Health-related quality of life at age 10 years in children born extremely preterm.

OBJECTIVE: To evaluate the association between prenatal maternal health and socioeconomic status (SES) and health-related quality of life (QoL) among 10-year-old children born extremely preterm. DESIGN/ METHODS: Retrospective analysis of the Extremely Low Gestational Age Newborns (ELGAN) Study cohort of infants born < 28 weeks gestational age. QoL was assessed at 10 years of age using the Pediatric Quality of Life Inventory. Multivariate regression models were used for analyses. RESULTS: Of 1198 participants who survived until 10 years of age, 889 (72.2%) were evaluated. Lower maternal age, lack of college education; receipt of public insurance and Supplemental Nutrition Assistance Program (SNAP) were associated with lower QoL scores. Specific maternal health factors were also associated with lower child QoL scores. CONCLUSIONS: Specific, potentially modifiable, maternal health and social factors are associated with lower scores on a measure of parent-reported child QoL across multiple domains for children born extremely preterm.

Social determinants of health rather than race impact health-related quality of life in 10-year-old children born extremely preterm.

Background: Reducing healthcare disparities among children is extremely important given the potential impact of these disparities on long-term health-related quality of life (HRQL). Race and parental socioeconomic status (SES) are associated with child HRQL, but these associations have not been studied in infants born extremely preterm (EP), a population at increased risk for physical, cognitive, and psychosocial impairments. Achieving health equity for infants born EP across their life course requires identifying the impact of racism and SES on HRQL. Objective: We aimed to evaluate the association between self-reported maternal race, SES factors, and HRQL among 10-year-old children born EP. Design/methods: Participants were identified from an ongoing multicenter prospective longitudinal study of Extremely Low Gestational Age Newborns (ELGAN Study), born between 2002 and 2004, and evaluated at 10 years of age using the Pediatric quality of life (QoL) Inventory completed by their parent or guardian, assessing physical, emotional, social, school, and total (composite) QoL domains. Multivariable regression models were used to evaluate the relationship between QoL scores and self-identified maternal race, adjusting for SES factors (education level, marital status, and public insurance). Results: Of 1,198 study participants who were alive at 10 years of age, 863 (72.0%) were evaluated at 10 years of age. Differences in mean 10-year QoL scores across racial groups were observed and were significant on univariate analysis. However, these associations attenuated when adjusted for the marital status, public insurance status, and education status of mothers. A comparison of children with English as the primary language spoken at home vs. any other language revealed a significant difference only in school QoL, in which non-English language was associated with more favorable school QoL scores. Conclusions: Among 10-year-old children born EP, differences in parent-reported QoL were associated with maternal SES factors but not with race. Our results suggest that interventions designed to improve the SES of mothers may enhance the QoL of children born EP. Furthermore, these results underscore that race is a social construct, rather than a biological variable, as we work toward greater equity in care provision.

Neonatal respiratory care practice among level III and IV NICUs in New England.

OBJECTIVES: To assess respiratory care guidelines and explore variations in management of very low birth weight (VLBW) infants within a collaborative care framework. Additionally, to gather clinical leaders' perspectives on guidelines and preferences for ventilation modalities. STUDY DESIGN: Leaders from each NICU participated in a practice survey regarding the prevalence of unit clinical guidelines, and management, at many stages of care. RESULTS: Units have an average of 4.3 (±2.1) guidelines, of 9 topics queried. Guideline prevalence was not associated with practice or outcomes. An FiO2 requirement of 0.3-0.4 and a CPAP of 6-7 cmH2O, are the most common thresholds for surfactant administration, which is most often done after intubation, and followed by weaning from ventilatory support. Volume targeted ventilation is commonly used. Extubation criteria vary widely. CONCLUSIONS: Results identify trends and areas of variation and suggest that the presence of guidelines alone is not predictive of outcome.

Long-Term Outcome of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation.

OBJECTIVES: Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are complications in preterm infants associated with high morbidity, mortality, impaired growth, and neurodevelopmental (ND) outcomes. Few studies have reported growth or ND outcomes of infants born extremely preterm with NEC/SIP beyond early childhood. Here, we compared anthropometric and ND outcomes, at 10 and 15 years, for children with medical NEC, surgical NEC, SIP, and neither NEC nor SIP. METHODS: Participants from the prospective longitudinal extremely low gestational age newborns study were evaluated at ages 10 and 15 years for anthropometrics, neurocognition, attention-deficit/hyperactivity disorder, epilepsy, and gross motor function. RESULTS: At age 10 years, 889 children were followed-up (medical NEC = 138, surgical NEC = 33, SIP = 29, no NEC/SIP = 689), and 694 children were followed up-at 15 years. Children with medical NEC had similar weight, BMI, height, and head circumference compared with controls at both 10 and 15 years. At 15 years, children with surgical NEC had lower weight z-score (adjusted ß: -0.75, 95% confidence interval [CI]: -1.25 to -0.25), lower BMI z-score (adjusted ß: -0.55, 95% CI: -1.09 to -0.01), and lower height z-score (adjusted ß: -0.65, 95% CI: -1.16 to -0.14). Children with SIP had lower weight and height z-scores at age 10 years when adjusted for sample attrition, but these differences were not significant when adjusted for confounders. We observed no differences in long-term ND outcomes. CONCLUSIONS: Surgical NEC- and SIP-associated growth impairment may persist through late childhood. ND outcomes among school-aged children born extremely preterm with any NEC or SIP are no different from children without NEC/SIP.

The Effects of COVID-19 Hospital Practices on Breastfeeding Initiation and Duration Postdischarge.

Background: Early in the COVID-19 pandemic, many birth hospitals separated SARS-CoV-2-positive mothers from their newborn infants and advised against breastfeeding to decrease postnatal SARS-CoV-2 transmission. Information on how these practices impacted breastfeeding postdischarge is limited. Objectives: In a statewide sample of SARS-CoV-2-positive mothers, we aimed to determine the extent to which (1) mother-infant separation and (2) a lack of breastfeeding initiation in-hospital were associated with breast milk feeding postdischarge. Design/Methods: From 11 birthing hospitals in Massachusetts, we identified 187 women who tested positive for SARS-CoV-2 from 14 days before to 72 hours after delivery (March 1-July 31, 2020) and their newborn infants. We abstracted chart data from the delivery hospitalization on main exposure variables (mother-infant separation, in-hospital breast milk feeding [expressed milk feeding and/or direct breastfeeding]) and from outpatient visits until 30 days postdischarge. We evaluated associations of in-hospital practices with outcomes up to 30 days postdischarge, adjusting for confounders using multivariable logistic and linear regression. Results: Mother-infant separation in-hospital was associated with a shorter duration of any breast milk feeding (regression coefficient estimate -5.29 days, 95% confidence intervals [CI] [-8.89 to -1.69]). Direct breastfeeding in-hospital was associated with higher odds of any breast milk feeding (adjusted odds ratios [AOR] 5.68, 95% CI [1.65-23.63]) and direct breastfeeding (AOR 8.19, 95% CI [2.99-24.91]) postdischarge; results were similar for any breast milk feeding in-hospital. Conclusions: Perinatal hospital care practices implemented early in the COVID-19 pandemic, specifically mother-infant separation and prevention of breast milk feeding initiation, were associated with adverse effects on breast milk feeding outcomes assessed up to 1 month postdischarge.

Utilizing near infra-red spectroscopy to identify physiologic variations during digital retinal imaging in preterm infants.

OBJECTIVE: Evaluate physiologic changes during digital retinal imaging (DRI) using near infra-red spectroscopy (NIRS). STUDY DESIGN: Prospective observational study of preterm infants undergoing retinopathy of prematurity screening via DRI using wide-field retinal camera. Cardiorespiratory (CR) and NIRS data were collected, trends correlated for changes and coefficient representing "slopes" of outcomes were plotted over time. The p value associated with each slope coefficient was tested to assess for slope differences from time of intervention (time = 0/or no slope). RESULTS: Thirty-one preterm infants were included in the study. There were no significant changes in pre- and post-slopes for cerebral or mesenteric oxygenation, or CR indices with eye drop administration compared to baseline. DRI resulted in significant increase in post exam slope in cerebral oxygenation, mesenteric oxygenation and respiratory rate. CONCLUSION: ROP examination using DRI was well tolerated with slight improvements in cerebral and mesenteric perfusion without significant safety concerns.

Leveraging the Massachusetts perinatal quality collaborative to address the COVID-19 pandemic among diverse populations.

OBJECTIVE: We leveraged the Massachusetts perinatal quality collaborative (PQC) to address the COVID-19 pandemic. Our goals were to: (1) implement perinatal practices thought to reduce mother-to-infant SARS-CoV-2 transmission while limiting disruption of health-promoting practices and (2) do so without inequities attributable to race/ethnicity, language status, and social vulnerability. METHODS: Main outcomes were cesarean and preterm delivery, rooming-in, and breastfeeding. We examined changes over time overall and according to race/ethnicity, language status, and social vulnerability from 03/20-07/20 at 11 hospitals. RESULTS: Of 255 mothers with SARS-CoV-2, 67% were black or Hispanic and 47% were non-English speaking. Cesarean decreased (49% to 35%), while rooming-in (55% to 86%) and breastfeeding (53% to 72%) increased. These changes did not differ by race/ethnicity, language, or social vulnerability. CONCLUSIONS: Leveraging the Massachusetts PQC led to rapid changes in perinatal care during the COVID-19 crisis in a short time, representing a novel use of statewide PQC structures.

Tidal volume measurements in the delivery room in preterm infants requiring positive pressure ventilation via endotracheal tube-feasibility study.

OBJECTIVE: Current delivery room (DR) resuscitation utilizes pressure-limited devices without tidal volume (TV) measurements. Clinicians use chest expansion as a surrogate, which is a poor indicator of TV. TV in early life can be highly variable due to rapidly changing lung compliance. Our objectives were to assess feasibility of measuring TV in DR, and to report the generated TV in intubated patients. STUDY DESIGN: Prospective, observational, feasibility study in infants <32 weeks GA and intubated in DR. TV was measured using a respiratory function monitor. RESULT: Ten infants with mean GA 23.9(±1.5) weeks and mean BW 618.5(±155) gram were included. Total of 178 min (mean 17.8 min/patient) with 8175 individual breaths (mean 817.5 breaths/patient) were analyzed. Goal TV of 4-6 ml/kg was provided 23.5% of times with high TV (>6 ml/kg) provided 47.7% of times. CONCLUSION: TV measurement in DR is feasible. It is associated with high intra and inter-patient variability.

Association of Maternal Perinatal SARS-CoV-2 Infection With Neonatal Outcomes During the COVID-19 Pandemic in Massachusetts.

Importance: The incidence of mother-to-newborn SARS-CoV-2 transmission appears low and may be associated with biological and social factors. However, data are limited on the factors associated with neonatal clinical or viral testing outcomes. Objective: To ascertain the percentage of neonates who were born to mothers with positive SARS-CoV-2 test results during the birth hospitalization, the clinical and sociodemographic factors associated with neonatal test result positivity, and the clinical and virological outcomes for newborns during hospitalization and 30 days after discharge. Design, Setting, and Participants: This multicenter cohort study included 11 academic or community hospitals in Massachusetts and mother-neonate dyads whose delivery and discharge occurred between March 1, 2020, and July 31, 2020. Eligible dyads were identified at each participating hospital through local COVID-19 surveillance and infection control systems. Neonates were born to mothers with positive SARS-CoV-2 test results within 14 days before to 72 hours after delivery, and neonates were followed up for 30 days after birth hospital discharge. Exposures: Hypothesized maternal risk factors in neonatal test result positivity included maternal COVID-19 symptoms, vaginal delivery, rooming-in practice, Black race or Hispanic ethnicity, and zip code-derived social vulnerability index. Delivery indicated by worsening maternal COVID-19 symptoms was hypothesized to increase the risk of adverse neonatal health outcomes. Main Outcomes and Measures: Primary outcomes for neonates were (1) positive SARS-CoV-2 test results, (2) indicators of adverse health, and (3) clinical signs and viral testing. Test result positivity was defined as at least 1 positive result on a specimen obtained by nasopharyngeal swab using a polymerase chain reaction-based method. Clinical and testing data were obtained from electronic medical records of nonroutine health care visits within 30 days after hospital discharge. Results: The cohort included 255 neonates (mean [SD] gestational age at birth, 37.9 [2.6] weeks; 62 [24.3%] with low birth weight or preterm delivery) with 250 mothers (mean [SD] age, 30.4 [6.3] years; 121 [48.4%] were of Hispanic ethnicity). Of the 255 neonates who were born to mothers with SARS-CoV-2 infection, 225 (88.2%) were tested for SARS-CoV-2 and 5 (2.2%) had positive results during the birth hospitalization. High maternal social vulnerability was associated with higher likelihood of neonatal test result positivity (adjusted odds ratio, 4.95; 95% CI, 1.53-16.01; P = .008), adjusted for maternal COVID-19 symptoms, delivery mode, and rooming-in practice. Adverse outcomes during hospitalization were associated with preterm delivery indicated by worsening maternal COVID-19 symptoms. Of the 151 newborns with follow-up data, 28 had nonroutine clinical visits, 7 underwent SARS-CoV-2 testing, and 1 had a positive result. Conclusions and Relevance: The findings emphasize the importance of both biological and social factors in perinatal SARS-CoV-2 infection outcomes. Newborns exposed to SARS-CoV-2 were at risk for both direct and indirect adverse health outcomes, supporting efforts of ongoing surveillance of the virus and long-term follow-up.

Predictors of successful patent ductus arteriosus closure with acetaminophen in preterm infants.

OBJECTIVE: Evaluate predictors of successful PDA closure following acetaminophen treatment. STUDY DESIGN: Retrospective cohort study of ≤30 weeks GA infants born from 1 January 2013-30 September 2019, and treated with single course acetaminophen by symptomatic PDA treatment strategy. Multiple maternal and neonatal variables were identified as potential predictors. Univariate analysis and multivariable regression models were applied to evaluate the strongest predictors. RESULTS: Sixty-six patients were included, 28 (42.4%) had successful PDA closure following acetaminophen. Success was associated with GA > 26 weeks (65% vs. 33%, AUC = 0.64), birthweight >750 g (53% vs. 32%, AUC = 0.61), PDA size ≤0.2 cm (63% vs. 32%, AUC = 0.64), and no prior indomethacin use (56% vs. 33%, AUC = 0.61). Multivariable model identified GA > 26 weeks (RR = 1.92, CI 1.20-3.09) and PDA size ≤0.2 cm (RR: 1.82, CI 1.11-2.98) as the strongest predictors. CONCLUSION: Acetaminophen may be more successful in targeted PDA closure in >26 weeks GA infants with PDA size ≤0.2 cm.

Effect of Fluid Bolus on Clinical Outcomes in Very Low Birth Weight Infants.

OBJECTIVE: Administration of fluid bolus in very low birth weight (VLBW) infants is a common practice in the NICU, but one without clear evidence demonstrating benefits in clinical outcomes. On the contrary, recent observational studies have suggested a potential detrimental effect of empiric fluid bolus in preterm infants, especially in the absence of clear indications. The aim of this study was to assess the impact of fluid bolus on various clinical outcomes in VLBW infants. METHODS: Retrospective cohort study of VLBW infants born at ≤34 weeks' gestation and/or ≤1500-g birth weight at a single level III NICU from January 1, 2008, to December 31, 2013, and who received at least one fluid bolus within the first 48 hours of life. Outcomes studied were in-hospital mortality, need for home oxygen, incidence of chronic lung disease (CLD), prevalence of patent ductus arteriosus (PDA), and intraventricular hemorrhage (IVH). RESULTS: Of 516 infants, 112 (21.7%) received a fluid bolus within the first 48 hours of life for various indications. Propensity models suggested no statistical difference for CLD or mortality, but exposed infants had an increased incidence of home on oxygen (p = 0.018), PDA prevalence (p = 0.008), and IVH prevalence (p = 0.038). CONCLUSIONS: Fluid bolus in the first 48 hours of life may be associated with increased incidence of need for home oxygen and higher prevalence of PDA and IVH in VLBW infants. Future studies are needed to address these important adverse outcomes.

Use of acetaminophen for patent ductus arteriosus treatment: a single center experience.

Purpose: Patent ductus arteriosus (PDA) continues to be one of the most common complications associated with preterm birth. Up to 70% of infants born before 28 weeks gestational age may require some form of medical or surgical treatment for PDA closure. Recent studies have suggested acetaminophen to be a promising new alternative to indomethacin and ibuprofen for closure of PDA with potentially fewer adverse effects. Our aim for the study was to report our experience regarding the efficacy of acetaminophen compared to indomethacin for treatment of hemodynamically significant PDA (hs-PDA) in infants born in our institution.Material and methods: Retrospective cohort study of all preterm infants born <34-week gestation with hs-PDA, treated with acetaminophen or indomethacin as the first line medication for hs-PDA. Primary outcome of successful PDA closure rate (small or no PDA) and secondary outcomes of short-term morbidities and immediate adverse events were compared between the two cohorts.Results: Of the 43 infants, 25 were treated with acetaminophen and 18 with indomethacin, as first line for hs-PDA. Successful PDA closure rate was slightly lower for acetaminophen compared to indomethacin, although statistically not significant (acetaminophen: 40% versus indomethacin: 55.5%, p = .31). No significant differences in short-term morbidities including necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), late onset sepsis (LOS), retinopathy of prematurity (ROP) and intraventricular hemorrhage (IVH), or immediate side effects including oliguria, hyponatremia, elevated BUN/creatinine, thrombocytopenia were found between the two cohorts.Conclusions: Acetaminophen treatment of hs-PDA resulted in similar successful PDA closure rate compared to indomethacin in our small cohort of patients.

Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth.

Bronchopulmonary dysplasia (BPD) remains the most common and serious chronic lung disease of premature infants. Severe BPD complicated with pulmonary hypertension (PH) increases the mortality of these infants. Riociguat is an allosteric soluble guanylate cyclase stimulator and is approved by the FDA for treating PH in adults. However, it has not been approved for use in neonates due to concern for adverse effects on long bone growth. To address this concern we investigated if administration of riociguat is beneficial in preventing hyperoxia-induced lung injury and PH without side effects on long bone growth in newborn rats. Newborn rats were randomized to normoxia (21% O2) or hyperoxia (85% O2) exposure groups within 24 hours of birth, and received riociguat or placebo by once daily intraperitoneal injections during continuous normoxia or hyperoxia exposure for 9 days. In the hyperoxia control group, radial alveolar count, mean linear intercept and vascular density were significantly decreased, the pathological hallmarks of BPD, and these were accompanied by an increased inflammatory response. There was also significantly elevated vascular muscularization of peripheral pulmonary vessels, right ventricular systolic pressure and right ventricular hypertrophy indicating PH. However, administration of riociguat significantly decreased lung inflammation, improved alveolar and vascular development, and decreased PH during hyperoxia by inducing cGMP production. Additionally, riociguat did not affect long bone growth or structure. These data indicate that riociguat is beneficial in preventing hyperoxia-induced lung injury and PH without affecting long bone growth and structure and hence, suggests riociguat may be a potential novel agent for preventing BPD and PH in neonates.

Rapidly involuting congenital haemangioma of the liver.

Rapidly involuting congenital haemangiomas (RICHs) are rare benign vascular tumours of infancy. They are generally asymptomatic, but can present with thrombocytopaenia and coagulopathy. Significant complications including life-threatening bleeding, high-output heart failure and liver failure, though rare, can occur. RICHs generally regress by 12-14 months of age and can be managed clinically with symptomatic treatment, watchful waiting and close monitoring of the size of the haemangioma. Medical management (corticosteroids, propranolol) has not shown to be effective, in contrast to infantile haemangioma which will not regress spontaneously and has been noted to respond to medical therapy. Awareness of this diagnosis is important to prevent unnecessary medical and surgical intervention. Here, we present a case of a full-term infant with RICH who presented with thrombocytopaenia and abnormal coagulation profile. The coagulopathy was treated symptomatically, while the lesion was observed with serial ultrasounds and gradually decreased in size.

Recombinant CCN1 prevents hyperoxia-induced lung injury in neonatal rats.

BackgroundCystein-rich protein 61 (Cyr61/CCN1) is a member of the CCN family of matricellular proteins that has an important role in tissue development and remodeling. However, the role of CCN1 in the pathogenesis of bronchopulmonary dysplasia (BPD) is unknown. Accordingly, we have investigated the effects of CCN1 on a hyperoxia-induced lung injury model in neonatal rats.MethodsIn experiment 1, newborn rats were randomized to room air (RA) or 85% oxygen (O2) for 7 or 14 days, and we assessed the expression of CCN1. In experiment 2, rat pups were exposed to RA or O2 and received placebo or recombinant CCN1 by daily intraperitoneal injection for 10 days. The effects of CCN1 on hyperoxia-induced lung inflammation, alveolar and vascular development, vascular remodeling, and right ventricular hypertrophy (RVH) were observed.ResultsIn experiment 1, hyperoxia downregulated CCN1 expression. In experiment 2, treatment with recombinant CCN1 significantly decreased macrophage and neutrophil infiltration, reduced inflammasome activation, increased alveolar and vascular development, and reduced vascular remodeling and RVH in the hyperoxic animals.ConclusionThese results demonstrate that hyperoxia-induced lung injury is associated with downregulated basal CCN1 expression, and treatment with CCN1 can largely reverse hyperoxic injury.

Inhibition of Rac1 Signaling Downregulates Inflammasome Activation and Attenuates Lung Injury in Neonatal Rats Exposed to Hyperoxia.

BACKGROUND: Inflammatory injury, particularly the production of active interleukin (IL)-1ß plays a major role in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. The release of active IL-1ß is controlled by posttranscriptional modifications of its proform (pro-IL-1ß) through the inflammasome. Rac1 is a member of the Rho family of GTPases that regulate the inflammatory process. OBJECTIVE: This study tested the hypothesis that Rac1 signaling increases inflammasome activation that results in damaging inflammation, and that the inhibition of Rac1 signaling prevents lung injury, by inhibiting inflammasome activation in a newborn rat model of BPD induced by hyperoxia. METHODS: Newborn rat pups were exposed to room air or hyperoxia (85% O2) and received daily intraperitoneal injections of placebo (normal saline) or NSC23766, a specific Rac1 inhibitor, for 10 days. The effects on lung inflammation, alveolarization, vascular development, vascular remodeling, right ventricular systolic pressure, and right ventricular hypertrophy (RVH) were then assessed. RESULTS: Hyperoxia exposure upregulated Rac1 and increased the production of active IL-1ß, which was accompanied by increasing expression of the inflammasome. In addition, hyperoxia induced the pathological hallmarks of BPD. However, treatment with NSC23766 significantly decreased inflammasome activation and macrophage infiltration, improved alveolar and vascular development, and reduced pulmonary vascular remodeling and RVH. CONCLUSION: These results indicate that Rac1 signaling regulates the expression of the inflammasome and plays a pivotal role in the pathogenesis of hyperoxia-induced neonatal lung injury. Therefore, targeting Rac1 signaling may provide a novel strategy to prevent and treat BPD in preterm infants.

From parenteral to enteral nutrition: a nutrition-based approach for evaluating postnatal growth failure in preterm infants.

BACKGROUND: Nutrition practices for preterm infants include phases of parenteral nutrition (PN), full enteral nutrition (EN), and the transitional phase in between. Our aim was to identify the nutrition phases during which infants are most likely to exhibit poor growth that would affect risk for growth failure (GF) at discharge and to examine factors associated with GF. METHODS: A retrospective chart review was conducted on infants born <32 weeks' gestation. The neonatal intensive care unit stay was divided into 3 nutrition phases: (1) full PN, (2) transitional PN + EN, and (3) full EN. Weekly growth rates were calculated, and for each growth velocity <10 g/kg/d, the coinciding phase was recorded. GF was defined as a discharge weight below the 10th percentile. The nutrition phases during which growth inadequacy predicted GF at discharge were determined, correcting for other clinical factors associated with GF. RESULTS: In total, 156 eligible infants were identified. Seventy-six infants (49%) were discharged with weights <10%. Incidence of poor growth was highest during the transitional phase (46%) and was predictive of GF when adjusted for gestational age, birth weight, and severity of illness. Although energy intakes during the transitional phase were comparable to baseline parenteral provision, protein intakes progressively decreased ( P < .0001), consistently providing 3 g/kg/d as PN was weaned. Serum urea nitrogen also declined and was correlated with protein intake (r = -0.32, P < .001). CONCLUSION: Growth was compromised during the transitional phase, likely related to decreased protein intake. Optimizing protein provision while PN is weaned is an important strategy to prevent postnatal growth failure.