Abstract
Background
Oral feeding skills of moderately preterm infants are not mature at birth.
Aims
To establish the relationship between postmenstrual age at introduction of first oral feeding and attainment of full oral feeding and hospital discharge for moderately preterm infants.
Study design
Multicenter retrospective analysis of a prospective cohort of moderately preterm infants admitted to a Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network hospital.
Subjects
6146 infants born at 29-33 weeks’ gestation from January 2012 to November 2013.
Outcome measures
Postmenstrual age at full oral feeding and at hospital discharge.
Results
The median postmenstrual age at first oral feeding was 33.9 weeks (interquartile range 33.1-34.3). For each week earlier at first oral feeding, full oral feeding occurred 4.5 days earlier (p<0.0001) and hospital stay was shortened by 3.4 days (p<0.0001). Higher birth weight (p<0.0001) and black maternal race (p=0.0001) were associated with younger postmenstrual age at full oral feeding and at discharge.
Conclusion
Moderately preterm infants with earlier introduction of oral feeding achieved earlier full oral feeding and hospital discharge.
Keywords: Hospital discharge, moderately preterm infants, oral feeding, pulmonary disease
INTRODUCTION
In 2015, approximately 83,000 out of 383,000 preterm infants born in the U.S. were born between 28 and 33 weeks’ gestation [1]. Given the number of infants born in this gestational age range, care of the moderately preterm (MPT) population accounts for significant resource use in the neonatal period, and evidence-based care practices to guide their care should be sought. Scandinavian population-based studies provide insight into the financial impact of prematurity and its associated morbidities [2,3]. In a Norwegian cohort, 1 in 12 adults born at 28-30 weeks and 1 in 24 adults born at 31-33 weeks received disability pension compared with 1 in 59 term-born adults [2]. Similarly, a Swedish cohort of adults born at 29-32 weeks showed a 70.1% employment rate and 5.6% disability rate compared with 74.1% employment and 1.5% disability for term-born adults [3]. Optimizing nutrition for infants in this gestational age range has the potential to enhance neurodevelopmental outcomes.
The importance of establishing early nutrition is increasingly recognized, especially among the extremely preterm and growth-restricted populations. The nutritional demands of MPT infants have not received the same attention, although a call for awareness of the feeding issues in this population has been made [4]. A body of evidence to guide practice for the MPT infant is lacking, and frequently the enteral nutrition of MPTs is managed in a similar manner as it is for extremely preterm infants. Beyond the timing of introduction and advancement of enteral feeding, oral feeding is a focus for the MPT population, as feeding-related difficulties are an often-cited reason for hospitalization beyond 36 weeks postmenstrual age (PMA). Oral feeding skills develop through the course of a full-term gestation with the emergence of coordinated sucking and swallowing at 32-34 weeks [5]. Even in the absence of respiratory disease, MPT infants typically have immature coordination of sucking and swallowing. Maturation of feeding behaviors, including sucking and swallowing, continues from 33 to 36 weeks PMA [6].
Feeding protocols based on infant cues place the infant in control of the frequency and quantity of oral intake. Non-nutritive sucking and cue-based feeding beginning as early as 32 weeks PMA have been shown to shorten the length of hospital stay [7,8]. Discharge criteria for newborns in the NICU include a consistent oral feeding pattern to support weight gain without compromising respiratory status. The impact of feeding practices on length of stay in the MPT population merits exploration. We hypothesized that MPT infants whose first oral feeding occurred at an earlier PMA would achieve full oral feeding sooner than those for whom oral feeding was introduced at a later PMA. Our secondary hypotheses were that MPT infants whose first oral feeding occurred at an earlier PMA would have a shorter length of hospitalization and would be less likely to remain hospitalized at 36 weeks PMA due to inadequate oral feeding.
MATERIAL AND METHODS
Subjects
This was a retrospective analysis of a prospective cohort of MPT infants, defined as those born at 29 through 33 weeks’ gestation, admitted to a Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network hospital within 72 hours of birth. The cohort has been previously described in comparison to more preterm infants [9]. Gestational age was determined by obstetrical best estimate based on last menstrual period, obstetrical parameters, and/or early prenatal ultrasound. If obstetrical estimate was not available, then the neonatologist’s estimate based on physical, neurological, and/or lens examination was used to determine gestational age. The gestational age range was selected to be in continuity with the more preterm infants evaluated by the NICHD Neonatal Research Network. The study period lasted 22 months from January 2012 through November 2013. Exclusion criteria included a prenatal decision to withdraw or limit intensive care, congenital anomalies, birth weight <750 g (to limit the inclusion of severely growth restricted infants), unknown date of first oral feeding, and death before achievement of full oral feeding.
Measurements
Data were collected prospectively by trained research coordinators and included maternal and neonatal characteristics, treatments, morbidities, and mortality. The institutional review board at each center approved the registry. The primary outcome for the analysis was the PMA at which full oral feeding was achieved. Full oral feeding was defined for this study as intake of 120 ml/kg/d. Secondary outcomes included PMA at hospital discharge and inadequate oral feeding as the primary indication for ongoing hospitalization at 36 weeks PMA. Research coordinators reviewed the medical record to determine the primary reason an infant remained hospitalized at 36 weeks PMA (respiratory, apnea/bradycardia, inadequate oral feeding, or other indication). If multiple problems documented, the research coordinator consulted with the NRN center principal investigator to determine the primary reason for ongoing hospitalization at 36 weeks PMA.
Data Analysis
Median regression was performed to examine relationships of continuous outcomes, such as PMA at full oral feeding and PMA at hospital discharge, to age at first oral feeding, and logistic regression analysis was used to examine such relationships for categorical outcomes. Median regression is robust to outliers and skewed distributions. Median regression estimates the conditional median of the response variable given certain values of the predictor variables or covariates, rather than estimating the conditional mean as in the case of least square methods. All models were adjusted for birth weight, small for gestational age (SGA) status, sex, multiple births, maternal race, surfactant exposure, treatment of patent ductus arteriosus (PDA), human milk exposure (maternal and/or donor), and center. Because feeding protocols were not standardized across the Network, center was included in all adjusted analyses. These variables were selected a priori as covariates for the model due to plausible relationships to the primary outcome. Adjusted median differences are reported for the continuous outcomes. Odds ratios and 95% confidence intervals (95% CIs) are reported for the categorical outcomes. Statistical significance was set at 0.05 and was, in general, associated with 95% CIs that did not cross 0 for continuous variables and 1 for categorical variables (odds ratios).
RESULTS
There were 7057 infants enrolled in the Moderate Preterm Registry; 6146 remained after exclusion for congenital anomalies (n=624), prenatal decision to withdraw or limit intensive care (n=2), birth weight <750 g (n=43), unknown date of first oral feeding (n=230), death prior to achievement of full oral feeding (n=9), or missing exclusion criteria data (n=3) (Figure 1).
Figure 1.
Flow chart of study patients.
Relationship of PMA at first oral feed to PMA at full oral feeding
Infants whose first oral feeding occurred before 33 weeks PMA had younger gestational age at birth than those whose first oral feeding occurred at or after 33 weeks PMA (p<0.0001, Table 1). Median regression analysis confirmed the highly significant association of PMA at first oral feeding with PMA at full oral feeding (Table 2). The median PMA at first oral feeding was 33.9 weeks (IQR 33.1-34.3). For each week of PMA earlier at first oral feeding, full oral feeding occurred 4.5 days sooner (95% CI 4.1-4.8, p<0.0001). Higher birth weight (p<0.0001), black maternal race (p=0.0001), and singleton status (p=0.021) were associated with younger PMA at full oral feeding. For every 100 gram increase in birth weight, the PMA at full oral feeding decreased by 0.5 days (95% CI 0.4-0.5, p<0.0001). Black infants achieved full oral feeding 1.6 days earlier than infants of other races (95% CI 0.8-2.4, p=0.0001). Singletons achieved full oral feeding 0.6 day earlier than infants who were part of multiple births (95 %CI 0.1-1.0, p=0.021). Factors associated with older PMA at full oral feeding included male sex (p<0.0001), SGA status (p=0.008), surfactant exposure (p<0.0001), PDA requiring treatment (p=0.007), and human milk exposure (p=0.022). Male infants achieved full oral feeding 1.3 days later than females (95% CI 0.9-1.8, p<0.0001). Those infants born SGA reached full oral feeding 0.9 days later than other infants (95% CI 0.2-1.6, p=0.008). Infants exposed to surfactant achieved full oral feeding 1.8 days later than infants who did not receive surfactant (95% CI 0.1-1.1, p=0.021). The infants who underwent pharmacologic or surgical treatment of a PDA achieved full oral feeding 3.4 days later than infants who did not receive treatment (95% CI 0.9-5.8, p=0.007). Infants exposed to any human milk in the first 28 days of life achieved full oral feeding 0.8 days later than infants who had no human milk exposure in the first 28 days (95% CI 0.1-1.4, p=0.023). Human milk exposure in the first 28 days varied by gestational age with the highest incidence in the infants born at 29 weeks’ gestation (91.9%) and the lowest incidence at 33 weeks’ gestation (82.2%, Table 3).
Table 1.
Characteristics of Study Cohort
| Characteristic | First Oral Feed at <33 Weeks PMA N=1170 |
First Oral Feed at ≥33 Weeks PMA N=4976 |
All Patients N=6146 |
P-valuea |
|---|---|---|---|---|
| Birth History | ||||
| Inborn (%) | 1082/1170 (92.5) | 4612/4976 (92.7) | 5694/6146 (92.6) | 0.808 |
| Male (%) | 599/1169 (51.2) | 2575/4973 (51.8) | 3174/6142 (51.7) | 0.740 |
| Gestational age (weeks) Median (IQR) |
31 (30–32) | 32 (31–33) | 32 (30–33) | <0.0001 |
| Multiple gestation (%) | 291/1170 (24.9) | 1559/4976 (31.3) | 1850/6146 (30.1) | <0.0001 |
| Antenatal steroid exposure (%) | 1023/1161 (88.1) | 4202/4934 (85.2) | 5225/6095 (85.7) | 0.010 |
| Cesarean delivery (%) | 657/1169 (56.2) | 3141/4975 (63.1) | 3798/6144 (61.8) | <0.0001 |
| Birth weight (grams) Median (IQR) |
1590 (1400–1810) | 1720 (1425–2000) | 1689 (1420–1970) | <0.0001 |
| Small for gestational age (%) | 82/1169 (7.0) | 869/4973 (17.5) | 951/6142 (15.5) | <0.0001 |
| Race | ||||
| Black | 487/1164 (41.8) | 1540/4957 (31.1) | 2027/6121 (33.1) | <0.0001 |
| White | 572/1164 (49.1) | 2856/4957 (57.6) | 3428/6121 (56.0) | <0.0001 |
| American Indian/Alaskan | 2/1164 (0.2) | 83/4957 (1.7) | 85/6121 (1.4) | <0.0001 |
| Asian | 38/1164 (3.3) | 184/4957 (3.7) | 222/6121 (3.6) | 0.463 |
| Native Hawaiian/Pacific Islander | 6/1164 (0.5) | 5/4957 (0.1) | 11/6121 (0.2) | 0.009 |
| More than one race | 16/1164 (1.4) | 64/4957 (1.3) | 80/6121 (1.3) | 0.822 |
| Unknown/not reported | 43/1164 (3.7) | 225/4957 (4.5) | 268/6121 (4.4) | 0.205 |
| Ethnicity (%) | ||||
| Hispanic/Latino | 132/1169 (11.3) | 748/4971 (15.0) | 880/6140 (14.3) | 0.001 |
| Non-Hispanic/non-Latino | 1004/1169 (85.9) | 4103/4971 (82.5) | 5107/6140 (83.2) | 0.006 |
| Unknown/not Reported | 33/1169 (2.8) | 120/4971 (2.4) | 153/6140 (2.5) | 0.420 |
| Neonatal Characteristics | ||||
| Surfactant exposure (%) | 270/1170 (23.1) | 1189/4975 (23.9) | 1459/6145 (23.7) | 0.552 |
| Early-onset sepsis (%) | 7/1170 (0.6) | 37/4975 (0.7) | 44/6145 (0.7) | 0.703 |
| Late-onset sepsis (%) | 32/1168 (2.7) | 121/4974 (2.4) | 153/6142 (2.5) | 0.545 |
| Necrotizing enterocolitis (%) | 24/1170 (2.1) | 104/4975 (2.1) | 128/6145 (2.1) | 0.933 |
| Patent ductus arteriosus (%) | 72/1170 (6.2) | 384/4974 (7.7) | 456/6144 (7.4) | 0.066 |
| Treated PDA | 16/1170 (1.4) | 112/4973 (2.3) | 128/6143 (2.1) | 0.057 |
| Supplemental O2 at 28 days (%) | 78/1134 (6.9) | 580/4782 (12.1) | 658/5916 (11.1) | <0.0001 |
| Positive pressure at 28 days (%) | 1/1128 (0.1) | 51/4775 (1.1) | 52/5903 (0.9) | 0.0003 |
| Hospitalized at 36 weeks (%) | 465/1089 (42.7) | 2816/4809 (58.6) | 3281/5898 (55.6) | <0.0001 |
PMA=postmenstrual age. PDA=patent ductus arteriosus.
P-values compare those with first oral feed <33 weeks PMA to those with first oral feed ≥33 weeks PMA. P-values for categorical outcomes were obtained by Chi-square test and Fisher’s exact test wherever the cell count was less than 5. For continuous outcomes, nonparametric Wilcoxon test was used.
Table 2.
Median Regression Analysis to Examine the Factors Associated with Postmenstrual Age at Full Oral Feeding
| Explanatory (Independent) Variable | Estimate | 95% Confidence Limits | p-value | |
|---|---|---|---|---|
|
| ||||
| PMA at first feed (in weeks) | 4.49 | 4.13 | 4.85 | <0.0001 |
|
|
||||
| Birth weight (per 100 grams) | −0.46 | −0.51 | −0.40 | <0.0001 |
|
|
|
|||
| SGA | 0.91 | 0.24 | 1.58 | 0.008 |
|
|
||||
| Male | 1.31 | 0.87 | 1.76 | <0.0001 |
|
|
||||
| Surfactant exposure | 2.43 | 1.87 | 3.00 | <0.0001 |
|
|
||||
| PDA requiring treatment | 3.37 | 0.93 | 5.81 | 0.007 |
|
|
||||
| Black race | −1.62 | −2.44 | −0.80 | 0.0001 |
|
| ||||
| Multiple gestation | 0.59 | 0.09 | 1.10 | 0.021 |
|
|
||||
| Human milk in the first 28 days | 0.77 | 0.11 | 1.44 | 0.023 |
Table 3.
Feeding Variables by Gestational Age at Birth
| Feeding Variable | Gestational Age at Birth (weeks) | ||||||
|---|---|---|---|---|---|---|---|
| 29 N=676 |
30 N=895 |
31 N=1086 |
32 N=1506 |
33 N=1983 |
Total N=6146 |
P-valuea | |
| Human Milk Exposure in First 28 Days (%) | 620/675 (91.9) |
813/894 (90.9) |
935/1086 (86.1) |
1243/1502 (82.8) |
1629/1981 (82.2) |
5240/6138 (85.4) |
<0.0001 |
| PMA First Oral Feeding (weeks) Median (IQR) | 33.4 (32.6–34.3) |
33.6 (32.7–34.1) |
33.6 (32.7–34.1) |
33.6 (33.0–34.1) |
34.0 (33.7–34.3) |
33.9 (33.1–34.3) |
<0.0001 |
| PMA Full Oral Feeding (weeks)b Median (IQR) | 35.7 (34.7–37.0) |
35.6 (34.7–36.7) |
35.4 (34.6–36.4) |
35.3 (34.6–36.3) |
35.3 (34.6–36.1) |
35.4 (34.6–36.4) |
<0.0001 |
| In Hospital at 36 Weeks PMA due to Inadequate Oral Feeding (%) | 146/653 (22.4) |
178/862 (20.6) |
212/1041 (20.4) |
320/1433 (22.3) |
393/1909 (20.6) |
1249/5898 (21.2) |
0.619 |
PMA=postmenstrual age.
P-values for testing the proportions for categorical variables were obtained using Chi-square test. P-values for testing the median across gestational ages were obtained using Kruskal-Wallis nonparametric test.
For this variable, N=615 at 29 weeks, N=834 at 30 weeks, N=1002 at 31 weeks, N=1400 at 32 weeks, N=1871 at 33 weeks for total N=5722.
Relationship of PMA at first oral feeding to PMA at hospital discharge
We analyzed the impact of the timing of introduction of oral feeding on the length of hospital stay. For each week earlier in PMA at first oral feeding, discharge occurred 3.4 days earlier when measured by PMA (95% CI 2.9-3.8, p<0.0001). Higher birth weight (p<0.0001), black maternal race (p=0.0001), and singleton status (p=0.0003) were associated with younger PMA at discharge. For every 100 g increase in birth weight, the PMA at discharge decreased by 0.7 days (95% CI 0.6-0.8, p<0.0001). Black infants were discharged at a younger PMA than infants of other races by 1.6 days (95% CI 0.8-2.4, p=0.0001). Singletons were discharged at a younger PMA than infants who were part of multiple births by 1.1 days (95% CI 0.5-1.6, p=0.0003). Male sex (p<0.0001), SGA status (p=0.0009), surfactant exposure (p<0.0001), and treatment of PDA (p=0.0004) were associated with an older PMA at discharge. Males were discharged at an older PMA than females by 1.6 days (95% CI 1.2-2.1, p<0.0001). SGA infants spent an additional 1.4 days hospitalized compared to other infants (95% CI 0.6-2.2, p=0.0009). Infants exposed to surfactant were discharged at an older PMA than infants not exposed to surfactant by 3.7 days (95% CI 3.0-4.4, p<0.0001). Infants who received treatment for a PDA were discharged at older PMAs than infants who did not receive treatment for a PDA by 3.1 days (95% CI 1.4-4.8, p=0.0004). Human milk exposure in the first 28 days did not have a significant effect on PMA at discharge (0.5 days, 95% CI −0.2-1.2, p=0.194).
Factors associated with ongoing hospitalization at 36 weeks PMA
The odds of remaining hospitalized at 36 weeks PMA due to inadequate oral feeding increased with each week delay in PMA at first oral feeding (OR 1.1, 95% CI 1.0-1.1, p<0.0001). Gestational age at birth by week of gestation did not have a significant effect on the likelihood of remaining hospitalized at 36 weeks PMA due to inadequate oral feeding (Table 3). Infants born with a lower birth weight (OR 1.0 for each 100 g, 95%CI 0.9-1.0, p=0.0004) and SGA infants (OR 1.4, 95% CI 1.2-1.8, p=0.0002) were more likely to remain hospitalized at 36 weeks PMA due to inadequate oral feeding. Also, male infants (OR 1.2, 95% CI 1.1-1.4, p=0.006) were more likely than females to remain hospitalized at 36 weeks PMA due to inadequate oral feeding. Surfactant exposure, treatment of PDA, maternal race, singleton status, and exposure to human milk in the first 28 days did not have a significant effect on the odds of remaining hospitalized at 36 weeks PMA due to inadequate oral feeding.
Relationship of PMA at first oral feeding to pulmonary disease
Pulmonary morbidities of prematurity impact oral feeding practices. The level of respiratory support impacted oral feeding in this MPT cohort (p<0.0001, Table 4). For those infants on no respiratory support at 28 days, 95% had experienced their first oral feeding compared with 58% of infants on nasal cannula and 13% of infants on non-invasive positive pressure support at 28 days.
Table 4.
Respiratory Support in Relation to the Occurrence of First Oral Feeding by 28 Days
| Respiratory Support at 28 Days | First Oral Feeding by 28a | ||
|---|---|---|---|
| Yes N=5312 |
No N=591 |
Total N=5903 |
|
| None (%) | 4956 (95) | 264 (5) | 5220 |
| Nasal Cannula (%) | 343 (58) | 249 (42) | 592 |
| Non-invasive Positive Pressure (%) | 10 (13) | 65 (87) | 75 |
| Intubated on Positive Pressure (%) | 3 (19) | 13 (81) | 16 |
P-value <0.0001 by Chi-square.
DISCUSSION
MPT infants with earlier introduction of oral feeding achieved full oral feeding and hospital discharge at younger PMAs. The median PMA at first oral feeding was 33 weeks. Introduction of oral feeding 1 week earlier, e.g. at 32 weeks rather than 33 weeks, was associated with achieving full oral feeding 4.5 days sooner. Higher birth weight and maternal black race were also associated with earlier attainment of full oral feeding. The association between PMA of first oral feeding and attainment of full oral feeding is not necessarily a causal relationship. An alternative explanation is that an infant with oral feeding cues at a younger PMA may have oral feeding introduced earlier.
Oral feeding may not be introduced as early as infant feeding skills allow. Reasons for this may include care practices that focus on minimizing morbidities of prematurity, including pulmonary disease. Not surprising were the effects of surfactant exposure, a surrogate for pulmonary disease, and male sex, both of which were associated with later attainment of full oral feeding and discharge. The sex difference for preterm morbidities has been well-described and often reported although not yet fully understood [10]. Others did not find infant sex to be predictive of PMA at attainment of full oral feeding. In a cohort of infants born before 32 weeks’ gestation, birth weight, moderate-severe bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, and PDA were predictive of PMA at full oral feeding, while sex, multiple gestation, mild BPD, and sepsis did not predict PMA at full oral feeding [11].
Requirement for pulmonary support is a common rationale for delaying introduction of oral feeding and, ultimately, attainment of full oral feeding and hospital discharge, although the evidence supporting such delay is, at best, limited. There is animal work evaluating the safety of oral feeding during noninvasive positive-pressure support in lambs [12,13]. Samson and colleagues observed no increase in cardiorespiratory events during bottle feeding in full-term lambs on nasal CPAP or high-flow nasal cannula compared to lambs on no respiratory support [12]. In related work, preterm lambs on nasal CPAP demonstrated more efficient bottle feeding and maintained higher oxygen saturation during bottle feeding compared to lambs receiving no respiratory support [13]. There is also emerging information regarding the safety and efficacy of oral feeding of preterm human infants receiving positive-pressure respiratory support. Hanin and colleagues found that oral feeding on CPAP compared to gavage feeding resulted in earlier attainment of full oral feeding and infants required less respiratory support two weeks after the introduction of oral feeding [14]. Glackin and colleagues demonstrated no difference in time to attain full oral feeding, time on respiratory support, or length of hospitalization for orally fed infants on CPAP compared to infants on high-flow nasal cannula [15]. In contrast, others have reported deep laryngeal penetration and aspiration with oral feeding of infants on CPAP [16]. The evidence for orally feeding infants on positive-pressure respiratory support is inconclusive.
Exposure to human milk in the first 28 days of life was associated with later achievement of full oral feeding. The difference, while statistically significant, was less than 1 day. Human milk exposure in the first 28 days did not affect PMA at discharge, and infants exposed to human milk were not more likely to remain hospitalized at 36 weeks PMA due to inadequate oral feeding. One possible explanation for the relationship between human milk exposure and later attainment of full oral feeding may reflect a difference in breast versus bottle feeding. Infants exposed to human milk in the first 28 days have a greater likelihood of achieving successful breastfeeding than infants not exposed to human milk in the first 28 days. We speculate that the long-term economic and health benefits of feeding breast milk would offset the cost of an additional day in the hospital in the event that oral feeding was the sole reason for an additional day of hospitalization [17,18].
The odds of remaining hospitalized at 36 weeks PMA due to inadequate oral feeding increased with each week of delay in introducing the first oral feeding. This has practice ramifications in a quality-focused and cost-conscious era. Within this MPT gestational age range, lower birth weight, SGA status, and male sex were all associated with higher likelihood of remaining hospitalized at 36 weeks PMA due to inadequate oral feeding. Other practice characteristics, such as the level of respiratory support with which oral feeding may be introduced, also may have a significant effect on a patient’s likelihood of remaining hospitalized at 36 weeks PMA due to inadequate oral feeding. Several patient variables associated with older PMA at discharge, specifically surfactant exposure, PDA requiring treatment, maternal race, and multiple births, were not associated with remaining hospitalized at 36 weeks PMA due to inadequate oral feeding.
Strengths of this study include the focus on the MPT cohort. MPT infants make up a significant portion of NICU admissions and account for significant economic burden for both families and the healthcare system. Therefore, practices affecting this population require investigation. A second strength is the size of the cohort (n=6146), which allowed for detection of relatively small differences in PMA for attainment of full oral feeding and hospital discharge as a function of the timing of introduction of oral feeding. Another strength of the study is its potential to impact collaborative practice in a cost-effective manner. Nurses, physicians, and allied health professionals, including speech pathologists and occupational therapists, collaborate on oral feeding practices, including timing of introduction of oral feeding. Assessment of oral feeding readiness at an earlier PMA, such as 32 weeks, may enable earlier introduction of oral feeding and therefore earlier attainment of full oral feeding, a milestone for every preterm infant.
Limitations of our study include the lack of data on non-oral enteral feeding to accompany the data on oral feeding. Our dataset does not contain information on introduction and attainment of full enteral feeding to supplement the data on oral feeding. An active trial underway is investigating the rate of advancement of enteral feedings in preterm infants born <32 weeks’ gestation [19]. The outcome of this trial will further inform feeding practices of moderate preterm infants. While our analysis adjusted for multiple variables that the investigators identified as relevant to feeding practices, specifically, birth weight, SGA status, sex, multiple births, maternal race, surfactant exposure, treatment of PDA, human milk exposure, and center, there may be additional confounding factors. Use of surfactant exposure as a surrogate for pulmonary disease has limitations as it does not differentiate between infants who require non-invasive respiratory support at birth and those who require no respiratory support.
Additionally, caution is warranted as the dataset contains only binary data for human milk exposure without any quantification to allow evaluation of a possible dose effect. Data on breastfeeding rates were not available to further inform interpretation of the relationship between human milk exposure and age at attainment of full oral feeding. Duration of breastfeeding prior to introduction of supplemental bottle feeding was not recorded. A meta-analysis done for the Cochrane Database found that avoidance of bottle feeding increased breastfeeding at discharge (exclusive breastfeeding risk ratio (RR) 1.47, 95% CI 1.19-1.80; any breastfeeding RR 1.11, 95% CI 1.06-1.16) [20]. No data were collected on the availability of donor breast milk at specific centers.
CONCLUSION
The timing of introduction of oral feeding is significantly associated with the timing at which full oral feeding and hospital discharge are attained for the MPT population. The next step is to evaluate if a practice change to earlier introduction of oral feeding enables earlier attainment of full oral feeding and hospital discharge on a prospective basis. Providers, healthcare systems, and families alike are invested in these milestones.
Highlights.
For moderate preterm infants, the timing of introduction of oral feeding is significantly associated with the timing at which full oral feeding and hospital discharge are attained.
The next step is to evaluate prospectively whether a practice change to earlier introduction of oral feeding enables earlier attainment of full oral feeding and hospital discharge.
Acknowledgments
The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Center for Advancing Translational Sciences provided grant support for the Neonatal Research Network’s Moderate Preterm Registry through cooperative agreements. Although NICHD staff had input into the study design and conduct, data analysis, and manuscript drafting, the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors acknowledge Dr. Rosemary Higgins for her leadership of the Neonatal Research Network.
Participating NRN sites collected data and transmitted it to RTI International, the data coordinating center (DCC) for the network, which stored, managed and analyzed the data for this study. One behalf of the NRN, Dr. Abhik Das (DCC Principal Investigator) and Ms. Sarah Kandefar (DCC Statistician) had full access to all of the data in the study, and with the NRN Center Principal Investigators, take responsibility for the integrity of the data and accuracy of the data analysis.
We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study. The following investigators, in addition to those listed as authors, participated in this study:
NRN Steering Committee Chair: Richard A. Polin, MD, Division of Neonatology, College of Physicians and Surgeons, Columbia University, (2011-present).
Alpert Medical School of Brown University and Women & Infants Hospital of Rhode Island (U10 HD27904) – Abbot R. Laptook, MD; Martin Keszler, MD; Betty R. Vohr, MD; Angelita M. Hensman, MS RNC-NIC BSN; Elisa Vieira, RN BSN.
Case Western Reserve University, Rainbow Babies & Children’s Hospital (U10 HD21364, M01 RR80) – Anna Marie Hibbs, MD; Nancy S. Newman, RN; Bonnie S. Siner, RN.
Children’s Mercy Hospital (U10 HD68284) – William E. Truog, MD; Eugenia K. Pallotto, MD MSCE; Howard W. Kilbride MD; Cheri Gauldin, RN MSN CCRC; Anne Holmes RN MSN MBA-HCM CCRC; Kathy Johnson RN, CCRC.
Cincinnati Children’s Hospital Medical Center, University of Cincinnati Medical Center, and Good Samaritan Hospital (U10 HD27853, UL1 TR77) – Brenda B. Poindexter, MD MS; Kurt Schibler, MD; Suhas G. Kallapur, MD; Cathy Grisby, BSN CCRC; Barbara Alexander, RN; Estelle E. Fischer, MHSA MBA; Lenora Jackson, CRC; Kristin Kirker, CRC; Jennifer Jennings, RN BSN; Sandra Wuertz, RN BSN CLC; Greg Muthig, BA.
Duke University School of Medicine, University Hospital, University of North Carolina, and Duke Regional Hospital (U10 HD40492, UL1 TR1117, UL1 TR1111) – C. Michael Cotten, MD MHS; Ronald N. Goldberg, MD; Joanne Finkle, RN JD; Kimberley A. Fisher, PhD FNP-BC IBCLC; Matthew M. Laughon, MD MPH; Carl L. Bose, MD; Janice Bernhardt, MS RN; Cindy Clark, RN.
Emory University, Children’s Healthcare of Atlanta, Grady Memorial Hospital, and Emory University Hospital Midtown (U10 HD27851, UL1 TR454) – Barbara J. Stoll, MD; David P. Carlton, MD; Ellen C. Hale, BS RN CCRC; Yvonne Loggins, RN; Diane I. Bottcher, RN MSN.
Eunice Kennedy Shriver National Institute of Child Health and Human Development – Rosemary D. Higgins, MD; Stephanie Wilson Archer, MA.
Indiana University, University Hospital, Methodist Hospital, Riley Hospital for Children at Indiana University Health, and Eskenazi Health (U10 HD27856, UL1 TR6) – Greg Sokol, MD; Dianne E. Herron, RN.
Nationwide Children’s Hospital and the Ohio State University Medical Center (U10 HD68278) – Pablo J. Sanchez, MD; Leif D. Nelin, MD; Sudarshan R. Jadcherla, MD; Patricia Luzader, RN; Nehal A. Parikh, DO MS; Marliese Dion Nist, BSN; Jennifer Fuller, MS RNC; Julie Gutentag, BSN; Marissa E. Jones, RN MBA; Sarah McGregor, BSN RNC; Elizabeth Rodgers, BSN; Jodi A. Ulloa, MSN APRN NNP-BC; Tara Wolfe, BSN.
RTI International (U10 HD36790) – Dennis Wallace, PhD; Kristin M. Zaterka-Baxter, RN BSN CCRP; Margaret Crawford, BS CCRP; Jenna Gabrio, BS CCRP; Sarah Kandefer, BS; Jeanette O’Donnell Auman, BS.
Stanford University and Lucile Packard Children’s Hospital (U10 HD27880, UL1 TR93) – David K. Stevenson, MD; M. Bethany Ball, BS CCRC; Melinda S. Proud, RCP.
University of Alabama at Birmingham Health System and Children’s Hospital of Alabama (U10 HD34216) – Waldemar A. Carlo, MD; Namasivayam Ambalavanan, MD; Monica V. Collins, RN BSN MaEd; Shirley S. Cosby, RN BSN.
University of California - Los Angeles, Mattel Children’s Hospital, Santa Monica Hospital, Los Robles Hospital and Medical Center, and Olive View Medical Center (U10 HD68270) – Uday Devaskar, MD; Meena Garg, MD; Teresa Chanlaw, MPH; Rachel Geller, RN BSN.
University of Iowa and Mercy Medical Center (U10 HD53109, UL1 TR442) – Tarah T. Colaizy, MD MPH; Dan L. Ellsbury, MD; Jane E. Brumbaugh, MD; Karen J. Johnson, RN BSN; Donia B. Campbell, RNC-NIC; Jacky R. Walker, RN.
University of New Mexico Health Sciences Center (U10 HD53089, UL1 TR41) – Kristi L. Watterberg, MD; Robin K. Ohls, MD; Conra Backstrom Lacy, RN; Sandy Sundquist Beauman, MSN,RNC-NIC; Carol Hartenberger, MPH, RN CCRC.
University of Pennsylvania, Hospital of the University of Pennsylvania, Pennsylvania Hospital, and Children’s Hospital of Philadelphia (U10 HD68244) – Barbara Schmidt, MD; Haresh Kirpalani, MB MSc; Sara B. DeMauro, MD MSCE; Noah Cook, MD; Aasma S. Chaudhary, BS RRT; Soraya Abbasi, MD; Toni Mancini, RN BSN CCRC; Dara Cucinotta.
University of Rochester Medical Center, Golisano Children’s Hospital, and the University of Buffalo Women’s and Children’s Hospital of Buffalo (U10 HD68263, UL1 TR42) – Carl T. D’Angio, MD; Satyan Lakshminrusimha, MD; Ronnie Guillet, MD PhD; Ann Marie Scorsone, MS; Julianne Hunn, BS; Rosemary Jensen; Holly I.M. Wadkins, MA; Stephanie Guilford, BS; Ashley Williams, M.S. Ed.
University of Texas Southwestern Medical Center at Dallas, Parkland Health & Hospital System, and Children’s Medical Center Dallas (U10 HD40689) – Myra Wyckoff, MD; Luc P. Brion, MD; Diana M. Vasil, RNC-NIC; Lijun Chen, PhD RN; Lizette E. Torres, RN.
University of Texas Health Science Center at Houston Medical School and Children’s Memorial Hermann Hospital (U10 HD21373) – Kathleen A. Kennedy, MD MPH; Jon E. Tyson, MD MPH; Julie Arldt-McAlister, RN BSN; Carmen Garcia, RN CCRP; Karen Martin, RN; Georgia E. McDavid, RN; Sharon L. Wright, MT (ASCP).
Wayne State University, University of Michigan, Hutzel Women’s Hospital, and Children’s Hospital of Michigan (U10 HD21385) – Seetha Shankaran, MD; Athina Pappas, MD; John Barks, MD; Rebecca Bara, RN BSN; Shelley Handel, AD; Diane F White, RT; Mary Christensen, RT; Stephanie A. Wiggins, MS.
Statement of financial support: The research was funded by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to the member centers of the NICHD Neonatal Research Network.
Footnotes
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Declaration of interest statement: The authors declare no conflict of interest.
CONFLICT OF INTEREST
The authors have no conflicts of interest to disclose.
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