respiratory	1: iNO (59) 2: Control (65)	1: 27.5 ± 1.6 2: 27.3 ± 1.8	–
Kluckow et al¹⁴⁶	2014	PDA	1: Indomethacin (44) 2: Placebo (48)	1: 26 ± 1.4 2: 26 ± 1.4	3
Konig et al¹⁴⁵	2014	Respiratory	1: Sildenafil (10) 2: Placebo (10)	1: 24^5/7 weeks ± 4.9 days 2: 24^5/7 weeks ± 6.5 days	–
Lago et al¹⁴⁴	2014	PDA	1: Ibuprofen bolus (56) 2: Ibuprofen continuous infusion (55)	1: 27.4 ± 2.7 2: 27.3 ± 2.1	–
Lepore et al¹⁴³,^*	2014	ROP	1: Bevacizumab (12) 2: Laser photoablation (12)	range 23-29	–
Mena et al¹⁴²	2014	Feeds/nutrition	1: Saline enemas with glycerol (50) 2: Stimulation (51)	1: 27.9 ± 2.1 2: 27.8 ± 2.0	–
Morgan et al¹⁴¹	2014	Feeds/nutrition	1: SCAMP nutrition (74) 2: Control (76)	1: 26.8 ± 1.3 2: 26.6 ± 1.4	–
Oncel et al¹⁴⁰	2014	PDA	1: Oral ibuprofen (40) 2: Oral acetaminophen (40)	1: 27.3 ± 2.1 2: 27.3 ± 1.7	–
Shin et al¹³⁹	2014	Sedation/pain	1: Low dose (5) 2: High dose (7)	1: 25^6/7 (range 24^3/7-31^6/7) 2: 26^1/7 (range 24^3/7-30^4/7)	0
Smith et al³⁸	2014	Other (neurodevelopment)	1: M Technique (9) 2: Control (9)	1: 26.7 (range 26-29) 2: 26.6 (range 26-29)	0
Wilinska et al¹³⁷,^*	2014	Respiratory	1: Control set range 87%-93% (Initial) (21) 2: Control set range 90%-93% (initial) (21)	27 (IQR 26-29)	–
Zapata et al¹³⁶	2014	Respiratory	1: Auto-mixer oxygen control (10) 2: Manual oxygen control (10)	1: 27.3 ± 1.7 2: 27.7 ± 1.7	–
Bagnoli et al¹⁸⁷	2013	PDA	1: IV ibuprofen (67) 2: Placebo (67)	1: 27^3/7 ± 2.5 2: 27^6/7 ± 4.0	–
Bell et al¹⁸⁶	2013	Feeds/nutrition	1: Vitamin E (62) 2: Placebo (31)	1: 25 (IQR 24-26) 2: 25 (IQR 24-26)	10
Bertini et al¹⁸⁵	2013	Infection/sepsis	1: AgION impregnated UVC (45) 2: Control (nonimpregnated) UVC (41)	1: 26.2 ± 2.0 2: 26.2 ± 1.5	–
BOOST II, Stenson et al¹⁷⁸	2013	Respiratory	1: Lower-target oxygen (1224) 2: Higher-target oxygen (1224)	1: 26.0 ± 1.22 2: 26.0 ± 1.23	–
Collins et al¹⁸³	2013	Respiratory	1: HHHFNC (9) 2: Vapotherm (9)	27.4 ± 1.5 (entire cohort)	–
Collins et al¹⁸⁴	2013	Respiratory	1: Vapotherm HHHFNC (67) 2: Nasal CPAP (65)	1: 27.9 ± 1.95 2: 27.6 ± 1.97	–
Cone et al¹⁸²,^*	2013	Sedation/pain	1: Control (10) 2: 4-handed (10)	25 (range 24-37)	–
Cristofalo et al¹⁸¹	2013	Feeds/nutrition	1: Bovine milk formula (24) 2: Human fortified milk (29)	1: 27.5 ± 2.4 2: 27.7 ± 1.5	–
Ditzenberger et al¹⁸⁰	2013	Feeds/nutrition	1: Control, <1000 g (15) 2: Intervention, <1000 g (13)	1: 27 ± 1.1 2: 26 ± 1.1	–
Gouna et al¹⁷⁹,^*	2013	Respiratory	1: Supine (19) 2: Left-lateral (19) 3: Prone (19)	27 ± 2	–
Jacobs et al¹⁷⁷,^*	2013	Feeds/nutrition	1: Probiotics (219) 2: Placebo (235)	<28 subgroup	–
Johnston et al¹⁷⁶	2013	Sedation/pain	1: Therapeutic touch (27) 2: Sham (28)	1: 27^2/7 ± 1/7 2: 27^3/7 ± 1/7	0
Kamlin et al¹⁷⁵	2013	Respiratory	1: Nasal tube (178) 2: Face mask (185)	1: 27.1 ± 1.5 2: 27.1 ± 1.5	0
Kanmaz et al¹⁷⁴	2013	PDA	1: Prophylactic ibuprofen (23) 2: Control/no treatment (23)	1: 25.6 ± 1.6 2: 26.4 ± 1.7	0
Kanmaz et al¹⁷³	2013	Feeds/nutrition	1: Standard fortification (23) 2: Moderate fortification (26) 3: Aggressive fortification (AF) (29)	1: 26.6 ± 2.03 2: 26.9 ± 1.94 3: 26.8 ± 2.05	0
Karen et al¹⁷²,^*	2013	Sedation/pain	1: Group 1 (20) 2: Group 2 (20)	26 (range 23-28)	–
Kirpalani et al¹⁷¹	2013	Respiratory	1: IPPV (504) 2: Nasal CPAP (503)	1: 26.1 ± 1.5 2: 26.2 ± 1.5	–
Manley et al¹⁷⁰	2013	Respiratory	1: Nasal cannula (152) 2: CPAP (151)	1: 27.7 ± 2.1 2: 27.5 ± 1.9	–
March et al¹⁶⁹	2013	Placental transfusion	1: Umbilical cord milking (36) 2: Standard cord clamping (39)	1: 25.9 (IQR 24.9-27.1) 2: 25.0 (IQR 24.3-26.4)	0
Mathew et al¹⁶⁸	2013	Thermoregulation	1: Vinyl bag (21) 2: Thermal mattress (21)	1: 26 ± 1.3 2: 26 ± 1.2	–
Ng et al¹⁶⁷	2013	Feeds/nutrition	1: Thyroxine (75) 2: Placebo (78)	1: 25.8 ± 1.3 2: 25.8 ± 1.4	–
Parikh et al¹⁶⁶	2013	Respiratory	1: Hydrocortisone (31) 2: Placebo (33)	1: 25 (IQR 24-26) 2: 25 (IQR 24-27)	2
Phelps et al¹⁶⁵	2013	Respiratory	1: Placebo (25) 2: Inositol 60 mg/kg (25) 3. Inositol 120 mg/kg (24)	1: 26.9 (range 24.0-29.3) 2: 26.7 (range 23.7-29.7) 3: 27.1 (range 23.7-29.7)	–
Pirr et al⁶⁴,^*	2013	Respiratory	1: Closed suctioning (15) 2: Open suctioning (15)	25^1/7 (range 23^6/7-29^0/7)	1
Scattolin et al¹⁶³	2013	Feeds/nutrition	1: Group S (55) 2: Group H (60)	1: 27.62 ± 2.04 2: 27.77 ± 1.96	–
Schmid et al¹⁶²,^*	2013	Respiratory	1: Protocol A (7) 2: Protocol B (9)	25.9 (range 22.6-30.4)	–
Schmidt et al¹⁶¹	2013	Respiratory	1: Target saturation 85-89% (578) 2: Target saturation 91-95% (569)	1: 25.6 ± 1.2 2: 25.6 ± 1.2	52
Stefanescu et al¹⁶⁰	2013	Other (oral hygiene)	1: BIOTENE oral care (20) 2: Sterile water oral care (21)	1: 24 (IQR 24-25) 2: 25 (IQR 24-25)	–
Taylor et al¹⁵⁹	2013	Feeds/nutrition	1: Iron supplementation (76) 2: Control (74)	1: 27.3 ± 2.0 2: 27.3 ± 2.0	1
Underwood et al¹⁵⁸	2013	Feeds/nutrition	1: F+Binf (6) 2: F+Blac (6) 3: H+Binf/Blac (4) 4: H+Blac/Binf (5)	1: 25 ± 2 2: 26 ± 2 3: 27 ± 2	–
Al-Hosni et al²⁰⁷	2012	Feeds/nutrition	1: Probiotic-supplemented (50) 2: Control (51)	1: 25.7 ± 1.4 2: 25.7 ± 1.4	–
Alsweiler et al²⁰⁶	2012	Other (glycemic control)	1: Tight group (43) 2: Control group (45)	1: 25 (IQR 24-27) 2: 25 (IQR 25-27)	2
Autrata et al²⁰⁵	2012	ROP	1: Intravitreal medication + laser (46) 2: Laser alone (41)	1: 24.7 ± 1.4 2: 25.1 ± 1.5	–
Batton et al²⁰⁴	2012	Hematologic	1: Placebo infusion (6) 2: Dopamine infusion (4)	1: 25 (range 23-26) 2: 25 (range 24-26)	1
Dani et al²⁰³	2012	PDA	1: Standard-dose ibuprofen (35) 2: High-dose ibuprofen (35)	1: 26.0 ± 1.7 2: 25.6 ± 1.8	–
Duman et al²⁰²	2012	Respiratory	1: Pressure-limited ventilation (22) 2: Volume guarantee ventilation (23)	1: 27.6 ± 2.1 2: 27.8 ± 1.7	–
Erdeve et al²⁰¹	2012	PDA	1: Oral ibuprofen (36) 2: IV ibuprofen (34)	1: 26.4 ± 1.1 2: 26.3 ± 1.3	–
Fergusson et al²⁰⁰	2012	Hematologic	1: RBCs stored 7 d or less (188) 2: Standard-issue RBCs (189)	1: 26.38 ± 1.5 2: 26.8 ± 1.8	–
Haiden et al¹⁹⁹	2012	Feeds/nutrition	1: Intervention (39) 2: Control (39)	1: 26^6/7 (range 24^1/7-30^5/7) 2: 26^6/7 (range 23^4/7-31^2/7)	–
Keller et al¹⁹⁸	2012	Respiratory	1: Late surfactant + iNO (43) 2: iNO alone (42)	1: 25.3 ± 1.4 2: 25.7 ± 1.3	–
McCain et al¹⁹⁷	2012	Feeds/nutrition	1: Controls (42) 2: Experimental (44)	1: 25.5 ± 1.5 2: 25.8 ± 1.4	–
Moya et al¹⁹⁶	2012	Feeds/nutrition	1: Control (72) 2: Liquid human milk fortifier (74)	1: 27.7 ± 0.2 2: 27.9 ± 0.2	–
O’Brien et al¹⁹⁵	2012	Respiratory	1: Biphasic nasal CPAP (67) 2: Nasal CPAP (69)	1: 27.3 ± 1.9 2: 27.4 ± 1.7	–
Ohls et al¹⁹⁴	2012	Hematologic	1: 1 × per week dosing (10) 2: 3 × per week dosing (10)	1: 27.9 ± 0.6 2: 27.8 ± 0.6	–
Ramanathan et al¹⁹³,^*	2012	Respiratory	1: Nasal intermittent positive pressure ventilation (24) 2: Nasal CPAP (25)	26-27^6/7 subgroup	0
Salvador et al¹⁹²	2012	Feeds/nutrition	1: Cycling (34) 2: Continuous (36)	1: 25.9 ± 2.0 2: 26.1 ± 2.0	–
Salvo et al¹⁹¹	2012	Respiratory	1: HFOV (44) 2: Conventional MV (44)	1: 26.4 ± 2.2 2: 26.5 ± 3.2	–
Sosenko et al¹⁹⁰	2012	PDA	1: Early ibuprofen (54) 2: Expectant management (51)	1: 26 (IQR 23-28) 2: 25 (IQR 24-29)	–
Todd et al¹⁸⁹	2012	Respiratory	1: CPAP wean method 1 (56) 2: CPAP wean method 2 (69) 3: CPAP wean method 3 (52)	1: 27.1 ± 1.4 2: 26.9 ± 1.6 3: 27.3 ± 1.5	–
Wheeler et al¹⁸⁸,^*	2012	Respiratory	1: Backup ventilation rate 30 breaths/min (26) 2: Backup ventilation rate 40 breaths/min (26) 3: Backup ventilation rate 50 breaths/min (26)	27 (IQR 26-30)	–
Balegar et al²¹⁸	2011	Hematological	1: IV furosemide (21) 2: Placebo (19)	1: 27.2 ± 1.8 2: 26.6 ± 1.7	–
Ballard et al²¹⁷	2011	Respiratory	1: Azithromycin (111) 2: Placebo (109)	1: 25.7 ± 1.5 2: 26 ± 1.6	–
Castoldi et al²¹⁶	2011	Respiratory	1: Lung recruitment maneuver in the first 3 h of life (10) 2: No lung recruitment maneuver (10)	1: 25 ± 2 2: 25 ± 2	–
Dawson et al²¹⁵	2011	Respiratory	1: T-piece resuscitation (41) 2: Self-inflating bag resuscitation (39)	1: 27 ± 1 2: 27 ± 1	0
Giannantonio et al²¹⁴,^*	2011	ROP	1: Ketorolac (47) 2: Placebo (47)	26.5 ± 1.7	–
Göpel et al²¹³	2011	Respiratory	1: LISA (108) 2: Standard treatment (112)	1: 27.6 ± 0.8 2: 27.5 ± 0.8	0
Mintz-Hittner et al, 2011²¹²	2011	ROP	1: Zone I ROP, intravitreal bevacizumab (33) 2: Zone I ROP, conventional laser (34) 3: Zone II posterior ROP, intravitreal bevacizumab (42) 4: Zone II posterior ROP, conventional laser (41)	1: 24.2 ± 1.3 2: 24.3 ± 1.6 3: 24.5 ± 1.2 4: 24.5 ± 1.4	–
Norman et al²¹¹	2011	Sedation/pain	1: Rapid induction/intubation (17) 2: Standard intubation (17)	1: 27.0 (IQR 25.6-28.5) 2: 26.6 (IQR 25.1-28.7)	–
Oh et al²¹⁰	2011	Placental transfusion	1: Immediate cord clamping (17) 2: Delayed cord clamping (16)	1: 26 ± 1.1 2: 26 ± 1.4	0
Sarafidis et al²⁰⁹	2011	Respiratory	1: SIMV (12) 2: HFOV (12)	1: 27 ± 1.8 2: 27.1 ± 1.5	–
Simon et al²⁰⁸	2011	Thermoregulation	1: Exothermic mattress (17) 2: Polyethylene wrap (19)	1: 26.0 ± 1.2 2: 25.9 ± 1.3	0
El-Naggar et al²²⁷	2010	Sedation/pain	1: Suprapubic aspiration (25) 2: Urine catheterization (23)	1: 27.4 ± 2.1 2: 27 ± 2.3	0
Fujii et al²²⁶	2010	Respiratory	1: Poractant alfa (25) 2: Beractant (25)	1: 27.1 ± 1.6 2: 26.7 ± 1.7	0
Mercado et al²²⁵	2010	Respiratory	1: Surfactant A (20) 2: Surfactant B (20)	1: 26 ± 2 2: 26 ± 1	–
Mercier et al²²⁴	2010	Respiratory	1: Placebo (401) 2: iNO (399)	1: 26.6 ± 1.3 2: 26.4 ± 1.3	0
Mihatsch et al²²³	2010	Feeds/nutrition	1: B lactis (91) 2: Placebo (89)	1: 26.6 ± 1.8 2: 26.7 ± 1.7	–
Sandri et al²²²	2010	Respiratory	1: Prophylactic surfactant (105) 2: Nasal CPAP (103)	1: 27.0 ± 1.0 2: 27.0 ± 1.0	0
Sullivan et al²²¹	2010	Feeds/nutrition	1: Human milk fortifier, 100 mL/kg/d (67) 2: Human milk fortifier, 40 mL/kg/d (71) 3: Bovine milk fortifier (69)	1: 27.2 ± 2.2 2: 27.1 ± 2.3 3: 27.3 ± 2.0	52
SUPPORT Study Group, Finer et al²²⁰	2010	Respiratory	1: CPAP (663) 2: Surfactant (653)	1: 26.2 ± 1.1 2: 26.2 ± 1.1	0
Trevisanuto et al²¹⁹	2010	Normothermic regulation	1: Cap (32) 2: Wrap (32) 3: Control (32)	1: 26.1 ± 1.4 2: 25.8 ± 1.5 3: 26.3 ± 1.0	–

Open in a new tab

ACV, assist-control ventilation; CPAP, continuous positive air pressure; FiO₂, fraction of inspired oxygen; FMM, fresh mother’s milk; FTMM, freeze-thawed mother’s milk; HFNC, high-flow nasal cannula; HHHFNC, heated, humidified high-flow nasal cannula; HFOV, high-frequency oscillatory ventilation; iNO, inhaled nitric oxide; IPPV, intermittent positive pressure ventilation; IV, intravenous; IVB, intravitreal injection of bevacizumab; IVH, intraventricular hemorrhage; LISA, less-invasive surfactant application; MV, mechanical ventilation; NAVA, neurally adjusted ventilatory assist; NIRS, near-infrared spectroscopy; PAV, proportional-assist ventilation; pCO₂, partial pressure of carbon dioxide; PDA, patent ductus arteriosus; PICC, peripherally inserted central catheter; PS, pressure support; PSV, pressure support ventilation; PVL, periventricular leukomalacia; RBCs, red blood cells; ROP, retinopathy of prematurity; SCAMP, standardized, concentrated with added macronutrients parenteral (nutrition); SIMV, synchronized intermittent mandatory ventilation; UVC, umbilical venous catheter.

“–” indicates unknown.

Gestational age and number of patients shown for entire group.

^†

As presented in the manuscript.

Table III.

General area of focus of included clinical trials (N = 201)

Respiratory	97 (48.3)
Feeds/nutrition/supplementation	38 (18.9)
PDA	13 (6.5)
Hematologic/hemostasis	10 (5.0)
ROP	9 (4.5)
Sedation/pain control/stress reduction	8 (4.0)
Infection/sepsis prevention or control	6 (3.0)
Normothermia/normothermic regulation	5 (2.5)
Placental transfusion	4 (2.0)
Other (does not fit into aforementioned categories)	11 (5.5)

Open in a new tab

Data shown as number/count (% of trials).

“Other” includes: oral hygiene/oral microbiota (n = 2); neurodevelopment and/or social outcomes (n = 2); IVH and/or PVL (n = 2); glucose and/or glycemic control (n = 2); circadian rhythm development (n = 1); immunization (n = 1); and PICC placement (n = 1).

A total of 32 552 infants were randomized among 201 clinical trials. The median number of infants was 73 (range 6-2448). Information regarding the mean or median gestational age of study participants is shown in Figure 2 (available at www.jpeds.com). Information on the sex characteristics of study participants was available for 83.6% of studies (n = 168); 47.5% (n = 14 416) were female. Information on race/ethnicity was available for 17 791 (54.7%) mothers or infants: White (n = 10 342, 58.1%); Black (n = 3780, 21.2%); Hispanic (n = 1111, 6.2%); Asian (n = 1060, 6.0%); and other or unknown (n = 1498, 8.4%). Fifty-eight studies (28.9%) described infants from multiple births enrolled in the trial (n = 4678).

Figure 2. — Bar graph showing distribution of gestational ages (mean or median) of study groups among trial manuscripts with available information (n = 197). * Gestational age could not be determined in 4 clinical trials with designated subgroups <28 weeks of gestation.

Among included clinical trials, 1603 eligibility criteria across 9 thematic categories were identified (Table IV). Rationales for stated inclusion and exclusion criteria were found for 301 eligibility criteria (18.8%). In 75 (37.3%) clinical trials, infants <24 weeks of gestation were eligible to participate; conversely, among 126 (62.7%) clinical studies, infants <24 weeks of gestation were either not eligible (n = 36) or eligibility could not be clearly determined (n = 90). Minimum gestational age thresholds (age requirements) were identified in 67 (33.3%) clinical trials: n = 3 at 22 weeks of gestation; n = 30 at 23 weeks of gestation; and n = 34 at ≥24 weeks of gestation. Twenty-one clinical trials (10.4%) provided only birth weight eligibility criteria.

Table IV.

Eligibility criteria (N = 1603): categorization and examples

Categories	Examples	No. (% of eligibility criteria)
Contraindications, confounding treatment(s) or condition(s)	• Diagnosis of necrotizing enterocolitis • Indications of kidney dysfunction or injury, metabolic dysfunction, and/or liver failure • Pre-existing condition with known increased risk for neurodevelopmental impairment	412 (25.7)
Trial-specific requirements	• On mechanical ventilation • Receiving parenteral nutrition	318 (19.8)
Age- and/or weight-based	• Born before 28 weeks of gestation • Gestational age of 23 weeks 0 days to 27 weeks 6 days • Birth weight <1000 g	279 (17.4)
Legal/logistical	• Inability to obtain informed consent • Inborn only	245 (15.3)
Chromosomal or congenital anomalies	• Major congenital malformations • Major congenital anomalies • Severe congenital anomalies • Chromosomal abnormalities • Complex congenital heart disease	206 (12.9)
Concern for prognosis	• Withholding life support • Limiting life supporting treatment • Decision to provide compassionate care	112 (7.0)
Concurrent enrollment	• Enrolled in other trial	18 (1.1)
Other	• Elevated peak systolic velocity of the fetal middle cerebral artery • Meconium-stained amniotic fluid	10 (0.6)
Spoken or written language ability	• English- or Spanish-speaking mothers only	3 (0.2)

Open in a new tab

Fifty-five clinical trials (27.4%) enrolled infants <24 weeks of gestation. Among 32 552 trial participants, 454 (1.4%) were identified as <24 weeks of gestation (n = 13, 22 weeks of gestation; n = 249, 23 weeks of gestation; and n = 192, 22 or 23 weeks of gestation). Justifications for exclusion of infants <24 weeks are included in Table V (available at www.jpeds.com). Compared with Epoch 1 (0.8%), we observed an increased proportion of infants <24 weeks of gestation participating in trials in Epoch 2 (1.9%; P < .01).

Table V.

Rationales provided for exclusion of infants <24 weeks from a trial

SUPPORT study group, provided by N. Finer, MD (N Engl J Med 2010;362:1970-9)	“…most units reported that very few infants of 23 weeks could be resuscitated without early intubation, and therefore they were excluded, per a preliminary feasibility study.”
Hair et al¹⁵¹	“Usually bedside attending would not allow us to approach family due to critical nature of 23 week infant or infants were too sick.”
Baud et al¹⁰³	“23-week infants were excluded from the PREMILOC trial because they were usually not resuscitated when the trial began. If the trial would start now probably this exclusion criteria won’t be used.”
Lemyre et al⁷⁴	“Infants born below 24 weeks were excluded as judged too unstable or not universally resuscitated by all participating centers to be included.”
Abou et al⁵²	“…for 22-23 + 6 we do resuscitation in some cases based on an internal pathway and guidelines looking at maternal history and the best interest of that fetus/baby (limits of viability pathway and guidelines); thus we decided to exclude, as not all would receive resuscitation.”
Reilly et al²²⁸	“Our decision to exclude these infants ≤23 weeks of gestation. from the main study was because of their much higher mortality rate (mortality was our primary outcome). We also recognized that at the time of our study, centres varied considerably regarding resuscitation of these infants.”
Onland et al³³	“Infants at 23 weeks’ are not resuscitated or provided life-sustaining measures.”

Open in a new tab

Numbers of eligibility criteria were associated with greater-quality studies (Table VI; available at www.jpeds.com). Clinical trials excluding infants born at <24 weeks of gestation were not associated with cohort size, study quality rating, journal impact factor, or respiratory focus (Table VII; available at www.jpeds.com); however, an association between epoch and exclusion of infants <24 weeks was observed (P < .01). This may be attributed to a greater number of studies in the second epoch providing clear definitions of inclusion or exclusion of these infants.

Table VI.

Eligibility criteria (univariable regression models)

Variables	Estimated mean (95% CI)	P value
Cohort sample size
<50	7.6 (7.1-8.4)	.72
50-99	8.3 (7.5-9.2)
100-199	8.1 (7.1-9.1)
200 or more	7.8 (6.8-8.7)
Epoch (publication year)
2010-2014	8.2 (7.6-8.8)	.22
2015-2019	7.7 (7.1-8.3)
Quality
High quality	8.2 (7.8-8.7)	.02
Moderate or low quality	7.1 (6.4-7.9)
Journal Impact Factor
<5	8.0 (7.5-8.5)	.78
≥5	7.9 (7.1-8.6)
Respiratory study focus
Respiratory focus	7.8 (7.2-8.4)	.56
Nonrespiratory focus	8.1 (7.5-8.6)

Open in a new tab

P value in bold indicate statistically significant differences.

Table VII.

Trial characteristics for age-based exclusion criteria

Trial characteristics	Infants <24 weeks eligible			P value*
Trial characteristics	Yes, No. (%)	No, No. (%)	Unknown, No. (%)	P value*
Cohort sample size
<50	16 (45.7)	24 (32.4)	41 (44.6)	.09
50-99	7 (20.0)	24 (32.4)	17 (18.4)
100-199	2 (5.7)	13 (17.6)	19 (20.7)
200 or more	10 (28.6)	13 (17.6)	15 (16.3)
Epoch (publication year)
2010-2014	15 (42.9)	23 (31.1)	54 (58.7)	.002
2015-2019	20 (57.1)	51 (68.9)	38 (41.3)
Quality
High quality	28 (80.0)	57 (77.0)	62 (67.4)	.24
Moderate or low quality	7 (20.0)	17 (23.0)	30 (32.6)
Journal Impact Factor
≥5	23 (69.7)	47 (66.2)	69 (77.5)	.27
<5	10 (30.3)	24 (33.8)	20 (22.5)
Respiratory study focus
Respiratory focus	12 (34.3)	40 (54.1)	50 (54.6)	.11
Nonrespiratory focus	23 (65.7)	34 (46.0)	42 (45.7)

Open in a new tab

P value in bold indicate statistically significant differences.

Discussion

In view of concerns about the safety and efficacy of extrapolating data from older, more mature infants, we sought to characterize the strength of available evidence from RCTs that included infants born extremely preterm.^2,3 Our systematic review revealed marked variability and widely ranging heterogeneity of the RCTs from which the data were drawn, most notably a lack of harmonized inclusion and exclusion criteria across trials. The present study helps to identify sources of variability across RCTs and reinforces the critical need for more consistent and transparent policies governing eligibility criteria and trial characteristics.^229,230

Previous investigators have reported differences in the willingness of healthcare providers to initiate or withhold treatment, as well as expectations for survival, among infants born at <24 weeks of gestation vs those born at ≥24 weeks of gestation.^4,15,231 This led to our a priori decision to classify infants born at <24 weeks gestation as a “high-risk” subgroup. Exclusion from representation in RCTs of infants born at <24 weeks of gestation leaves this group of infants in an area of “therapeutic uncertainty,” including the potential for increased harm from inappropriate generalizations of results from trials with larger, more mature infants.^11,13 Careful analyses of stratified data among lower gestational age subgroups may identify heterogeneity in treatment responses.^22,229 However, to establish the necessary evidence base, greater inclusion of infants born at <24 weeks of gestation in well-designed and rigorously monitored clinical trials is paramount. The National Institutes of Health recently established the Inclusion Across the Lifespan Policy, with a goal of expanding representation of underrepresented patient populations in clinical research.^229,232 Although the policy has been applied largely to ensure that older adults are not inappropriately excluded from clinical trials, studies among subgroups of patients at the opposite end of the life spectrum (eg, <24 weeks of gestation) are needed.^229,233

Traditionally, investigators have argued that racial/ethnic disparities among infants born extremely preterm contribute to differences in short- and longer-term outcomes. In the US, infant mortality rates are greater among Black infants than among White infants.²³⁴ However, a recent large multicenter cohort study observed no racial/ethnic differences in mortality rate trends among infants born extremely preterm, with mortality decreasing over time across all groups.²⁰ To begin to answer fundamental questions on the impact of racial/ethnic differences on important outcomes, more granular, transparent information on the race/ethnicity of mother–infant dyads participating in clinical studies is needed.²²⁹ Given that we were unable to discern the race/ethnicity of a significant proportion of infants born extremely preterm in the present study, the provision of anonymized, individual-level data on race/ethnicity from RCTs would be valuable.^11,13

Contemporary clinical trials are challenged by limited funding sources, high costs, and mounting regulatory deterrents. These barriers serve to motivate healthcare providers to design and conduct RCTs with strict eligibility criteria, resulting in studies that are smaller, less expensive, and more readily executed. However, the benefits of strict eligibility criteria are offset by the risk of excluding patients who represent the populations treated in everyday clinical settings. As noted by Song and Bianchi, “…the exclusion of populations simply because they may take more time to include or are considered vulnerable is unacceptable and stands in contrast to the ethical principles of equity and justice” (p 337).²³⁰ To enable healthcare providers to evaluate more clearly the generalizability of the results, each eligibility criterion should be justified clearly within the methods section (or appendix) that is accessible and apparent to the reader.^11,13 In addition, nonspecific exclusionary terms such as “congenital anomalies” should be avoided and replaced with more specific criteria (eg, infants with Trisomy 13 or Trisomy 18).^9,13

The present study has several important limitations. In contrast to studies among adult patients, classification of the eligibility criteria (strongly justified, potentially justified, poorly justified) was not possible, given the marked heterogeneity in study design and trial characteristics.¹³ We acknowledge that the fundamental question of whether managing infants <24 weeks of gestation is different than managing infants at ≥24 weeks gestation remains unanswered, and that factors beyond gestational age (eg, birth weight, infant sex, antenatal corticosteroids) contribute to short- and longer-term outcomes.²³⁵ Although the average gestational ages of infants included in the analysis were <28 weeks of gestation, some infants born beyond 28 weeks of gestation were included. Although we made considerable efforts to identify eligibility criteria, including searching for criteria beyond the primary paper (eg, using ClinicalTrials.gov), our observations may underestimate the true number of inclusions and exclusions. Some trials did not report participant flow (eg, study flow diagram), making it challenging to determine the numbers of infants excluded from participation. Although we used publication year to define the 2 epochs, we acknowledge delays in publication following trial completion. Although we observed differences between epoch and the exclusion of infants <24 weeks of gestation, subgroups were small.

We used a transparent framework for adjudication to describe authors’ rationales for their chosen eligibility criteria, but such a classification is inherently subjective. Because RCTs are the best method to assess therapeutic efficacy, observational studies were excluded; however, we acknowledge that, in the absence of sufficient data, healthcare providers may have to rely on observational data to guide clinical care.²³⁶ We separated RCTs into high- and low-impact studies; however, this distinction was largely arbitrary and that article citation counts are influenced by a number of factors beyond study quality.²³⁷ We recognize limitations in the use of the modified Jadad scale to evaluate highly diverse studies.²⁴ For example, the Jadad scale decreases the quality of a RCT for nonblinding, which cannot be overcome easily when comparing different forms of respiratory therapy in infants born preterm (eg, continuous positive airway pressure vs high-flow nasal cannula). Finally, it is conceivable that relevant published peer-reviewed evidence was not identified, and disagreements about whether specific trials should have been included (or excluded) may be justified.

In conclusion, we identified wide heterogeneity of the RCTs we examined, including a lack of harmonized inclusion and exclusion criteria. To provide the necessary evidence-base among highly vulnerable subgroups (eg, infants <24 weeks of gestation), prespecified subgroup analyses will be paramount. In RCTs among infants born extremely preterm, justification of eligibility criteria and transparent reporting is critically needed.

Supplementary Material

suppl 1

NIHMS1823121-supplement-suppl_1.doc^{(64.5KB, doc)}

suppl 2

NIHMS1823121-supplement-suppl_2.docx^{(12.3KB, docx)}

Acknowledgments

Funded by the Ohio Perinatal Research Network (OPRN) within the Nationwide Children’s Hospital Abigail Wexner Research Institute. The authors declare no conflicts of interest.

We thank the Research Librarians at Nationwide Children’s Hospital, Alison Gehred, Susan Jones, and Cailin Coane for their assistance in the database searches and interlibrary loan requests for articles that were not otherwise available. We also thank the physicians and fellow researchers who responded to our email queries and provided additional information.

References

1.Lau C, Ambalavanan N, Chakraborty H, Wingate MS, Carlo WA. Extremely low birth weight and infant mortality rates in the United States. Pediatrics 2013;131:855–60. [DOI] [PubMed] [Google Scholar]
2.Kimland E, Odlind V. Off-label drug use in pediatric patients. Clin Pharmacol Ther 2012;91:796–801. [DOI] [PubMed] [Google Scholar]
3.Nasr VG, Davis JM. Anesthetic use in newborn infants: the urgent need for rigorous evaluation. Pediatr Res 2015;78:2–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Patel RM, Rysavy MA, Bell EF, Tyson JE. Survival of infants born at periviable gestational ages. Clin Perinatol 2017;44:287–303. [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Younge N, Goldstein RF, Bann CM, Hintz SR, Patel RM, Smith PB, et al. Survival and neurodevelopmental outcomes among periviable infants. N Engl J Med 2017;376:617–28. [DOI] [PMC free article] [PubMed] [Google Scholar]
6.Willhelm C, Girisch W, Gottschling S, Graber S, Wahl H, Meyer S. Systematic Cochrane reviews in neonatology: a critical appraisal. Pediatr Neonatol 2013;54:261–6. [DOI] [PubMed] [Google Scholar]
7.Guyatt GH, Haynes RB, Jaeschke RZ, Cook DJ, Green L, Naylor CD, et al. Users’ Guides to the Medical Literature: XXV. Evidence-based medicine: principles for applying the Users’ Guides to patient care. Evidence-Based Medicine Working Group. JAMA 2000;284:1290–6. [DOI] [PubMed] [Google Scholar]
8.Rothwell PM. External validity of randomised controlled trials: “to whom do the results of this trial apply?” Lancet 2005;365:82–93. [DOI] [PubMed] [Google Scholar]
9.Guyatt GH, Sackett DL, Cook DJ. Users’ guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA 1993;270:2598–601. [DOI] [PubMed] [Google Scholar]
10.Patel HC, Hayward C, Dungu JN, Papadopoulou S, Saidmeerasah A, Ray R, et al. Assessing the eligibility criteria in phase III randomized controlled trials of drug therapy in heart failure with preserved ejection fraction: the critical play-off between a “pure” patient phenotype and the generalizability of trial findings. J Card Fail 2017;23:517–24. [DOI] [PubMed] [Google Scholar]
11.Van Spall HG, Toren A, Kiss A, Fowler RA. Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA 2007;297:1233–40. [DOI] [PubMed] [Google Scholar]
12.Florisson S, Aagesen EK, Bertelsen AS, Nielsen LP, Rosholm JU. Are older adults insufficiently included in clinical trials?-An umbrella review. Basic Clin Pharmacol Toxicol 2021;128:213–23. [DOI] [PubMed] [Google Scholar]
13.Gurwitz JH, Col NF, Avorn J. The exclusion of the elderly and women from clinical trials in acute myocardial infarction. JAMA 1992;268: 1417–22. [PubMed] [Google Scholar]
14.Lam M, Zhu JW, Maqbool T, Adam G, Tadrous M, Rochon P, et al. Inclusion of older adults in randomized clinical trials for systemic medications for atopic dermatitis: a systematic review. JAMA Dermatol 2020;156:1240–5. [DOI] [PubMed] [Google Scholar]
15.Rysavy MA, Li L, Bell EF, Das A, Hintz SR, Stoll BJ, et al. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med 2015;372:1801–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
16.Booth A, Clarke M, Ghersi D, Moher D, Petticrew M, Stewart L. An international registry of systematic-review protocols. Lancet 2011;377:108–9. [DOI] [PubMed] [Google Scholar]
17.Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62:1006–12. [DOI] [PubMed] [Google Scholar]
18.Richardson WS, Wilson MC, Nishikawa J, Hayward RS. The well-built clinical question: a key to evidence-based decisions. ACP J Club 1995;123:A12–3. [PubMed] [Google Scholar]
19.Balk EM, Chung M, Hadar N, Patel K, Yu WW, Trikalinos TA, et al. Accuracy of data extraction of non-english language trials with google translate. methods research report (Prepared by the Tufts Evidence-based Practice Center under Contract No. 290-2007-10055 I.). Rockville (MD): Agency for Healthcare Research and Quality; 2012. [PubMed] [Google Scholar]
20.Travers CP, Carlo WA, McDonald SA, Das A, Ambalavanan N, Bell EF, et al. Racial/ethnic disparities among extremely preterm infants in the United States fFrom 2002 to 2016. JAMA Netw Open 2020;3:e206757. [DOI] [PMC free article] [PubMed] [Google Scholar]
21.Journal Impact Search. Accessed March 17, 2021. https://www.bioxbio.com
22.Raju TNK, Mercer BM, Burchfield DJ, Joseph GF Jr. Periviable birth: executive summary of a joint workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists. Obstet Gynecol 2014;123:1083–96. [DOI] [PubMed] [Google Scholar]
23.United States Food and Drug Administration. Public workshop: evaluating inclusion and exclusion criteria in clinical trials. Workshop Report. Silver Spring (MD): USFDA; 2018. [Google Scholar]
24.Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1–12. [DOI] [PubMed] [Google Scholar]
25.Oremus M, Wolfson C, Perrault A, Demers L, Momoli F, Moride Y. Interrater reliability of the modified Jadad quality scale for systematic reviews of Alzheimer’s disease drug trials. Dement Geriatr Cogn Disord 2001;12:232–6. [DOI] [PubMed] [Google Scholar]
26.Zhang Y, Zhou L, Liu X, Liu L, Wu Y, Zhao Z, et al. The effectiveness of the problem-based learning teaching model for use in introductory Chinese undergraduate medical courses: a systematic review and meta-analysis. PLoS One 2015;10:e0120884. [DOI] [PMC free article] [PubMed] [Google Scholar]
27.Wejryd E, Marchini G, Frimmel V, Jonsson B, Abrahamsson T. Probiotics promoted head growth in extremely low birth weight infants in a double-blind placebo-controlled trial. Acta Paediatr 2019;108:62–9. [DOI] [PubMed] [Google Scholar]
28.Thomson L, Elleri D, Bond S, Howlett J, Dunger DB, Beardsall K. Targeting glucose control in preterm infants: pilot studies of continuous glucose monitoring. Arch Dis Child Fetal Neonatal Ed 2019;104:F353–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
29.Reynolds PR, Miller TL, Volakis LI, Holland N, Dungan GC, Roehr CC, et al. Randomised cross-over study of automated oxygen control for preterm infants receiving nasal high flow. Arch Dis Child Fetal Neonatal Ed 2019;104:F366–71. [DOI] [PubMed] [Google Scholar]
30.Rath CP, Thomas M, Sullivan D, Kluckow M. Does the use of an iodine-containing contrast agent to visualise the PICC tip in preterm babies cause hypothyroidism? A randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2019;104:F212–4. [DOI] [PubMed] [Google Scholar]
31.Pereira SS, Sinha AK, Morris JK, Wertheim DF, Shah DK, Kempley ST. Blood pressure intervention levels in preterm infants: pilot randomised trial. Arch Dis Child Fetal Neonatal Ed 2019;104:F298–305. [DOI] [PubMed] [Google Scholar]
32.Parker LA, Weaver M, Murgas Torrazza RJ, Shuster J, Li N, Krueger C, et al. Effect of gastric residual evaluation on enteral intake in extremely preterm infants: a randomized clinical trial. JAMA Pediatr 2019;173: 534–43. [DOI] [PMC free article] [PubMed] [Google Scholar]
33.Onland W, Cools F, Kroon A, Rademaker K, Merkus MP, Dijk PH, et al. Effect of hydrocortisone therapy initiated 7 to 14 days after birth on mortality or bronchopulmonary dysplasia among very preterm infants receiving mechanical ventilation: a randomized clinical trial. JAMA 2019;321:354–63. [DOI] [PMC free article] [PubMed] [Google Scholar]
34.O’Currain E, O’Shea JE, McGrory L, Owen LS, Kamlin O, Dawson JA, et al. Smaller facemasks for positive pressure ventilation in preterm infants: a randomised trial. Resuscitation 2019;134:91–8. [DOI] [PubMed] [Google Scholar]
35.Marr BL, Mettelman BB, Bode MM, Gross SJ. Randomized trial of 42-day compared with 9-day courses of dexamethasone for the treatment of evolving bronchopulmonary dysplasia in extremely preterm infants. J Pediatr 2019;211:20–6.e1. [DOI] [PubMed] [Google Scholar]
36.Ley D, Hallberg B, Hansen-Pupp I, Dani C, Ramenghi LA, Marlow N, et al. rhIGF-1/rhIGFBP-3 in preterm infants: a phase 2 randomized controlled trial. J Pediatr 2019;206:56–65.e8. [DOI] [PMC free article] [PubMed] [Google Scholar]
37.Latremouille S, Shalish W, Kanbar L, Lamer P, Rao S, Kearney RE, et al. The effects of nasal continuous positive airway pressure and high flow nasal cannula on heart rate variability in extremely preterm infants after extubation: a randomized crossover trial. Pediatr Pulmonol 2019;54:788–96. [DOI] [PubMed] [Google Scholar]
38.Kochan M, Leonardi B, Firestine A, McPadden J, Cobb D, Shah TA, et al. Elevated midline head positioning of extremely low birth weight infants: effects on cardiopulmonary function and the incidence of periventricular-intraventricular hemorrhage. J Perinatol 2019;39:54–62. [DOI] [PubMed] [Google Scholar]
39.Kluckow M, Carlisle H, Broom M, Woods P, Jeffery M, Desai D, et al. A pilot randomised blinded placebo-controlled trial of paracetamol for later treatment of a patent ductus arteriosus. J Perinatol 2019;39:102–7. [DOI] [PubMed] [Google Scholar]
40.Kirpalani H, Ratcliffe SJ, Keszler M, Davis PG, Foglia EE, Te Pas A, et al. Effect of sustained inflations vs intermittent positive pressure ventilation on bronchopulmonary dysplasia or death among extremely preterm infants: the SAIL randomized clinical trial. JAMA 2019;321:1165–75. [DOI] [PMC free article] [PubMed] [Google Scholar]
41.Hunt K, Dassios T, Ali K, Greenough A. Volume targeting levels and work of breathing in infants with evolving or established bronchopulmonary dysplasia. Arch Dis Child Fetal Neonatal Ed 2019;104:F46–9. [DOI] [PubMed] [Google Scholar]
42.Gajdos M, Waitz M, Mendler MR, Braun W, Hummler H. Effects of a new device for automated closed loop control of inspired oxygen concentration on fluctuations of arterial and different regional organ tissue oxygen saturations in preterm infants. Arch Dis Child Fetal Neonatal Ed 2019;104:F360–5. [DOI] [PubMed] [Google Scholar]
43.Fischer HS, Buhrer C, Czernik C. Hazards to avoid in future neonatal studies of nasal high-frequency oscillatory ventilation: lessons from an early terminated trial. BMC Res Notes 2019;12:237. [DOI] [PMC free article] [PubMed] [Google Scholar]
44.El-Naggar W, Simpson D, Hussain A, Armson A, Dodds L, Warren A, et al. Cord milking versus immediate clamping in preterm infants: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2019;104:F145–50. [DOI] [PubMed] [Google Scholar]
45.de Vries LS, Groenendaal F, Liem KD, Heep A, Brouwer AJ, van ’t Verlaat E, et al. Treatment thresholds for intervention in posthaemorrhagic ventricular dilation: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2019;104:F70–5. [DOI] [PubMed] [Google Scholar]
46.Curley A, Stanworth SJ, Willoughby K, Fustolo-Gunnink SF, Venkatesh V, Hudson C, et al. Randomized trial of platelet-transfusion thresholds in neonates. N Engl J Med 2019;380:242–51. [DOI] [PubMed] [Google Scholar]
47.Clyman RI, Liebowitz M, Kaempf J, Erdeve O, Bulbul A, Hakansson S, et al. PDA-TOLERATE Trial: an exploratory randomized controlled trial of treatment of moderate-to-large patent ductus arteriosus at 1 week of age. J Pediatr 2019;205:41–8.e6. [DOI] [PMC free article] [PubMed] [Google Scholar]
48.Claassen CC, Hillman NH, Brown K, Williams HL, Strand ML. Comparison of Bubble CPAP Devices Using RAM Cannula for Extubation Failure in Very Low Birth Weight Infants: Randomized and Cohort Studies. Neonatology 2019;115:28–35. [DOI] [PubMed] [Google Scholar]
49.Chuang LJ, Wang SH, Ma MC, Lin CN, Chen CL, Huang MC. A modified developmental care bundle reduces pain and stress in preterm infants undergoing examinations for retinopathy of prematurity: A randomised controlled trial. J Clin Nurs 2019;28:545–59. [DOI] [PubMed] [Google Scholar]
50.Balasubramanian H, Malpani P, Sindhur M, Kabra NS, Ahmed J, Srinivasan L. Effect of umbilical cord blood sampling versus admission blood sampling on requirement of blood transfusion in extremely preterm infants: a randomized controlled trial. J Pediatr 2019;211:39–45.e2. [DOI] [PubMed] [Google Scholar]
51.Arsenault AB, Gunsalus KTW, Laforce-Nesbitt SS, Przystac L, DeAngelis EJ, Hurley ME, et al. Dietary supplementation with medium-chain triglycerides reduces Candida gastrointestinal colonization in preterm infants. Pediatr Infect Dis J 2019;38:164–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
52.Abounahia FF, Abu-Jarir R, Abounahia MF, Al-Badriyeh D, Abushanab D, Abu-Ghalwa M, et al. Prophylactic sildenafil in preterm infants at risk of bronchopulmonary dysplasia: a pilot randomized, double-blinded, placebo-controlled trial. Clin Drug Investig 2019;39:1093–107. [DOI] [PMC free article] [PubMed] [Google Scholar]
53.van den Heuvel MEN, van Zanten HA, Bachman TE, Te Pas AB, van Kaam AH, Onland W. Optimal target range of closed-loop inspired oxygen support in preterm infants: a randomized cross-over study. J Pediatr 2018;197:36–41. [DOI] [PubMed] [Google Scholar]
54.Travers CP, Carlo WA, Nakhmani A, Bhatia S, Gentle SJ, Amperayani VA, et al. Environmental or nasal cannula supplemental oxygen for preterm infants: a randomized cross-over trial. J Pediatr 2018;200:98–103. [DOI] [PMC free article] [PubMed] [Google Scholar]
55.Strunk T, Pupala S, Hibbert J, Doherty D, Patole S. Topical coconut oil in very preterm infants: an open-label randomised controlled trial. Neonatology 2018;113:146–51. [DOI] [PubMed] [Google Scholar]
56.Spittle AJ, Treyvaud K, Lee KJ, Anderson PJ, Doyle LW. The role of social risk in an early preventative care programme for infants born very preterm: a randomized controlled trial. Dev Med Child Neurol 2018;60: 54–62. [DOI] [PubMed] [Google Scholar]
57.Salas AA, Li P, Parks K, Lal CV, Martin CR, Carlo WA. Early progressive feeding in extremely preterm infants: a randomized trial. Am J Clin Nutr 2018;107:365–70. [DOI] [PMC free article] [PubMed] [Google Scholar]
58.Rüegger CM, Lorenz L, Kamlin COF, Manley BJ, Owen LS, Bassler D, et al. The effect of noninvasive high-frequency oscillatory ventilation on desaturations and bradycardia in very preterm infants: a randomized crossover trial. J Pediatr 2018;201:269–73.e2. [DOI] [PubMed] [Google Scholar]
59.Rosterman JL, Pallotto EK, Truog WE, Escobar H, Meinert KA, Holmes A, et al. The impact of neurally adjusted ventilatory assist mode on respiratory severity score and energy expenditure in infants: a randomized crossover trial. J Perinatol 2018;38:59–63. [DOI] [PubMed] [Google Scholar]
60.Phelps DL, Watterberg KL, Nolen TL, Cole CA, Cotten CM, Oh W, et al. Effects of myo-inositol on type 1 retinopathy of prematurity among preterm infants <28 weeks’ gestational age: a randomized clinical trial. JAMA 2018;320:1649–58. [DOI] [PMC free article] [PubMed] [Google Scholar]
61.McGrory L, Owen LS, Thio M, Dawson JA, Rafferty AR, Malhotra A, et al. A randomized trial of conditioned or unconditioned gases for stabilizing preterm infants at birth. J Pediatr 2018;193:47–53. [DOI] [PubMed] [Google Scholar]
62.Klotz D, Schneider H, Schumann S, Mayer B, Fuchs H. Non-invasive high-frequency oscillatory ventilation in preterm infants: a randomised controlled cross-over trial. Arch Dis Child Fetal Neonatal Ed 2018;103:F1–5. [DOI] [PubMed] [Google Scholar]
63.Kieran EA, O’Sullivan A, Miletin J, Twomey AR, Knowles SJ, O’Donnell CPF. 2% chlorhexidine-70% isopropyl alcohol versus 10% povidone-iodine for insertion site cleaning before central line insertion in preterm infants: a randomised trial. Arch Dis Child Fetal Neonatal Ed 2018;103:F101–6. [DOI] [PubMed] [Google Scholar]
64.Imbulana DI, Owen LS, Dawson JA, Bailey JL, Davis PG, Manley BJ. A randomized controlled trial of a barrier dressing to reduce nasal injury in preterm infants receiving binasal noninvasive respiratory support. J Pediatr 2018;201:34–9.e3. [DOI] [PubMed] [Google Scholar]
65.Hochwald O, Mainzer G, Borenstein-Levin L, Jubran H, Dinur G, Zucker M, et al. Adding paracetamol to ibuprofen for the treatment of patent ductus arteriosus in preterm infants: a double-blind, randomized, placebo-controlled pilot study. Am J Perinatol 2018;35:1319–25. [DOI] [PubMed] [Google Scholar]
66.Gerges A, Gelfer P, Kennedy K. Randomized trial of earlier versus later oral feeding in very premature infants. J Perinatol 2018;38:687–92. [DOI] [PubMed] [Google Scholar]
67.Eze N, Murphy D, Dhar V, Rehan VK. Comparison of sprinting vs non-sprinting to wean nasal continuous positive airway pressure off in very preterm infants. J Perinatol 2018;38:164–8. [DOI] [PubMed] [Google Scholar]
68.Bottino R, Pontiggia F, Ricci C, Gambacorta A, Paladini A, Chijenas V, et al. Nasal high-frequency oscillatory ventilation and CO2 removal: a randomized controlled crossover trial. Pediatr Pulmonol 2018;53:1245–51. [DOI] [PubMed] [Google Scholar]
69.Amaro CM, Bello JA, Jain D, Ramnath A, D’Ugard C, Vanbuskirk S, et al. Early caffeine and weaning from mechanical ventilation in preterm infants: a randomized, placebo-controlled trial. J Pediatr 2018;196:52–7. [DOI] [PubMed] [Google Scholar]
70.Williams FLR, Ogston S, Hume R, Watson J, Stanbury K, Willatts P, et al. Supplemental iodide for preterm infants and developmental outcomes at 2 years: an RCT. Pediatrics 2017;139:e20163703. [DOI] [PubMed] [Google Scholar]
71.Shetty S, Hunt K, Peacock J, Ali K, Greenough A. Crossover study of assist control ventilation and neurally adjusted ventilatory assist. Eur J Pediatr 2017;176:509–13. [DOI] [PubMed] [Google Scholar]
72.Najm S, Lofqvist C, Hellgren G, Engstrom E, Lundgren P, Hard AL, et al. Effects of a lipid emulsion containing fish oil on polyunsaturated fatty acid profiles, growth and morbidities in extremely premature infants: a randomized controlled trial. Clin Nutr ESPEN 2017;20:17–23. [DOI] [PMC free article] [PubMed] [Google Scholar]
73.Mukerji A, Sarmiento K, Lee B, Hassall K, Shah V. Non-invasive high-frequency ventilation versus bi-phasic continuous positive airway pressure (BP-CPAP) following CPAP failure in infants <1250 g: a pilot randomized controlled trial. J Perinatol 2017;37:49–53. [DOI] [PubMed] [Google Scholar]
74.Lemyre B, Fusch C, Schmolzer GM, Rouvinez Bouali N, Reddy D, Barrowman N, et al. Poractant alfa versus bovine lipid extract surfactant for infants 24+0 to 31+6 weeks gestational age: a randomized controlled trial. PLoS One 2017;12:e0175922. [DOI] [PMC free article] [PubMed] [Google Scholar]
75.Kugelman A, Peniakov M, Zangen S, Shiff Y, Riskin A, Iofe A, et al. Inhaled hydrofluoalkane-beclomethasone dipropionate in bronchopulmonary dysplasia. A double-blind, randomized, controlled pilot study. J Perinatol 2017;37:197–202. [DOI] [PubMed] [Google Scholar]
76.Jiravisitkul P, Rattanasiri S, Nuntnarumit P. Randomised controlled trial of sustained lung inflation for resuscitation of preterm infants in the delivery room. Resuscitation 2017;111:68–73. [DOI] [PubMed] [Google Scholar]
77.Hasan SU, Potenziano J, Konduri GG, Perez JA, Van Meurs KP, Walker MW, et al. Effect of inhaled nitric oxide on survival without bronchopulmonary dysplasia in preterm infants: a randomized clinical trial. JAMA Pediatr 2017;171:1081–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
78.Hansen-Pupp I, Hellstrom A, Hamdani M, Tocoian A, Kreher NC, Ley D, et al. Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: evaluation of feasibility in a phase II study. Growth Horm IGF Res 2017;36:44–51. [DOI] [PubMed] [Google Scholar]
79.Glackin SJ, O’Sullivan A, George S, Semberova J, Miletin J. High flow nasal cannula versus NCPAP, duration to full oral feeds in preterm infants: a randomised controlled trial. Arch Dis Child-Fetal 2017;102:F329–32. [DOI] [PubMed] [Google Scholar]
80.El-Mashad AE, El-Mahdy H, El Amrousy D, Elgendy M. Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates. Eur J Pediatr 2017;176:233–40. [DOI] [PubMed] [Google Scholar]
81.Collins CT, Makrides M, McPhee AJ, Sullivan TR, Davis PG, Thio M, et al. Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants. N Engl J Med 2017;376:1245–55. [DOI] [PubMed] [Google Scholar]
82.Brandon DH, Silva SG, Park J, Malcolm W, Kamhawy H, Holditch-Davis D. Timing for the introduction of cycled light for extremely preterm infants: a randomized controlled trial. Res Nurs Health 2017;40:294–310. [DOI] [PMC free article] [PubMed] [Google Scholar]
83.Ben Jmaa W, Hernandez AI, Sutherland MR, Cloutier A, Germain N, Lachance C, et al. Cardio-respiratory events and inflammatory response after primary immunization in preterm infants < 32 weeks gestational age: a randomized controlled study. Pediatr Infect Dis J 2017;36:988–94. [DOI] [PubMed] [Google Scholar]
84.Beker F, Opie G, Noble E, Jiang Y, Bloomfield FH. Smell and taste to improve nutrition in very preterm infants: a randomized controlled pilot trial. Neonatology 2017;111:260–6. [DOI] [PubMed] [Google Scholar]
85.Alkan Ozdemir S, Arun Ozer E, Ilhan O, Sutcuoglu S. Impact of targeted-volume ventilation on pulmonary dynamics in preterm infants with respiratory distress syndrome. Pediatr Pulmonol 2017;52:213–6. [DOI] [PubMed] [Google Scholar]
86.Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, et al. Intratracheal administration of budesonide/surfactant to prevent bronchopulmonary dysplasia. Am J Respir Crit Care Med 2016;193:86–95. [DOI] [PubMed] [Google Scholar]
87.Victor S, Roberts SA, Mitchell S, Aziz H, Lavender T, Extubate Trial G. Biphasic positive airway pressure or continuous positive airway pressure: a randomized trial. Pediatrics 2016;138:e20154095. [DOI] [PubMed] [Google Scholar]
88.Vesoulis ZA, McPherson C, Neil JJ, Mathur AM, Inder TE. Early high-dose caffeine increases seizure burden in extremely preterm neonates: a preliminary study. J Caffeine Res 2016;6:101–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
89.Sohn K, Kalanetra KM, Mills DA, Underwood MA. Buccal administration of human colostrum: impact on the oral microbiota of premature infants. J Perinatol 2016;36:106–11. [DOI] [PubMed] [Google Scholar]
90.Shetty S, Hickey A, Rafferty GF, Peacock JL, Greenough A. Work of breathing during CPAP and heated humidified high-flow nasal cannula. Arch Dis Child Fetal Neonatal Ed 2016;101:F404–7. [DOI] [PubMed] [Google Scholar]
91.Shetty S, Bhat P, Hickey A, Peacock JL, Milner AD, Greenough A. Proportional assist versus assist control ventilation in premature infants. Eur J Pediatr 2016;175:57–61. [DOI] [PubMed] [Google Scholar]
92.Robinson DT, Caplan M, Carlson SE, Yoder R, Murthy K, Frost B. Early docosahexaenoic and arachidonic acid supplementation in extremely-low-birth-weight infants. Pediatr Res 2016;80:505–10. [DOI] [PubMed] [Google Scholar]
93.Phelps DL, Ward RM, Williams RL, Nolen TL, Watterberg KL, Oh W, et al. Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants. Pediatr Res 2016;80:209–17. [DOI] [PMC free article] [PubMed] [Google Scholar]
94.Ng E, Schurr P, Reilly M, Dunn M, Beck J. Impact of feeding method on diaphragm electrical activity and central apnea in preterm infants (FEAdi study). Early Hum Dev 2016;101:33–7. [DOI] [PubMed] [Google Scholar]
95.Levit OL, Calkins KL, Gibson LC, Kelley-Quon L, Robinson DT, Elashoff DA, et al. Low-dose intravenous soybean oil emulsion for prevention of cholestasis in preterm neonates. JPEN J Parenter Enteral Nutr 2016;40:374–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
96.Jain D, Claure N, D’Ugard C, Bello J, Bancalari E. Volume guarantee ventilation: effect on preterm infants with frequent hypoxemia episodes. Neonatology 2016;110:129–34. [DOI] [PubMed] [Google Scholar]
97.Ishihara C, Ibara S, Ohsone Y, Kato E, Tokuhisa T, Yamamoto Y, et al. Effects of infant flow Bi-NCPAP on apnea of prematurity. Pediatr Int 2016;58:456–60. [DOI] [PubMed] [Google Scholar]
98.Hascoet JM, Picaud JC, Ligi I, Blanc T, Moreau F, Pinturier MF, et al. Late surfactant administration in very preterm neonates with prolonged respiratory distress and pulmonary outcome at 1 year of age: a randomized clinical trial. JAMA Pediatr 2016;170:365–72. [DOI] [PubMed] [Google Scholar]
99.Greze E, Benard M, Hamon I, Casper C, Haddad FE, Boutroy MJ, et al. Doxapram dosing for apnea of prematurity based on postmenstrual age and gender: a randomized controlled trial. Paediatr Drugs 2016;18:443–9. [DOI] [PubMed] [Google Scholar]
100.Fort P, Salas AA, Nicola T, Craig CM, Carlo WA, Ambalavanan N. A Comparison of 3 vitamin D dosing regimens in extremely preterm infants: a randomized controlled trial. J Pediatr 2016;174:132–8.e1. [DOI] [PMC free article] [PubMed] [Google Scholar]
101.Costeloe K, Hardy P, Juszczak E, Wilks M, Millar MR. Probiotics in Preterm Infants Study Collaborative Group. Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial. Lancet 2016;387:649–60. [DOI] [PubMed] [Google Scholar]
102.Bellagamba MP, Carmenati E, D’Ascenzo R, Malatesta M, Spagnoli C, Biagetti C, et al. One extra gram of protein to preterm infants from birth to 1800 g: a single-blinded randomized clinical trial. J Pediatr Gastroenterol Nutr 2016;62:879–84. [DOI] [PubMed] [Google Scholar]
103.Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C, et al. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet 2016;387:1827–36. [DOI] [PubMed] [Google Scholar]
104.Ballard RA, Keller RL, Black DM, Ballard PL, Merrill JD, Eichenwald EC, et al. Randomized trial of late surfactant treatment in ventilated preterm infants receiving inhaled nitric oxide. J Pediatr 2016;168:23–9.e4. [DOI] [PMC free article] [PubMed] [Google Scholar]
105.Backes CH, Huang H, Iams JD, Bauer JA, Giannone PJ. Timing of umbilical cord clamping among infants born at 22 through 27 weeks’ gestation. J Perinatol 2016;36:35–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
106.Waitz M, Schmid MB, Fuchs H, Mendler MR, Dreyhaupt J, Hummler HD. Effects of automated adjustment of the inspired oxygen on fluctuations of arterial and regional cerebral tissue oxygenation in preterm infants with frequent desaturations. J Pediatr 2015;166:240–4.e1. [DOI] [PubMed] [Google Scholar]
107.van Kaam AH, Hummler HD, Wilinska M, Swietlinski J, Lal MK, te Pas AB, et al. Automated versus manual oxygen control with different saturation targets and modes of respiratory support in preterm infants. J Pediatr 2015;167:545-50.e1–550.e2. [DOI] [PubMed] [Google Scholar]
108.Thome UH, Genzel-Boroviczeny O, Bohnhorst B, Schmid M, Fuchs H, Rohde O, et al. Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial. Lancet Respir Med 2015;3:534–43. [DOI] [PubMed] [Google Scholar]
109.Tang J, Reid S, Lutz T, Malcolm G, Oliver S, Osborn DA. Randomised controlled trial of weaning strategies for preterm infants on nasal continuous positive airway pressure. BMC Pediatr 2015;15:147. [DOI] [PMC free article] [PubMed] [Google Scholar]
110.Schulzke SM, Deshmukh M, Nathan EA, Doherty DA, Patole SK. Nebulized pentoxifylline for reducing the duration of oxygen supplementation in extremely preterm neonates. J Pediatr 2015;166:1158–62.e2. [DOI] [PubMed] [Google Scholar]
111.Salas AA, Cuna A, Bhat R, McGwin G Jr, Carlo WA, Ambalavanan N. A randomised trial of re-feeding gastric residuals in preterm infants. Arch Dis Child Fetal Neonatal Ed 2015;100:F224–8. [DOI] [PubMed] [Google Scholar]
112.Rios DR, Kaiser JR. Vasopressin versus dopamine for treatment of hypotension in extremely low birth weight infants: a randomized, blinded pilot study. J Pediatr 2015;166:850–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
113.Reilly MC, Vohra S, Rac VE, Dunn M, Ferrelli K, Kiss A, et al. Randomized trial of occlusive wrap for heat loss prevention in preterm infants. J Pediatr 2015;166:262–8.e2. [DOI] [PubMed] [Google Scholar]
114.Omarsdottir S, Casper C, Naver L, Legnevall L, Gustafsson F, Grillner L, et al. Cytomegalovirus infection and neonatal outcome in extremely preterm infants after freezing of maternal milk. Pediatr Infect Dis J 2015;34:482–9. [DOI] [PubMed] [Google Scholar]
115.Okulu E, Arsan S, Mungan Akin I, Alan S, Kilic A, Atasay B. Early or later prophylactic INSURE in preterm infants of less than 30 weeks’ gestation. Turk J Pediatr 2015;57:1–8. [PubMed] [Google Scholar]
116.Newnam KM, McGrath JM, Salyer J, Estes T, Jallo N, Bass WT. A comparative effectiveness study of continuous positive airway pressure-related skin breakdown when using different nasal interfaces in the extremely low birth weight neonate. Appl Nurs Res 2015;28:36–41. [DOI] [PubMed] [Google Scholar]
117.Nasef N, El-Gouhary E, Schurr P, Reilly M, Beck J, Dunn M, et al. High-flow nasal cannulae are associated with increased diaphragm activation compared with nasal continuous positive airway pressure in preterm infants. Acta Paediatr 2015;104:e337–43. [DOI] [PubMed] [Google Scholar]
118.Nair V, Swarnam K, Rabi Y, Amin H, Howlett A, Akierman A, et al. Effect of nasal continuous positive airway pressure (NCPAP) Cycling and continuous NCPAP on successful weaning: a randomized controlled trial. Indian J Pediatr 2015;82:787–93. [DOI] [PubMed] [Google Scholar]
119.McPherson C, Neil JJ, Tjoeng TH, Pineda R, Inder TE. A pilot randomized trial of high-dose caffeine therapy in preterm infants. Pediatr Res 2015;78:198–204. [DOI] [PMC free article] [PubMed] [Google Scholar]
120.Lista G, Boni L, Scopesi F, Mosca F, Trevisanuto D, Messner H, et al. Sustained lung inflation at birth for preterm infants: a randomized clinical trial. Pediatrics 2015;135:e457–64. [DOI] [PubMed] [Google Scholar]
121.Lee J, Kim HS, Jung YH, Shin SH, Choi CW, Kim EK, et al. Non-invasive neurally adjusted ventilatory assist in preterm infants: a randomised phase II crossover trial. Arch Dis Child Fetal Neonatal Ed 2015;100:F507–13. [DOI] [PubMed] [Google Scholar]
122.Lee J, Kim HS, Jung YH, Choi KY, Shin SH, Kim EK, et al. Oropharyngeal colostrum administration in extremely premature infants: an RCT. Pediatrics 2015;135:e357–66. [DOI] [PubMed] [Google Scholar]
123.Lal M, Tin W, Sinha S. Automated control of inspired oxygen in ventilated preterm infants: crossover physiological study. Acta Paediatr 2015;104:1084–9. [DOI] [PubMed] [Google Scholar]
124.Laborie S, Denis A, Dassieu G, Bedu A, Tourneux P, Pinquier D, et al. Shielding parenteral nutrition solutions from light: a randomized controlled trial. JPEN J Parenter Enteral Nutr 2015;39:729–37. [DOI] [PubMed] [Google Scholar]
125.Kribs A, Roll C, Gopel W, Wieg C, Groneck P, Laux R, et al. Nonintubated surfactant application vs conventional therapy in extremely preterm infants: a randomized clinical trial. JAMA Pediatr 2015;169:723–30. [DOI] [PubMed] [Google Scholar]
126.Kong L, Bhatt AR, Demny AB, Coats DK, Li A, Rahman EZ, et al. Pharmacokinetics of bevacizumab and its effects on serum VEGF and IGF-1 in infants with retinopathy of prematurity. Invest Ophthalmol Vis Sci 2015;56:956–61. [DOI] [PubMed] [Google Scholar]
127.Katheria AC, Sauberan JB, Akotia D, Rich W, Durham J, Finer NN. A pilot randomized controlled trial of early versus routine caffeine in extremely premature infants. Am J Perinatol 2015;32:879–86. [DOI] [PubMed] [Google Scholar]
128.Hyttel-Sorensen S, Pellicer A, Alderliesten T, Austin T, van Bel F, Benders M, et al. Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial. BMJ 2015;350:g7635. [DOI] [PMC free article] [PubMed] [Google Scholar]
129.Clarke A, Yeomans E, Elsayed K, Medhurst A, Berger P, Skuza E, et al. A randomised crossover trial of clinical algorithm for oxygen saturation targeting in preterm infants with frequent desaturation episodes. Neonatology 2015;107:130–6. [DOI] [PubMed] [Google Scholar]
130.Bravo MC, Lopez-Ortego P, Sanchez L, Riera J, Madero R, Cabanas F, et al. Randomized, placebo-controlled trial of dobutamine for low superior vena cava flow in infants. J Pediatr 2015;167:572-8.e1–578.e2. [DOI] [PubMed] [Google Scholar]
131.Bozdag S, Dilli D, Gokmen T, Dilmen U. Comparison of two natural surfactants for pulmonary hemorrhage in very low-birth-weight infants: a randomized controlled trial. Am J Perinatol 2015;32:211–8. [DOI] [PubMed] [Google Scholar]
132.Bhat P, Patel DS, Hannam S, Rafferty GF, Peacock JL, Milner AD, et al. Crossover study of proportional assist versus assist control ventilation. Arch Dis Child Fetal Neonatal Ed 2015;100:F35–8. [DOI] [PubMed] [Google Scholar]
133.Beker F, Rogerson SR, Hooper SB, Sehgal A, Davis PG. Hemodynamic effects of nasal continuous positive airway pressure in preterm infants with evolving chronic lung disease, a crossover randomized trial. J Pediatr 2015;166:477–9. [DOI] [PubMed] [Google Scholar]
134.Bassler D, Plavka R, Shinwell ES, Hallman M, Jarreau PH, Carnielli V, et al. Early inhaled budesonide for the prevention of bronchopulmonary dysplasia. N Engl J Med 2015;373:1497–506. [DOI] [PubMed] [Google Scholar]
135.Anell-Olofsson M, Lonnqvist PA, Bitkover C, Lundeberg S, Larsson BA, Eksborg S, et al. Plasma concentrations of levobupivacaine associated with two different intermittent wound infusion regimens following surgical ductus ligation in preterm infants. Paediatr Anaesth 2015;25:711–8. [DOI] [PubMed] [Google Scholar]
136.Zapata J, Gomez JJ, Araque Campo R, Matiz Rubio A, Sola A. A randomised controlled trial of an automated oxygen delivery algorithm for preterm neonates receiving supplemental oxygen without mechanical ventilation. Acta Paediatr 2014;103:928–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
137.Wilinska M, Bachman T, Swietlinski J, Kostro M, Twardoch-Drozd M. Automated FiO2-SpO2 control system in neonates requiring respiratory support: a comparison of a standard to a narrow SpO2 control range. BMC Pediatr 2014;14:130. [DOI] [PMC free article] [PubMed] [Google Scholar]
138.Smith JR, McGrath J, Brotto M, Inder T. A randomized-controlled trial pilot study examining the neurodevelopmental effects of a 5-week M Technique intervention on very preterm infants. Adv Neonatal Care 2014;14:187–200. [DOI] [PMC free article] [PubMed] [Google Scholar]
139.Shin SH, Kim HS, Lee J, Choi KY, Lee JH, Kim EK, et al. A comparative study of two remifentanil doses for procedural pain in ventilated preterm infants: a randomized, controlled study. Pediatr Crit Care Med 2014;15:451–5. [DOI] [PubMed] [Google Scholar]
140.Oncel MY, Yurttutan S, Erdeve O, Uras N, Altug N, Oguz SS, et al. Oral paracetamol versus oral ibuprofen in the management of patent ductus arteriosus in preterm infants: a randomized controlled trial. J Pediatr 2014;164:510–4.e1. [DOI] [PubMed] [Google Scholar]
141.Morgan C, McGowan P, Herwitker S, Hart AE, Turner MA. Postnatal head growth in preterm infants: a randomized controlled parenteral nutrition study. Pediatrics 2014;133:e120–8. [DOI] [PubMed] [Google Scholar]
142.Mena NP, Leon Del PJ, Sandino PD, Ralmolfo BP, Sabatelli D, Llanos MA, et al. Meconium evacuation to improve feeding tolerance in very low birth weight preterm infants (Emita Protocol). Rev Chil Pediatr 2014;85:304–11. [DOI] [PubMed] [Google Scholar]
143.Lepore D, Quinn GE, Molle F, Baldascino A, Orazi L, Sammartino M, et al. Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings. Ophthalmology 2014;121:2212–9. [DOI] [PubMed] [Google Scholar]
144.Lago P, Salvadori S, Opocher F, Ricato S, Chiandetti L, Frigo AC. Continuous infusion of ibuprofen for treatment of patent ductus arteriosus in very low birth weight infants. Neonatology 2014;105:46–54. [DOI] [PubMed] [Google Scholar]
145.Konig K, Barfield CP, Guy KJ, Drew SM, Andersen CC. The effect of sildenafil on evolving bronchopulmonary dysplasia in extremely preterm infants: a randomised controlled pilot study. J Matern Fetal Neonatal Med 2014;27:439–44. [DOI] [PubMed] [Google Scholar]
146.Kluckow M, Jeffery M, Gill A, Evans N. A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus. Arch Dis Child Fetal Neonatal Ed 2014;99:F99–104. [DOI] [PubMed] [Google Scholar]
147.Kinsella JP, Cutter GR, Steinhorn RH, Nelin LD, Walsh WF, Finer NN, et al. Noninvasive inhaled nitric oxide does not prevent bronchopulmonary dysplasia in premature newborns. J Pediatr 2014;165:1104–8.e1. [DOI] [PMC free article] [PubMed] [Google Scholar]
148.Kaufman DA, Blackman A, Conaway MR, Sinkin RA. Nonsterile glove use in addition to hand hygiene to prevent late-onset infection in preterm infants: randomized clinical trial. JAMA Pediatr 2014;168:909–16. [DOI] [PubMed] [Google Scholar]
149.Hochwald O, Palegra G, Osiovich H. Adding hydrocortisone as 1st line of inotropic treatment for hypotension in very low birth weight infants. Indian J Pediatr 2014;81:808–10. [DOI] [PubMed] [Google Scholar]
150.Hallenberger A, Poets CF, Horn W, Seyfang A, Urschitz MS, Group CS. Closed-loop automatic oxygen control (CLAC) in preterm infants: a randomized controlled trial. Pediatrics 2014;133:e379–85. [DOI] [PubMed] [Google Scholar]
151.Hair AB, Blanco CL, Moreira AG, Hawthorne KM, Lee ML, Rechtman DJ, et al. Randomized trial of human milk cream as a supplement to standard fortification of an exclusive human milk-based diet in infants 750-1250 g birth weight. J Pediatr 2014;165:915–20. [DOI] [PubMed] [Google Scholar]
152.Doglioni N, Cavallin F, Mardegan V, Palatron S, Filippone M, Vecchiato L, et al. Total body polyethylene wraps for preventing hypothermia in preterm infants: a randomized trial. J Pediatr 2014;165:261–6.e1. [DOI] [PubMed] [Google Scholar]
153.Deshpande G, Simmer K, Deshmukh M, Mori TA, Croft KD, Kristensen J. Fish Oil (SMOFlipid) and olive oil lipid (Clinoleic) in very preterm neonates. J Pediatr Gastroenterol Nutr 2014;58:177–82. [DOI] [PubMed] [Google Scholar]
154.Buzzella B, Claure N, D’Ugard C, Bancalari E. A randomized controlled trial of two nasal continuous positive airway pressure levels after extubation in preterm infants. J Pediatr 2014;164:46–51. [DOI] [PubMed] [Google Scholar]
155.Bravo MC, Cabanas F, Riera J, Perez-Fernandez E, Quero J, Perez-Rodriguez J, et al. Randomised controlled clinical trial of standard versus echocardiographically guided ibuprofen treatment for patent ductus arteriosus in preterm infants: a pilot study. J Matern Fetal Neonatal Med 2014;27:904–9. [DOI] [PubMed] [Google Scholar]
156.Benjamin DK Jr, Hudak ML, Duara S, Randolph DA, Bidegain M, Mundakel GT, et al. Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants: a randomized clinical trial. JAMA 2014;311:1742–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
157.AlKharfy T, Ba-Abbad R, Hadi A, AlFaleh K. Use of topical petroleum jelly for prevention of sepsis in very low-birthweight infants: a prospective, randomised controlled trial. Paediatr Int Child Health 2014;34:194–7. [DOI] [PubMed] [Google Scholar]
158.Underwood MA, Kalanetra KM, Bokulich NA, Lewis ZT, Mirmiran M, Tancredi DJ, et al. A comparison of two probiotic strains of bifidobacteria in premature infants. J Pediatr 2013;163:1585–91.e9. [DOI] [PMC free article] [PubMed] [Google Scholar]
159.Taylor TA, Kennedy KA. Randomized trial of iron supplementation versus routine iron intake in VLBW infants. Pediatrics 2013;131:e433–8. [DOI] [PubMed] [Google Scholar]
160.Stefanescu BM, Hetu C, Slaughter JC, O’Shea TM, Shetty AK. A pilot study of Biotene OralBalance(R) gel for oral care in mechanically ventilated preterm neonates. Contemp Clin Trials 2013;35:33–9. [DOI] [PubMed] [Google Scholar]
161.Schmidt B, Whyte RK, Asztalos EV, Moddemann D, Poets C, Rabi Y, et al. Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial. JAMA 2013;309:2111–20. [DOI] [PubMed] [Google Scholar]
162.Schmid MB, Hopfner RJ, Lenhof S, Hummler HD, Fuchs H. Cerebral desaturations in preterm infants: a crossover trial on influence of oxygen saturation target range. Arch Dis Child Fetal Neonatal Ed 2013;98:F392–8. [DOI] [PubMed] [Google Scholar]
163.Scattolin S, Gaio P, Betto M, Palatron S, De Terlizzi F, Intini F, et al. Parenteral amino acid intakes: possible influences of higher intakes on growth and bone status in preterm infants. J Perinatol 2013;33:33–9. [DOI] [PubMed] [Google Scholar]
164.Pirr SM, Lange M, Hartmann C, Bohnhorst B, Peter C. Closed versus open endotracheal suctioning in extremely low-birth-weight neonates: a randomized, crossover trial. Neonatology 2013;103:124–30. [DOI] [PubMed] [Google Scholar]
165.Phelps DL, Ward RM, Williams RL, Watterberg KL, Laptook AR, Wrage LA, et al. Pharmacokinetics and safety of a single intravenous dose of myo-inositol in preterm infants of 23-29 wk. Pediatr Res 2013;74:721–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
166.Parikh NA, Kennedy KA, Lasky RE, McDavid GE, Tyson JE. Pilot randomized trial of hydrocortisone in ventilator-dependent extremely preterm infants: effects on regional brain volumes. J Pediatr 2013;162:685–90.e1. [DOI] [PMC free article] [PubMed] [Google Scholar]
167.Ng SM, Turner MA, Gamble C, Didi M, Victor S, Manning D, et al. An explanatory randomised placebo controlled trial of levothyroxine supplementation for babies born <28 weeks’ gestation: results of the TIPIT trial. Trials 2013;14:211. [DOI] [PMC free article] [PubMed] [Google Scholar]
168.Mathew B, Lakshminrusimha S, Sengupta S, Carrion V. Randomized controlled trial of vinyl bags versus thermal mattress to prevent hypothermia in extremely low-gestational-age infants. Am J Perinatol 2013;30:317–22. [DOI] [PubMed] [Google Scholar]
169.March MI, Hacker MR, Parson AW, Modest AM, de Veciana M. The effects of umbilical cord milking in extremely preterm infants: a randomized controlled trial. J Perinatol 2013;33:763–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
170.Manley BJ, Owen LS, Doyle LW, Andersen CC, Cartwright DW, Pritchard MA, et al. High-flow nasal cannulae in very preterm infants after extubation. N Engl J Med 2013;369:1425–33. [DOI] [PubMed] [Google Scholar]
171.Kirpalani H, Millar D, Lemyre B, Yoder BA, Chiu A, Roberts RS, et al. A trial comparing noninvasive ventilation strategies in preterm infants. N Engl J Med 2013;369:611–20. [DOI] [PubMed] [Google Scholar]
172.Karen T, Vatlach S, Poets A, Maas C, Poets CF, Bassler D. The impact of oral sucrose on apnea and bradycardia in preterm infants: a randomised cross-over trial. Arch Dis Child Fetal Neonatal Ed 2013;98:F93–4. [DOI] [PubMed] [Google Scholar]
173.Kanmaz HG, Mutlu B, Erdeve O, Canpolat FE, Oguz SS, Uras N, et al. Does enteral protein intake affect renal glomerular and tubular functions in very low birth weight infants? Clin Nephrol 2013;80:355–60. [DOI] [PubMed] [Google Scholar]
174.Kanmaz G, Erdeve O, Canpolat FE, Oguz SS, Uras N, Altug N, et al. Serum ibuprofen levels of extremely preterm infants treated prophylactically with oral ibuprofen to prevent patent ductus arteriosus. Eur J Clin Pharmacol 2013;69:1075–81. [DOI] [PubMed] [Google Scholar]
175.Kamlin CO, Schilleman K, Dawson JA, Lopriore E, Donath SM, Schmolzer GM, et al. Mask versus nasal tube for stabilization of preterm infants at birth: a randomized controlled trial. Pediatrics 2013;132: e381–8. [DOI] [PubMed] [Google Scholar]
176.Johnston C, Campbell-Yeo M, Rich B, Whitley J, Filion F, Cogan J, et al. Therapeutic touch is not therapeutic for procedural pain in very preterm neonates: a randomized trial. Clin J Pain 2013;29:824–9. [DOI] [PubMed] [Google Scholar]
177.Jacobs SE, Tobin JM, Opie GF, Donath S, Tabrizi SN, Pirotta M, et al. Probiotic effects on late-onset sepsis in very preterm infants: a randomized controlled trial. Pediatrics 2013;132:1055–62. [DOI] [PubMed] [Google Scholar]
178.Boost II United Kingdom Collaborative Group, Boost II Australia Collaborative Group, Boost II New Zealand Collaborative Group, Stenson BJ, Tarnow-Mordi WO, Darlow BA, et al. Oxygen saturation and outcomes in preterm infants. N Engl J Med 2013;368:2094–104. [DOI] [PubMed] [Google Scholar]
179.Gouna G, Rakza T, Kuissi E, Pennaforte T, Mur S, Storme L. Positioning effects on lung function and breathing pattern in premature newborns. J Pediatr 2013;162:1133–7. 7.e1. [DOI] [PubMed] [Google Scholar]
180.Ditzenberger GR, Wallen LD, Phelan L, Escoe S, Collins SD. Supplemental protein and postnatal growth of very low birth weight infants: a randomized trial. J Neonatal Perinatal Med 2013;6:285–94. [DOI] [PubMed] [Google Scholar]
181.Cristofalo EA, Schanler RJ, Blanco CL, Sullivan S, Trawoeger R, Kiechl-Kohlendorfer U, et al. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. J Pediatr 2013;163:1592–5 e1. [DOI] [PubMed] [Google Scholar]
182.Cone S, Pickler RH, Grap MJ, McGrath J, Wiley PM. Endotracheal suctioning in preterm infants using four-handed versus routine care. J Obstet Gynecol Neonatal Nurs 2013;42:92–104. [DOI] [PMC free article] [PubMed] [Google Scholar]
183.Collins CL, Holberton JR, Konig K. Comparison of the pharyngeal pressure provided by two heated, humidified high-flow nasal cannulae devices in premature infants. J Paediatr Child Health 2013;49:554–6. [DOI] [PubMed] [Google Scholar]
184.Collins CL, Holberton JR, Barfield C, Davis PG. A randomized controlled trial to compare heated humidified high-flow nasal cannulae with nasal continuous positive airway pressure postextubation in premature infants. J Pediatr 2013;162:949–54.e1. [DOI] [PubMed] [Google Scholar]
185.Bertini G, Elia S, Ceciarini F, Dani C. Reduction of catheter-related bloodstream infections in preterm infants by the use of catheters with the AgION antimicrobial system. Early Hum Dev 2013;89:21–5. [DOI] [PubMed] [Google Scholar]
186.Bell EF, Hansen NI, Brion LP, Ehrenkranz RA, Kennedy KA, Walsh MC, et al. Serum tocopherol levels in very preterm infants after a single dose of vitamin E at birth. Pediatrics 2013;132:e1626–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
187.Bagnoli F, Rossetti A, Messina G, Mori A, Casucci M, Tomasini B. Treatment of patent ductus arteriosus (PDA) using ibuprofen: renal side-effects in VLBW and ELBW newborns. J Matern Fetal Neonatal Med 2013;26:423–9. [DOI] [PubMed] [Google Scholar]
188.Wheeler KI, Morley CJ, Hooper SB, Davis PG. Lower back-up rates improve ventilator triggering during assist-control ventilation: a randomized crossover trial. J Perinatol 2012;32:111–6. [DOI] [PubMed] [Google Scholar]
189.Todd DA, Wright A, Broom M, Chauhan M, Meskell S, Cameron C, et al. Methods of weaning preterm babies <30 weeks gestation off CPAP: a multicentre randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2012;97:F236–40. [DOI] [PubMed] [Google Scholar]
190.Sosenko IR, Fajardo MF, Claure N, Bancalari E. Timing of patent ductus arteriosus treatment and respiratory outcome in premature infants: a double-blind randomized controlled trial. J Pediatr 2012;160:929–35.e1. [DOI] [PubMed] [Google Scholar]
191.Salvo V, Zimmermann LJ, Gavilanes AW, Barberi I, Ricotti A, Abella R, et al. First intention high-frequency oscillatory and conventional mechanical ventilation in premature infants without antenatal glucocorticoid prophylaxis. Pediatr Crit Care Med 2012;13:72–9. [DOI] [PubMed] [Google Scholar]
192.Salvador A, Janeczko M, Porat R, Sekhon R, Moewes A, Schutzman D. Randomized controlled trial of early parenteral nutrition cycling to prevent cholestasis in very low birth weight infants. J Pediatr 2012;161:229–33.e1. [DOI] [PubMed] [Google Scholar]
193.Ramanathan R, Sekar KC, Rasmussen M, Bhatia J, Soll RF. Nasal intermittent positive pressure ventilation after surfactant treatment for respiratory distress syndrome in preterm infants <30 weeks’ gestation: a randomized, controlled trial. J Perinatol 2012;32:336–43. [DOI] [PubMed] [Google Scholar]
194.Ohls RK, Roohi M, Peceny HM, Schrader R, Bierer R. A randomized, masked study of weekly erythropoietin dosing in preterm infants. J Pediatr 2012;160:790–5.e1. [DOI] [PMC free article] [PubMed] [Google Scholar]
195.O’Brien K, Campbell C, Brown L, Wenger L, Shah V. Infant flow biphasic nasal continuous positive airway pressure (BP- NCPAP) vs. infant flow NCPAP for the facilitation of extubation in infants’ </= 1,250 grams: a randomized controlled trial. BMC Pediatr 2012;12:43. [DOI] [PMC free article] [PubMed] [Google Scholar]
196.Moya F, Sisk PM, Walsh KR, Berseth CL. A new liquid human milk fortifier and linear growth in preterm infants. Pediatrics 2012;130: e928–35. [DOI] [PubMed] [Google Scholar]
197.McCain GC, Del Moral T, Duncan RC, Fontaine JL, Pino LD. Transition from gavage to nipple feeding for preterm infants with bronchopulmonary dysplasia. Nurs Res 2012;61:380–7. [DOI] [PubMed] [Google Scholar]
198.Keller RL, Merrill JD, Black DM, Steinhorn RH, Eichenwald EC, Durand DJ, et al. Late administration of surfactant replacement therapy increases surfactant protein-B content: a randomized pilot study. Pediatr Res 2012;72:613–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
199.Haiden N, Norooz F, Klebermass-Schrehof K, Horak AS, Jilma B, Berger A, et al. The effect of an osmotic contrast agent on complete meconium evacuation in preterm infants. Pediatrics 2012;130:e1600–6. [DOI] [PubMed] [Google Scholar]
200.Fergusson DA, Hebert P, Hogan DL, LeBel L, Rouvinez-Bouali N, Smyth JA, et al. Effect of fresh red blood cell transfusions on clinical outcomes in premature, very low-birth-weight infants: the ARIPI randomized trial. JAMA 2012;308:1443–51. [DOI] [PubMed] [Google Scholar]
201.Erdeve O, Yurttutan S, Altug N, Ozdemir R, Gokmen T, Dilmen U, et al. Oral versus intravenous ibuprofen for patent ductus arteriosus closure: a randomised controlled trial in extremely low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2012;97:F279–83. [DOI] [PubMed] [Google Scholar]
202.Duman N, Tuzun F, Sutcuoglu S, Yesilirmak CD, Kumral A, Ozkan H. Impact of volume guarantee on synchronized ventilation in preterm infants: a randomized controlled trial. Intensive Care Med 2012;38:1358–64. [DOI] [PubMed] [Google Scholar]
203.Dani C, Vangi V, Bertini G, Pratesi S, Lori I, Favelli F, et al. High-dose ibuprofen for patent ductus arteriosus in extremely preterm infants: a randomized controlled study. Clin Pharmacol Ther 2012;91:590–6. [DOI] [PubMed] [Google Scholar]
204.Batton BJ, Li L, Newman NS, Das A, Watterberg KL, Yoder BA, et al. Feasibility study of early blood pressure management in extremely preterm infants. J Pediatr 2012;161:65–9.e1. [DOI] [PMC free article] [PubMed] [Google Scholar]
205.Autrata R, Senkova K, Holousova M, Krejcirova I, Dolezel Z, Borek I. Effects of intravitreal pegaptanib or bevacizumab and laser in treatment of threshold retinopathy of prematurity in zone I and posterior zone II—four years results. Cesk Slov Oftalmol 2012;68:29–36. [PubMed] [Google Scholar]
206.Alsweiler JM, Harding JE, Bloomfield FH. Tight glycemic control with insulin in hyperglycemic preterm babies: a randomized controlled trial. Pediatrics 2012;129:639–47. [DOI] [PubMed] [Google Scholar]
207.Al-Hosni M, Duenas M, Hawk M, Stewart LA, Borghese RA, Cahoon M, et al. Probiotics-supplemented feeding in extremely low-birth-weight infants. J Perinatol 2012;32:253–9. [DOI] [PubMed] [Google Scholar]
208.Simon P, Dannaway D, Bright B, Krous L, Wlodaver A, Burks B, et al. Thermal defense of extremely low gestational age newborns during resuscitation: exothermic mattresses vs polyethylene wrap. J Perinatol 2011;31:33–7. [DOI] [PubMed] [Google Scholar]
209.Sarafidis K, Stathopoulou T, Agakidou E, Taparkou A, Soubasi V, Diamanti E, et al. Comparable effect of conventional ventilation versus early high-frequency oscillation on serum CC16 and IL-6 levels in preterm neonates. J Perinatol 2011;31:104–11. [DOI] [PubMed] [Google Scholar]
210.Oh W, Fanaroff AA, Carlo WA, Donovan EF, McDonald SA, Poole WK, et al. Effects of delayed cord clamping in very-low-birth-weight infants. J Perinatol 2011;31(suppl 1):S68–71. [DOI] [PMC free article] [PubMed] [Google Scholar]
211.Norman E, Wikstrom S, Hellstrom-Westas L, Turpeinen U, Hamalainen E, Fellman V. Rapid sequence induction is superior to morphine for intubation of preterm infants: a randomized controlled trial. J Pediatr 2011;159:893–9.e1. [DOI] [PubMed] [Google Scholar]
212.Mintz-Hittner HA, Kennedy KA, Chuang AZ, Group B-RC. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med 2011;364:603–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
213.Gopel W, Kribs A, Ziegler A, Laux R, Hoehn T, Wieg C, et al. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet 2011;378:1627–34. [DOI] [PubMed] [Google Scholar]
214.Giannantonio C, Papacci P, Purcaro V, Cota F, Tesfagabir MG, Molle F, et al. Effectiveness of ketorolac tromethamine in prevention of severe retinopathy of prematurity. J Pediatr Ophthalmol Strabismus 2011;48:247–51. [DOI] [PubMed] [Google Scholar]
215.Dawson JA, Schmolzer GM, Kamlin CO, Te Pas AB, O’Donnell CP, Donath SM, et al. Oxygenation with T-piece versus self-inflating bag for ventilation of extremely preterm infants at birth: a randomized controlled trial. J Pediatr 2011;158:912-8.e1–918.e2. [DOI] [PubMed] [Google Scholar]
216.Castoldi F, Daniele I, Fontana P, Cavigioli F, Lupo E, Lista G. Lung recruitment maneuver during volume guarantee ventilation of preterm infants with acute respiratory distress syndrome. Am J Perinatol 2011;28:521–8. [DOI] [PubMed] [Google Scholar]
217.Ballard HO, Shook LA, Bernard P, Anstead MI, Kuhn R, Whitehead V, et al. Use of azithromycin for the prevention of bronchopulmonary dysplasia in preterm infants: a randomized, double-blind, placebo controlled trial. Pediatr Pulmonol 2011;46:111–8. [DOI] [PubMed] [Google Scholar]
218.Balegar VK, Kluckow M. Furosemide for packed red cell transfusion in preterm infants: a randomized controlled trial. J Pediatr 2011;159:913–8.e1. [DOI] [PubMed] [Google Scholar]
219.Trevisanuto D, Doglioni N, Cavallin F, Parotto M, Micaglio M, Zanardo V. Heat loss prevention in very preterm infants in delivery rooms: a prospective, randomized, controlled trial of polyethylene caps. J Pediatr 2010;156:914–7.e1. [DOI] [PubMed] [Google Scholar]
220.Support Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, et al. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med 2010;362:1970–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
221.Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawoger R, Kiechl-Kohlendorfer U, et al. An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr 2010;156:562–7.e1. [DOI] [PubMed] [Google Scholar]
222.Sandri F, Plavka R, Ancora G, Simeoni U, Stranak Z, Martinelli S, et al. Prophylactic or early selective surfactant combined with nCPAP in very preterm infants. Pediatrics 2010;125:e1402–9. [DOI] [PubMed] [Google Scholar]
223.Mihatsch WA, Vossbeck S, Eikmanns B, Hoegel J, Pohlandt F. Effect of Bifidobacterium lactis on the incidence of nosocomial infections in very-low-birth-weight infants: a randomized controlled trial. Neonatology 2010;98:156–63. [DOI] [PubMed] [Google Scholar]
224.Mercier JC, Hummler H, Durrmeyer X, Sanchez-Luna M, Carnielli V, Field D, et al. Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): a randomised controlled trial. Lancet 2010;376:346–54. [DOI] [PubMed] [Google Scholar]
225.Mercado VV, Cristea I, Ali N, Pham CC, Buescher E, Yang J, et al. Does surfactant type cause a differential proinflammatory response in preterm infants with respiratory distress syndrome? Adv Ther 2010;27: 476–82. [DOI] [PubMed] [Google Scholar]
226.Fujii A, Allen R, Doros G, O’Brien S. Patent ductus arteriosus hemodynamics in very premature infants treated with poractant alfa or beractant for respiratory distress syndrome. J Perinatol 2010;30:671–6. [DOI] [PubMed] [Google Scholar]
227.El-Naggar W, Yiu A, Mohamed A, Shah V, Manley J, McNamara P, et al. Comparison of pain during two methods of urine collection in preterm infants. Pediatrics 2010;125:1224–9. [DOI] [PubMed] [Google Scholar]
228.Reilly MC, Vohra S, Rac VE, Zayack D, Wimmer J, Vincer M. Parallel exploratory rct of polyethylene wrap for heat loss prevention in infants born at less than 24 weeks’ gestation. Neonatology 2019;116:37–41. [DOI] [PubMed] [Google Scholar]
229.Bernard MA, Clayton JA, Lauer MS. Inclusion across the lifespan: NIH policy for clinical research. JAMA 2018;320:1535–6. [DOI] [PubMed] [Google Scholar]
230.Spong CY, Bianchi DW. Improving public health requires inclusion of underrepresented populations in research. JAMA 2018;319:337–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
231.Guillen U, Weiss EM, Munson D, Maton P, Jefferies A, Norman M, et al. Guidelines for the management of extremely premature deliveries: a systematic review. Pediatrics 2015;136:343–50. [DOI] [PubMed] [Google Scholar]
232.National Institutes of Health. Revision: NIH policy and guidelines on inclusion of individuals across the lifespan as participants in research involving human subjects. Accessed October 16, 2020. https://grants.nih.gov/grants/guide/notice-files/NOTOD-18-116.htm
233.Zulman DM, Sussman JB, Chen X, Cigolle CT, Blaum CS, Hayward RA. Examining the evidence: a systematic review of the inclusion and analysis of older adults in randomized controlled trials. J Gen Intern Med 2011;26:783–90. [DOI] [PMC free article] [PubMed] [Google Scholar]
234.Singh GK, Yu SM. Infant mortality in the United States: trends, differentials, and projections, 1950 through 2010. Am J Public Health 1995;85:957–64. [DOI] [PMC free article] [PubMed] [Google Scholar]
235.Tyson JE, Parikh NA, Langer J, Green C, Higgins RD, National Institute of Child H, et al. Intensive care for extreme prematurity—moving beyond gestational age. N Engl J Med 2008;358:1672–81. [DOI] [PMC free article] [PubMed] [Google Scholar]
236.Foglia EE, DeMauro SB, Dysart K, Kirpalani H. When has enough evidence accumulated to change neonatal practice? Semin Fetal Neonatal Med 2015;20:424–30. [DOI] [PubMed] [Google Scholar]
237.Bala MM, Akl EA, Sun X, Bassler D, Mertz D, Mejza F, et al. Randomized trials published in higher vs. lower impact journals differ in design, conduct, and analysis. J Clin Epidemiol 2013;66:286–95. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

suppl 1

NIHMS1823121-supplement-suppl_1.doc^{(64.5KB, doc)}

suppl 2

NIHMS1823121-supplement-suppl_2.docx^{(12.3KB, docx)}

[R1] 1.Lau C, Ambalavanan N, Chakraborty H, Wingate MS, Carlo WA. Extremely low birth weight and infant mortality rates in the United States. Pediatrics 2013;131:855–60. [DOI] [PubMed] [Google Scholar]

[R2] 2.Kimland E, Odlind V. Off-label drug use in pediatric patients. Clin Pharmacol Ther 2012;91:796–801. [DOI] [PubMed] [Google Scholar]

[R3] 3.Nasr VG, Davis JM. Anesthetic use in newborn infants: the urgent need for rigorous evaluation. Pediatr Res 2015;78:2–6. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R4] 4.Patel RM, Rysavy MA, Bell EF, Tyson JE. Survival of infants born at periviable gestational ages. Clin Perinatol 2017;44:287–303. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R5] 5.Younge N, Goldstein RF, Bann CM, Hintz SR, Patel RM, Smith PB, et al. Survival and neurodevelopmental outcomes among periviable infants. N Engl J Med 2017;376:617–28. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R6] 6.Willhelm C, Girisch W, Gottschling S, Graber S, Wahl H, Meyer S. Systematic Cochrane reviews in neonatology: a critical appraisal. Pediatr Neonatol 2013;54:261–6. [DOI] [PubMed] [Google Scholar]

[R7] 7.Guyatt GH, Haynes RB, Jaeschke RZ, Cook DJ, Green L, Naylor CD, et al. Users’ Guides to the Medical Literature: XXV. Evidence-based medicine: principles for applying the Users’ Guides to patient care. Evidence-Based Medicine Working Group. JAMA 2000;284:1290–6. [DOI] [PubMed] [Google Scholar]

[R8] 8.Rothwell PM. External validity of randomised controlled trials: “to whom do the results of this trial apply?” Lancet 2005;365:82–93. [DOI] [PubMed] [Google Scholar]

[R9] 9.Guyatt GH, Sackett DL, Cook DJ. Users’ guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA 1993;270:2598–601. [DOI] [PubMed] [Google Scholar]

[R10] 10.Patel HC, Hayward C, Dungu JN, Papadopoulou S, Saidmeerasah A, Ray R, et al. Assessing the eligibility criteria in phase III randomized controlled trials of drug therapy in heart failure with preserved ejection fraction: the critical play-off between a “pure” patient phenotype and the generalizability of trial findings. J Card Fail 2017;23:517–24. [DOI] [PubMed] [Google Scholar]

[R11] 11.Van Spall HG, Toren A, Kiss A, Fowler RA. Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA 2007;297:1233–40. [DOI] [PubMed] [Google Scholar]

[R12] 12.Florisson S, Aagesen EK, Bertelsen AS, Nielsen LP, Rosholm JU. Are older adults insufficiently included in clinical trials?-An umbrella review. Basic Clin Pharmacol Toxicol 2021;128:213–23. [DOI] [PubMed] [Google Scholar]

[R13] 13.Gurwitz JH, Col NF, Avorn J. The exclusion of the elderly and women from clinical trials in acute myocardial infarction. JAMA 1992;268: 1417–22. [PubMed] [Google Scholar]

[R14] 14.Lam M, Zhu JW, Maqbool T, Adam G, Tadrous M, Rochon P, et al. Inclusion of older adults in randomized clinical trials for systemic medications for atopic dermatitis: a systematic review. JAMA Dermatol 2020;156:1240–5. [DOI] [PubMed] [Google Scholar]

[R15] 15.Rysavy MA, Li L, Bell EF, Das A, Hintz SR, Stoll BJ, et al. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med 2015;372:1801–11. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R16] 16.Booth A, Clarke M, Ghersi D, Moher D, Petticrew M, Stewart L. An international registry of systematic-review protocols. Lancet 2011;377:108–9. [DOI] [PubMed] [Google Scholar]

[R17] 17.Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62:1006–12. [DOI] [PubMed] [Google Scholar]

[R18] 18.Richardson WS, Wilson MC, Nishikawa J, Hayward RS. The well-built clinical question: a key to evidence-based decisions. ACP J Club 1995;123:A12–3. [PubMed] [Google Scholar]

[R19] 19.Balk EM, Chung M, Hadar N, Patel K, Yu WW, Trikalinos TA, et al. Accuracy of data extraction of non-english language trials with google translate. methods research report (Prepared by the Tufts Evidence-based Practice Center under Contract No. 290-2007-10055 I.). Rockville (MD): Agency for Healthcare Research and Quality; 2012. [PubMed] [Google Scholar]

[R20] 20.Travers CP, Carlo WA, McDonald SA, Das A, Ambalavanan N, Bell EF, et al. Racial/ethnic disparities among extremely preterm infants in the United States fFrom 2002 to 2016. JAMA Netw Open 2020;3:e206757. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R21] 21.Journal Impact Search. Accessed March 17, 2021. https://www.bioxbio.com

[R22] 22.Raju TNK, Mercer BM, Burchfield DJ, Joseph GF Jr. Periviable birth: executive summary of a joint workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists. Obstet Gynecol 2014;123:1083–96. [DOI] [PubMed] [Google Scholar]

[R23] 23.United States Food and Drug Administration. Public workshop: evaluating inclusion and exclusion criteria in clinical trials. Workshop Report. Silver Spring (MD): USFDA; 2018. [Google Scholar]

[R24] 24.Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1–12. [DOI] [PubMed] [Google Scholar]

[R25] 25.Oremus M, Wolfson C, Perrault A, Demers L, Momoli F, Moride Y. Interrater reliability of the modified Jadad quality scale for systematic reviews of Alzheimer’s disease drug trials. Dement Geriatr Cogn Disord 2001;12:232–6. [DOI] [PubMed] [Google Scholar]

[R26] 26.Zhang Y, Zhou L, Liu X, Liu L, Wu Y, Zhao Z, et al. The effectiveness of the problem-based learning teaching model for use in introductory Chinese undergraduate medical courses: a systematic review and meta-analysis. PLoS One 2015;10:e0120884. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R27] 27.Wejryd E, Marchini G, Frimmel V, Jonsson B, Abrahamsson T. Probiotics promoted head growth in extremely low birth weight infants in a double-blind placebo-controlled trial. Acta Paediatr 2019;108:62–9. [DOI] [PubMed] [Google Scholar]

[R28] 28.Thomson L, Elleri D, Bond S, Howlett J, Dunger DB, Beardsall K. Targeting glucose control in preterm infants: pilot studies of continuous glucose monitoring. Arch Dis Child Fetal Neonatal Ed 2019;104:F353–9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R29] 29.Reynolds PR, Miller TL, Volakis LI, Holland N, Dungan GC, Roehr CC, et al. Randomised cross-over study of automated oxygen control for preterm infants receiving nasal high flow. Arch Dis Child Fetal Neonatal Ed 2019;104:F366–71. [DOI] [PubMed] [Google Scholar]

[R30] 30.Rath CP, Thomas M, Sullivan D, Kluckow M. Does the use of an iodine-containing contrast agent to visualise the PICC tip in preterm babies cause hypothyroidism? A randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2019;104:F212–4. [DOI] [PubMed] [Google Scholar]

[R31] 31.Pereira SS, Sinha AK, Morris JK, Wertheim DF, Shah DK, Kempley ST. Blood pressure intervention levels in preterm infants: pilot randomised trial. Arch Dis Child Fetal Neonatal Ed 2019;104:F298–305. [DOI] [PubMed] [Google Scholar]

[R32] 32.Parker LA, Weaver M, Murgas Torrazza RJ, Shuster J, Li N, Krueger C, et al. Effect of gastric residual evaluation on enteral intake in extremely preterm infants: a randomized clinical trial. JAMA Pediatr 2019;173: 534–43. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R33] 33.Onland W, Cools F, Kroon A, Rademaker K, Merkus MP, Dijk PH, et al. Effect of hydrocortisone therapy initiated 7 to 14 days after birth on mortality or bronchopulmonary dysplasia among very preterm infants receiving mechanical ventilation: a randomized clinical trial. JAMA 2019;321:354–63. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R34] 34.O’Currain E, O’Shea JE, McGrory L, Owen LS, Kamlin O, Dawson JA, et al. Smaller facemasks for positive pressure ventilation in preterm infants: a randomised trial. Resuscitation 2019;134:91–8. [DOI] [PubMed] [Google Scholar]

[R35] 35.Marr BL, Mettelman BB, Bode MM, Gross SJ. Randomized trial of 42-day compared with 9-day courses of dexamethasone for the treatment of evolving bronchopulmonary dysplasia in extremely preterm infants. J Pediatr 2019;211:20–6.e1. [DOI] [PubMed] [Google Scholar]

[R36] 36.Ley D, Hallberg B, Hansen-Pupp I, Dani C, Ramenghi LA, Marlow N, et al. rhIGF-1/rhIGFBP-3 in preterm infants: a phase 2 randomized controlled trial. J Pediatr 2019;206:56–65.e8. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R37] 37.Latremouille S, Shalish W, Kanbar L, Lamer P, Rao S, Kearney RE, et al. The effects of nasal continuous positive airway pressure and high flow nasal cannula on heart rate variability in extremely preterm infants after extubation: a randomized crossover trial. Pediatr Pulmonol 2019;54:788–96. [DOI] [PubMed] [Google Scholar]

[R38] 38.Kochan M, Leonardi B, Firestine A, McPadden J, Cobb D, Shah TA, et al. Elevated midline head positioning of extremely low birth weight infants: effects on cardiopulmonary function and the incidence of periventricular-intraventricular hemorrhage. J Perinatol 2019;39:54–62. [DOI] [PubMed] [Google Scholar]

[R39] 39.Kluckow M, Carlisle H, Broom M, Woods P, Jeffery M, Desai D, et al. A pilot randomised blinded placebo-controlled trial of paracetamol for later treatment of a patent ductus arteriosus. J Perinatol 2019;39:102–7. [DOI] [PubMed] [Google Scholar]

[R40] 40.Kirpalani H, Ratcliffe SJ, Keszler M, Davis PG, Foglia EE, Te Pas A, et al. Effect of sustained inflations vs intermittent positive pressure ventilation on bronchopulmonary dysplasia or death among extremely preterm infants: the SAIL randomized clinical trial. JAMA 2019;321:1165–75. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R41] 41.Hunt K, Dassios T, Ali K, Greenough A. Volume targeting levels and work of breathing in infants with evolving or established bronchopulmonary dysplasia. Arch Dis Child Fetal Neonatal Ed 2019;104:F46–9. [DOI] [PubMed] [Google Scholar]

[R42] 42.Gajdos M, Waitz M, Mendler MR, Braun W, Hummler H. Effects of a new device for automated closed loop control of inspired oxygen concentration on fluctuations of arterial and different regional organ tissue oxygen saturations in preterm infants. Arch Dis Child Fetal Neonatal Ed 2019;104:F360–5. [DOI] [PubMed] [Google Scholar]

[R43] 43.Fischer HS, Buhrer C, Czernik C. Hazards to avoid in future neonatal studies of nasal high-frequency oscillatory ventilation: lessons from an early terminated trial. BMC Res Notes 2019;12:237. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R44] 44.El-Naggar W, Simpson D, Hussain A, Armson A, Dodds L, Warren A, et al. Cord milking versus immediate clamping in preterm infants: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2019;104:F145–50. [DOI] [PubMed] [Google Scholar]

[R45] 45.de Vries LS, Groenendaal F, Liem KD, Heep A, Brouwer AJ, van ’t Verlaat E, et al. Treatment thresholds for intervention in posthaemorrhagic ventricular dilation: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2019;104:F70–5. [DOI] [PubMed] [Google Scholar]

[R46] 46.Curley A, Stanworth SJ, Willoughby K, Fustolo-Gunnink SF, Venkatesh V, Hudson C, et al. Randomized trial of platelet-transfusion thresholds in neonates. N Engl J Med 2019;380:242–51. [DOI] [PubMed] [Google Scholar]

[R47] 47.Clyman RI, Liebowitz M, Kaempf J, Erdeve O, Bulbul A, Hakansson S, et al. PDA-TOLERATE Trial: an exploratory randomized controlled trial of treatment of moderate-to-large patent ductus arteriosus at 1 week of age. J Pediatr 2019;205:41–8.e6. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R48] 48.Claassen CC, Hillman NH, Brown K, Williams HL, Strand ML. Comparison of Bubble CPAP Devices Using RAM Cannula for Extubation Failure in Very Low Birth Weight Infants: Randomized and Cohort Studies. Neonatology 2019;115:28–35. [DOI] [PubMed] [Google Scholar]

[R49] 49.Chuang LJ, Wang SH, Ma MC, Lin CN, Chen CL, Huang MC. A modified developmental care bundle reduces pain and stress in preterm infants undergoing examinations for retinopathy of prematurity: A randomised controlled trial. J Clin Nurs 2019;28:545–59. [DOI] [PubMed] [Google Scholar]

[R50] 50.Balasubramanian H, Malpani P, Sindhur M, Kabra NS, Ahmed J, Srinivasan L. Effect of umbilical cord blood sampling versus admission blood sampling on requirement of blood transfusion in extremely preterm infants: a randomized controlled trial. J Pediatr 2019;211:39–45.e2. [DOI] [PubMed] [Google Scholar]

[R51] 51.Arsenault AB, Gunsalus KTW, Laforce-Nesbitt SS, Przystac L, DeAngelis EJ, Hurley ME, et al. Dietary supplementation with medium-chain triglycerides reduces Candida gastrointestinal colonization in preterm infants. Pediatr Infect Dis J 2019;38:164–8. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R52] 52.Abounahia FF, Abu-Jarir R, Abounahia MF, Al-Badriyeh D, Abushanab D, Abu-Ghalwa M, et al. Prophylactic sildenafil in preterm infants at risk of bronchopulmonary dysplasia: a pilot randomized, double-blinded, placebo-controlled trial. Clin Drug Investig 2019;39:1093–107. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R53] 53.van den Heuvel MEN, van Zanten HA, Bachman TE, Te Pas AB, van Kaam AH, Onland W. Optimal target range of closed-loop inspired oxygen support in preterm infants: a randomized cross-over study. J Pediatr 2018;197:36–41. [DOI] [PubMed] [Google Scholar]

[R54] 54.Travers CP, Carlo WA, Nakhmani A, Bhatia S, Gentle SJ, Amperayani VA, et al. Environmental or nasal cannula supplemental oxygen for preterm infants: a randomized cross-over trial. J Pediatr 2018;200:98–103. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R55] 55.Strunk T, Pupala S, Hibbert J, Doherty D, Patole S. Topical coconut oil in very preterm infants: an open-label randomised controlled trial. Neonatology 2018;113:146–51. [DOI] [PubMed] [Google Scholar]

[R56] 56.Spittle AJ, Treyvaud K, Lee KJ, Anderson PJ, Doyle LW. The role of social risk in an early preventative care programme for infants born very preterm: a randomized controlled trial. Dev Med Child Neurol 2018;60: 54–62. [DOI] [PubMed] [Google Scholar]

[R57] 57.Salas AA, Li P, Parks K, Lal CV, Martin CR, Carlo WA. Early progressive feeding in extremely preterm infants: a randomized trial. Am J Clin Nutr 2018;107:365–70. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R58] 58.Rüegger CM, Lorenz L, Kamlin COF, Manley BJ, Owen LS, Bassler D, et al. The effect of noninvasive high-frequency oscillatory ventilation on desaturations and bradycardia in very preterm infants: a randomized crossover trial. J Pediatr 2018;201:269–73.e2. [DOI] [PubMed] [Google Scholar]

[R59] 59.Rosterman JL, Pallotto EK, Truog WE, Escobar H, Meinert KA, Holmes A, et al. The impact of neurally adjusted ventilatory assist mode on respiratory severity score and energy expenditure in infants: a randomized crossover trial. J Perinatol 2018;38:59–63. [DOI] [PubMed] [Google Scholar]

[R60] 60.Phelps DL, Watterberg KL, Nolen TL, Cole CA, Cotten CM, Oh W, et al. Effects of myo-inositol on type 1 retinopathy of prematurity among preterm infants <28 weeks’ gestational age: a randomized clinical trial. JAMA 2018;320:1649–58. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R61] 61.McGrory L, Owen LS, Thio M, Dawson JA, Rafferty AR, Malhotra A, et al. A randomized trial of conditioned or unconditioned gases for stabilizing preterm infants at birth. J Pediatr 2018;193:47–53. [DOI] [PubMed] [Google Scholar]

[R62] 62.Klotz D, Schneider H, Schumann S, Mayer B, Fuchs H. Non-invasive high-frequency oscillatory ventilation in preterm infants: a randomised controlled cross-over trial. Arch Dis Child Fetal Neonatal Ed 2018;103:F1–5. [DOI] [PubMed] [Google Scholar]

[R63] 63.Kieran EA, O’Sullivan A, Miletin J, Twomey AR, Knowles SJ, O’Donnell CPF. 2% chlorhexidine-70% isopropyl alcohol versus 10% povidone-iodine for insertion site cleaning before central line insertion in preterm infants: a randomised trial. Arch Dis Child Fetal Neonatal Ed 2018;103:F101–6. [DOI] [PubMed] [Google Scholar]

[R64] 64.Imbulana DI, Owen LS, Dawson JA, Bailey JL, Davis PG, Manley BJ. A randomized controlled trial of a barrier dressing to reduce nasal injury in preterm infants receiving binasal noninvasive respiratory support. J Pediatr 2018;201:34–9.e3. [DOI] [PubMed] [Google Scholar]

[R65] 65.Hochwald O, Mainzer G, Borenstein-Levin L, Jubran H, Dinur G, Zucker M, et al. Adding paracetamol to ibuprofen for the treatment of patent ductus arteriosus in preterm infants: a double-blind, randomized, placebo-controlled pilot study. Am J Perinatol 2018;35:1319–25. [DOI] [PubMed] [Google Scholar]

[R66] 66.Gerges A, Gelfer P, Kennedy K. Randomized trial of earlier versus later oral feeding in very premature infants. J Perinatol 2018;38:687–92. [DOI] [PubMed] [Google Scholar]

[R67] 67.Eze N, Murphy D, Dhar V, Rehan VK. Comparison of sprinting vs non-sprinting to wean nasal continuous positive airway pressure off in very preterm infants. J Perinatol 2018;38:164–8. [DOI] [PubMed] [Google Scholar]

[R68] 68.Bottino R, Pontiggia F, Ricci C, Gambacorta A, Paladini A, Chijenas V, et al. Nasal high-frequency oscillatory ventilation and CO2 removal: a randomized controlled crossover trial. Pediatr Pulmonol 2018;53:1245–51. [DOI] [PubMed] [Google Scholar]

[R69] 69.Amaro CM, Bello JA, Jain D, Ramnath A, D’Ugard C, Vanbuskirk S, et al. Early caffeine and weaning from mechanical ventilation in preterm infants: a randomized, placebo-controlled trial. J Pediatr 2018;196:52–7. [DOI] [PubMed] [Google Scholar]

[R70] 70.Williams FLR, Ogston S, Hume R, Watson J, Stanbury K, Willatts P, et al. Supplemental iodide for preterm infants and developmental outcomes at 2 years: an RCT. Pediatrics 2017;139:e20163703. [DOI] [PubMed] [Google Scholar]

[R71] 71.Shetty S, Hunt K, Peacock J, Ali K, Greenough A. Crossover study of assist control ventilation and neurally adjusted ventilatory assist. Eur J Pediatr 2017;176:509–13. [DOI] [PubMed] [Google Scholar]

[R72] 72.Najm S, Lofqvist C, Hellgren G, Engstrom E, Lundgren P, Hard AL, et al. Effects of a lipid emulsion containing fish oil on polyunsaturated fatty acid profiles, growth and morbidities in extremely premature infants: a randomized controlled trial. Clin Nutr ESPEN 2017;20:17–23. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R73] 73.Mukerji A, Sarmiento K, Lee B, Hassall K, Shah V. Non-invasive high-frequency ventilation versus bi-phasic continuous positive airway pressure (BP-CPAP) following CPAP failure in infants <1250 g: a pilot randomized controlled trial. J Perinatol 2017;37:49–53. [DOI] [PubMed] [Google Scholar]

[R74] 74.Lemyre B, Fusch C, Schmolzer GM, Rouvinez Bouali N, Reddy D, Barrowman N, et al. Poractant alfa versus bovine lipid extract surfactant for infants 24+0 to 31+6 weeks gestational age: a randomized controlled trial. PLoS One 2017;12:e0175922. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R75] 75.Kugelman A, Peniakov M, Zangen S, Shiff Y, Riskin A, Iofe A, et al. Inhaled hydrofluoalkane-beclomethasone dipropionate in bronchopulmonary dysplasia. A double-blind, randomized, controlled pilot study. J Perinatol 2017;37:197–202. [DOI] [PubMed] [Google Scholar]

[R76] 76.Jiravisitkul P, Rattanasiri S, Nuntnarumit P. Randomised controlled trial of sustained lung inflation for resuscitation of preterm infants in the delivery room. Resuscitation 2017;111:68–73. [DOI] [PubMed] [Google Scholar]

[R77] 77.Hasan SU, Potenziano J, Konduri GG, Perez JA, Van Meurs KP, Walker MW, et al. Effect of inhaled nitric oxide on survival without bronchopulmonary dysplasia in preterm infants: a randomized clinical trial. JAMA Pediatr 2017;171:1081–9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R78] 78.Hansen-Pupp I, Hellstrom A, Hamdani M, Tocoian A, Kreher NC, Ley D, et al. Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: evaluation of feasibility in a phase II study. Growth Horm IGF Res 2017;36:44–51. [DOI] [PubMed] [Google Scholar]

[R79] 79.Glackin SJ, O’Sullivan A, George S, Semberova J, Miletin J. High flow nasal cannula versus NCPAP, duration to full oral feeds in preterm infants: a randomised controlled trial. Arch Dis Child-Fetal 2017;102:F329–32. [DOI] [PubMed] [Google Scholar]

[R80] 80.El-Mashad AE, El-Mahdy H, El Amrousy D, Elgendy M. Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates. Eur J Pediatr 2017;176:233–40. [DOI] [PubMed] [Google Scholar]

[R81] 81.Collins CT, Makrides M, McPhee AJ, Sullivan TR, Davis PG, Thio M, et al. Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants. N Engl J Med 2017;376:1245–55. [DOI] [PubMed] [Google Scholar]

[R82] 82.Brandon DH, Silva SG, Park J, Malcolm W, Kamhawy H, Holditch-Davis D. Timing for the introduction of cycled light for extremely preterm infants: a randomized controlled trial. Res Nurs Health 2017;40:294–310. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R83] 83.Ben Jmaa W, Hernandez AI, Sutherland MR, Cloutier A, Germain N, Lachance C, et al. Cardio-respiratory events and inflammatory response after primary immunization in preterm infants < 32 weeks gestational age: a randomized controlled study. Pediatr Infect Dis J 2017;36:988–94. [DOI] [PubMed] [Google Scholar]

[R84] 84.Beker F, Opie G, Noble E, Jiang Y, Bloomfield FH. Smell and taste to improve nutrition in very preterm infants: a randomized controlled pilot trial. Neonatology 2017;111:260–6. [DOI] [PubMed] [Google Scholar]

[R85] 85.Alkan Ozdemir S, Arun Ozer E, Ilhan O, Sutcuoglu S. Impact of targeted-volume ventilation on pulmonary dynamics in preterm infants with respiratory distress syndrome. Pediatr Pulmonol 2017;52:213–6. [DOI] [PubMed] [Google Scholar]

[R86] 86.Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, et al. Intratracheal administration of budesonide/surfactant to prevent bronchopulmonary dysplasia. Am J Respir Crit Care Med 2016;193:86–95. [DOI] [PubMed] [Google Scholar]

[R87] 87.Victor S, Roberts SA, Mitchell S, Aziz H, Lavender T, Extubate Trial G. Biphasic positive airway pressure or continuous positive airway pressure: a randomized trial. Pediatrics 2016;138:e20154095. [DOI] [PubMed] [Google Scholar]

[R88] 88.Vesoulis ZA, McPherson C, Neil JJ, Mathur AM, Inder TE. Early high-dose caffeine increases seizure burden in extremely preterm neonates: a preliminary study. J Caffeine Res 2016;6:101–7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R89] 89.Sohn K, Kalanetra KM, Mills DA, Underwood MA. Buccal administration of human colostrum: impact on the oral microbiota of premature infants. J Perinatol 2016;36:106–11. [DOI] [PubMed] [Google Scholar]

[R90] 90.Shetty S, Hickey A, Rafferty GF, Peacock JL, Greenough A. Work of breathing during CPAP and heated humidified high-flow nasal cannula. Arch Dis Child Fetal Neonatal Ed 2016;101:F404–7. [DOI] [PubMed] [Google Scholar]

[R91] 91.Shetty S, Bhat P, Hickey A, Peacock JL, Milner AD, Greenough A. Proportional assist versus assist control ventilation in premature infants. Eur J Pediatr 2016;175:57–61. [DOI] [PubMed] [Google Scholar]

[R92] 92.Robinson DT, Caplan M, Carlson SE, Yoder R, Murthy K, Frost B. Early docosahexaenoic and arachidonic acid supplementation in extremely-low-birth-weight infants. Pediatr Res 2016;80:505–10. [DOI] [PubMed] [Google Scholar]

[R93] 93.Phelps DL, Ward RM, Williams RL, Nolen TL, Watterberg KL, Oh W, et al. Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants. Pediatr Res 2016;80:209–17. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R94] 94.Ng E, Schurr P, Reilly M, Dunn M, Beck J. Impact of feeding method on diaphragm electrical activity and central apnea in preterm infants (FEAdi study). Early Hum Dev 2016;101:33–7. [DOI] [PubMed] [Google Scholar]

[R95] 95.Levit OL, Calkins KL, Gibson LC, Kelley-Quon L, Robinson DT, Elashoff DA, et al. Low-dose intravenous soybean oil emulsion for prevention of cholestasis in preterm neonates. JPEN J Parenter Enteral Nutr 2016;40:374–82. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R96] 96.Jain D, Claure N, D’Ugard C, Bello J, Bancalari E. Volume guarantee ventilation: effect on preterm infants with frequent hypoxemia episodes. Neonatology 2016;110:129–34. [DOI] [PubMed] [Google Scholar]

[R97] 97.Ishihara C, Ibara S, Ohsone Y, Kato E, Tokuhisa T, Yamamoto Y, et al. Effects of infant flow Bi-NCPAP on apnea of prematurity. Pediatr Int 2016;58:456–60. [DOI] [PubMed] [Google Scholar]

[R98] 98.Hascoet JM, Picaud JC, Ligi I, Blanc T, Moreau F, Pinturier MF, et al. Late surfactant administration in very preterm neonates with prolonged respiratory distress and pulmonary outcome at 1 year of age: a randomized clinical trial. JAMA Pediatr 2016;170:365–72. [DOI] [PubMed] [Google Scholar]

[R99] 99.Greze E, Benard M, Hamon I, Casper C, Haddad FE, Boutroy MJ, et al. Doxapram dosing for apnea of prematurity based on postmenstrual age and gender: a randomized controlled trial. Paediatr Drugs 2016;18:443–9. [DOI] [PubMed] [Google Scholar]

[R100] 100.Fort P, Salas AA, Nicola T, Craig CM, Carlo WA, Ambalavanan N. A Comparison of 3 vitamin D dosing regimens in extremely preterm infants: a randomized controlled trial. J Pediatr 2016;174:132–8.e1. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R101] 101.Costeloe K, Hardy P, Juszczak E, Wilks M, Millar MR. Probiotics in Preterm Infants Study Collaborative Group. Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial. Lancet 2016;387:649–60. [DOI] [PubMed] [Google Scholar]

[R102] 102.Bellagamba MP, Carmenati E, D’Ascenzo R, Malatesta M, Spagnoli C, Biagetti C, et al. One extra gram of protein to preterm infants from birth to 1800 g: a single-blinded randomized clinical trial. J Pediatr Gastroenterol Nutr 2016;62:879–84. [DOI] [PubMed] [Google Scholar]

[R103] 103.Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C, et al. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet 2016;387:1827–36. [DOI] [PubMed] [Google Scholar]

[R104] 104.Ballard RA, Keller RL, Black DM, Ballard PL, Merrill JD, Eichenwald EC, et al. Randomized trial of late surfactant treatment in ventilated preterm infants receiving inhaled nitric oxide. J Pediatr 2016;168:23–9.e4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R105] 105.Backes CH, Huang H, Iams JD, Bauer JA, Giannone PJ. Timing of umbilical cord clamping among infants born at 22 through 27 weeks’ gestation. J Perinatol 2016;36:35–40. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R106] 106.Waitz M, Schmid MB, Fuchs H, Mendler MR, Dreyhaupt J, Hummler HD. Effects of automated adjustment of the inspired oxygen on fluctuations of arterial and regional cerebral tissue oxygenation in preterm infants with frequent desaturations. J Pediatr 2015;166:240–4.e1. [DOI] [PubMed] [Google Scholar]

[R107] 107.van Kaam AH, Hummler HD, Wilinska M, Swietlinski J, Lal MK, te Pas AB, et al. Automated versus manual oxygen control with different saturation targets and modes of respiratory support in preterm infants. J Pediatr 2015;167:545-50.e1–550.e2. [DOI] [PubMed] [Google Scholar]

[R108] 108.Thome UH, Genzel-Boroviczeny O, Bohnhorst B, Schmid M, Fuchs H, Rohde O, et al. Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial. Lancet Respir Med 2015;3:534–43. [DOI] [PubMed] [Google Scholar]

[R109] 109.Tang J, Reid S, Lutz T, Malcolm G, Oliver S, Osborn DA. Randomised controlled trial of weaning strategies for preterm infants on nasal continuous positive airway pressure. BMC Pediatr 2015;15:147. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R110] 110.Schulzke SM, Deshmukh M, Nathan EA, Doherty DA, Patole SK. Nebulized pentoxifylline for reducing the duration of oxygen supplementation in extremely preterm neonates. J Pediatr 2015;166:1158–62.e2. [DOI] [PubMed] [Google Scholar]

[R111] 111.Salas AA, Cuna A, Bhat R, McGwin G Jr, Carlo WA, Ambalavanan N. A randomised trial of re-feeding gastric residuals in preterm infants. Arch Dis Child Fetal Neonatal Ed 2015;100:F224–8. [DOI] [PubMed] [Google Scholar]

[R112] 112.Rios DR, Kaiser JR. Vasopressin versus dopamine for treatment of hypotension in extremely low birth weight infants: a randomized, blinded pilot study. J Pediatr 2015;166:850–5. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R113] 113.Reilly MC, Vohra S, Rac VE, Dunn M, Ferrelli K, Kiss A, et al. Randomized trial of occlusive wrap for heat loss prevention in preterm infants. J Pediatr 2015;166:262–8.e2. [DOI] [PubMed] [Google Scholar]

[R114] 114.Omarsdottir S, Casper C, Naver L, Legnevall L, Gustafsson F, Grillner L, et al. Cytomegalovirus infection and neonatal outcome in extremely preterm infants after freezing of maternal milk. Pediatr Infect Dis J 2015;34:482–9. [DOI] [PubMed] [Google Scholar]

[R115] 115.Okulu E, Arsan S, Mungan Akin I, Alan S, Kilic A, Atasay B. Early or later prophylactic INSURE in preterm infants of less than 30 weeks’ gestation. Turk J Pediatr 2015;57:1–8. [PubMed] [Google Scholar]

[R116] 116.Newnam KM, McGrath JM, Salyer J, Estes T, Jallo N, Bass WT. A comparative effectiveness study of continuous positive airway pressure-related skin breakdown when using different nasal interfaces in the extremely low birth weight neonate. Appl Nurs Res 2015;28:36–41. [DOI] [PubMed] [Google Scholar]

[R117] 117.Nasef N, El-Gouhary E, Schurr P, Reilly M, Beck J, Dunn M, et al. High-flow nasal cannulae are associated with increased diaphragm activation compared with nasal continuous positive airway pressure in preterm infants. Acta Paediatr 2015;104:e337–43. [DOI] [PubMed] [Google Scholar]

[R118] 118.Nair V, Swarnam K, Rabi Y, Amin H, Howlett A, Akierman A, et al. Effect of nasal continuous positive airway pressure (NCPAP) Cycling and continuous NCPAP on successful weaning: a randomized controlled trial. Indian J Pediatr 2015;82:787–93. [DOI] [PubMed] [Google Scholar]

[R119] 119.McPherson C, Neil JJ, Tjoeng TH, Pineda R, Inder TE. A pilot randomized trial of high-dose caffeine therapy in preterm infants. Pediatr Res 2015;78:198–204. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R120] 120.Lista G, Boni L, Scopesi F, Mosca F, Trevisanuto D, Messner H, et al. Sustained lung inflation at birth for preterm infants: a randomized clinical trial. Pediatrics 2015;135:e457–64. [DOI] [PubMed] [Google Scholar]

[R121] 121.Lee J, Kim HS, Jung YH, Shin SH, Choi CW, Kim EK, et al. Non-invasive neurally adjusted ventilatory assist in preterm infants: a randomised phase II crossover trial. Arch Dis Child Fetal Neonatal Ed 2015;100:F507–13. [DOI] [PubMed] [Google Scholar]

[R122] 122.Lee J, Kim HS, Jung YH, Choi KY, Shin SH, Kim EK, et al. Oropharyngeal colostrum administration in extremely premature infants: an RCT. Pediatrics 2015;135:e357–66. [DOI] [PubMed] [Google Scholar]

[R123] 123.Lal M, Tin W, Sinha S. Automated control of inspired oxygen in ventilated preterm infants: crossover physiological study. Acta Paediatr 2015;104:1084–9. [DOI] [PubMed] [Google Scholar]

[R124] 124.Laborie S, Denis A, Dassieu G, Bedu A, Tourneux P, Pinquier D, et al. Shielding parenteral nutrition solutions from light: a randomized controlled trial. JPEN J Parenter Enteral Nutr 2015;39:729–37. [DOI] [PubMed] [Google Scholar]

[R125] 125.Kribs A, Roll C, Gopel W, Wieg C, Groneck P, Laux R, et al. Nonintubated surfactant application vs conventional therapy in extremely preterm infants: a randomized clinical trial. JAMA Pediatr 2015;169:723–30. [DOI] [PubMed] [Google Scholar]

[R126] 126.Kong L, Bhatt AR, Demny AB, Coats DK, Li A, Rahman EZ, et al. Pharmacokinetics of bevacizumab and its effects on serum VEGF and IGF-1 in infants with retinopathy of prematurity. Invest Ophthalmol Vis Sci 2015;56:956–61. [DOI] [PubMed] [Google Scholar]

[R127] 127.Katheria AC, Sauberan JB, Akotia D, Rich W, Durham J, Finer NN. A pilot randomized controlled trial of early versus routine caffeine in extremely premature infants. Am J Perinatol 2015;32:879–86. [DOI] [PubMed] [Google Scholar]

[R128] 128.Hyttel-Sorensen S, Pellicer A, Alderliesten T, Austin T, van Bel F, Benders M, et al. Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial. BMJ 2015;350:g7635. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R129] 129.Clarke A, Yeomans E, Elsayed K, Medhurst A, Berger P, Skuza E, et al. A randomised crossover trial of clinical algorithm for oxygen saturation targeting in preterm infants with frequent desaturation episodes. Neonatology 2015;107:130–6. [DOI] [PubMed] [Google Scholar]

[R130] 130.Bravo MC, Lopez-Ortego P, Sanchez L, Riera J, Madero R, Cabanas F, et al. Randomized, placebo-controlled trial of dobutamine for low superior vena cava flow in infants. J Pediatr 2015;167:572-8.e1–578.e2. [DOI] [PubMed] [Google Scholar]

[R131] 131.Bozdag S, Dilli D, Gokmen T, Dilmen U. Comparison of two natural surfactants for pulmonary hemorrhage in very low-birth-weight infants: a randomized controlled trial. Am J Perinatol 2015;32:211–8. [DOI] [PubMed] [Google Scholar]

[R132] 132.Bhat P, Patel DS, Hannam S, Rafferty GF, Peacock JL, Milner AD, et al. Crossover study of proportional assist versus assist control ventilation. Arch Dis Child Fetal Neonatal Ed 2015;100:F35–8. [DOI] [PubMed] [Google Scholar]

[R133] 133.Beker F, Rogerson SR, Hooper SB, Sehgal A, Davis PG. Hemodynamic effects of nasal continuous positive airway pressure in preterm infants with evolving chronic lung disease, a crossover randomized trial. J Pediatr 2015;166:477–9. [DOI] [PubMed] [Google Scholar]

[R134] 134.Bassler D, Plavka R, Shinwell ES, Hallman M, Jarreau PH, Carnielli V, et al. Early inhaled budesonide for the prevention of bronchopulmonary dysplasia. N Engl J Med 2015;373:1497–506. [DOI] [PubMed] [Google Scholar]

[R135] 135.Anell-Olofsson M, Lonnqvist PA, Bitkover C, Lundeberg S, Larsson BA, Eksborg S, et al. Plasma concentrations of levobupivacaine associated with two different intermittent wound infusion regimens following surgical ductus ligation in preterm infants. Paediatr Anaesth 2015;25:711–8. [DOI] [PubMed] [Google Scholar]

[R136] 136.Zapata J, Gomez JJ, Araque Campo R, Matiz Rubio A, Sola A. A randomised controlled trial of an automated oxygen delivery algorithm for preterm neonates receiving supplemental oxygen without mechanical ventilation. Acta Paediatr 2014;103:928–33. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R137] 137.Wilinska M, Bachman T, Swietlinski J, Kostro M, Twardoch-Drozd M. Automated FiO2-SpO2 control system in neonates requiring respiratory support: a comparison of a standard to a narrow SpO2 control range. BMC Pediatr 2014;14:130. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R138] 138.Smith JR, McGrath J, Brotto M, Inder T. A randomized-controlled trial pilot study examining the neurodevelopmental effects of a 5-week M Technique intervention on very preterm infants. Adv Neonatal Care 2014;14:187–200. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R139] 139.Shin SH, Kim HS, Lee J, Choi KY, Lee JH, Kim EK, et al. A comparative study of two remifentanil doses for procedural pain in ventilated preterm infants: a randomized, controlled study. Pediatr Crit Care Med 2014;15:451–5. [DOI] [PubMed] [Google Scholar]

[R140] 140.Oncel MY, Yurttutan S, Erdeve O, Uras N, Altug N, Oguz SS, et al. Oral paracetamol versus oral ibuprofen in the management of patent ductus arteriosus in preterm infants: a randomized controlled trial. J Pediatr 2014;164:510–4.e1. [DOI] [PubMed] [Google Scholar]

[R141] 141.Morgan C, McGowan P, Herwitker S, Hart AE, Turner MA. Postnatal head growth in preterm infants: a randomized controlled parenteral nutrition study. Pediatrics 2014;133:e120–8. [DOI] [PubMed] [Google Scholar]

[R142] 142.Mena NP, Leon Del PJ, Sandino PD, Ralmolfo BP, Sabatelli D, Llanos MA, et al. Meconium evacuation to improve feeding tolerance in very low birth weight preterm infants (Emita Protocol). Rev Chil Pediatr 2014;85:304–11. [DOI] [PubMed] [Google Scholar]

[R143] 143.Lepore D, Quinn GE, Molle F, Baldascino A, Orazi L, Sammartino M, et al. Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings. Ophthalmology 2014;121:2212–9. [DOI] [PubMed] [Google Scholar]

[R144] 144.Lago P, Salvadori S, Opocher F, Ricato S, Chiandetti L, Frigo AC. Continuous infusion of ibuprofen for treatment of patent ductus arteriosus in very low birth weight infants. Neonatology 2014;105:46–54. [DOI] [PubMed] [Google Scholar]

[R145] 145.Konig K, Barfield CP, Guy KJ, Drew SM, Andersen CC. The effect of sildenafil on evolving bronchopulmonary dysplasia in extremely preterm infants: a randomised controlled pilot study. J Matern Fetal Neonatal Med 2014;27:439–44. [DOI] [PubMed] [Google Scholar]

[R146] 146.Kluckow M, Jeffery M, Gill A, Evans N. A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus. Arch Dis Child Fetal Neonatal Ed 2014;99:F99–104. [DOI] [PubMed] [Google Scholar]

[R147] 147.Kinsella JP, Cutter GR, Steinhorn RH, Nelin LD, Walsh WF, Finer NN, et al. Noninvasive inhaled nitric oxide does not prevent bronchopulmonary dysplasia in premature newborns. J Pediatr 2014;165:1104–8.e1. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R148] 148.Kaufman DA, Blackman A, Conaway MR, Sinkin RA. Nonsterile glove use in addition to hand hygiene to prevent late-onset infection in preterm infants: randomized clinical trial. JAMA Pediatr 2014;168:909–16. [DOI] [PubMed] [Google Scholar]

[R149] 149.Hochwald O, Palegra G, Osiovich H. Adding hydrocortisone as 1st line of inotropic treatment for hypotension in very low birth weight infants. Indian J Pediatr 2014;81:808–10. [DOI] [PubMed] [Google Scholar]

[R150] 150.Hallenberger A, Poets CF, Horn W, Seyfang A, Urschitz MS, Group CS. Closed-loop automatic oxygen control (CLAC) in preterm infants: a randomized controlled trial. Pediatrics 2014;133:e379–85. [DOI] [PubMed] [Google Scholar]

[R151] 151.Hair AB, Blanco CL, Moreira AG, Hawthorne KM, Lee ML, Rechtman DJ, et al. Randomized trial of human milk cream as a supplement to standard fortification of an exclusive human milk-based diet in infants 750-1250 g birth weight. J Pediatr 2014;165:915–20. [DOI] [PubMed] [Google Scholar]

[R152] 152.Doglioni N, Cavallin F, Mardegan V, Palatron S, Filippone M, Vecchiato L, et al. Total body polyethylene wraps for preventing hypothermia in preterm infants: a randomized trial. J Pediatr 2014;165:261–6.e1. [DOI] [PubMed] [Google Scholar]

[R153] 153.Deshpande G, Simmer K, Deshmukh M, Mori TA, Croft KD, Kristensen J. Fish Oil (SMOFlipid) and olive oil lipid (Clinoleic) in very preterm neonates. J Pediatr Gastroenterol Nutr 2014;58:177–82. [DOI] [PubMed] [Google Scholar]

[R154] 154.Buzzella B, Claure N, D’Ugard C, Bancalari E. A randomized controlled trial of two nasal continuous positive airway pressure levels after extubation in preterm infants. J Pediatr 2014;164:46–51. [DOI] [PubMed] [Google Scholar]

[R155] 155.Bravo MC, Cabanas F, Riera J, Perez-Fernandez E, Quero J, Perez-Rodriguez J, et al. Randomised controlled clinical trial of standard versus echocardiographically guided ibuprofen treatment for patent ductus arteriosus in preterm infants: a pilot study. J Matern Fetal Neonatal Med 2014;27:904–9. [DOI] [PubMed] [Google Scholar]

[R156] 156.Benjamin DK Jr, Hudak ML, Duara S, Randolph DA, Bidegain M, Mundakel GT, et al. Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants: a randomized clinical trial. JAMA 2014;311:1742–9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R157] 157.AlKharfy T, Ba-Abbad R, Hadi A, AlFaleh K. Use of topical petroleum jelly for prevention of sepsis in very low-birthweight infants: a prospective, randomised controlled trial. Paediatr Int Child Health 2014;34:194–7. [DOI] [PubMed] [Google Scholar]

[R158] 158.Underwood MA, Kalanetra KM, Bokulich NA, Lewis ZT, Mirmiran M, Tancredi DJ, et al. A comparison of two probiotic strains of bifidobacteria in premature infants. J Pediatr 2013;163:1585–91.e9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R159] 159.Taylor TA, Kennedy KA. Randomized trial of iron supplementation versus routine iron intake in VLBW infants. Pediatrics 2013;131:e433–8. [DOI] [PubMed] [Google Scholar]

[R160] 160.Stefanescu BM, Hetu C, Slaughter JC, O’Shea TM, Shetty AK. A pilot study of Biotene OralBalance(R) gel for oral care in mechanically ventilated preterm neonates. Contemp Clin Trials 2013;35:33–9. [DOI] [PubMed] [Google Scholar]

[R161] 161.Schmidt B, Whyte RK, Asztalos EV, Moddemann D, Poets C, Rabi Y, et al. Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial. JAMA 2013;309:2111–20. [DOI] [PubMed] [Google Scholar]

[R162] 162.Schmid MB, Hopfner RJ, Lenhof S, Hummler HD, Fuchs H. Cerebral desaturations in preterm infants: a crossover trial on influence of oxygen saturation target range. Arch Dis Child Fetal Neonatal Ed 2013;98:F392–8. [DOI] [PubMed] [Google Scholar]

[R163] 163.Scattolin S, Gaio P, Betto M, Palatron S, De Terlizzi F, Intini F, et al. Parenteral amino acid intakes: possible influences of higher intakes on growth and bone status in preterm infants. J Perinatol 2013;33:33–9. [DOI] [PubMed] [Google Scholar]

[R164] 164.Pirr SM, Lange M, Hartmann C, Bohnhorst B, Peter C. Closed versus open endotracheal suctioning in extremely low-birth-weight neonates: a randomized, crossover trial. Neonatology 2013;103:124–30. [DOI] [PubMed] [Google Scholar]

[R165] 165.Phelps DL, Ward RM, Williams RL, Watterberg KL, Laptook AR, Wrage LA, et al. Pharmacokinetics and safety of a single intravenous dose of myo-inositol in preterm infants of 23-29 wk. Pediatr Res 2013;74:721–9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R166] 166.Parikh NA, Kennedy KA, Lasky RE, McDavid GE, Tyson JE. Pilot randomized trial of hydrocortisone in ventilator-dependent extremely preterm infants: effects on regional brain volumes. J Pediatr 2013;162:685–90.e1. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R167] 167.Ng SM, Turner MA, Gamble C, Didi M, Victor S, Manning D, et al. An explanatory randomised placebo controlled trial of levothyroxine supplementation for babies born <28 weeks’ gestation: results of the TIPIT trial. Trials 2013;14:211. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R168] 168.Mathew B, Lakshminrusimha S, Sengupta S, Carrion V. Randomized controlled trial of vinyl bags versus thermal mattress to prevent hypothermia in extremely low-gestational-age infants. Am J Perinatol 2013;30:317–22. [DOI] [PubMed] [Google Scholar]

[R169] 169.March MI, Hacker MR, Parson AW, Modest AM, de Veciana M. The effects of umbilical cord milking in extremely preterm infants: a randomized controlled trial. J Perinatol 2013;33:763–7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R170] 170.Manley BJ, Owen LS, Doyle LW, Andersen CC, Cartwright DW, Pritchard MA, et al. High-flow nasal cannulae in very preterm infants after extubation. N Engl J Med 2013;369:1425–33. [DOI] [PubMed] [Google Scholar]

[R171] 171.Kirpalani H, Millar D, Lemyre B, Yoder BA, Chiu A, Roberts RS, et al. A trial comparing noninvasive ventilation strategies in preterm infants. N Engl J Med 2013;369:611–20. [DOI] [PubMed] [Google Scholar]

[R172] 172.Karen T, Vatlach S, Poets A, Maas C, Poets CF, Bassler D. The impact of oral sucrose on apnea and bradycardia in preterm infants: a randomised cross-over trial. Arch Dis Child Fetal Neonatal Ed 2013;98:F93–4. [DOI] [PubMed] [Google Scholar]

[R173] 173.Kanmaz HG, Mutlu B, Erdeve O, Canpolat FE, Oguz SS, Uras N, et al. Does enteral protein intake affect renal glomerular and tubular functions in very low birth weight infants? Clin Nephrol 2013;80:355–60. [DOI] [PubMed] [Google Scholar]

[R174] 174.Kanmaz G, Erdeve O, Canpolat FE, Oguz SS, Uras N, Altug N, et al. Serum ibuprofen levels of extremely preterm infants treated prophylactically with oral ibuprofen to prevent patent ductus arteriosus. Eur J Clin Pharmacol 2013;69:1075–81. [DOI] [PubMed] [Google Scholar]

[R175] 175.Kamlin CO, Schilleman K, Dawson JA, Lopriore E, Donath SM, Schmolzer GM, et al. Mask versus nasal tube for stabilization of preterm infants at birth: a randomized controlled trial. Pediatrics 2013;132: e381–8. [DOI] [PubMed] [Google Scholar]

[R176] 176.Johnston C, Campbell-Yeo M, Rich B, Whitley J, Filion F, Cogan J, et al. Therapeutic touch is not therapeutic for procedural pain in very preterm neonates: a randomized trial. Clin J Pain 2013;29:824–9. [DOI] [PubMed] [Google Scholar]

[R177] 177.Jacobs SE, Tobin JM, Opie GF, Donath S, Tabrizi SN, Pirotta M, et al. Probiotic effects on late-onset sepsis in very preterm infants: a randomized controlled trial. Pediatrics 2013;132:1055–62. [DOI] [PubMed] [Google Scholar]

[R178] 178.Boost II United Kingdom Collaborative Group, Boost II Australia Collaborative Group, Boost II New Zealand Collaborative Group, Stenson BJ, Tarnow-Mordi WO, Darlow BA, et al. Oxygen saturation and outcomes in preterm infants. N Engl J Med 2013;368:2094–104. [DOI] [PubMed] [Google Scholar]

[R179] 179.Gouna G, Rakza T, Kuissi E, Pennaforte T, Mur S, Storme L. Positioning effects on lung function and breathing pattern in premature newborns. J Pediatr 2013;162:1133–7. 7.e1. [DOI] [PubMed] [Google Scholar]

[R180] 180.Ditzenberger GR, Wallen LD, Phelan L, Escoe S, Collins SD. Supplemental protein and postnatal growth of very low birth weight infants: a randomized trial. J Neonatal Perinatal Med 2013;6:285–94. [DOI] [PubMed] [Google Scholar]

[R181] 181.Cristofalo EA, Schanler RJ, Blanco CL, Sullivan S, Trawoeger R, Kiechl-Kohlendorfer U, et al. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. J Pediatr 2013;163:1592–5 e1. [DOI] [PubMed] [Google Scholar]

[R182] 182.Cone S, Pickler RH, Grap MJ, McGrath J, Wiley PM. Endotracheal suctioning in preterm infants using four-handed versus routine care. J Obstet Gynecol Neonatal Nurs 2013;42:92–104. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R183] 183.Collins CL, Holberton JR, Konig K. Comparison of the pharyngeal pressure provided by two heated, humidified high-flow nasal cannulae devices in premature infants. J Paediatr Child Health 2013;49:554–6. [DOI] [PubMed] [Google Scholar]

[R184] 184.Collins CL, Holberton JR, Barfield C, Davis PG. A randomized controlled trial to compare heated humidified high-flow nasal cannulae with nasal continuous positive airway pressure postextubation in premature infants. J Pediatr 2013;162:949–54.e1. [DOI] [PubMed] [Google Scholar]

[R185] 185.Bertini G, Elia S, Ceciarini F, Dani C. Reduction of catheter-related bloodstream infections in preterm infants by the use of catheters with the AgION antimicrobial system. Early Hum Dev 2013;89:21–5. [DOI] [PubMed] [Google Scholar]

[R186] 186.Bell EF, Hansen NI, Brion LP, Ehrenkranz RA, Kennedy KA, Walsh MC, et al. Serum tocopherol levels in very preterm infants after a single dose of vitamin E at birth. Pediatrics 2013;132:e1626–33. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R187] 187.Bagnoli F, Rossetti A, Messina G, Mori A, Casucci M, Tomasini B. Treatment of patent ductus arteriosus (PDA) using ibuprofen: renal side-effects in VLBW and ELBW newborns. J Matern Fetal Neonatal Med 2013;26:423–9. [DOI] [PubMed] [Google Scholar]

[R188] 188.Wheeler KI, Morley CJ, Hooper SB, Davis PG. Lower back-up rates improve ventilator triggering during assist-control ventilation: a randomized crossover trial. J Perinatol 2012;32:111–6. [DOI] [PubMed] [Google Scholar]

[R189] 189.Todd DA, Wright A, Broom M, Chauhan M, Meskell S, Cameron C, et al. Methods of weaning preterm babies <30 weeks gestation off CPAP: a multicentre randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2012;97:F236–40. [DOI] [PubMed] [Google Scholar]

[R190] 190.Sosenko IR, Fajardo MF, Claure N, Bancalari E. Timing of patent ductus arteriosus treatment and respiratory outcome in premature infants: a double-blind randomized controlled trial. J Pediatr 2012;160:929–35.e1. [DOI] [PubMed] [Google Scholar]

[R191] 191.Salvo V, Zimmermann LJ, Gavilanes AW, Barberi I, Ricotti A, Abella R, et al. First intention high-frequency oscillatory and conventional mechanical ventilation in premature infants without antenatal glucocorticoid prophylaxis. Pediatr Crit Care Med 2012;13:72–9. [DOI] [PubMed] [Google Scholar]

[R192] 192.Salvador A, Janeczko M, Porat R, Sekhon R, Moewes A, Schutzman D. Randomized controlled trial of early parenteral nutrition cycling to prevent cholestasis in very low birth weight infants. J Pediatr 2012;161:229–33.e1. [DOI] [PubMed] [Google Scholar]

[R193] 193.Ramanathan R, Sekar KC, Rasmussen M, Bhatia J, Soll RF. Nasal intermittent positive pressure ventilation after surfactant treatment for respiratory distress syndrome in preterm infants <30 weeks’ gestation: a randomized, controlled trial. J Perinatol 2012;32:336–43. [DOI] [PubMed] [Google Scholar]

[R194] 194.Ohls RK, Roohi M, Peceny HM, Schrader R, Bierer R. A randomized, masked study of weekly erythropoietin dosing in preterm infants. J Pediatr 2012;160:790–5.e1. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R195] 195.O’Brien K, Campbell C, Brown L, Wenger L, Shah V. Infant flow biphasic nasal continuous positive airway pressure (BP- NCPAP) vs. infant flow NCPAP for the facilitation of extubation in infants’ </= 1,250 grams: a randomized controlled trial. BMC Pediatr 2012;12:43. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R196] 196.Moya F, Sisk PM, Walsh KR, Berseth CL. A new liquid human milk fortifier and linear growth in preterm infants. Pediatrics 2012;130: e928–35. [DOI] [PubMed] [Google Scholar]

[R197] 197.McCain GC, Del Moral T, Duncan RC, Fontaine JL, Pino LD. Transition from gavage to nipple feeding for preterm infants with bronchopulmonary dysplasia. Nurs Res 2012;61:380–7. [DOI] [PubMed] [Google Scholar]

[R198] 198.Keller RL, Merrill JD, Black DM, Steinhorn RH, Eichenwald EC, Durand DJ, et al. Late administration of surfactant replacement therapy increases surfactant protein-B content: a randomized pilot study. Pediatr Res 2012;72:613–9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R199] 199.Haiden N, Norooz F, Klebermass-Schrehof K, Horak AS, Jilma B, Berger A, et al. The effect of an osmotic contrast agent on complete meconium evacuation in preterm infants. Pediatrics 2012;130:e1600–6. [DOI] [PubMed] [Google Scholar]

[R200] 200.Fergusson DA, Hebert P, Hogan DL, LeBel L, Rouvinez-Bouali N, Smyth JA, et al. Effect of fresh red blood cell transfusions on clinical outcomes in premature, very low-birth-weight infants: the ARIPI randomized trial. JAMA 2012;308:1443–51. [DOI] [PubMed] [Google Scholar]

[R201] 201.Erdeve O, Yurttutan S, Altug N, Ozdemir R, Gokmen T, Dilmen U, et al. Oral versus intravenous ibuprofen for patent ductus arteriosus closure: a randomised controlled trial in extremely low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2012;97:F279–83. [DOI] [PubMed] [Google Scholar]

[R202] 202.Duman N, Tuzun F, Sutcuoglu S, Yesilirmak CD, Kumral A, Ozkan H. Impact of volume guarantee on synchronized ventilation in preterm infants: a randomized controlled trial. Intensive Care Med 2012;38:1358–64. [DOI] [PubMed] [Google Scholar]

[R203] 203.Dani C, Vangi V, Bertini G, Pratesi S, Lori I, Favelli F, et al. High-dose ibuprofen for patent ductus arteriosus in extremely preterm infants: a randomized controlled study. Clin Pharmacol Ther 2012;91:590–6. [DOI] [PubMed] [Google Scholar]

[R204] 204.Batton BJ, Li L, Newman NS, Das A, Watterberg KL, Yoder BA, et al. Feasibility study of early blood pressure management in extremely preterm infants. J Pediatr 2012;161:65–9.e1. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R205] 205.Autrata R, Senkova K, Holousova M, Krejcirova I, Dolezel Z, Borek I. Effects of intravitreal pegaptanib or bevacizumab and laser in treatment of threshold retinopathy of prematurity in zone I and posterior zone II—four years results. Cesk Slov Oftalmol 2012;68:29–36. [PubMed] [Google Scholar]

[R206] 206.Alsweiler JM, Harding JE, Bloomfield FH. Tight glycemic control with insulin in hyperglycemic preterm babies: a randomized controlled trial. Pediatrics 2012;129:639–47. [DOI] [PubMed] [Google Scholar]

[R207] 207.Al-Hosni M, Duenas M, Hawk M, Stewart LA, Borghese RA, Cahoon M, et al. Probiotics-supplemented feeding in extremely low-birth-weight infants. J Perinatol 2012;32:253–9. [DOI] [PubMed] [Google Scholar]

[R208] 208.Simon P, Dannaway D, Bright B, Krous L, Wlodaver A, Burks B, et al. Thermal defense of extremely low gestational age newborns during resuscitation: exothermic mattresses vs polyethylene wrap. J Perinatol 2011;31:33–7. [DOI] [PubMed] [Google Scholar]

[R209] 209.Sarafidis K, Stathopoulou T, Agakidou E, Taparkou A, Soubasi V, Diamanti E, et al. Comparable effect of conventional ventilation versus early high-frequency oscillation on serum CC16 and IL-6 levels in preterm neonates. J Perinatol 2011;31:104–11. [DOI] [PubMed] [Google Scholar]

[R210] 210.Oh W, Fanaroff AA, Carlo WA, Donovan EF, McDonald SA, Poole WK, et al. Effects of delayed cord clamping in very-low-birth-weight infants. J Perinatol 2011;31(suppl 1):S68–71. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R211] 211.Norman E, Wikstrom S, Hellstrom-Westas L, Turpeinen U, Hamalainen E, Fellman V. Rapid sequence induction is superior to morphine for intubation of preterm infants: a randomized controlled trial. J Pediatr 2011;159:893–9.e1. [DOI] [PubMed] [Google Scholar]

[R212] 212.Mintz-Hittner HA, Kennedy KA, Chuang AZ, Group B-RC. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med 2011;364:603–15. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R213] 213.Gopel W, Kribs A, Ziegler A, Laux R, Hoehn T, Wieg C, et al. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet 2011;378:1627–34. [DOI] [PubMed] [Google Scholar]

[R214] 214.Giannantonio C, Papacci P, Purcaro V, Cota F, Tesfagabir MG, Molle F, et al. Effectiveness of ketorolac tromethamine in prevention of severe retinopathy of prematurity. J Pediatr Ophthalmol Strabismus 2011;48:247–51. [DOI] [PubMed] [Google Scholar]

[R215] 215.Dawson JA, Schmolzer GM, Kamlin CO, Te Pas AB, O’Donnell CP, Donath SM, et al. Oxygenation with T-piece versus self-inflating bag for ventilation of extremely preterm infants at birth: a randomized controlled trial. J Pediatr 2011;158:912-8.e1–918.e2. [DOI] [PubMed] [Google Scholar]

[R216] 216.Castoldi F, Daniele I, Fontana P, Cavigioli F, Lupo E, Lista G. Lung recruitment maneuver during volume guarantee ventilation of preterm infants with acute respiratory distress syndrome. Am J Perinatol 2011;28:521–8. [DOI] [PubMed] [Google Scholar]

[R217] 217.Ballard HO, Shook LA, Bernard P, Anstead MI, Kuhn R, Whitehead V, et al. Use of azithromycin for the prevention of bronchopulmonary dysplasia in preterm infants: a randomized, double-blind, placebo controlled trial. Pediatr Pulmonol 2011;46:111–8. [DOI] [PubMed] [Google Scholar]

[R218] 218.Balegar VK, Kluckow M. Furosemide for packed red cell transfusion in preterm infants: a randomized controlled trial. J Pediatr 2011;159:913–8.e1. [DOI] [PubMed] [Google Scholar]

[R219] 219.Trevisanuto D, Doglioni N, Cavallin F, Parotto M, Micaglio M, Zanardo V. Heat loss prevention in very preterm infants in delivery rooms: a prospective, randomized, controlled trial of polyethylene caps. J Pediatr 2010;156:914–7.e1. [DOI] [PubMed] [Google Scholar]

[R220] 220.Support Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, et al. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med 2010;362:1970–9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R221] 221.Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawoger R, Kiechl-Kohlendorfer U, et al. An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr 2010;156:562–7.e1. [DOI] [PubMed] [Google Scholar]

[R222] 222.Sandri F, Plavka R, Ancora G, Simeoni U, Stranak Z, Martinelli S, et al. Prophylactic or early selective surfactant combined with nCPAP in very preterm infants. Pediatrics 2010;125:e1402–9. [DOI] [PubMed] [Google Scholar]

[R223] 223.Mihatsch WA, Vossbeck S, Eikmanns B, Hoegel J, Pohlandt F. Effect of Bifidobacterium lactis on the incidence of nosocomial infections in very-low-birth-weight infants: a randomized controlled trial. Neonatology 2010;98:156–63. [DOI] [PubMed] [Google Scholar]

[R224] 224.Mercier JC, Hummler H, Durrmeyer X, Sanchez-Luna M, Carnielli V, Field D, et al. Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): a randomised controlled trial. Lancet 2010;376:346–54. [DOI] [PubMed] [Google Scholar]

[R225] 225.Mercado VV, Cristea I, Ali N, Pham CC, Buescher E, Yang J, et al. Does surfactant type cause a differential proinflammatory response in preterm infants with respiratory distress syndrome? Adv Ther 2010;27: 476–82. [DOI] [PubMed] [Google Scholar]

[R226] 226.Fujii A, Allen R, Doros G, O’Brien S. Patent ductus arteriosus hemodynamics in very premature infants treated with poractant alfa or beractant for respiratory distress syndrome. J Perinatol 2010;30:671–6. [DOI] [PubMed] [Google Scholar]

[R227] 227.El-Naggar W, Yiu A, Mohamed A, Shah V, Manley J, McNamara P, et al. Comparison of pain during two methods of urine collection in preterm infants. Pediatrics 2010;125:1224–9. [DOI] [PubMed] [Google Scholar]

[R228] 228.Reilly MC, Vohra S, Rac VE, Zayack D, Wimmer J, Vincer M. Parallel exploratory rct of polyethylene wrap for heat loss prevention in infants born at less than 24 weeks’ gestation. Neonatology 2019;116:37–41. [DOI] [PubMed] [Google Scholar]

[R229] 229.Bernard MA, Clayton JA, Lauer MS. Inclusion across the lifespan: NIH policy for clinical research. JAMA 2018;320:1535–6. [DOI] [PubMed] [Google Scholar]

[R230] 230.Spong CY, Bianchi DW. Improving public health requires inclusion of underrepresented populations in research. JAMA 2018;319:337–8. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R231] 231.Guillen U, Weiss EM, Munson D, Maton P, Jefferies A, Norman M, et al. Guidelines for the management of extremely premature deliveries: a systematic review. Pediatrics 2015;136:343–50. [DOI] [PubMed] [Google Scholar]

[R232] 232.National Institutes of Health. Revision: NIH policy and guidelines on inclusion of individuals across the lifespan as participants in research involving human subjects. Accessed October 16, 2020. https://grants.nih.gov/grants/guide/notice-files/NOTOD-18-116.htm

[R233] 233.Zulman DM, Sussman JB, Chen X, Cigolle CT, Blaum CS, Hayward RA. Examining the evidence: a systematic review of the inclusion and analysis of older adults in randomized controlled trials. J Gen Intern Med 2011;26:783–90. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R234] 234.Singh GK, Yu SM. Infant mortality in the United States: trends, differentials, and projections, 1950 through 2010. Am J Public Health 1995;85:957–64. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R235] 235.Tyson JE, Parikh NA, Langer J, Green C, Higgins RD, National Institute of Child H, et al. Intensive care for extreme prematurity—moving beyond gestational age. N Engl J Med 2008;358:1672–81. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R236] 236.Foglia EE, DeMauro SB, Dysart K, Kirpalani H. When has enough evidence accumulated to change neonatal practice? Semin Fetal Neonatal Med 2015;20:424–30. [DOI] [PubMed] [Google Scholar]

[R237] 237.Bala MM, Akl EA, Sun X, Bassler D, Mertz D, Mejza F, et al. Randomized trials published in higher vs. lower impact journals differ in design, conduct, and analysis. J Clin Epidemiol 2013;66:286–95. [DOI] [PubMed] [Google Scholar]

PERMALINK

Eligibility Criteria and Representativeness of Randomized Clinical Trials That Include Infants Born Extremely Premature: A Systematic Review

Leeann R Pavlek, MD

Brian K Rivera, MS

Charles V Smith, PhD

Joanie Randle, RN

Cory Hanlon, BS

Kristi Small, BS

Edward F Bell, MD

Matthew A Rysavy, MD, PhD

Sara Conroy, PhD

Carl H Backes, MD

Abstract

Objective

Study design

Results

Conclusions

Methods

Data Sources

Data Abstraction and Study Definitions

Data Extraction

Study Quality

Data Synthesis

Results

Figure 1.

Table I.

Table II.

Table III.

Figure 2.

Table IV.

Table V.

Table VI.

Table VII.

Discussion

Supplementary Material

Acknowledgments

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases