Infant feeding and criticality in children

Abstract

Background

Data support the protective effects of human breast milk (HBM) feeding in acute illness but little is known about the impact of HBM feeding on the criticality of infants.

Aim

To explore the relationship between early HBM feeding and severity of illness and recovery in critically ill children requiring intubation and mechanical ventilation for acute respiratory failure (ARF).

Study design

Prospective cohort study of mothers of patients aged 1–36 months who participated in the acute and follow‐up phases of the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial. Participants completed a survey describing HBM dose fed during their infant's first month of life.

Results

Of 138 patients, 70 (51%) received exclusive HBM feedings (90%–100% total feeds) and 68 (49%) did not. We found no group differences in severity of illness on paediatric intensive care unit (PICU) admission or severity of paediatric acute respiratory distress syndrome (PARDS) within the first 24–48 h of intubation/mechanical ventilation (Pediatric Risk of Mortality [PRISM] III‐12 score median: 5 vs. 5, p = .88; moderate/severe PARDS: 53% vs. 54%, p = .63). While median time to recovery from ARF was reduced by 1 day in patients who received exclusive HBM feedings, the difference between groups was not statistically significant (median 1.5 vs. 2.6 days, hazard ratio 1.40 [95% confidence interval, 0.99–1.97], p = .06).

Conclusions

Human breast milk dose was not associated with severity of illness on PICU admission in children requiring mechanical ventilation for ARF.

Relevance to Clinical Practice

Data support the protective effects of HBM during acute illness and data from this study support a clinically important reduction in time to recovery of ARF. Paediatric nurses should continue to champion HBM feeding to advance improvements in infant health.

What is known about the topic

• Human breast milk (HBM) feeding is linked with reduced severity of illness during acute respiratory illness in infants and children.

• HBM feeding contributes to downregulation of inflammation and oxidative stress.

What this paper adds

• Severity of illness in infants with acute respiratory failure was no different in children exclusively fed HBM in the first month of life compared to those fed not‐exclusive HBM.

• Median time to recovery from acute respiratory failure was reduced by 1 day in patients who received exclusive HBM feedings and may be clinically significant but not statistically significant.

• Further HBM feeding studies in paediatric critical care are warranted.

1. INTRODUCTION AND BACKGROUND

Severity of illness at paediatric intensive care unit (PICU) admission directly impacts patient outcomes, including the duration of mechanical ventilation and mortality. ¹ , ² , ³ Unknown is whether the severity of illness at PICU admission can be modified by patient‐related factors including infant feeding practices. Feeding milk from the infant's own mother (human breast milk; HBM) at high doses (e.g., exclusive HBM feeding) in the early post‐birth period influences the infant's gut microbiome, gut metabolome, enzymatic and hormonal pathways and specific immunomodulatory responses, ⁴ , ⁵ , ⁶ , ⁷ all functioning synergistically to down‐regulate inflammation and oxidative stress. Multiple HBM components, such as commensal bacteria, growth factors, proteins, oligosaccharides and immunoregulatory factors, have been linked to a reduction in infectious illnesses, control of inflammatory signalling and cellular growth. ⁸ , ⁹ , ¹⁰ , ¹¹ Several studies have linked the dose and exposure period of HBM feedings and long‐term health outcomes, including respiratory illness, hospitalization in term infants and death. ¹² , ¹³ , ¹⁴ Further investigations have demonstrated reduced hospitalization rates in HBM‐fed infants infected with respiratory syncytial virus (RSV) compared to those without HBM feeding. ¹³ , ¹⁵ , ¹⁶

Although current studies support the protective effects of HBM feeding in acute illness, little is known about the impact of early HBM exposure on the criticality of infants admitted to the PICU. Here, we explore the relationship between early HBM feeding, severity of illness and recovery in critically ill children requiring intubation and mechanical ventilation for acute respiratory failure (ARF). We hypothesized that critically ill children 1–36 months of age who received exclusive HBM feedings for their first month of life (reflecting the influence of early post‐birth period) would present to the PICU with less severe illness, would be less likely to experience moderate/severe paediatric acute respiratory distress syndrome (PARDS) within the first 24–48 h of intubation/mechanical ventilation, would recover from acute respiratory failure (ARF) more quickly and have improved outcomes at 6 months post‐discharge compared to children who did not receive exclusive HBM feedings for their first month of life.

2. METHODS

2.1. Design and participants

This was a prospective cohort ancillary study of infants participating in the follow‐up phase of the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial. ¹⁷ , ¹⁸ RESTORE was a 31‐centre cluster randomized trial that evaluated the effect of a nurse‐led PICU sedation protocol on the duration of mechanical ventilation in children with ARF. Participating PICUs were randomized to implement the RESTORE sedation protocol or to continue usual sedation practices. The trial enrolled 2449 children, of whom 2002 consented to follow‐up 6 months after their critical illness. During the follow‐up phase, parents were interviewed on telephone to assess their child's functional health and quality of life. The study was approved by the University of Pennsylvania Institutional Review Board (IRB) in 2008. Full details of this study have been reported elsewhere. ¹⁷ , ¹⁸

2.2. Participants

Mothers whose infants were 1–36 months of age at PICU admission, who spoke English and stated they could answer questions about their infant's feeding history were invited to participate and interviewed. Interviews were completed between May 2015 and July 2016. Importantly, the rate of HBM feeding in the United States has not had a significant change since that time. Parent participation implied consent.

2.3. Materials and procedures

The HBM tool was designed as an interview guide. It included 16 items that were pretested for item clarity and flow with 10 mothers of diverse racial/ethnic backgrounds and reviewed by research experts in HBM feeding and paediatric critical care (Data S1). HBM feeding dose (amount of HBM feeding as proportion of total feed volume) and exposure (timing and duration of post‐birth feeds) ¹⁹ were measured by maternal recall of the contribution of HBM feeding in percent of the total feeding over the first month of life. Patients were divided into two groups: patients who received HBM for 90%–100% of total feeds (defined as exclusive HBM feed group) and patients who received HBM for 0%–89% of total feeds (defined as not‐exclusive HBM feed group). Reflecting US norms, patients were considered to be exclusively fed HBM while receiving small amounts of water, vitamins or cultural feedings. ²⁰

Severity of illness was operationalized in three ways: Pediatric Risk of Mortality III‐12 (PRISM III‐12) score, PARDS severity and time to recovery of ARF. The PRISM III‐12 measure assesses 17 physiologic variables during the first 12 h of PICU admission. ³ Scores range from 0 to 74 with higher scores indicating greater risk for mortality. PARDS severity was defined using the Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria that is based on either the oxygenation index (OI) or oxygenation saturation index (OSI), with OI 8.0–<16.0 or OSI 7.5–<12.3 indicating moderate PARDS and OI ≥ 16.0 or OSI ≥ 12.3 indicating severe PARDS. ²¹ OI was calculated for subjects with an arterial line and OSI was calculated replacing the partial pressure of arterial oxygenation value with oxygen saturation in subjects without an arterial line. PARDS severity was based on the worst OI or OSI on the day of intubation (Day 0) or Day 1. Time to recovery of ARF was defined as the duration from the time of intubation to the time that the subject initially qualified for an extubation readiness test (ERT). Subjects qualified for an ERT when they were spontaneously breathing and had an OI/OSI < 6.0, regardless of study arm. ¹⁷ Duration of weaning was defined as the duration from the time that the patient first met criteria for an ERT to the time of successful extubation (patient remained extubated for >24 h). Post‐PICU discharge outcomes were measured by Pediatric Cerebral Performance Category (PCPC) and Pediatric Overall Performance Category (POPC), ²² decline in functional status from baseline to follow‐up, hospital readmission and impaired health‐related quality of life based on the Infant and Toddler Quality of Life ²³ growth and development score.

2.4. Statistical analysis

We compared patient characteristics between enrolled patients and those eligible not enrolled or excluded from the analysis, and patient characteristics, admission characteristics, hospital course and post‐PICU discharge outcomes between subjects exclusively fed HBM and those not exclusively fed HBM. Patient characteristics were compared using Wilcoxon rank‐sum tests for continuous variables and Fisher's exact tests for categorical variables. For admission characteristics, hospital course and post‐PICU discharge outcomes, linear, logistic and proportional hazards regression were used to evaluate the relationship between dose of HBM feeding and log‐transformed continuous, binary and time‐to‐event variables, respectively. Group comparisons of admission characteristics were adjusted for age at PICU admission, while comparisons of hospital course and post‐PICU discharge outcomes were adjusted for age and PRISM III‐12 score.

Based on the RESTORE trial cohort, we estimated that 63% of children who were not exclusively fed HBM would have moderate/severe PARDS on Day 0/1. A 40% treatment effect size corresponds to an absolute reduction in the proportion of children with moderate/severe PARDS of 25%, or a decrease from 63% to 38%. With α = .05 and power of 0.80, this would require 62 patients each in the not‐exclusive and exclusive HBM groups, or 124 total patients for this study. Data analyses were conducted using SAS (version 9.4; SAS Institute, ²⁴ ).

2.5. Ethical considerations

This research study was granted IRB approval with a waiver of informed consent as a low risk study. Mothers of children who were enrolled in the RESTORE clinical trial ¹⁷ , ¹⁸ voluntarily participated and completion of the survey implied consent. Participants were able to stop the survey at any point during the process, thereby mitigating potential for harm. Confidentiality and anonymity of the participants was maintained as participants were only identified by research identification number.

3. RESULTS

A total of 635 patients were eligible for this study (Figure 1). There were no differences in age at admission, sex and total number of people living in the household between those enrolled and those not enrolled or excluded from analysis (Table S1). However, more enrolled patients were non‐Hispanic White, resided in areas with higher median household income, had college graduate/postgraduate mothers and had a primary diagnosis of bronchiolitis or asthma, while fewer enrolled patients had baseline cognitive or functional impairment.

FIGURE 1.

Consort statement.

A total of 138 subjects were enrolled in this study and included in analyses (Figure 1); 70 subjects (51%) were exclusively fed HBM and 68 subjects (49%) were not exclusively fed HBM (dose median 15%, range 0%–80%). Baseline characteristics are presented in Table 1. Across both groups, subjects were primarily non‐Hispanic White (71%), residing in areas with higher median incomes. Subjects commonly had bronchiolitis or asthma (61%) followed by pneumonia or aspiration pneumonia (24%). There were no statistically significant differences between groups exclusively fed or not exclusively fed HBM for the first month of life, except that more college graduate/postgraduate mothers exclusively fed HBM to their infants.

TABLE 1.

Patient characteristics according to human breastfeeding dose during the first month of life.

Characteristics a	Exclusive HBM (n = 70)	Not‐exclusive HBM (n = 68)
Age at PICU admission, median (IQR), mo	7.8 (2.2–16.6)	5.2 (2.2–10.7)
Female, n (%)	36 (51)	31 (46)
Race/ethnicity, n (%)
Non‐Hispanic White	54 (77)	44 (65)
Non‐Hispanic Black	5 (7)	10 (15)
Hispanic of any race	6 (9)	8 (12)
Other	5 (7)	6 (9)
Cognitive impairment (baseline PCPC > 1), n (%)	0	0
Functional impairment (baseline POPC > 1), n (%)	2 (3)	1 (1)
Parent education, n (%)
Some high school	1 (2)	2 (4)
High school graduate/GED	3 (6)	10 (20)
Some college or technical school	14 (27)	23 (45)
College graduate/postgraduate	33 (65)	16 (31)
Unknown, n	19	17
Total number of people in living in household, median (IQR) b	4 (4–5)	4 (4–5)
Median household income of zip code of residence, n (%) c
<$40 000	5 (7)	9 (13)
$40 000–$79 999	43 (61)	46 (68)
≥$80 000	22 (31)	13 (19)
Primary diagnosis, n (%)
Bronchiolitis or asthma (or reactive airway disease)	40 (57)	44 (65)
Pneumonia or aspiration pneumonia	18 (26)	15 (22)
Sepsis‐related acute respiratory failure	6 (9)	5 (7)
Other d	6 (9)	4 (6)

Abbreviations: GED, General Educational Development; HBM, human breast milk; IQR, interquartile range; mo, months; PCPC, Pediatric Cerebral Performance Category; PICU, paediatric intensive care unit; POPC, Pediatric Overall Performance Category.

^a There were no statistically significant between‐group differences in baseline characteristics, except for parent education (p = .004).

^b Reported for 109 patients.

^c Median household income of zip code of residence in 2011 (SOI Tax stats—individual income tax statistics—ZIP code data [SOI]. ²⁵ [Accessed March 1, 2017]. Available from: https://www.irs.gov/uac/soi‐tax‐stats‐individual‐income‐tax‐statistics‐zip‐code‐data‐soi).

^d Other primary diagnoses include laryngotracheobronchitis, pertussis, pulmonary edema and thoracic trauma.

For subjects exclusively fed HBM, the median PRISM III‐12 score was 5, ranging from 2 to 8 (Table 2). For subjects not exclusively fed HBM, the median PRISM III‐12 score was 5, ranging from 0 to 10. Controlling for age at PICU admission, there was no significant association between HBM feeding in the first month of life and severity of illness at PICU admission (exclusively vs. not exclusively fed HBM: mean difference −0.02 [95% confidence interval (CI), −0.34 to 0.29], p = .88).

TABLE 2.

Admission and hospital course characteristics and post‐paediatric intensive care unit discharge outcomes according to human breastfeeding dose during the first month of life.

Characteristics	Exclusive HBM (n = 70)	Not‐exclusive HBM (n = 68)	p a
Admission characteristics
PRISM III‐12 score, median (IQR)	5 (2–8)	5 (0–10)	.88
Risk of mortality based on PRISM III‐12 score, median (IQR)	1.7 (0.9–3.8)	1.7 (0.5–6.5)	.40
Moderate/severe PARDS based on worst OI or OSI on day 0/1, n (%)	37 (53)	37 (54)	.63
Number of organ dysfunctions on day 0/1, median (IQR)	1 (1–2)	2 (1–2)	.21
RESTORE intervention group, n (%)	46 (66)	42 (62)	.44
Hospital course characteristics
Time to recovery of acute respiratory failure, median (IQR), day b	1.5 (0.8–3.6)	2.6 (1.4–4.4)	.06
Duration of weaning from mechanical ventilation, median (IQR), day b	3.1 (1.3–5.2)	2.2 (1.1–4.1)	.06
Total duration of mechanical ventilation through day 28, median (IQR), day	5.5 (3.7–7.2)	5.4 (3.9–7.3)	.94
PICU length of stay, median (IQR), day	8.2 (5.5–10.8)	8.0 (5.5–10.3)	.93
Moderate/severe PARDS based on worst OI or OSI during hospitalization, n (%)	41 (59)	42 (62)	.60
MODS, n (%)	43 (61)	44 (65)	.73
Ever received vasoactive medications, n (%)	21 (30)	21 (31)	.99
PCPC > 1 at hospital discharge, n (%)	3 (4)	1 (1)	.46
POPC > 1 at hospital discharge, n (%)	4 (6)	4 (6)	.86
6 months post‐PICU discharge
PCPC > 1 at follow‐up, n/total (%)	1/44 (2)	2/39 (5)	.39
POPC > 1 at follow‐up, n/total (%)	2/44 (5)	4/39 (10)	.34
Decline in functional status (from baseline to follow‐up), n/total (%)	1/44 (2)	4/39 (10)	.16
Readmitted to a hospital, n/total (%)	8/44 (18)	13/39 (33)	.18
Impaired health‐related quality of life based on ITQOL growth and development score, n/total (%)	3/31 (10)	2/29 (7)	.96

Abbreviations: HBM, human breast milk; IQR, interquartile range; ITQOL, Infant and Toddler Quality of Life Questionnaire; MODS, multiple organ dysfunction syndrome; OI, oxygenation index; OSI, oxygen saturation index; PARDS, paediatric acute respiratory distress syndrome; PCPC, Pediatric Cerebral Performance Category; PICU, paediatric intensive care unit; POPC, Pediatric Overall Performance Category; PRISM III‐12, Pediatric Risk of Mortality III score from first 12 h in the PICU.

^a p values for the comparison between groups were calculated using linear, logistic and proportional hazards regression, adjusting for age at PICU admission and PRISM III‐12 score, for log‐transformed continuous, binary and time‐to‐event variables, respectively, unless otherwise specified. Regression analyses of admission characteristics adjusted for age at PICU admission only.

^b For four patients who never met criteria to be tested for extubation readiness but were successfully extubated by Day 28, the duration of recovery was set equal to the duration of mechanical ventilation. The duration of weaning from mechanical ventilation excludes these four patients.

For subjects exclusively fed HBM, 37 (53%) had moderate/severe PARDS on day 0/1 (Table 2). For subjects not exclusively fed HBM, 37 (54%) had moderate/severe PARDS on day 0/1. When controlling for age at PICU admission, there was no significant relationship between HBM dose in the first month of life and PARDS severity (exclusively vs. not exclusively fed HBM: odds ratio 0.85 [95% CI, 0.43–1.68], p = .63).

Median time to recovery of ARF for all subjects was 2.2 days (interquartile range 1.1–4.2 days). For those exclusively fed and not exclusively fed HBM, the median time to recovery of ARF was 1.5 days (0.8–3.6 days) and 2.6 days (1.4–4.4 days), respectively (Table 2). After controlling for age and severity of illness on PICU admission, there was no significant relationship between HBM feeding in the first month of life and time to recovery of ARF (exclusively vs. not exclusively fed HBM: hazard ratio 1.40 [95% CI, 0.99–1.97], p = .06).

Of interest, 44 exclusively and 41 not exclusively fed HBM infants had evaluable data at 6 months post‐PICU discharge. As outlined in Table 2, there were no significant differences in 6 month post‐PICU discharge outcomes including PCPC, POPC, readmission to the hospital or health‐related quality of life between those exclusively and not exclusively fed HBM.

4. DISCUSSION

This study, embedded in a large clinical trial of critically ill paediatric patients with acute respiratory failure, found no significant associations between the dose of mother's own milk feeding during the first month of life and their severity of illness on PICU admission, or criticality of PARDS in the first 24–48 h of mechanical ventilation, and time to recovery of ARF. In addition, 6 months post‐PICU discharge outcomes were similar between children exclusively fed HBM during the first month of life and those who were not. These data do not support previous studies that report an association of HBM with illness severity as measured by a decreased rate of acute illness hospitalization ¹³ , ¹⁴ , ¹⁵ , ²⁶ and a reduction in ICU hospitalization when infants were exclusively fed HBM for 45 days compared to 15 days. ²⁶ To our knowledge, this is the first study to examine the relationship between HBM feeding and criticality in children with PARDS.

We report outcomes after 1 month of exclusive compared to not‐exclusive HBM feeds whereas 6 months of HBM feeding is the current recommendation supporting infant health. ²⁷ There is increasing evidence that this recommendation may need revisions. Gomez‐Aceba et al. ²⁸ demonstrated any HBM feeding from birth to discharge from the hospital reduced the number of bronchiolitis episodes and was sustained at 2, 4 and 6 months while others evidenced ever HBM fed or any duration of HBM feeding reduced the incidence of bronchiolitis. ²⁹ Neonatal mortality is reduced in newborns fed HBM in the first hour of life. ³⁰ Notably, findings from Geller et al. ³¹ secondary analysis report on exclusive HBM feeding compared to partial HBM feeding up to 3 months of age is associated with a 48% odds reduction in bronchiolitis hospitalization. Furthermore, we found a clinically meaningful 1.1 day reduction in time to recovery of ARF in the exclusive HBM‐fed group. While not statistically significant, the clinical significance is notable and may result in reduction in exposure to PICU therapies sooner. These data suggest the protective effect of exclusive HBM feeding may be programmed earlier than 6 months.

The mechanisms of protection afforded by HBM support the hypothesis that early exclusive HBM feedings programme critical immunomodulatory, epigenetic, anti‐inflammatory and anti‐oxidative processes, as well as metabolic and hormonal pathways ⁵ , ⁶ , ¹⁰ potentially impacting severity of illness in acutely ill children. The immature infant gut undergoes marked growth in epithelial cell mass, maturation of enzymatic pathways and protection via a multitude of mechanisms ¹⁰ , ³² , ³³ as a result of colostrum ³⁴ providing concentrated antibodies, growth factors and immune cells. Notably, in mothers with COVID‐19, anti‐SARS‐CoV‐2 IgA and IgG were present in their milk and neutralized viral infectivity in vitro, ³⁵ potentially protecting the infant from disease. Furthermore, these high molecular weight components pass through open paracellular pathways in the mammary gland to those in the infant gut during the first few days post‐birth. These protective components migrate to distal organs, including the lungs, during the early post‐birth period. For example, receptors for epidermal growth factor, highly concentrated in colostrum, are present in the human infant organs, including the lungs. Commensal bacteria within the mother‐specific milk microbiome as well as pattern recognition receptors and highly complex oligosaccharides programme the gut microbiome and metabolome in a dose–response relationship over the first 30 days post‐birth. ³⁶ Among the multiple beneficial outcomes for the infant is immunomodulatory programming . ⁴ , ⁵ , ⁷ , ¹⁰

Equally compelling is evidence revealing marked differences in nasopharyngeal microbial community in healthy infants exclusively fed HBM compared to infants fed formula only. ³⁷ In post hoc analyses, the incidence of respiratory tract symptoms was lower in exclusively HBM‐fed infants. Subsequent follow‐up of this same cohort found healthy infants exclusively fed HBM up to 1.5 months of life had a more stable nasopharyngeal microbiome over the first 2 years of life ³⁸ with fewer respiratory infections over the study period. ³⁷ , ³⁸ Furthermore, HBM feeding has been linked with healthy microbiota development and stability ³⁹ as well as microbiota profiles associated with reduced likelihood of severe bronchiolitis. ⁴⁰

Bringing this information to the bedside nurse is critically important. While HBM feeding is a common discussion in the care of healthy infants, critically ill infants require stabilization and nutrition support typically starts soon afterwards. In the absence of mothers at the bedside, accessibility to HBM may be limited. Therefore, it is important for paediatric critical care nurses to not only encourage mothers to participate in HBM feeding but to advocate for continued HBM feeding during illness. Supporting HBM by provision of pumping equipment, facilities and storage of the pumped milk is important. Furthermore, supporting mothers with fluids, nutrition and support to maintain their milk supply is necessary.

There are limitations to this study. Only surviving subjects who were enrolled in the parent study and consented for follow‐up were eligible for this study. It is unclear if there were a greater proportion of non‐surviving subjects in either group. Non‐participants were more likely to be Hispanic of any race and non‐Hispanic Black, less highly educated with lower median household income creating a potential participation bias. This study was powered for a large effect size when comparing children exclusively fed HBM during the first month of life to those who were not, with a power analysis to detect an absolute reduction in the proportion of children with moderate/severe PARDS of 25%. A larger sample size would be required to detect a smaller effect size and may ultimately result in a statistically significant reduction in ARF recovery time. In addition, maternal recall may have impacted responses to the survey questions. Literature on maternal recall suggests mothers recall any HBM feeding accurately although there is both over‐ and underreporting of HBM dose when exact duration of feeding is being studied. ⁴¹ , ⁴² However, this survey instrument included questions asking mothers to rate the certainty of their recall of infant feeding with the majority of mothers rating their recall with greater than 95% certainty for HBM feeding regardless of elapsed time since infant feeding. ⁴³ Furthermore, although this study analysed the effect of more covariates than previous studies in this area, we were limited by not having data about birth weight, daycare attendance, number of siblings and exposure to cigarette smoke.

Given the inconsistency in the literature, further prospective cohort studies are recommended. Future studies should collect data on infant feeding and known confounding variables at hospital admission. Similar to this study, further investigations should compare risk‐adjusted clinical outcomes. The outcome of this study does not support a protective effect of exclusive HBM feeding up to 1 month of age and it is unclear if 1 month of exclusive HBM feeding is adequate to protect children from severe disease or if severe disease overwhelms immunomodulatory programming. To help elucidate this, exploring the relationship between HBM feeding, biologic changes of pro‐ and anti‐inflammatory proteins and the gut microbiome during critical illness may provide some direction.

In conclusion, critically ill infants who were intubated and ventilated for ARF and were exclusively fed human breast milk in the first month of life did not have reduced severity of illness on PICU admission, reduced criticality of PARDS in the first 24–48 h of mechanical ventilation or a statistically significant reduction in ARF recovery time.

AUTHOR CONTRIBUTIONS

Lauren R. Sorce conceived, co‐designed and interpreted the results of this study. Lisa A. Asaro processed the data and performed the statistical analysis. Martha A. Q. Curley co‐designed and interpreted the results of this study. All authors contributed to drafting the manuscript, read it and approved this final manuscript.

FUNDING INFORMATION

This work was supported by Diane Cronin‐Stubbs Memorial Award, Rush University College of Nursing; Dean's Scholarship, Rush University College of Nursing (Sorce); Medela Nursing Research Scholars Grant (Sorce); National Heart, Lung, and Blood Institute and the National Institute of Nursing Research, National Institutes of Health (U01 HL086622 and HL086649; Curley and Wypij).

CONFLICT OF INTEREST STATEMENT

Lauren R. Sorce is an elected member of the Executive Committee and serves as President of the Society of Critical Care Medicine (SCCM) 2024–2025. The research presented is that of the author and does not represent SCCM. Dr. Asaro and Dr. Curley have no conflicts of interest related to this research.

ETHICS STATEMENT

This study was approved by the University of Pennsylvania Institutional Review Board (IRB).

Supporting information

Data S1. Supporting information.

Table S1. Patient characteristics according to participation in human breast milk study.

APPENDIX A.

Randomized evaluation of sedation titration for respiratory failure (restore) study investigators

The Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) Study Investigators include Martha A. Q. Curley (Principal Investigator; Research Institute, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Family and Community Health, University of Pennsylvania School of Nursing, Philadelphia, PA); David Wypij (Principal Investigator—Data Coordinating Center; Department of Biostatistics, Harvard T.H. Chan School of Public Health; Department of Pediatrics, Harvard Medical School; Department of Cardiology, Boston Children's Hospital, Boston, MA); Geoffrey L. Allen (Children's Mercy Hospital, Kansas City, MO); Derek C. Angus (Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Pittsburgh, PA); Lisa A. Asaro (Department of Cardiology, Boston Children's Hospital, Boston, MA); Judy A. Ascenzi (The Johns Hopkins Hospital, Baltimore, MD); Scot T. Bateman (University of Massachusetts Memorial Children's Medical Center, Worcester, MA); Santiago Borasino (Children's Hospital of Alabama, Birmingham, AL); Cindy Darnell Bowens (Children's Medical Center of Dallas, Dallas, TX); G. Kris Bysani (Medical City Children's Hospital, Dallas, TX); Ira M. Cheifetz (Duke Children's Hospital, Durham, NC); Allison S. Cowl (Connecticut Children's Medical Center, Hartford, CT); Brenda L. Dodson (Department of Pharmacy, Boston Children's Hospital, Boston, MA); E. Vincent S. Faustino (Yale‐New Haven Children's Hospital, New Haven, CT); Lori D. Fineman (University of California San Francisco Benioff Children's Hospital at San Francisco, San Francisco, CA); Heidi R. Flori (University of California at San Francisco Benioff Children's Hospital at Oakland, Oakland, CA); Linda S. Franck (University of California at San Francisco School of Nursing, San Francisco, CA); Rainer G. Gedeit (Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI); Mary Jo C. Grant (Primary Children's Hospital, Salt Lake City, UT); Andrea L. Harabin (National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD); Catherine Haskins‐Kiefer (Florida Hospital for Children, Orlando, FL); James H. Hertzog (Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE); Larissa Hutchins (The Children's Hospital of Philadelphia, Philadelphia, PA); Aileen L. Kirby (Oregon Health & Science University Doernbecher Children's Hospital, Portland, OR); Ruth M. Lebet (School of Nursing, University of Pennsylvania, Philadelphia, PA); Michael A. Matthay (University of California at San Francisco School of Medicine, San Francisco, CA); Gwenn E. McLaughlin (Holtz Children's Hospital, Jackson Health System, Miami, FL); JoAnne E. Natale (University of California Davis Children's Hospital, Sacramento, CA); Phineas P. Oren (St. Louis Children's Hospital, St. Louis, MO); Nagendra Polavarapu (Advocate Children's Hospital‐Oak Lawn, Oak Lawn, IL); James B. Schneider (Cohen Children's Medical Center of New York, Hyde Park, NY); Adam J. Schwarz (Children's Hospital of Orange County, Orange, CA); Thomas P. Shanley (C. S. Mott Children's Hospital at the University of Michigan, Ann Arbor, MI); Shari Simone (University of Maryland Medical Center, Baltimore, MD); Lewis P. Singer (The Children's Hospital at Montefiore, Bronx, NY); Edward J. Truemper (Children's Hospital and Medical Center, Omaha, NE); Michele A. Vander Heyden (Children's Hospital at Dartmouth, Dartmouth, NH); R. Scott Watson (Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, WA); Claire R. Wells (University of Arizona Medical Center, Tucson, AZ).

Sorce LR, Asaro LA, Curley MAQ, for the RESTORE Study Investigators . Infant feeding and criticality in children. Nurs Crit Care. 2025;30(2):e13103. doi: 10.1111/nicc.13103

DATA AVAILABILITY STATEMENT

Data from the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) have been shared as per the National Institutes of Health Data Sharing policy. Survey data are available upon request.