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Background: The risk of neonatal SARS-CoV-2 infection from the mother's own milk (MoM) in neonates who are exposed to maternal SARS-CoV-2 during the perinatal period remains unclear. We conducted a systematic review to assess the association between MoM feeding and neonatal SARS-CoV-2 infection in neonates who were born to SARS-CoV-2-positive pregnant persons. Methods: PubMed Central and Google Scholar were searched for studies published by 14 March 2024 that reported neonatal SARS-CoV-2 infection by feeding type. This search, including Scopus, was updated on 17 December 2024. The primary outcome was neonatal SARS-CoV-2 infection. The meta-analysis was conducted using a random effects model with two planned subgroup analyses: time of maternal PCR testing (at admission vs. previous 2 weeks) and dyad handling (isolation vs. some precautions vs. variable/NA). Results: The primary outcome was available in both arms of nine studies, including 5572 neonates who received MoM and 2215 who received no MoM. The GRADE rating was low quality, because the studies were observational (cohorts). The frequency of SARS-CoV-2 infection was similar in both arms (2.7% MoM vs. 2.2% no MoM), with a common risk ratio of 0.82 (95% confidence interval 0.44, 1.53, p = 0.54). No significant differences were observed in the subgroup analyses. Limitations include observational and incomplete data, other possible infection sources, small sample sizes for subgroup analyses, and neonates with more than one feeding type. Conclusions: Feeding MoM was not associated with an increased risk of neonatal SARS-CoV-2 infection among neonates who were born to mothers with perinatal infection. These data, along with reports showing a lack of active replicating SARS-CoV-2 virus in MoM, further support women with perinatal SARS-CoV-2 infection feeding MoM. Registration: PROSPERO ID CRD42021268576.

Objective:  This study aimed to develop a predictive model of feeding mother's own milk (MOM) at discharge using social determinants of health (SDOH), maternal and neonatal factors after deliveries at <33 weeks of gestational age (GA), or birth weight <1,500 g., Study Design:  Secondary analysis of a retrospective cohort in an inner-city hospital before (Epoch-1, 2018-2019) and after (Epoch-2, 2020-2021) implementing a donor human milk (DHM) program., Results:  Among 986 neonates, 495 were born in Epoch-1 (320 Hispanic White, 142 Non-Hispanic Black, and 33 Other) and 491 in Epoch-2 (327, 137, and 27, respectively). Feeding any MOM was less frequent in infants of non-Hispanic Black mothers than in those of Hispanic mothers ( p  < 0.05) but did not change with epoch ( p  = 0.46). Among infants who received any MOM, continued feeding MOM to the time of discharge was less frequent in infants of non-Hispanic Black mothers versus those of Hispanic mothers, 94/237 (40%) versus 339/595 (57%; p  < 0.05), respectively. In multivariate analysis including SDOH and maternal variables, the odds of feeding MOM at discharge were lower with SDOH including neighborhoods with higher poverty levels, multiparity, substance use disorder, non-Hispanic Black versus Hispanic and young maternal age and increased with GA but did not change after implementing DHM. The predictive model including SDOH, maternal and early neonatal variables had good discrimination (area under the curve 0.85) and calibration and was internally validated. It showed the odds of feeding MOM at discharge were lower in infants of non-Hispanic Black mothers and with feeding DHM, higher need for respiratory support and later initiation of feeding MOM., Conclusion:  Feeding MOM at discharge was associated with SDOH, and maternal and neonatal factors but did not change after implementing DHM. Disparity in feeding MOM at discharge was explained by less frequent initiation and shorter duration of feeding MOM but not by later initiation of feeding MOM., Key Points: · In this cohort study of preterm infants, factors of feeding MOM at discharge included (1) SDOH; (2) postnatal age at initiation of feeding MOM; and (3) maternal and neonatal factors.. · Feeding MOM at the time of discharge was less frequent in infants of non-Hispanic Black mothers versus those of Hispanic mothers.. · Disparity in feeding MOM at discharge was explained by less frequent initiation and shorter duration of MOM feeding but not by later postnatal age at initiation of feeding MOM.., Competing Interests: None declared., (Thieme. All rights reserved.)

Zinc (Zn) is one of the most prevalent and essential micronutrients, found in 10% of all human proteins and involved in numerous cellular enzymatic pathways. Zn is important in the neonatal brain, due to its involvement in neurotransmission, synaptic plasticity, and neural signaling. It acts as a neuronal modulator and is highly concentrated in certain brain regions, such as the hippocampus, and the retina. Low Zn intake is frequent in several countries and in populations with high poverty index. Preterm infants are at risk for Zn deficiency for prenatal (missing fetal Zn) and postnatal reasons (less intestinal absorption and insufficient intake in maternal milk to match fetal accretion). The amount of Zn needed for preterm infants is not known and remains the subject of controversy. Recent nutritional recommendations favored an increase in daily Zn supplementation. Systematic reviews of randomized trials have shown that Zn supplementation in preterm infants increases weight gain and may decrease mortality. In this review we will summarize the role of Zn in brain functions and outcomes in preterm newborns, gaps in knowledge and areas of future research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Chamakioti, Brion, Viswanathan, Lair and Angelis.)

The importance of a Neonatal Intensive Care Unit (NICU) database lies in its critical role in improving the quality of care for very preterm neonates and other high-risk newborns. These databases contain extensive information regarding maternal exposures, pregnancy complications, and neonatal care. They support quality improvement (QI) initiatives, facilitate clinical research, and track health outcomes in order to identify best practices and improve clinical guidelines. The Parkland Memorial Hospital NICU database was originally part of the Maternal and Neonatal Data Acquisition, Transmission and Evaluation project funded by the Robert Wood Johnson Foundation to assess perinatal-neonatal care in Dallas County Texas, 1977-1982. Clinical data points were defined, transcribed and validated in 1977; revalidation has occurred multiple times. Data are prospectively extracted from health records of high-risk neonates among >11,000 births annually. The database contains clinical information on >50,000 neonates, including all initially admitted to the NICU regardless of gestational age or birthweight and since 10/03/2011, all neonates admitted for observation and transferred to the term newborn nursery. The database has provided the basis for QI studies and research designed to assess and improve neonatal care. We discuss the history, evolution, administration, impact on neonatal outcomes, and future directions of our database. IMPACT: A single neonatal intensive care unit (NICU) database was designed for prospective data collection, validated and maintained for 46yrs. This database has supported quality improvement assessment, original clinical research, education and administrative requirements and impacted clinical neonatal care., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective:  No available scale, at the time of initial evaluation for necrotizing enterocolitis (NEC), accurately predicts, that is, with an area under the curve (AUC) ≥0.9, which preterm infants will undergo surgery for NEC stage III or die within a week., Study Design:  This is a retrospective cohort study ( n  = 261) of preterm infants with <33 weeks' gestation or <1,500 g birth weight with either suspected or with definite NEC born at Parkland Hospital between 2009 and 2021. A prediction model using the new HASOFA score (Hyperglycemia, Hyperkalemia, use of inotropes for Hypotension during the prior week, Acidemia, Neonatal Sequential Organ Failure Assessment [nSOFA] score) was compared with a similar model using the nSOFA score., Results:  Among 261 infants, 112 infants had NEC stage I, 68 with NEC stage II, and 81 with NEC stage III based on modified Bell's classification. The primary outcome, surgery for NEC stage III or death within a week, occurred in 81 infants (surgery in 66 infants and death in 38 infants). All infants with pneumoperitoneum or abdominal compartment syndrome either died or had surgery. The HASOFA and the nSOFA scores were evaluated in 254 and 253 infants, respectively, at the time of the initial workup for NEC. Both models were internally validated. The HASOFA model was a better predictor of surgery for NEC stage III or death within a week than the nSOFA model, with greater AUC 0.909 versus 0.825, respectively, p  < 0.001. Combining HASOFA at initial assessment with concurrent or later presence of abdominal wall erythema or portal gas improved the prediction surgery for NEC stage III or death with AUC 0.942 or 0.956, respectively., Conclusion:  Using this new internally validated prediction model, surgery for NEC stage III or death within a week can be accurately predicted at the time of initial assessment for NEC., Key Points: · No available scale, at initial evaluation, accurately predicts which preterm infants will undergo surgery for NEC stage III or die within a week.. · In this retrospective cohort study of 261 preterm infants with either suspected or definite NEC we developed a new prediction model (HASOFA score).. · The HASOFA-model had high discrimination (AUC: 0.909) and excellent calibration and was internally validated.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective:  Delivery management interventions (DMIs) were recommended to prevent delivery-associated transmission of maternal SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) to infants without evidence of effect on early neonatal SARS-CoV-2 infection (ENI) and neonatal death <28 days of life (ND). This systematic review describes different DMI combinations and the frequency of ENI and ND., Study Design:  Individual patient data were collected from articles published from January 1, 2020 to December 31, 2021 from Cochrane review databases, Medline, and Google Scholar. Article inclusion criteria were: documented maternal SARS-CoV-2 polymerase chain reaction (PCR)-positive status 10 days before delivery or symptomatic at delivery with a positive test within 48 hours, known delivery method, and known infant SARS-CoV-2 PCR result. Primary outcomes were ENI (positive PCR at 12 hours to 10 days) and ND. All characteristics were pooled using the DerSimonian-Laird inverse variance method. Primary outcome analyses were performed using logit transformation and random effect. Pooled results were expressed as percentages (95% confidence intervals). Continuity correction was applied for all pooled results if any included study has 0 event., Results:  A total of 11,075 publications were screened. 117 publications representing 244 infants and 230 mothers were included. All publications were case reports. ENI and ND were reported in 23.4% (18.2-29.18) and 2.1% (0.67-4.72) of cases, respectively. Among cases with available information, DMIs were reported for physical environment (85-100%), delivery-specific interventions (47-100%), and infant care practices (80-100%). No significant comparisons could be performed between different DMI combinations due to small sample size., Conclusion:  The evidence supporting any DMI in SARS-CoV-2-infected mothers to prevent ENI or ND is extremely limited. Limitations of this meta-analysis include high risk of bias, small sample size, and large confidence intervals. This identifies the need for multinational database generation and specific studies designed to provide evidence of DMI guidelines best suited to prevent transmission from mother to neonate., Key Points: · In this review we analyzed 2 years of maternal SARS-CoV-2 published cases.. · We assessed association of delivery management interventions with infant SARS-CoV-2 infection.. · We found no evidence supporting any DMI for that purpose.., Competing Interests: J.M.H. received compensation as neonatology board member of AbbVie France; fees from Nestec SA (Switzerland) and Nutricia Research (Holland) for consulting service on clinical trials; and from Baxter (United States) as a speaker in an international education program on advanced nutrition; all were outside and unrelated to the submitted work., (Thieme. All rights reserved.)

Objective: The aim of this study was to determine which late-preterm (35-36 weeks' gestational age [GA]) and term neonates with early-onset hypoglycemia in the first 72 hours postnatal required a continuous glucose infusion to achieve and successfully maintain euglycemia., Study Design: This is a retrospective cohort study of late preterm and term neonates born in 2010-2014 and admitted to the Mother-Baby Unit at Parkland Hospital who had laboratory-proven blood glucose concentration < 40 mg/dL (2.2 mmol/L) during the first 72 hours of life. Among the subgroup needing intravenous (IV) glucose infusion, we analyzed which factors predicted a maximum glucose infusion rate (GIR) ≥ 10 mg/kg/min. The entire cohort was randomly divided into a derivation cohort ( n  = 1,288) and a validation cohort ( n  = 1,298)., Results: In multivariate analysis, the need for IV glucose infusion was associated with small size for GA, low initial glucose concentration, early-onset infection, and other perinatal variables in both cohorts. A GIR ≥ 10 mg/kg / min was required in 14% of neonates with blood glucose value < 20 mg/dL during the first 3 hours of observation. The likelihood of a GIR ≥ 10 mg/kg/min was associated with lower initial blood glucose value and lower umbilical arterial pH., Conclusion: Need for IV glucose infusion was associated with small size for GA, low initial glucose concentration, early-onset infection, and variables associated with perinatal hypoxia-asphyxia. The likelihood of a maximum GIR ≥ 10 mg/kg/min was greater in neonates with lower blood glucose value during the first 3 hours of observation and lower umbilical arterial pH., Key Points: · We studied 51,973 neonates ≥ 35 weeks' GA.. · We established a model predicting the need for IV glucose.. · We also predicted the need for a high rate of IV glucose.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Necrotizing enterocolitis (NEC) primarily affects preterm, especially small for gestational age (SGA), infants. This study was designed to (1) describe frequency and timing of NEC in SGA versus non-SGA infants and (2) assess whether NEC is independently associated with the severity of intrauterine growth failure., Study Design: Retrospective cohort study of infants without severe congenital malformations born <33 weeks' gestational age (GA) carried out from 2009 to 2021. The frequency and time of NEC were compared between SGA and non-SGA infants. Multivariate logistic regression was used to assess whether NEC was independently associated with intrauterine growth restriction. Severe growth restriction was defined as birth weight Z -score <  -2., Results: Among 2,940 infants, the frequency of NEC was higher in SGA than in non-SGA infants (25/268 [9.3%] vs. 110/2,672 [4.1%], respectively, p  < 0.001). NEC developed 2 weeks later in SGA than non-SGA infants. In multivariate analysis, the adjusted odds of NEC increased with extreme prematurity (<28 weeks' GA) and with severe but not moderate growth restriction. The adjusted odds of NEC increased with urinary tract infection or sepsis within a week prior to NEC, were lower in infants fed their mother's own milk until discharge, and did not change over five epochs. NEC was independently associated with antenatal steroid (ANS) exposure in infants with birth weight (BW) Z -score < 0., Conclusion: NEC was more frequent in SGA than in non-SGA infants and developed 2 weeks later in SGA infants. NEC was independently associated with severe intrauterine growth failure and with ANS exposure in infants with BW Z -score < 0., Key Points: · We studied 2,940 infants <33 weeks' GA.. · We assessed NEC.. · NEC was more frequent in SGA infants.. · NEC occurred 2 weeks later in SGA infants.. · NEC was associated with severe growth restriction.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: A ventricle-to-brain index (VBI) >0.35 is associated with low scores on the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) in preterm infants with birth weight <1,250 g. However, VBI obtained at the third ventricle has only moderate interobserver reliability. The objective of this study was to test (1) reliability of VBI measured at the foramen of Monro on the latest ultrasonogram (US) before discharge using the intraclass correlation coefficient (ICC) and (2) the relationship between VBI and BSID-III scores at ≥18 months corrected age., Study Design: The present study is a single-center retrospective cohort study., Results: The study included 270 preterm infants born at 23 0/7 to 28 6/7 weeks of gestational age. The ICC of VBI between independent measurements by two study radiologists on the first 50 patients was 0.934. Factors associated with the value of VBI included severe intraventricular hemorrhage, bronchopulmonary dysplasia, and systemic steroid administration for BPD but not postmenstrual age. In multivariate analysis, VBI was negatively and independently associated with cognitive ( p  = 0.002), language ( p  = 0.004), and motor ( p  < 0.001) BSID-III scores. The association between VBI and BSID-III scores was observed even in infants in whom the latest US was obtained before term equivalent age. The association between VBI and BSID-III scores was also observed after excluding those with severe intraventricular hemorrhage., Conclusion: In this very preterm cohort the measurement of VBI had excellent reliability. Moreover, VBI measurements were negatively associated with motor, language, and cognitive BSID-III scores., Key Points: · Mean values of VBI are stable with postmenstrual age.. · Values at the foramen of Monro are reliable and reproducible.. · VBI is negatively associated with Bayley scores.. · The association is observed even before term age.., Competing Interests: None declared, (Thieme. All rights reserved.)

Introduction: Our aim was to determine if maternal body mass index (BMI) is associated with necrotizing enterocolitis (NEC) in a large urban delivery center., Methods: This single center retrospective case-control study included 291 infants under gestational age of 33 weeks admitted to the neonatal intensive care unit (NICU) during a 10-year period. Cases of stage 2 and 3 NEC were matched at a ratio of 2 controls (n = 194) to 1 case (n = 97). Maternal BMI was categorized as normal (≤24.9), overweight (25-29.9) and obese (≥30). Chi-square and stepwise logistic regression were used for analysis. A power analysis was performed to determine if sample size was sufficient to detect an association., Results: Stepwise logistic regression demonstrated no association between NEC and maternal obesity. Maternal hypertension, pre-eclampsia, premature rupture of membranes, maternal exposure to antibiotics, placental abruption and gestational diabetes were not associated with NEC. Power analysis showed the sample size was sufficient to detect an association of NEC with maternal BMI in three groups analyzed. In this case-control study, there was an association between NEC and maternal overweight but not obesity at delivery., Discussion: Our results did not show a significant association of NEC with maternal obesity. The percent of overweight and obese mothers prior to pregnancy and at delivery was significantly higher in our population than the national average and may be responsible for the limited ability to reveal any association between maternal obesity and NEC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Stumpf et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The primary objectives were to compare body mass index (BMI) Z-score (Z), systolic blood pressure (SBP), serum leptin:adiponectin (L:A) ratio and estimated glomerular filtration rate (eGFR) at ~3 years adjusted age between two arms of a randomized controlled trial (RCT) comparing two modes of human milk fortification for very low-birthweight infants in the neonatal intensive care unit., Study Design: Follow-up of RCT at 33-48 months., Results: Follow-up data are available in 82/120 infants. Infants in the experimental arm have anthropometric data consistent with central obesity and higher serum L:A ratio (sensitivity analysis adjusting for sex and using all available data), but have similar eGFR and SBP at follow-up compared with controls. Serum L:A ratio is strongly correlated with anthropometric measurements suggesting central obesity., Conclusions: Infants in the experimental arm have central obesity and higher serum L:A ratio compared with controls. Notably, serum L:A ratio is strongly correlated with weight gain., Trial Registration: This randomized controlled trial was registered at ClinicalTrials.gov NCT02372136., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Several reports demonstrated that perinatal SARS-CoV-2 has significant impact on maternal and neonatal health outcomes. However, the relationship between severity of maternal illness with outcomes remains less clear., Methods: This is a single-center retrospective cohort study of mother/infant dyads with positive maternal test for SARS-CoV-2 between 14 days prior and 3 days after delivery from 3/30/2020 to 12/28/2021., Results: Among 538 mothers, those with moderate/severe/critical illness were more likely to undergo induction, receive oxygen, mechanical ventilation or ECMO. Mortality was significantly higher among the mothers with severe illness than asymptomatic and those with mild illness (6% vs 0% and 0%, respectively, P < 0.05). Neonates born to mothers with moderate/severe/critical illness were more likely to be preterm with lower birth weight, and to be admitted to the NICU (P < 0.05) but not to be small for gestational age. Mild maternal illness was only associated with NICU admission for isolation precaution and decreased rate of breastfeeding., Conclusions: Maternal illness severity was significantly associated with prematurity and several adverse maternal and neonatal outcomes.

Background: Hypophosphatemia is associated with prolonged mechanical ventilation and may affect growth, bone mineralization, nephrocalcinosis, and mortality in preterm infants. Optimal nutrition practices may decrease risk for hypophosphatemia and improve outcome., Methods: A quality improvement project was established to improve parenteral and enteral phosphorus intake with the goal to decrease prevalence and duration of hypophosphatemia in the first 14 days in infants <32 weeks' gestation., Results: Among 406 preterm infants, the prevalence of moderate hypophosphatemia decreased from 44% to 19% (P < 0.01) over 4 years. The median duration of moderate hypophosphatemia decreased from 72 h (48-128) to 24 (24-53) (P < 0.01). Daily intakes of parenteral calcium and phosphorus on the fourth day of life increased from 1.5 to 2.5 mEq/kg/day (P < 0.01) and 0.6 to 1.3 mmol/kg/day (P < 0.01), respectively. The median postnatal age of first serum phosphorus concentration assessment decreased from 53 h (41-64) to 32 (24-40) (P < 0.01)., Conclusion: During this quality improvement project, reduced prevalence and duration of hypophosphatemia in infants <32 weeks' gestation in the first 14 days of life was achieved through the optimization of parenteral and enteral phosphorus intake and improved response to acute hypophosphatemia., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Hyperglycemia is commonly encountered in extremely preterm newborns and physiologically can be attributed to immaturity in several biochemical pathways related to glucose metabolism. Although hyperglycemia is associated with a variety of adverse outcomes frequently described in this population, evidence for causality is lacking. Variations in definitions and treatment approaches have further complicated the understanding and implications of hyperglycemia on the immediate and long-term effects in preterm newborns. In this review, we describe the relationship between hyperglycemia and organ development, outcomes, treatment options, and potential gaps in knowledge that need further research. IMPACT: Hyperglycemia is common and less well described than hypoglycemia in extremely preterm newborns. Hyperglycemia can be attributed to immaturity in several cellular pathways involved in glucose metabolism in this age group. Hyperglycemia has been shown to be associated with a variety of adverse outcomes frequently described in this population; however, evidence for causality is lacking. Variations in definitions and treatment approaches have complicated the understanding and the implications of hyperglycemia on the immediate and long-term effects outcomes. This review describes the relationship between hyperglycemia and organ development, outcomes, treatment options, and potential gaps in knowledge that need further research., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: To estimate if the odds of spontaneous intestinal perforation (SIP) are increased when antenatal steroids (ANS) given close to delivery are combined with indomethacin on day 1 after birth (Indo-D1)., Study Design: A retrospective cohort study using the Neonatal Research Network (NRN) database of inborn infants, gestational age 22 0 -28 6  weeks or birth weight of 401-1000 g, born between January 1, 2016 and December 31, 2019, and surviving >12 hours. The primary outcome was SIP through 14 days. Time of last ANS dose prior to delivery was analyzed as a continuous variable (using 169 hours for durations >168 hours or no steroid exposure). Associations between ANS, Indo-D1, and SIP were obtained from a multilevel hierarchical generalized linear mixed model after covariate adjustment. This yielded aOR and 95% CI., Results: Of 6851 infants, 243 had SIP (3.5%). ANS exposure occurred in 6393 infants (93.3%) and IndoD1 was given to 1863 infants (27.2%). The time (median, IQR) from last dose of ANS to delivery was 32.5 hours (6-81) vs 37.1 hours (7-110) for infants with or without SIP, respectively (P = .10). Indo-D1 was given to 51.9 vs 26.3% of infants with SIP vs no SIP, respectively (P < .0001). Adjusted analysis indicated no interaction between time of last ANS dose and Indo-D1 for SIP (P = .7). Indo-D1 but not ANS was associated with increased odds of SIP (aOR: 1.73, 1.21-2.48, P = .003)., Conclusion: The odds of SIP were increased after receipt of Indo-D1. Exposure to ANS prior to Indo-D1 was not associated with an increase in SIP., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study aimed to evaluate if early (within the first 3 hours after birth) transient neonatal hypoglycemia (TNH) is associated with poor academic performance in infants at-risk for hypoglycemia., Study Design: This was a retrospective cohort study of at risk-infants (late preterm infants, small and large for gestational age infants, and infants of diabetic mothers [IDMs]) who were born in 1998 and 1999 at the University of Arkansas for Medical Sciences and had ≥1 recorded glucose concentration. The outcome measure was proficiency on 4th grade literacy and mathematics achievement tests. Three glucose concentration cutoffs for defining hypoglycemia (<35, <40, and <45 mg/dL) were investigated. Logistic regression models were developed to examine the association between early TNH and achievement test proficiency based on perinatal factors., Results: Among 726 infants, 472 had one, 233 had two, and 21 had three risk factor(s). Early TNH (glucose concentration <35, <40, and <45 mg/dL) was observed in 6.3, 11.6, and 20.5% of the study cohort, respectively. Irrespective of the cutoff used, the frequency of early TNH (number of patients with early TNH in a risk category divided by the total number of patients in that category) was significantly greater among infants with multiple risk factors. After controlling for perinatal factors, early TNH (cutoffs <35 and <40 mg/dL) was significantly associated with decreased probability of proficiency in literacy but not mathematics. Despite that early TNH was more common in IDMs and infants with three risk factors, the category or number of risk factors did not impact academic proficiency., Conclusion: Early TNH (<35 and <40 mg/dL) was associated with lower adjusted probability of proficiency on 4th grade literacy achievement tests in at-risk infants. The impact of early TNH on academic performance was similar irrespective of category or number of risk factors., Key Points: · Transient hypoglycemia was associated with lower proficiency on 4th grade tests in at-risk infants.. · The category of risk factors among at-risk infants did not impact 4th grade academic proficiency.. · The number of risk factors among at-risk infants did not impact 4th grade academic proficiency.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Donor breast milk (DBM) feeding has been associated with less growth than formula in preterm infants. Zinc content in DBM is insufficient to support growth in preterm infants., Objective: To compare growth from birth to discharge, macro- and micronutrient intake and the frequency of poor growth before (Epoch-1) and after (Epoch-2) implementing a DBM program., Methods: Retrospective cohort study of 1069 infants born at < 33 weeks' gestational age or birthweight < 1500 g and fed using our adjustable feeding protocol with accurate serial length measurements. Growth was assessed by changes in Z-scores of weight, length and fronto-occipital circumference from birth to discharge., Results: Growth did not decrease significantly in Epoch-2. However, energy and protein intake increased by 5% and frequency of zinc and vitamin D supplementation increased by >30%., Conclusions: DBM implementation did not significantly decrease growth from birth to discharge using our adjustable feeding protocol., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Human milk supplementation for preterm infants in the neonatal intensive care unit (NICU) can be based on optimized nutrition (feeding adjustments based on growth and measurements of serum nutrients) or individualized nutrition (measurements of macronutrients in mother's own milk)., Objective: To compare Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18-38mo adjusted age in infants who had been randomly allocated to individualized+optimized nutrition (experimental group) vs optimized nutrition alone (control) in the NICU., Methods: Double-blinded randomized controlled trial in neonates <29wks gestational age (GA) and those <34wks GA and small for GA., Results: Bayley scores were assessed in 91/114 (80%) infants. The two study groups had similar frequencies of low cognitive, motor and language Bayley scores and similar age-adjusted Bayley scores in bivariate and multivariate analyses., Conclusions: The type of human milk supplementation provided had no significant effect on Bayley scores assessed at 18-38mo., Trial Registration: This randomized controlled trial was registered at ClinicalTrials.gov NCT02372136., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN) has been a leader in neonatal research since 1986. In this chapter we review its history and achievements in (1) continuing observation of populations, treatments, short and longer-term outcomes, and trends over time; (2) "negative studies" (trials with non-significant primary outcomes) and trials stopped for futility or adverse events, which have influenced practice and subsequent trial design; and, (3) landmark trials that have changed neonatal care. Its consistent framework has enabled the NRN to be a pioneer in conducting longer-term, school-age follow-up. Leveraging its established infrastructure, the NRN has also partnered with other NIH institutes, governmental agencies, and industry to more effectively advance neonatal care. As current examples of its evolution with changing times, the Network has instituted a process to open specific network trials to external institutions and is adding a parent and participant component to future endeavors., Competing Interests: Conflicts of Interest The other authors have no conflicts to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Recent contributions of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) regarding obstetrical perinatal interventions and neonatal delivery room practices include the following: the impact of multiple antepartum factors including maternal diabetes, hypertension, obesity and mode of delivery on outcomes of extremely preterm newborns, effects of delayed delivery interval for extremely preterm multiples, effects of antenatal steroids on preterm newborn outcomes and the impact of antenatal magnesium sulfate therapy on neurodevelopmental outcomes for extremely preterm infants. NRN studies also contribute important evidence for neonatal delivery room resuscitation guidelines including umbilical cord management and maintenance of euthermia immediately after birth. The updated NRN outcome calculator helps better counsel families regarding possible outcomes for the most immature newborns if resuscitation is attempted at birth. Thus, the NRN provides substantial information regarding effects of perinatal management on newborn infants., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Randomized trials of antenatal steroid administration (ANS) for extreme or moderate preterm pregnancies excluded women with diabetes mellitus (DM) and included few with preeclampsia., Methods: Cohort study (n = 1,813) including moderate preterm births [29 0/7 -33 6/7 wks' gestational age GA)] before (Epoch-1) and after (Epoch-2) expansion of ANS administration to women with hypertensive disorders (HTN) and/or DM. We compared surfactant administration in Group-1 (neither HTN nor DM), Group-2a (HTN not DM), Group-2b (DM not HTN) and Group-2c (DM and HTN)., Results: Surfactant administration was less frequent after ANS in Group-1 [adjusted odds ratio (aOR) 0.54, 95% confidence interval (CI) 0.31, 0.93, P = 0.03], Group-2a (aOR 0.36, CI 0.22, 0.58, P < 0.001) and Group-2c (aOR 0.29, CI 0.12, 0.71, P = 0.007) but not Group-2b (P = 0.64)., Conclusions: ANS administration was independently associated with less surfactant administration in moderately preterm neonates whose mothers had neither HTN nor DM, and those with HTN, but not those with DM without HTN., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: We previously reported an increase in pneumothorax after implementing delivery room (DR) continuous positive airway pressure (CPAP) for labored breathing or persistent cyanosis in ≥35-week gestational age (GA) neonates unexposed to DR-positive pressure ventilation (DR-PPV). We hypothesized that pneumothorax would decrease after de-implementing DR-CPAP in those unexposed to DR-PPV or DR-O 2 supplementation (DR-PPV/O 2 )., Study Design: In a retrospective cohort excluding DR-PPV the primary outcome was DR-CPAP-related pneumothorax (1st chest radiogram, 1st day of life). In a subgroup treated by the resuscitation team and admitted to the NICU, the primary outcome was DR-CPAP-associated pneumothorax (1st radiogram, no prior PPV) without DR-PPV/O 2 ., Results: In the full cohort, occurrence of DR-CPAP-related pneumothorax decreased after the intervention (11.0% vs 6.0%, P < 0.001). In the subgroup, occurrence of DR-CPAP-associated pneumothorax decreased after the intervention (1.4% vs. 0.06%, P < 0.001)., Conclusion: The occurrence of CPAP-associated pneumothorax decreased after avoiding DR-CPAP in ≥35-week GA neonates without DR-PPV/O 2 ., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Endotracheal intubation is a commonly performed procedure in neonates, the risks of which are well-described. Some endotracheal tubes (ETT) are equipped with a cuff that can be inflated after insertion of the ETT in the airway to limit leak or aspiration. Cuffed ETTs have been shown in larger children and adults to reduce gas leak around the ETT, ETT exchange, accidental extubation, and exposure of healthcare workers to anesthetic gas during surgery. With improved understanding of neonatal airway anatomy and the widespread use of cuffed ETTs by anesthesiologists, the use of cuffed tubes is increasing in neonates., Objectives: To assess the benefits and harms of cuffed ETTs (inflated or non-inflated) compared to uncuffed ETTs for respiratory support in neonates., Search Methods: We searched CENTRAL, PubMed, and CINAHL on 20 August 2021; we also searched trial registers and checked reference lists to identify additional studies., Selection Criteria: We included randomized controlled trials (RCTs), quasi-RCTs, and cluster-randomized trials comparing cuffed (inflated and non-inflated) versus uncuffed ETTs in newborns. We sought to compare 1. inflated, cuffed versus uncuffed ETT; 2. non-inflated, cuffed versus uncuffed ETT; and 3. inflated, cuffed versus non-inflated, cuffed ETT., Data Collection and Analysis: We used the standard methods of Cochrane Neonatal. Two review authors independently assessed studies identified by the search strategy for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence., Main Results: We identified one eligible RCT for inclusion that compared the use of cuffed (inflated if ETT leak greater than 20% with cuff pressure 20 cm H 2 O or less) versus uncuffed ETT. The author provided a spreadsheet with individual data. Among 76 infants in the original manuscript, 69 met the inclusion and exclusion criteria for this Cochrane Review. We found possible bias due to lack of blinding and other bias. We are very uncertain about frequency of postextubation stridor, because the confidence intervals (CI) of the risk ratio (RR) were very wide (RR 1.36, 95% CI 0.35 to 5.25; risk difference (RD) 0.03, -0.11 to 0.18; 1 study, 69 participants; very low-certainty evidence). No neonate was diagnosed with postextubation subglottic stenosis; however, endoscopy was not available to confirm the clinical diagnosis. We are very uncertain about reintubation for stridor or subglottic stenosis because the CIs of the RR were very wide (RR 0.27, 95% CI 0.01 to 6.49; RD -0.03, 95% CI -0.11 to 0.05; 1 study, 69 participants; very low-certainty evidence). No neonate had surgical intervention (e.g. endoscopic balloon dilation, cricoid split, tracheostomy) for stridor or subglottic stenosis (1 study, 69 participants). Neonates randomized to cuffed ETT may be less likely to have a reintubation for any reason (RR 0.06, 95% CI 0.01 to 0.45; RD -0.39, 95% CI -0.57 to -0.21; number needed to treat for an additional beneficial outcome 3, 95% CI 2 to 5; 1 study, 69 participants; very low-certainty evidence). We are very uncertain about accidental extubation because the CIs of the RR were wide (RR 0.82, 95% CI 0.12 to 5.46; RD -0.01, 95% CI -0.12 to 0.10; 1 study, 69 participants; very low-certainty evidence). We are very uncertain about all-cause mortality during initial hospitalization because the CIs of the RR were extremely wide (RR 2.46, 95% CI 0.10 to 58.39; RD 0.03, 95% CI -0.05 to 0.10; 1 study, 69 participants; very low-certainty evidence). There is one ongoing trial. We classified two studies as awaiting classification because outcome data were not reported separately for newborns and older infants., Authors' Conclusions: Evidence for comparing cuffed versus uncuffed ETTs in neonates is limited by a small number of babies in a single RCT with possible bias. There is very low certainty evidence for all outcomes of this review. CIs of the estimate for postextubation stridor were wide. No neonate had clinical evidence for subglottic stenosis; however, endoscopy results were not available to assess the anatomy. Additional RCTs are necessary to evaluate the benefits and harms of cuffed ETTs (inflated and non-inflated) in the neonatal population. These studies must include neonates and be conducted both for short-term use (in the setting of the operating room) and chronic use (in the setting of chronic lung disease) of cuffed ETTs., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Neonatal hypoglycemia may affect long-term neurodevelopment., Methods: Quality improvement (QI) initiative for Mother-Baby-Unit (MBU) admissions (birthweight ≥ 2100 g; ≥35 weeks' gestation) over two epochs from 2016-2019 to reduce the frequency of early (≤3 h) neonatal hypoglycemia in small and large newborns., Intervention: New algorithm using Olsen's growth curves, hypoglycemia thresholds of <2.22 mmol/L [40 mg/dL] (0-3 h) and <2.61 mmol/L [47 mg/dL] (>3 to 24 h), feeding optimization and 24-hour glucose checks for small for gestational age and preterm newborns., Results: Among 39,460 newborns, using subsets with identical screening criteria, early hypoglycemia decreased significantly after QI implementation among large for gestational age newborns with birthweight >3850 g (66%) and small for gestational age newborns with birthweight <2500 g (70%). Among all MBU admissions, the adjusted odds of any hypoglycemia in 24 h decreased (P < 0.001)., Conclusions: Feeding optimization may decrease early hypoglycemia frequency in large and small newborns., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Randomized trials of antenatal steroids (ANS) included women at 24-33 weeks gestational age (GA); however, few women had preeclampsia and women with diabetes mellitus (DM) were excluded., Methods: Cohort study including preterm births at 23 0/7 -28 6/7 weeks GA before (Epoch-1) and after (Epoch-2) expansion of ANS administration to women with DM and hypertensive disorders (HTN). We compared Group-A (neither DM nor HTN) and Group-B (DM and/or HTN)., Results: Among 747 neonates the adjusted odds ratio (aOR) for surfactant administration, in-hospital mortality, severe intraventricular hemorrhage (IVH) and death or severe IVH were lower in ANS-exposed neonates than unexposed neonates. In Group-B, ANS administration was independently associated with less severe IVH and less death or severe IVH, but not less surfactant use or mortality., Conclusions: Increased ANS administration in women with DM and/or HTN was independently associated with less severe IVH and less death or severe IVH but without decrease in surfactant administration., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: To assess if the adjusted odds of low composite cognitive Bayley-III scores changed after implementing a single-institution quality improvement (QI) project designed to decrease discharge Z-scores for weight, body mass index (BMI), and weight-for-length, but not length or fronto-occipital circumference (FOC) in infants 23-28 weeks gestational age (GA)., Methods: Compare Bayley-III outcomes at ≥18 months corrected age (postnatal age adjusted for prematurity) in infants tested before (Epoch-1) and after (Epoch-2) QI implementation., Results: Bayley testing was available in 134/156 infants (86%) in Epoch-1 and 139/175 (79%) in Epoch-2. There was no change in frequency of low (<85) cognitive score (p = 0.5) or in median cognitive scores (80 in Epoch-1 vs. 85 Epoch-2, p = 0.35). The adjusted odds of low cognitive scores was not different between Epochs., Conclusion: No change in cognitive outcome at ≥18 months corrected age was observed after implementing a QI project designed to reduce discharge weight-for-length disproportion in very preterm infants.

This manuscript includes (1) a narrative review of Zinc as an essential nutrient for fetal and neonatal growth and brain growth and development and (2) a scoping review of studies assessing the effects of Zinc supplementation on survival, growth, brain growth, and neurodevelopment in neonates. Very preterm infants and small for gestational age infants are at risk for Zinc deficiency. Zinc deficiency can cause several complications including periorificial lesions, delayed wound healing, hair loss, diarrhea, immune deficiency, growth failure with stunting, and brain atrophy and dysfunction. Zinc is considered essential for oligodendrogenesis, neurogenesis, neuronal differentiation, white matter growth, and multiple biological and physiological roles in neurobiology. Data support the possibility that the critical period of Zinc delivery for brain growth in the mouse starts at 18 days of a 20-21-day pregnancy and extends during lactation and in human may start at 26 weeks of gestation and extend until at least 44 weeks of postmenstrual age. Studies are needed to better elucidate Zinc requirement in extremely low gestational age neonates to minimize morbidity, optimize growth, and brain growth, prevent periventricular leukomalacia and optimize neurodevelopment. IMPACT: Zinc is essential for growth and brain growth and development. In the USA, very preterm small for gestational age infants are at risk for Zinc deficiency. Data support the possibility that the critical period of Zinc delivery for brain growth in the mouse starts at 18 days of a 20-21-day pregnancy and extends during lactation and in human may start at 26 weeks' gestation and extend until at least 44 weeks of postmenstrual age. Several randomized trials of Zinc supplementation in neonates have shown improvement in growth when using high enough dose, for long duration in patients likely to or proven to have a Zinc deficiency. Studies are needed to better elucidate Zinc requirement in extremely low gestational age neonates to minimize morbidity, optimize growth and brain growth, prevent periventricular leukomalacia and optimize neurodevelopment.

Objective: To describe relationship between cord blood (representing fetal) myo-inositol concentrations and gestational age (GA) and to determine trends of blood concentrations in enterally and parenterally fed infants from birth to 70 days of age., Design/methods: Samples were collected in 281 fed or unfed infants born in 2005 and 2006. Myo-inositol concentrations were displayed in scatter plots and analyzed with linear regression models of natural log-transformed values., Results: In 441 samples obtained from 281 infants, myo-inositol concentrations varied from nondetectable to 1494 μmol/L. Cord myo-inositol concentrations decreased an estimated 11.9% per week increase in GA. Postnatal myo-inositol concentrations decreased an estimated 14.3% per week increase in postmenstrual age (PMA) and were higher for enterally fed infants compared to unfed infants (51% increase for fed vs. unfed infants)., Conclusions: Fetal myo-inositol concentrations decreased with increasing GA. Postnatal concentrations decreased with increasing PMA and were higher among enterally fed than unfed infants.

Objective: To assess the relationship of size for age with zinc deficiency in extremely low gestational age (GA) infants (23-28 weeks, ELGANs) who had insufficient linear growth despite optimizing other nutrients and to analyze changes in fronto-occipital circumference (FOC), weight and length with zinc supplementation., Study Design: Retrospective cohort study., Results: Among 302 ELGANs, a serum zinc concentration was obtained in 52 with insufficient linear growth (17%). Zinc deficiency (serum concentration <0.74 mcg/ml) was diagnosed in 8 of 24 (33%) small for GA (SGA) compared to 35 of 278 (13%) non-SGA infants (P = 0.01). Zinc supplementation for >2 weeks improved FOC growth to discharge or 50 weeks postmenstrual age in infants with Zn deficiency. However, neither linear growth nor weight gain improved with Zn supplementation., Conclusion: Zinc deficiency was diagnosed in 14% ELGANs in this cohort. Zinc supplementation for >2 weeks improved FOC growth but not linear growth or weight gain.

Objective: To assess whether in very preterm infants (1) body mass index (BMI) Z-score and weight-for-length (WtFL) Z-score at 1 year of age and (2) head growth from discharge to 1 year are associated with breastfeeding at discharge and the age of onset and type of complementary foods., Study Design: Observational cohort study., Results: Infants started on only ready-made complementary (RMC) feedings at ≤26 weeks adjusted age had the highest adjusted BMI Z-score and WtFL Z-score at 1 year of age. Adjusted change in fronto-occipital circumference was highest in infants either discharged on breastmilk or receiving home-made complementary food with/without RMC (HMM) at ≤26 weeks adjusted age., Conclusions: Infants started on RMC ≤26 weeks adjusted age had the highest BMI Z-score and WtFL Z-score at 1 year. Head growth from discharge to 1 year was highest in infants either discharged on breastmilk or receiving HMM at ≤26 weeks adjusted age.

Objective: In preterm neonates fed human milk, fortification may be adjusted by (1) optimization, based on growth rate and serum nutrient analyses, or (2) individualization, based on serial milk nutrient analyses. The primary aim was to determine whether individualized plus optimized nutrition (experimental) improves velocity of weight gain and linear growth from birth to endpoint (36 weeks postmenstrual age or discharge) when compared with optimized nutrition alone (controls)., Study Design: Double-blinded parallel group randomized trial in 120 neonates <29 weeks gestational age (GA) or <35 weeks and small for GA (birth weight < 10th centile)., Result: Weight-gain velocity (13.1 ± 2.1, n = 57 controls, vs. 13.0 ± 2.6 g kg -1  day -1 , n = 59 experimental, P = 0.87), linear growth (0.9 ± 0.2, n = 55, vs. 0.9 ± 0.2 cm week -1 , n = 52, P = 0.90) and frequency of weight/length disproportion (2% vs. 2%, P = 0.98) were similar in both groups., Conclusions: Individualized plus optimized nutrition does not improve weight gain, linear growth, or weight/length disproportion at endpoint versus optimized nutrition alone.

Background: Patent ductus arteriosus (PDA) management varies widely among neonatologists., Local Problem: Lack of institution-specific evidence-based guidelines for therapeutic closure of PDA., Methods: Quality improvement project among infants <30 weeks gestational age (GA) designed to determine whether the odds of therapy for closing the PDA, adjusted for GA, decreased after implementing evidence-based guidelines., Intervention: Implementation of guidelines with conservative approach to PDA management., Results: The frequency of PDA treatment decreased from 446/1125 (40%) in Epoch 1 to 96/482 (20%) in Epoch 2. PDA treatment was more frequent in neonates 23-26 weeks GA than those of 27-29 weeks GA (43% vs. 28%, respectively). Among 542 infants receiving indomethacin for PDA, 25% had subsequent ligation; the odds of ligation after indomethacin were lower in neonates 27-29 weeks GA and decreased during Epoch 2., Conclusions: The frequency of medical and surgical treatment for therapeutic closure of PDA decreased after implementing evidence-based treatment guidelines.

Background: In 2011, the Neonatal Resuscitation Program (NRP) added consideration of continuous positive airway pressure (CPAP) for spontaneously breathing infants with labored breathing or hypoxia in the delivery room (DR). The objective of this study was to determine if DR-CPAP is associated with symptomatic pneumothorax in infants 35 to 42 weeks' gestational age., Methods: We included (1) a retrospective birth cohort study of neonates born between 2001 and 2015 and (2) a nested cohort of those born between 2005 and 2015 who had a resuscitation call leading to admission to the NICU and did not receive positive-pressure ventilation., Results: In the birth cohort ( n = 200 381), pneumothorax increased after implementation of the 2011 NRP from 0.4% to 0.6% ( P < .05). In the nested cohort ( n = 6913), DR-CPAP increased linearly over time ( r = 0.71; P = .01). Administration of DR-CPAP was associated with pneumothorax (odds ratio [OR]: 5.5; 95% confidence interval [CI]: 4.4-6.8); the OR was higher ( P < .001) in infants receiving 21% oxygen (OR: 8.5; 95% CI: 5.9-12.3; P < .001) than in those receiving oxygen supplementation (OR: 3.5; 95% CI: 2.5-5.0; P < .001). Among those with DR-CPAP, pneumothorax increased with gestational age and decreased with oxygen administration., Conclusions: The use of DR-CPAP is associated with increased odds of pneumothorax in late-preterm and term infants, especially in those who do not receive oxygen in the DR. These findings could be used to clarify NRP guidelines regarding DR-CPAP in late-preterm and term infants., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Background: Preterm very-low-birth-weight (≤1500 g) infants exhibit disproportionate weight-for-length growth in the Neonatal Intensive Care Unit., Local Problem: High frequency of body mass index (BMI) > 90th centile at discharge and 1-year postnatal age associated with elevated blood pressure and serum leptin in infancy and adolescence., Methods: Single-institution quality improvement project in appropriately grown infants born at 23 0/7 -28 6/7 weeks gestational age and discharged home., Intervention: Adjustable feeding protocol based on valid serial length measurements (board or caliper)., Results: The average monthly percentage of weight-for-length disproportion at discharge decreased from 13% in Epoch 1 to 0% in Epoch 2 (P < 0.05). Although the average Z-score for BMI at discharge was lower in Epoch 2 versus Epoch 1 (P < 0.01), this was absent by 1 year follow-up (P = 0.91)., Conclusions: Adjustable feedings plus use of accurate serial length measurements decreases weight-for-length disproportion at hospital discharge but not at 1 year.

Background: The lack of a valid and safe method for measuring length in critically ill preterm neonates has led to a primary focus on weight gain., Local Problem: Paucity of valid length measurements, precluding the accurate analysis of growth patterns., Methods: Quality improvement project among infants < 29 weeks or small for gestational age < 35 weeks with embedded validation of (1) a caliper (infantometer) for length measurements and (2) length measurements during the first week to estimate birth length., Intervention: Implementation of valid methods to measure length., Results: We validated infantometer measurements and first week length measurements. The percentage of neonates with valid measurements during the first week rose from 10% to 78%, resulting in increased identification of classifiable growth patterns from < 10% to 89%., Conclusions: By increasing the percentage of neonates with valid length measurements in the first week postnatal, we identified an increased number of neonates with classifiable growth abnormalities.

Importance: Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety., Objective: To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks' gestational age., Design, Setting, and Participants: Randomized clinical trial included 638 infants younger than 28 weeks' gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group., Interventions: A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks., Main Outcomes and Measures: Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP., Results: Among 638 infants (mean, 26 weeks' gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the myo-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83], P = .01). All-cause death before 55 weeks' postmenstrual age occurred in 18% of the myo-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43], P = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for myo-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%)., Conclusions and Relevance: Among premature infants younger than 28 weeks' gestational age, treatment with myo-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of myo-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.

Objectives: To identify variables associated with successful elective extubation, and to determine neonatal morbidities associated with extubation failure in extremely preterm neonates., Study Design: This study was a secondary analysis of the National Institute of Child Health and Human Development Neonatal Research Network's Surfactant, Positive Pressure, and Oxygenation Randomized Trial that included extremely preterm infants born at 24 0/7 to 27 6/7 weeks' gestation. Patients were randomized either to a permissive ventilatory strategy (continuous positive airway pressure group) or intubation followed by early surfactant (surfactant group). There were prespecified intubation and extubation criteria. Extubation failure was defined as reintubation within 5 days of extubation., Results: Of 1316 infants in the trial, 1071 were eligible; 926 infants had data available on extubation status; 538 were successful and 388 failed extubation. The rate of successful extubation was 50% (188/374) in the continuous positive airway pressure group and 63% (350/552) in the surfactant group. Successful extubation was associated with higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within the first 24 hours of age and prior to extubation, lower partial pressure of carbon dioxide prior to extubation, and non-small for gestational age status after adjustment for the randomization group assignment. Infants who failed extubation had higher adjusted rates of mortality (OR 2.89), bronchopulmonary dysplasia (OR 3.06), and death/ bronchopulmonary dysplasia (OR 3.27)., Conclusions: Higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within first 24 hours of age, lower partial pressure of carbon dioxide and fraction of inspired oxygen prior to extubation, and nonsmall for gestational age status were associated with successful extubation. Failed extubation was associated with significantly higher likelihood of mortality and morbidities., Trial Registration: ClinicalTrials.gov: NCT00233324., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To assess whether mortality in patients with evolving bronchopulmonary dysplasia (BPD, defined as ⩾28 days of oxygen exposure with lung disease) is independently associated with pulmonary arterial hypertension (PAH) and surgery., Study Design: Single institution retrospective birth cohort of preterm infants with gestational age (GA) 23 0/7 to 36 6/7 weeks, and evolving BPD delivered between 2001 and 2014. Surgery was classified as minor or major using published criteria. Mortality was analyzed by stepwise logistic regression analysis., Results: Among 577 patients with evolving BPD, 33 (6%) died prior to discharge. Mortality decreased with GA (adjusted odds ratio (aOR): 0.69; 95% confidence interval (CI): 0.55, 0.87), birth weight Z-score (aOR: 0.69, 95% CI: 0.47, 0.996) and increased with PAH (aOR: 30, 95% CI: 2.1, 415), major surgery (aOR; 2.8, 95% CI: 1.3, 6.3), and PAH and surgery (aOR: 10.3, 95% CI: 2.5, 42.1)., Conclusion: Among preterm patients with evolving BPD, PAH and surgery are independently associated with mortality.