Nutrition and the gut-brain axis in neonatal brain injury and development.

Early nutritional exposures, including during embryogenesis and the immediate postnatal period, affect offspring outcomes in both the short- and long-term. Alterations of these modifiable exposures shape the developing gut microbiome, intestinal development, and even neurodevelopmental outcomes. A gut-brain axis exists, and it is intricately connected to early life feeding and nutritional exposures. Here, we seek to discuss the (1) origins of the gut-brain access and relationship with neurodevelopment, (2) components of human milk (HM) beyond nutrition and their role in the developing newborn, and (3) clinical application of nutritional practices, including fluid management and feeding on the development of the gut-brain axis, and long-term neurodevelopmental outcomes. We conclude with a discussion on future directions and unanswered questions that are critical to provide further understanding and insight into how clinicians and healthcare providers can optimize early nutritional practices to ensure children not only survive, but thrive, free of neurodevelopmental impairment.

Contemporary definitions of infant growth failure and neurodevelopmental and behavioral outcomes in extremely premature infants at two years of age.

BACKGROUND: Associations of 2-year neurodevelopmental and behavioral outcomes with growth trajectories of preterm infants are unknown. METHODS: This secondary analysis of a preterm cohort examined in-hospital and discharge to 2-year changes in anthropometric z-scores. Two-year follow-up included Bayley Scales of Infant Development (BSID-III) and Child Behavior Checklist. RESULTS: Among 590 infants, adjusted in-hospital growth was not associated with any BSID-III subscale. Occipitofrontal circumference (OFC) growth failure (GF) in-hospital was associated with increased adjusted odds of attention problems (aOR 1.65 [1.03, 2.65]), aggressive behavior (aOR 2.34 [1.12, 4.89]), and attention-deficit-hyperactivity symptoms (aOR 1.86 [1.05, 3.30]). Infants with OFC GF at 2 years had lower adjusted BSID-III language scores (-4.0 [-8.0, -0.1]), increased odds of attention problems (aOR 2.29 [1.11, 4.74]), aggressive behavior (aOR 3.09 [1.00, 9.56]), and externalizing problems (aOR 3.01 [1.07, 8.45]) compared to normal OFC growth cohort. CONCLUSION: Infants with OFC GF are at risk for neurodevelopmental and behavioral impairment. CLINICAL TRIAL REGISTRATION: This study is a secondary analysis of pre-existing data from the PENUT Trial Registration: NCT01378273.

Time to regain birthweight and association with neurodevelopmental outcomes among extremely preterm newborns.

OBJECTIVE: Determine association between time to regain birthweight and 2-year neurodevelopment among extremely preterm (EP) newborns. STUDY DESIGN: Secondary analysis of the Preterm Erythropoietin Neuroprotection Trial evaluating time to regain birthweight, time from birth to weight nadir, time from nadir to regain birthweight, and cumulative weight loss with 2-year corrected Bayley Scales of Infant and Toddler Development 3rd edition. RESULTS: Among n = 654 EP neonates, those with shorter nadir-to-regain had lower cognitive scores (≤1 day versus ≥8 days: -5.0 points, [CI -9.5, -0.6]) and lower motor scores (≤1 day versus ≥8 days: -4.6 points [CI -9.2, -0.03]) in adjusted stepwise forward regression modeling. Increasingly cumulative weight loss was associated with lower cognitive scores (≤-50 percent-days: -5.6, [CI -9.4, -1.8]), motor scores (≤-50 percent-days: -4.2, [CI -8.2, -0.2]); and language scores (≤-50 percent-days: -6.0, [CI -10.1, -1.9]). CONCLUSION: Faster nadir-to-regain and excessive cumulative weight loss are associated with adverse 2-year neurodevelopmental outcomes. TRIAL REGISTRATION: PENUT Trial Registration: NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273 . CLINICAL TRIAL REGISTRATION: This study is a post-hoc secondary analysis of pre-existing data from the PENUT Trial (NCT #01378273).

Maternal Nutritional Status and the Microbiome across the Pregnancy and the Post-Partum Period.

Appropriate nutrition during pregnancy and the post-partum period is vital for both the mothers and their offspring. Both under- and over-nourished status may have important microbial implications on the maternal and infant gut microbiomes. Alterations in the microbiome can have implications for a person's risk of obesity and metabolic diseases. In this review, we examine alterations in the maternal gut, vaginal, placental, and milk microbiomes in the context of pre-pregnancy BMI, gestational weight gain, body composition, gestational diabetes, and maternal diet. We also investigate how the infant gut microbiome may be altered by these different parameters. Many of the microbial changes seen in under- and over-nourished states in birthing parents may result in long-term implications for the health of offspring. Differences in diet appear to be a major driver of the maternal and subsequently milk and offspring microbiomes. Further prospective longitudinal cohort studies are needed to examine nutrition and the microbiome to better understand its implications. Additionally, trials involving dietary interventions in child-bearing age adults should be explored to improve the mother and child's risks for metabolic diseases.

Gut Microbes and Circulating Cytokines in Preterm Infants with Growth Failure.

BACKGROUND: Growth failure (GF) is a multifactorial problem in preterm infants. The intestinal microbiome and inflammation may contribute to GF. OBJECTIVES: This study's objective was to compare the gut microbiome and plasma cytokines in preterm infants with and without GF. METHODS: This was a prospective cohort study of infants with birth weights of <1750 g. Infants with a weight or length z-score change from birth to discharge or death that was less than or equal to -0.8 (GF group) were compared with infants without GF [control (CON) group]. The primary outcome was the gut microbiome (at weeks 1-4 of age), assessed by 16S rRNA gene sequencing using Deseq2. Secondary outcomes included inferred metagenomic function and plasma cytokines. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States determined metagenomic function, which was compared using ANOVA. Cytokines were measured by 2-multiplexed immunometric assays and compared using Wilcoxon tests and linear mixed models. RESULTS: GF (n = 14) and CON group (n = 13) had similar median (IQR) birth weight (1380 [780-1578] g vs. 1275 [1013-1580] g) and gestational age (29 [25-31] weeks vs. 30 [29-32] weeks). Compared with the CON group, the GF group had a greater abundance of Escherichia/Shigella in weeks 2 and 3, Staphylococcus in week 4, and Veillonella in weeks 3 and 4 (P-adjusted < 0.001 for all). Plasma cytokine concentrations did not differ significantly between the cohorts. When all time points are combined, fewer microbes were involved in TCA cycle activity in the GF group compared with the CON group (P = 0.023). CONCLUSIONS: In this study, when compared with CON infants, GF infants had a distinct microbial signature with increased Escherichia/Shigella and Firmicutes and fewer microbes associated with energy production at later weeks of hospitalization. These findings may suggest a mechanism for aberrant growth.

Pregnancies complicated by gestational diabetes and fetal growth restriction: an analysis of maternal and fetal body composition using magnetic resonance imaging.

INTRODUCTION: Maternal body composition may influence fetal body composition. OBJECTIVE: The objective of this pilot study was to investigate the relationship between maternal and fetal body composition. METHODS: Three pregnant women cohorts were studied: healthy, gestational diabetes (GDM), and fetal growth restriction (FGR). Maternal body composition (visceral adipose tissue volume (VAT), subcutaneous adipose tissue volume (SAT), pancreatic and hepatic proton-density fat fraction (PDFF) and fetal body composition (abdominal SAT and hepatic PDFF) were measured using MRI between 30 to 36 weeks gestation. RESULTS: Compared to healthy and FGR fetuses, GDM fetuses had greater hepatic PDFF (5.2 [4.2, 5.5]% vs. 3.2 [3, 3.3]% vs. 1.9 [1.4, 3.7]%, p = 0.004). Fetal hepatic PDFF was associated with maternal SAT (r = 0.47, p = 0.02), VAT (r = 0.62, p = 0.002), and pancreatic PDFF (r = 0.54, p = 0.008). When controlling for maternal SAT, GDM increased fetal hepatic PDFF by 0.9 ([0.51, 1.3], p = 0.001). CONCLUSION: In this study, maternal SAT, VAT, and GDM status were positively associated with fetal hepatic PDFF.

Video simulation to learn pediatric resuscitation skills tailored to a low resource setting: A pilot program in Iquitos, Peru.

INTRODUCTION: The Hospital Regional de Loreto in Peru partners with the University of California Los Angeles Global Health Program to enhance educational experiences for US and Peruvian trainees. University of California Los Angeles Pediatric faculty led intermittent in-person code simulation sessions for Peruvian residents, and there is a need for regular education on this topic. METHODS: University of California Los Angeles residents created a video simulation of a patient in respiratory distress. The video was presented to Hospital Regional de Loreto trainees in pediatrics. Stakeholder interviews and reuse of the video after initial presentation assessed acceptability of this mode of education by the site. Pre- and post-surveys using numerical rating scales evaluated the educational utility of this specific simulation video. Paired t-tests compared the pre- and post-surveys in the effectiveness of increasing the trainees' comfort of specific resuscitation skills. RESULTS: Stakeholder interviews revealed the video simulation was integrated into formal intern orientation trainings as well as used for resident and physician trainings multiple times in the year after the introduction. Twenty trainees completed the pre-intervention survey and 19 completed the post-intervention survey. Trainee comfort with code team leadership (2.6 ± 0.9, 3.5 ± 0.09, p = 0.03) and arrhythmia recognition/automated external defibrillator (AED) management (2.4 ± 0.9, 3.1 ± 0.9, p = 0.03) increased significantly with the video intervention. There was no significant difference in comfort with other skills. Overall, trainees rated the helpfulness of the video as an average of 4.2 (±1.1) out of 5. The most common positive feedback included the utility of reviewing medication dosing and the skill of performing chest compressions. The most common suggestions for improvement were to review more pathophysiology and simulate available resources at Hospital Regional de Loreto more realistically. CONCLUSION: E-learning is an acceptable mode of education in a resource-limited setting when tailored to the local context. This pilot project demonstrated short-term improvement in reported confidence and skills with some aspects of pediatric resuscitation.

Interval growth across gestation in pregnancies with fetal gastroschisis.

BACKGROUND: Gastroschisis is often complicated by fetal growth restriction, preterm delivery, and prolonged neonatal hospitalization. Prenatal management and delivery decisions are often based on estimated fetal weight and interval growth; however, appropriate interval growth from week to week across gestation for these fetuses is poorly understood. OBJECTIVE: This study aimed to determine the median increase in overall estimated fetal weight and individual biometric measurements across each week of gestation in pregnancies with fetal gastroschisis and to assess whether lower in utero fetal weight gain is predictive of postnatal growth or adverse neonatal outcomes. STUDY DESIGN: This was a retrospective cohort study of pregnancies with gastroschisis evaluated at 5 institutions of the University of California Fetal-Maternal Consortium from December 2014 to December 2019. The inclusion criteria were prenatally diagnosed gastroschisis with at least 1 ultrasound performed at a University of California Fetal-Maternal Consortium institution. Estimated fetal weight and individual biometric measurements were recorded for each ultrasound performed at a University of California Fetal-Maternal Consortium institution from the time of gastroschisis diagnosis to delivery. Median estimated fetal weight and biometric measurements were calculated for each gestational age in 1-week increments. Neonatal outcomes collected were birthweight, length of stay, complications of gastroschisis (bowel atresia, bowel stricture, ischemic bowel before closure, or severe pulmonary hypoplasia), and growth failure at discharge. RESULTS: We identified 95 pregnancies with fetal gastroschisis who, in aggregate, had 360 growth ultrasounds at a University of California Fetal-Maternal Consortium institution. The median interval growth was 130 g/wk. The median estimated fetal weight and abdominal circumference in fetal gastroschisis cases were approximately the tenth percentile on the Hadlock growth curve across gestation. Moreover, the median biparietal diameter, head circumference, and femur length measurements remained below the 50th percentile on the Hadlock growth curve across gestation. The median birthweight for neonates with less than the median weekly prenatal weight gain was less than for those with greater than the median weekly prenatal weight gain (2185 g vs 2780 g; P<.01). There was no difference in prenatal weight gain trajectory when comparing neonates who had or did not have bowel complications of gastroschisis. CONCLUSION: In this multicenter cohort of pregnancies with fetal gastroschisis, the median interval growth was 130 g/wk, and overall, in utero growth closely followed the tenth percentile on the Hadlock curve. Poor prenatal growth in cases of fetal gastroschisis correlates with lower neonatal weights but did not predict a more complicated course.

The Neonate with Ambiguous Genitalia.

Neonates with ambiguous genitalia have various clinical presentations, etiologies, and outcomes, ranging from benign to life-threatening. This review provides a summary of these findings. Some diagnoses may lead to delayed sex assignment. A systematic approach to the evaluation of disorders of sex development can allow for timely treatment and family counseling.

Growth Failure Prevalence in Neonates with Gastroschisis : A Statewide Cohort Study.

OBJECTIVES: To perform a multicenter study to assess growth failure in hospitalized infants with gastroschisis. STUDY DESIGN: This study included neonates with gastroschisis within sites in the University of California Fetal Consortium. The study's primary outcome was growth failure at hospital discharge, defined as a weight or length z score decrease >0.8 from birth. Regression analysis was performed to assess changes in z scores over time. RESULTS: Among 125 infants with gastroschisis, the median gestational age was 37 weeks (IQR 35-37). Length of stay was 32 days (23-60); 55% developed weight or length growth failure at discharge (28% had weight growth failure, 42% had length growth failure, and 15% had both weight and length growth failure). Weight and length z scores at 14 days, 30 days, and discharge were less than birth (P < .01 for all). Weight and length z scores declined from birth to 30 days (-0.10 and -0.11 z score units/week, respectively, P < .001). Length growth failure at discharge was associated with weight and length z score changes over time (P < .05 for both). Lower gestational age was associated with weight growth failure (OR 0.70 for each gestational age week, 95% CI 0.55-0.89, P = .004). CONCLUSIONS: Growth failure, in particular linear growth failure, is common in infants with gastroschisis. These data suggest the need to improve nutritional management in these infants.

Growth from Birth to 30 months for Infants Born with Congenital Gastrointestinal Anomalies and Disorders.

OBJECTIVE: This study aimed to investigate growth among neonates with gastrointestinal disorders. STUDY DESIGN: Inclusion criteria included neonates with gastroschisis, omphalocele, intestinal atresia, tracheoesophageal fistula, Hirschsprung's disease, malabsorption disorders, congenital diaphragmatic hernia, and imperforate anus born between 2010 and 2018. Anthropometrics were collected for the first 30 months, and a subgroup analysis was performed for gastroschisis infants. RESULTS: In 61 subjects, 13% developed severe growth failure within the first month. One-, four-, and nine-month weight and length z-scores were less than birth weight in all infants (p < 0.05). In infants with gastroschisis, a similar pattern was observed for weight z-scores only (p < 0.05). From birth to 15 months, head circumference z-score increased over time in all infants (p = 0.001), while in gastroschisis infants, weight, length, and head circumference z-scores increased over time (p < 0.05). CONCLUSION: In a cohort of infants with gastrointestinal disorders, growth failure was followed by catch-up growth.

Essential Fatty Acid Deficiency in an Extremely Premature Infant With Intestinal Failure.

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Maternal-Neonatal Dyad Outcomes of Maternal COVID-19 Requiring Extracorporeal Membrane Support: A Case Series.

OBJECTIVE: This study aimed to describe two cases of acute respiratory distress syndrome (ARDS) secondary to novel coronavirus disease 2019 (COVID-19) in pregnant women requiring extracorporeal membrane oxygenation (ECMO), and resulting in premature delivery. STUDY DESIGN: The clinical course of two women hospitalized with ARDS due to COVID-19 care in our intensive care (ICU) is summarized; both participants provided consent to be included in this case series. RESULTS: Both women recovered with no clinical sequelae. Neonatal outcomes were within the realm of expected for prematurity with the exception of coagulopathy. There was no vertical transmission to the neonates. CONCLUSION: This case series highlights that ECMO is a feasible treatment in the pregnant woman with severe COVID-19 and that delivery can be performed safely on ECMO with no additional risk to the fetus. While ECMO carries its natural risks, it should be considered a viable option during pregnancy and the postpartum period. KEY POINTS: · COVID-19 may present with a more severe course in pregnancy.. · ECMO may be used in pregnant woman with severe COVID-19.. · Delivery can be performed on ECMO without added fetal risk..

Burkitt-like lymphoma in a pediatric patient with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant condition that predisposes to multiple malignancies, most commonly colorectal carcinoma, but has rarely been associated with lymphoma. We discuss one patient found to have Burkitt-like Lymphoma (BLL) with 11q aberration in the setting of previously undiagnosed FAP. We review the literature of FAP and associated malignancies and the provisional WHO classification of Burkitt-like lymphoma with 11q aberration. Both FAP and Burkitt-like lymphoma with 11q aberration involve perturbation of the MYC network and this may provide insight into a connection between these two diagnoses. However, further study is needed to elucidate if there is an increased risk of BLL and other subtypes of lymphoma among patients with FAP in order to provide optimal counseling and surveillance for patients with FAP.