Nutritional interventions to prevent retinopathy of prematurity.

Very preterm infants are at high risk of growth failure. Poor weight gain is a prominent risk factor for retinopathy of prematurity (ROP) and optimizing nutrition could potentially promote growth and reduce ROP. Most infants at risk of ROP need parenteral nutrition initially and studies of enhanced parenteral provision of lipids and amino acids have suggested a beneficial effect on ROP. Higher amino acid intake was associated with lower incidence of hyperglycemia, a risk factor for ROP. For very preterm infants, providing unpasteurized fortified raw maternal breast milk appears to have a dose-dependent preventive effect on ROP. These infants become deficient in arachidonic acid (ArA) and docosahexaenoic acid (DHA) after birth when the maternal supply is lost. Earlier studies have investigated the impact of omega-3 fatty acids on ROP with mixed results. In a recent study, early enteral supplementation of ArA 100 mg/kg/d and DHA 50 mg/kg/d until term equivalent age reduced the incidence of severe ROP by 50%. IMPACT: Previous reviews of nutritional interventions to prevent morbidities in preterm infants have mainly addressed bronchopulmonary dysplasia, brain lesions and neurodevelopmental outcome. This review focusses on ROP. Neonatal enteral supplementation with arachidonic acid and docosahexaenoic acid, at levels similar to the fetal accretion rate, has been found to reduce severe ROP by 50% in randomized controlled trials.

Assessment trial of the effect of enteral insulin on the preterm infant intestinal microbiota.

BACKGROUND: Insulin might be associated with changes in infant gastrointestinal microbiota. The objective of this randomized controlled trial was to assess the efficacy of two doses of recombinant human(rh) enteral insulin administration compared to placebo in intestinal microbiota. METHODS: 19 preterm patients were recruited at the NICU of La Paz University Hospital (Madrid, Spain). Subjects received 2000 µIU of rh enteral insulin/ml(n = 8), 400 µIU of rh enteral insulin/ml(n = 6) or placebo(n = 5) for 28 days administered once per day. Extracted DNA from fecal samples collected at the beginning and end of treatment were analyzed. The 16S rRNA V4 region was amplified and sequenced in a Miseq(Illumina®) sequencer using 2 × 250 bp paired end. Resulting reads were filtered and analyzed using Qiime2 software. Metabolic activity was assessed by GC. RESULTS: Gestational age and birth weight did not differ between groups. At the phylum level, both insulin treated groups increased the relative abundance of Bacillota, while Pseudomonadota decreased. No change was observed in infants receiving placebo. At the genus level, insulin at both doses showed enriching effects on Clostridium. We found a significant increase in concentrations of fecal propionate in both rh insulin treated groups. CONCLUSION: Rh insulin may modify neonatal intestinal microbiota and SCFAs in preterm infants. IMPACT STATEMENT: Decrease of Pseudomonadota (former Proteobacteria phylum) and increase of Bacillota (former Firmicutes phylum) obtained in this study are the changes observed previously in low-risk infants for NEC. The administration of recombinant enteral insulin may modify the microbiota of preterm new-borns and SCFAs. Modulation of the microbiota may be a mechanism whereby insulin contributes to neonatal intestinal maturation and/or protection.

The role of nutritional interventions in the prevention and treatment of chronic lung disease of prematurity.

Chronic lung disease of prematurity or bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Nutrition may affect incidence and severity of BPD. In this context, the Section on Nutrition, Gastroenterology and Metabolism, the Pulmonary Section of the European Society for Paediatric Research (ESPR) and SPR have joined forces to review the current knowledge on nutritional issues related to BPD. The aim of this narrative review is to discuss the clinical implications for nutritional practice. Nutrient deficiencies may influence pathogenesis of BPD. Adequate nutrition and growth can play a crucial role in the prevention of and recovery from BPD. Optimal nutrition strategy is an important principle, especially in the early postnatal period. As optimal energy intake in infants at risk of BPD or with evolving BPD is not yet defined, further research with well-designed studies on nutritional strategies for preterm infants with BPD is urgently needed. IMPACT: Based on current evidence it seems reasonable to recommend that BPD diagnosed infants should receive an energy supply ranging from 120 to 150 Kcal/kg/d. Exclusive MOM feed with adequate fortification should be encouraged as this is associated with a significant reduction in the risk of BPD. Suboptimal nutritional delivery is often seen in preterm infants with BPD compared to controls.

Postnatal catch-up growth in term newborns with altered fetal weight patterns. The GROWIN study.

BACKGROUND: Small for gestational age (SGA) perform a postnatal catch-up growth to recover their genetic trajectory. We studied the postnatal catch-up growth pattern of fetuses born with an appropriate-for-gestational-age (AGA) weight but with fetal growth deceleration (FGD) to explore whether they catch up. METHODS: Nine hundred and sixty-six newborns at Villalba University General Hospital (HUGV), were followed from 34 to 37 weeks to birth. Z-scores, adjusted for sex and age, of weight, length, and BMI at 3, 6, 9, and 12 months were calculated. We define catch-up as an increase in z-score greater than 0.67 SD in the growth curves. RESULTS: AGA FGD had lower mean weight and length than AGA non-FGD at all time points; BMI was lower until 3 months. AGA FGD had a lower weight, length, and BMI z-score (until 9, 6 months, and at birth, respectively) than AGA non-FGD. AGA FGD newborns had a significantly increased likelihood of weight catch-up at 3 months (OR 1.79; 95% CI: 1.16, 2.78; p = 0.009) and BMI in all investigated periods (OR 1.90; 95% CI 1.30, 2.78; p < 0.001 at 3 months), compared to AGA non-FGD newborns. CONCLUSIONS: AGA FGD newborns perform catch-up growth, especially in weight and BMI, in the first year of life, compared to AGA non-FGD. IMPACT: Appropriate-for-gestational-age (AGA) newborns with fetal growth deceleration (FGD), between the third trimester of pregnancy and delivery, present a lower weight and height, during the first year of life, compared to AGA non-FGD. Appropriate-for-gestational-age (AGA) newborns with fetal growth deceleration (FGD), between the third trimester of pregnancy and delivery, present a higher likelihood of weight catch-up in the first 3 months of life and of BMI in the first year compared to AGA non-FGD. AGA FGD experienced early weight and BMI catch-up, especially in the first 3 months of life, like SGA. This finding should be considered in the future follow-up.

Nutrition and Intestinal Rehabilitation of Children With Short Bowel Syndrome: A Position Paper of the ESPGHAN Committee on Nutrition. Part 2: Long-Term Follow-Up on Home Parenteral Nutrition.

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The preferred treatment for IF is parenteral nutrition which may be required until adulthood. The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their expertise. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. This second part of the position paper is dedicated to the long-term management of children with SBS-IF. The paper mainly focuses on how to achieve intestinal rehabilitation, treatment of complications, and on possible surgical and medical management to increase intestinal absorption.

Nutrition and Intestinal Rehabilitation of Children With Short Bowel Syndrome: A Position Paper of the ESPGHAN Committee on Nutrition. Part 1: From Intestinal Resection to Home Discharge.

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The mainstay of treatment for IF is parenteral nutrition (PN). The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their experience. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. The first part of this position paper focuses on the physiological mechanism of intestinal adaptation after surgical resection. It subsequently provides some clinical practice recommendations for the primary management of children with SBS from surgical resection until discharged home on PN.

Neuropathological Findings in Short-Chain enoyl-CoA Hydratase 1 Deficiency (ECHS1D): Case Report and Differential Diagnosis.

Short-chain enoyl-CoA hydratase 1 (ECHS1) is an enzyme that participates in the metabolism of valine, transforming methacrylyl-CoA in ß-hydroxy-isobutyryl-CoA. There is an accumulation of intermediate acids and ammonium as a consequence of its deficit. This background generates a harmful environment for the brain causing neuronal death and severe brain lesions. We present a case of a 39 weeks newborn that died at 31 hours old. We found vacuolization in basal areas, brain stem, cerebellum and spinal cord white matter (spongiform myelinopathy). These vacuoles were periodic acid-Schiff stain negative, there were neither acompanion gliosis nor macrophagic reaction. These findings were suggestive of metabolism acid disorders. The final diagnosis was confirmed by genetic study by massive parallel sequencing, showing 2 previously described pathogenic variants (c.160C > T and c.394G > A) of short-chain enoyl-CoA hydratase 1 gene. To our knowledge, this is the first case reporting the histological changes in short-chain enoyl-CoA hydratase 1 deficiency. Histological study provides useful information to orientate the diagnostic and clarify the clinical manifestations, especially in hospitals where urine or blood samples are not taking routinely or where genetic studies may not be performed.Synopsis: The main neuropathological findings in Short-chain enoyl-CoA hydratase 1 deficiency are the presence of whitte matter vacuoles in basal areas, brain stem and spinal cord.

Research priorities in pediatric parenteral nutrition: a consensus and perspective from ESPGHAN/ESPEN/ESPR/CSPEN.

Parenteral nutrition is used to treat children that cannot be fully fed by the enteral route. While the revised ESPGHAN/ESPEN/ESPR/CSPEN pediatric parenteral nutrition guidelines provide clear guidance on the use of parenteral nutrition in neonates, infants, and children based on current available evidence, they have helped to crystallize areas where research is lacking or more studies are needed in order to refine recommendations. This paper collates and discusses the research gaps identified by the authors of each section of the guidelines and considers each nutrient or group of nutrients in turn, together with aspects around delivery and organization. The 99 research priorities identified were then ranked in order of importance by clinicians and researchers working in the field using a survey methodology. The highest ranked priority was the need to understand the relationship between total energy intake, rapid catch-up growth, later metabolic function, and neurocognitive outcomes. Research into the optimal intakes of macronutrients needed in order to achieve optimal outcomes also featured prominently. Identifying research priorities in PN should enable research to be focussed on addressing key issues. Multicentre trials, better definition of exposure and outcome variables, and long-term metabolic and developmental follow-up will be key to achieving this. IMPACT: The recent ESPGHAN/ESPEN/ESPR/CSPEN guidelines for pediatric parenteral nutrition provided updated guidance for providing parenteral nutrition to infants and children, including recommendations for practice. However, in several areas there was a lack of evidence to guide practice, or research questions that remained unanswered. This paper summarizes the key priorities for research in pediatric parenteral nutrition, and ranks them in order of importance according to expert opinion.

Gut microbes and health. / Microbiota intestinal y salud.

The human body is populated by myriads of microorganisms throughout its surface and in the cavities connected to the outside. The microbial colonisers of the intestine (microbiota) are a functional and non-expendable part of the human organism: they provide genes (microbiome) and additional functions to the resources of our species and participate in multiple physiological processes (somatic development, nutrition, immunity, etc.). Some chronic non-communicable diseases of developed society (atopias, metabolic syndrome, inflammatory diseases, cancer and some behaviour disorders) are associated with dysbiosis: loss of species richness in the intestinal microbiota and deviation from the ancestral microbial environment. Changes in the vertical transmission of the microbiome, the use of antiseptics and antibiotics, and dietary habits in industrialised society appear to be at the origin of dysbiosis. Generating and maintaining diversity in the microbiota is a new clinical target for health promotion and disease prevention.

Cohort study showed that growth rate increment has not been enough to prevent growth retardation of preterm infants and raised concerns about unbalanced growth.

AIM: We describe the postnatal weight gain, linear and head growth trends of surviving preterm infants from 2005 to 2017. METHODS: Multicentre cohort study, including surviving preterm infants <32 weeks (n = 21 084), from the Spanish Neonatal Network database, without major congenital malformations who were less than 50 weeks postmenstrual age at discharge. Outcomes were weight gain (g/kg/day), linear and head growth (cm/week) and changes in weight, length and head circumference z-scores from birth to discharge. The study period was divided into 2005-8, 2009-11, 2012-14 and 2015-17. RESULTS: Weight gain, linear growth and head growth were slightly higher in 2015-2017 than in 2005-2008: 12.2 ± 2.6 to 13.1 ± 2.5 g/kg/day, 0.98 ± 0.6 to 1.03 ± 0.6 cm/week and 0.76 ± 0.2 to 0.77 ± 0.3 cm/week, respectively. It was associated with a decreased fall in weigh, length and head circumference z-scores from birth to discharge (-1.32 ± 0.9 to -1.01 ± 0.84, -1.38 ± 1.2 to -1.18 ± 1.2 and -0.41 ± 1.2 to -0.33 ± 1.3, respectively). CONCLUSION: Postnatal growth restriction remained a common complication of prematurity despite some increment over the last years. Growth disproportionality seemed to be worsening as weight gain was increased more than linear growth.

Effects of Arachidonic and Docosohexahenoic Acid Supplementation during Gestation in Rats. Implication of Placental Oxidative Stress.

Arachidonic and docosahexaenoic acids (ARA and DHA) are important during pregnancy. However, the effects of dietary supplementation on fetal growth and oxidative stress are inconclusive. We aimed to assess the effect of high ARA and DHA diet during rat gestation on: (1) ARA and DHA availability in plasma and placenta, (2) fetal growth, and (3) placental oxidative stress, analyzing the influence of sex. Experimental diet (ED) was prepared by substituting soybean oil in the control diet (CD) by a fungi/algae-based oil containing ARA and DHA (2:1). Rats were fed with CD or ED during gestation; plasma, placenta, and fetuses were obtained at gestational day 20. DHA, ARA, and their precursors were analyzed in maternal plasma and placenta by gas chromatography/mass spectrophotometry. Fetuses and placentas were weighed, the proportion of fetuses with intrauterine growth restriction (IUGR) determined, and placental lipid and protein oxidation analyzed. ED fetuses exhibited lower body weight compared to CD, being >40% IUGR; fetal weight negatively correlated with maternal plasma ARA, but not DHA. Only ED female placenta exhibited higher lipid and protein oxidation compared to its CD counterparts; lipid peroxidation is negatively associated with fetal weight. In conclusion, high ARA during gestation associates with IUGR, through placental oxidative stress, with females being more susceptible.

The impact of intrauterine and extrauterine weight gain in premature infants on later body composition.

BackgroundThe impact of intrauterine and extrauterine growth on later insulin resistance and fat mass (FM) in very low birth weight (VLBW) infants is not well established. The aim of our study was to evaluate the effects of intrauterine and early/late extrauterine growth on later insulin resistance and body composition in VLBW infants from 6 months' corrected age (CA) to 36 months.MethodsProspective measurements of body composition by dual-energy X-ray absorptiometry and insulin resistance by homeostasis model assessment insulin resistance (HOMA-IR) along with other fasting plasma biochemistries were made in 95 VLBW infants at 6, 12, 18, and 24 months' CA and 36 months' postnatal age. Mixed-effect models were used to evaluate the effects of age, sex, maturation status, and Δweight SD score on percentage FM (PFM), FM index (FMI), fat-free mass index (FFMI), and HOMA-IR.ResultsPFM and FMI were negatively associated with a decrease in weight-SD scores from birth to 36 weeks' postmenstrual age (PMA; P=0.001) and from 36 weeks' PMA to 6 months' CA (P=0.003). PFM and FMI were higher in AGA than in small for gestational age (SGA) infants. HOMA-IR was not associated with the Δweight-SD scores in either period.ConclusionsCatch-down growth in terms of weight is associated with persistently lower adiposity but not insulin resistance up to 36 months of age.

Safe and efficient practice of parenteral nutrition in neonates and children aged 0-18 years - The role of licensed multi-chamber bags.

Parenteral nutrition (PN) is recognized as a complex high-risk therapy. Its practice is highly variable and frequently suboptimal in pediatric patients. Optimizing care requires evidence, consensus-based guidelines, audits of practice, and standardized strategies. Several pediatric scientific organizations, expert panels, and authorities have recently recommended that standardized PN should generally be used over individualized PN in the majority of pediatric patients including very low birth weight premature infants. In addition, PN admixtures produced and validated by a suitably qualified institution are recommended over locally produced PN. Licensed multi chamber bags are standardized PN bags that comply with Good Manufacturing Practice and high-quality standards for the finished product in the frame of their full manufacturing license. The purpose of this article is to review the practical aspects of PN and the evidence for using such multi-chamber bags in pediatric patients. It highlights the safety characteristics and the limitations of the different PN practices and provides some guidance for ensuring safe and efficient therapy in pediatric patients.

Dietitian-nutritionist incorporation in a university hospital: position statement of the Commission on Nutrition, Hospital Universitario La Paz.

Introduction: The present document has the objective of justifying the incorporation of a dietician/nutritionist to the multidisciplinary teams of specialized care that provide education, food anamnesis, nutritional recommendations, treatment and follow up of those patients in risk of malnutrition in Madrid. The appropriate nutritional status of hospitalized patients bears a close relationship with the existence of dieticians at hospitals. Dieticians use nutrition therapy as a cost-effective means to achieve significant health benefits by preventing or altering the course of diabetes, obesity, hypertension, lipid metabolism disorders, heart failure, osteoporosis, celiac disease, and chronic kidney disease, among other diseases.

Introducción: El presente documento tiene como objetivo plantear y justificar la incorporación del dietista-nutricionista en los equipos multidisciplinares de atención integrada en la educación, el tratamiento y el seguimiento de aquellos pacientes con patologías que cursen con alteraciones del estado nutricional, tanto en su defecto como en su exceso, en el área sanitaria de la Comunidad Autónoma de Madrid. El estado nutricional de los pacientes hospitalizados se beneficiará de la incorporación del dietista-nutricionista al equipo multidisciplinar que, actualmente, se ocupa de la atención de estos. El manejo de la terapia nutricional por dietistas-nutricionistas ha demostrado ser costo-efectiva, habida cuenta de la repercusión sanitaria que tiene el estado nutricional en la evolución clínica y prevención de enfermedades como la diabetes, los trastornos de la conducta alimentaria, la obesidad, el cáncer, la insuficiencia cardiaca, la osteoporosis, la enfermedad celiaca y la enfermedad renal crónica, entre otras.

Exclusive Fish Oil Lipid Emulsion Rescue Strategy Improves Cholestasis in Neonates on Partially Fish Oil-Based Lipid Emulsion: A Pilot Study.

Resolution of parenteral nutrition-associated liver disease has been identified in infants receiving SMOFlipid™ or a 100% fish oil lipid emulsion (FOLE). However, the effect of FOLE is unknown when the previous emulsion received is a mixed lipid emulsion containing fish oil. This observational pilot study reports data regarding the use of Omegaven™ after the diagnosis of cholestasis while receiving SMOFlipid™. We conducted a retrospective review of medical charts of neonates in which a partially fish oil-based lipid emulsion was replaced by a fish oil lipid emulsion at 1 g/kg/day due to cholestasis. Thirty-eight infants (92.1% preterm, being 44.7% born below 28 weeks' gestation), received FOLE. Birth weight was 1390 (743.0; 2298) grams. The age that cholestasis diagnosed was 15.0 (10.0; 24.8) days. The fish oil emulsion was administered for 38.5 (11.2; 51.8) days. In 73.7% (28/38) of the neonates, the cholestasis was resolved. In 34.2% (13/38), resolution happened before FOLE discontinuation. In addition, in the rest of the neonates (15) in whom cholestasis resolved, resolution occurred after FOLE discontinuation. Nine of the neonates died. In conclusion, the use of a 100% fish oil-based emulsion in neonates afflicted with cholestasis developed while on a partially fish oil-based emulsion is associated with a bilirubin decrease.

Effects of infant feeding with goat milk formula or cow milk formula on atopic dermatitis: protocol of the randomised controlled Goat Infant Formula Feeding and Eczema (GIraFFE) trial.

INTRODUCTION: Atopic dermatitis (AD) is a chronic, inflammatory skin condition significantly affecting quality of life. A small randomised trial showed an approximately one-third lower incidence of AD in goat milk formula-fed compared with cow milk formula-fed infants. However, due to limited statistical power, AD incidence difference was not found to be significant. This study aims to explore a potential risk reduction of AD by feeding a formula based on whole goat milk (as a source of protein and fat) compared with a formula based on cow milk proteins and vegetable oils. METHODS AND ANALYSIS: This two-arm (1:1 allocation), parallel, randomised, double-blind, controlled nutritional trial shall enrol up to 2296 healthy term-born infants until 3 months of age, if parents choose to start formula feeding. Ten study centres in Spain and Poland are participating. Randomised infants receive investigational infant and follow-on formulas either based on whole goat milk or on cow milk until the age of 12 months. The goat milk formula has a whey:casein ratio of 20:80 and about 50% of the lipids are milk fat from whole goat milk, whereas the cow milk formula, used as control, has a whey:casein ratio of 60:40 and 100% of the lipids are from vegetable oils. The energy and nutrient levels in both goat and cow milk formulas are the same. The primary endpoint is the cumulative incidence of AD until the age of 12 months diagnosed by study personnel based on the UK Working Party Diagnostic Criteria. The secondary endpoints include reported AD diagnosis, measures of AD, blood and stool markers, child growth, sleep, nutrition and quality of life. Participating children are followed until the age of 5 years. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethical committees of all participating institutions. TRIAL REGISTRATION NUMBER: NCT04599946.

Influence of Full Oral Feeding Acquisition on Growth of Premature Infants.

Objective: The main objective was to describe the impact of full oral feeding achievement in very low birth weight infants on weight, length, and head circumference, measured as the change in z-score from 32 weeks to discharge, the time at which full oral feeding occurs. Methods: This was a longitudinal retrospective observational study on infants younger than 30 weeks of gestational age, admitted to the Neonatology Unit of La Paz University Hospital, Madrid (Spain), from January 1, 2019 to December 31, 2019. The infant's anthropometric characteristics (weight, height, and head circumference) were compared at birth, at 32, 34, and 36 weeks of gestational age, at the time of full oral feeding, and at discharge from the unit. Results: A total of 66 infants were included, gestational age at birth range from 24 to 30. Full oral intake occurred at 37.1 ± 2.1 weeks postmenstrual age (PMA). We found an inverse correlation between gestational age at birth and birth weight with PMA at which full oral feeding (FOF) is achieved. PMA at discharge was 38.6 ± 2.5 weeks. Age of full oral intake and discharge occurred later in infants who had patent ductus arteriosus, retinopathy of prematurity, and sepsis or received a blood transfusion. A positive correlation was found between days of oxygen and both parameters. However, we found no relationship between necrotizing enterocolitis or intraventricular hemorrhage with age at full oral feeding or age at discharge. Conclusions: The transition from gastric tube to oral intake did not affect growth. We found a close relationship between preterm infants birth, earlier younger than 30 weeks of gestational age, and low birth weight, with a delay in full oral feeding achievement that correlated with age at discharge.

Efficacy and Safety of Enteral Recombinant Human Insulin in Preterm Infants: A Randomized Clinical Trial.

IMPORTANCE: Feeding intolerance is a common condition among preterm infants owing to immaturity of the gastrointestinal tract. Enteral insulin appears to promote intestinal maturation. The insulin concentration in human milk declines rapidly post partum and insulin is absent in formula; therefore, recombinant human (rh) insulin for enteral administration as a supplement to human milk and formula may reduce feeding intolerance in preterm infants. OBJECTIVE: To assess the efficacy and safety of 2 different dosages of rh insulin as a supplement to both human milk and preterm formula. DESIGN, SETTING, AND PARTICIPANTS: The FIT-04 multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 46 neonatal intensive care units throughout Europe, Israel, and the US. Preterm infants with a gestational age (GA) of 26 to 32 weeks and a birth weight of 500 g or more were enrolled between October 9, 2016, and April 25, 2018. Data were analyzed in January 2020. INTERVENTIONS: Preterm infants were randomly assigned to receive low-dose rh insulin (400-µIU/mL milk), high-dose rh insulin (2000-µIU/mL milk), or placebo for 28 days. MAIN OUTCOMES AND MEASURES: The primary outcome was time to achieve full enteral feeding (FEF) defined as an enteral intake of 150 mL/kg per day or more for 3 consecutive days. RESULTS: The final intention-to-treat analysis included 303 preterm infants (low-dose group: median [IQR] GA, 29.1 [28.1-30.4] weeks; 65 boys [59%]; median [IQR] birth weight, 1200 [976-1425] g; high-dose group: median [IQR] GA, 29.0 [27.7-30.5] weeks; 52 boys [55%]; median [IQR] birth weight, 1250 [1020-1445] g; placebo group: median [IQR] GA, 28.8 [27.6-30.4] weeks; 54 boys [55%]; median [IQR] birth weight, 1208 [1021-1430] g). The data safety monitoring board advised to discontinue the study early based on interim futility analysis (including the first 225 randomized infants), as the conditional power did not reach the prespecified threshold of 35% for both rh-insulin dosages. The study continued while the data safety monitoring board analyzed and discussed the data. In the final intention-to-treat analysis, the median (IQR) time to achieve FEF was significantly reduced in 94 infants receiving low-dose rh insulin (10.0 [7.0-21.8] days; P = .03) and in 82 infants receiving high-dose rh insulin (10.0 [6.0-15.0] days; P = .001) compared with 85 infants receiving placebo (14.0 [8.0-28.0] days). Compared with placebo, the difference in median (95% CI) time to FEF was 4.0 (1.0-8.0) days for the low-dose group and 4.0 (1.0-7.0) days for the high-dose group. Weight gain rates did not differ significantly between groups. Necrotizing enterocolitis (Bell stage 2 or 3) occurred in 7 of 108 infants (6%) in the low-dose group, 4 of 88 infants (5%) in the high-dose group, and 10 of 97 infants (10%) in the placebo group. None of the infants developed serum insulin antibodies. CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial revealed that enteral administration of 2 different rh-insulin dosages was safe and compared with placebo, significantly reduced time to FEF in preterm infants with a GA of 26 to 32 weeks. These findings support the use of rh insulin as a supplement to human milk and preterm formula. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02510560.

Norovirus-associated White Matter Injury in a Term Newborn With Seizures.

Neonatal seizures with white matter injury have been associated with rotavirus, enterovirus and parechovirus. Neurological symptoms caused by norovirus have been occasionally reported in older children. We describe a case of a neonate with seizures and white matter lesions, with detection of human norovirus in stool samples from the patient and her mother.

Survival and Survival without Major Morbidity Seem to Be Consistently Better throughout Gestational Age in 24- to 30-Week Gestational Age Very-Low-Birth-Weight Female Infants Compared to Males.

INTRODUCTION: Several studies showed advantages in outcomes for very-low-birth-weight (VLBW) female infants. It has been suggested that recent advances in perinatal care might have benefited boys relatively more than girls, making differences disappear. OBJECTIVES: The aims of the study were (1) to determine if sex differences in survival and survival without morbidity in VLBW infants are still present in the context of more advanced perinatal care and (2) to know whether these differences are consistent throughout gestational age (GA). METHODS: Retrospective cohort study in seven countries participating in the Spanish SEN1500 and the South American NEOCOSUR neonatal networks. We included VLBW infants 24-30 weeks' GA, born alive without major congenital anomalies (2013-2016). Major morbidity, survival, and survival without morbidity were compared between male and female infants overall and stratified by GA. RESULTS: 10,565 patients were included: 5,620 (53.2%) males and 4,945 (46.8%) females. Female infants exhibited a lower incidence rate ratio (95% CI) of respiratory distress syndrome: 0.91 (0.88, 0.94), necrotizing enterocolitis: 0.83 (0.74, 0.93), major brain damage: 0.79 (0.72, 0.86), moderate-severe bronchopulmonary dysplasia (BPD): 0.77 (0.72, 0.83), higher survival: 1.03 (1.01, 1.05), survival without BPD: 1.11 (1.07, 1.16), survival without major brain damage: 1.05 (1.02, 1.08), and survival without major morbidity: 1.14 (1.07, 1.21). Survival and survival without morbidity were almost consistently favourable to females throughout GA. CONCLUSIONS: Our findings suggest that perinatal results continue to be favourable for VLBW female infants in the context of current perinatology, and that they are almost consistent throughout GA.