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Purpose of review Fetal intervention is a dynamic field with wide-reaching implications on neonatal ICU admissions and the care of neonates with congenital anomalies. The aim of this review is to summarize recent advancements in fetal surgery and provide a broad understanding of how these topics interrelate. Recent findings Advancements in prenatal imaging and diagnosis have dramatically expanded the indications for fetal intervention. Most recently, there has been a large focus on evaluating minimally invasive strategies of fetal intervention, notably fetoscopic surgery, and the use of stem cells for fetal treatment of myelomeningocele. With the advances in fetal intervention, neonatal care has adapted to the needs of these various patients to help improve the outcomes of this unique population. Summary Fetal intevention relies on a multidisciplinary team from prenatal imaging and maternal fetal medicine to fetal surgery and postnatal subspecialty care, particuarly neonatology. Fetal intervention uniquely involves two patients, both mother and fetus, and therefore, has unique risks and considerations, particularly in the advancement of the field. As the number of conditions suited to fetal intervention grows, awareness and advancement of the postnatal intensive care necessary for these patients are essential.

INTRODUCTION AND OBJECTIVE:With the advent of novel fetal interventions, including amnioinfusion, there has been increased interest in fetal intervention for previously “lethal” anomalies such as b...

Importance: The novel coronavirus 2019 (SARS-CoV-2) has been well described in adults. Further, the impact on older children and during the perinatal time is becoming better studied. As community spread increases, it is important to recognize that neonates are vulnerable to community spread as well. The impact that community-acquired SARS-CoV-2 has in the neonatal time period is unclear, as this population has unique immunity considerations. Objective: To report on a case series of SARS-CoV-2 in neonates through community acquisition in the USA. Design: This is an early retrospective study of patients admitted to the Neonatal Intensive Care Unit (NICU) identified as having SAR-CoV-2 through positive real-time polymerase chain reaction assay of nasopharyngeal swabs. Findings: Three patients who required admission to the NICU between the ages of 17 and 33 days old were identified. All 3 had ill contacts in the home or had been to the pediatrician and presented with mild to moderate symptoms including fever, rhinorrhea, and hypoxia, requiring supplemental oxygen during their hospital stay. One patient was admitted with neutropenia, and the other 2 patients became neutropenic during hospitalization. None of the patients had meningitis or multiorgan failure. Conclusions and Relevance: Infants with community-acquired SARS-CoV-2 may require hospitalization due to rule-out sepsis guidelines if found to have fever and/or hypoxia. Caregivers of neonates should exercise recommended guidelines before contact with neonates to limit community spread of SARS-CoV-2 to this potentially vulnerable population, including isolation, particularly as asymptomatic cases become prevalent.

Context Boys with XXY have greater adiposity and a higher risk of cardiovascular disease. Infants with XXY have lower testosterone concentrations than typical boys, but no studies have evaluated adiposity in infants with XXY or the physiologic effects of giving testosterone replacement. Objective To determine the effect of testosterone on body composition in infants with XXY. Design Prospective, randomized trial. Setting Tertiary care pediatric referral center. Participants 20 infants 6 to 15 weeks of age with 47,XXY. Intervention Testosterone cypionate 25 mg intramuscularly monthly for three doses vs no treatment. Main Outcome Measures Difference in change in adiposity (percent fat mass z scores); other body composition measures, penile length, and safety outcomes between treated and untreated infants; and comparison with typical infants. Results The increase in percent fat mass (%FM) z scores was greater in the untreated group than in the treated group (+0.92 ± 0.62 vs −0.12 ± 0.65, P = 0.004). Increases in secondary outcomes were greater in the testosterone-treated group for total mass, fat-free mass, length z score, stretched penile length, and growth velocity (P < 0.002 for all). At 5 months of age, adiposity in untreated infants with XXY was 26.7% compared with 23.2% in healthy male infants of the same age (P = 0.0037); there was no difference in %FM between the treated XXY boys and controls. Reported side effects were minimal and self-limited; no serious adverse events occurred. Conclusions Adiposity of untreated infants was 15% greater than that of male controls by 5 months of age. Testosterone treatment for infants with XXY resulted in positive changes in body composition.

Robust evidence for specific nutrition therapy for gestational diabetes (GDM) is lacking. Preliminary data suggested our CHOICE diet, higher in complex carbohydrate (60%) and lower in fat (25%) reduced fasting glucose (FBG), free fatty acids (FFA), and newborn adiposity (NB%fat). We tested the hypothesis that 7-8 wks of CHOICE would improve insulin resistance, reduce FFA and NB%fat (2-wk PeaPod; 1° powered outcome) vs. a conventional low-carbohydrate (40%), higher fat (45%) diet (LC/CONV). After diagnosis (∼28-30 wks), 59 BMI-matched diet-controlled GDM women (mean±SD; BMI 32±5) were randomized to a eucaloric CHOICE or LC/CONV diet (7.2±1 wks; ALL MEALS PROVIDED). At baseline, a 2-hr 75g OGTT (with insulins) was performed and diet initiated. On day-4, a breakfast meal was given (30% of total calories) with fasting and hourly blood drawn x5 (gluc, insulin, FFA, triglycerides[TG]) for area-under-the curve (AUC). Measures were repeated at 36-37 wks. Of 59, 13 met exclusions (4 diet failures, 2/group). By ANCOVA (n=23/group), total and weight gain during diet were similar (CHOICE 1.9 vs. LC/CONV 1.8 kg) as was delivery wk (39.2 vs. 39.3 wks). At 37 wks, the meal gluc (p=0.001) and insulin AUCs (p=0.013) were lower for LC/CONV, though fasting gluc/insulin were similar. TG increased similarly. The FFA AUC decreased from 30-37 wks on CHOICE but rose on LC/CONV (p=0.016), and was lower for CHOICE at 37 wks (p=0.009). By the 37-wk OGTT, FBG decreased within both groups (CHOICE -7.2, LC/CONV -3.5 mg/dL, both p Disclosure T.L. Hernandez: None. S.S. Farabi: None. J. Arbet: None. N. Hirsch: None. E.Z. Dunn: None. K.P. Heiss: None. J. Martin Carli: None. N.F. Krebs: None. T.L. Powell: None. R. Reynolds: None. R.E. Van Pelt: None. J.E. Friedman: None. L.A. Barbour: None. Funding National Institutes of Health (R01DK101659, UL1TR002535); Janssen Research & Development, LLC

OBJECTIVE To model breastfed infant growth and body composition patterns over the first 4 months with multiple bioactive components of human milk (HM) and clinical factors (including maternal BMI status), which are related to growth. METHODS Longitudinal observation of infant growth and body composition from 0 to 4 months among 41 predominantly breastfed infants (25 mothers of Normal-weight and 16 mothers with overweight/obesity). Fasted morning HM samples were collected at 5 time-points. Macronutrients, leptin, adiponectin, ghrelin, insulin, cytokines and n-6:n-3 esterified fatty acid ratio were measured. Infant weight-for-length Z-score (WLZ) trajectory, fat-free mass (FFM) gain, fat mass gain and %fat gain were modelled controlling for clinical covariates. RESULTS HM insulin negatively associated with WLZ trajectory among infants of NW mothers (P = 0.028), but not associated with WLZ trajectory among infants of OW/Ob mothers. HM glucose (P

A prenatal ultrasound (US) at 21 weeks estimated gestational age (EGA) identified a left intrathoracic homogenously echogenic microcystic mass with mediastinal shift and a CPAM volume ratio (CVR) of 0.78 (Fig. 1). A fetal magnetic resonance imaging (MRI) study confirmed the US findings. MRI and US were repeated at 35 weeks EGA demonstrating a CVR of 0.36 and a spontaneous decrease in size of the previously identified mass. Moreover, an intralesional, fluid filled dilated bronchus was identified that connected to the esophagus and showed mild branching. This finding was thought to represent an esophageal bronchus. Prenatal echocardiogram demonstrated normal cardiac anatomy and function. The patient was delivered vaginally at 38 weeks EGA with no respiratory distress after delivery. The patient was discharged at this time with planned outpatient follow-up. Outpatient contrast CT at three months of age demonstrated a left BPS supplied by the celiac axis and a fluid filled branching structure within the sequestration suspicious for esophageal bronchus. At four months of age, the patient underwent a left, muscle sparing thoracotomy, where the bronchopulmonary sequestration was excised and an adjacent cyst was enucleated. Pathology demonstrated extralobar bronchopulmonary sequestration with a separate foregut malformation most consistent with bronchogenic cyst.

Fetuses with anti-SSA-mediated complete atrioventricular block (CAVB) are at high risk for perinatal death if they present at

Objectives Neonatal adiposity is associated with chronic metabolic sequelae such as diabetes and obesity. Identifying fetuses at risk for excess neonatal body fat may lead to research aimed at limiting nutritional excess in the prenatal period. We sought to determine whether fetal arm and leg soft tissue measurements at 28 weeks' gestation were predictive of neonatal percent body fat Methods In this prospective observational cohort study of singleton term pregnancies, we performed sonography at 28 and 36 weeks' gestation, including soft tissue measurements of the fetal arm and thigh (fractional limb volume and cross-sectional area). We estimated the neonatal body composition (percent body fat) using anthropometric measurements and air displacement plethysmography. We estimated Spearman correlations between sonographic findings and percent body fat and performed modeling to predict neonatal percent body fat using maternal characteristics and sonographic findings. Results Our analysis of 44 women yielded a mean maternal age of 30 years, body mass index of 26 kg/m2, and birth weight of 3382 g. Mean neonatal percent body fat was 8.1% by skin folds at birth and 12.2% by air displacement plethysmography 2 weeks after birth. Fractional thigh volume measurements at 28 weeks yielded the most accurate model for predicting neonatal percent body fat (R2 = 0.697; P = .001), outperforming models that used abdominal circumference (R2= 0.516) and estimated fetal weight (R2= 0.489). Conclusions Soft tissue measurements of the fetal thigh at 28 weeks correlated better with neonatal percent body fat than currently used sonographic measurements. After validation in a larger cohort, our models may be useful for prenatal intervention strategies aimed at the prevention of excess fetal fat accretion and, potentially, optimization of long-term metabolic health.

OBJECTIVE Diet therapy in gestational diabetes mellitus (GDM) has focused on carbohydrate restriction but is poorly substantiated. In this pilot randomized clinical trial, we challenged the conventional low-carbohydrate/higher-fat (LC/CONV) diet, hypothesizing that a higher–complex carbohydrate/lower-fat (CHOICE) diet would improve maternal insulin resistance (IR), adipose tissue (AT) lipolysis, and infant adiposity. RESEARCH DESIGN AND METHODS At 31 weeks, 12 diet-controlled overweight/obese women with GDM were randomized to an isocaloric LC/CONV (40% carbohydrate/45% fat/15% protein; n = 6) or CHOICE (60%/25%/15%; n = 6) diet. All meals were provided. AT was biopsied at 37 weeks. RESULTS After ∼7 weeks, fasting glucose (P = 0.03) and free fatty acids (P = 0.06) decreased on CHOICE, whereas fasting glucose increased on LC/CONV (P = 0.03). Insulin suppression of AT lipolysis was improved on CHOICE versus LC/CONV (56 vs. 31%, P = 0.005), consistent with improved IR. AT expression of multiple proinflammatory genes was lower on CHOICE (P < 0.01). Infant adiposity trended lower with CHOICE (10.1 ± 1.4 vs. 12.6 ± 2%, respectively). CONCLUSIONS A CHOICE diet may improve maternal IR and infant adiposity, challenging recommendations for a LC/CONV diet.

Summary Background Infant adiposity better predicts childhood obesity/metabolic risk than weight, but technical challenges fuel controversy over the accuracy of adiposity estimates. Objective We prospectively measured adiposity (%fat) in term newborns (NB) at 2 weeks (n = 41) and 1 year (n = 30). Methods %fat was measured by dual X-ray absorptiometry (DXA), PEAPOD and skin-folds (SF). DXAs were analyzed using Hologic Apex software 3.2(DXAv1) and a new version 5.5.2(DXAv2). Results NB %fat by DXAv2 was 55% higher than DXAv1 (14.2% vs. 9.1%), 45% higher than SF (9.8%), and 36% higher than PEAPOD (10.4%). Among NB, Pearson correlations were 0.73–0.89, but agreement (intra-class correlations) poor between DXAv2 and DXAv1 (0.527), SF (0.354) and PEAPOD (0.618). At 1 year, %fat by DXAv2 was 51% higher than DXAv1 (33.6% vs. 22.4%), and twice as high compared with SF (14.6%). Agreement was poor between DXAv2 and DXAv1 (0.204), and SF (0.038). The absolute increase in %fat from 2 weeks to 1 year was 19.7% (DXAv2), 13.6% (DXAv1) and only 4.8% by SF. Conclusion Analysis of the same DXA scans using new software yielded considerably higher adiposity estimates at birth and 1 year compared with the previous version. Using different modalities to assess body composition longitudinally is problematic. Standardization is gravely needed to determine how early life exposures affect childhood obesity/metabolic risk.

Objectives To examine associations between exposure to prenatal smoking and early-life changes in fat mass (FM), fat-free mass (FFM), and anthropometrics. Methods About 670 mother–offspring pairs were analyzed in the longitudinal Healthy Start study. Maternal smoking data were collected during prenatal research visits. Offspring body composition and size were measured by air displacement plethysmography at delivery and postnatal follow-up (5 months) visits. Results Comparing exposed and unexposed offspring, exposure to prenatal smoking was significantly associated with reduced neonatal FM (P = 0.007) and FFM (P = 0.02). In contrast, at 5 months, exposed offspring had comparable FM (P = 0.61) and FFM (P = 0.41). After subsequent adjustment for birth weight, offspring exposed to prenatal smoking had significantly greater FFM (154.7 g, 0.5, 309.0; P = 0.049) and sum of skinfolds (2.7 mm, 0.06, 5.3; P = 0.04). From delivery to follow-up, exposed offspring had significantly greater increases in FFM (156.4 g, 2.8, 310.1; P = 0.046) and sum of skinfolds (2.7 mm, 0.06, 5.3; P = 0.04), even after adjustment for respective delivery measures. Conclusions Exposure to prenatal smoking was significantly associated with rapid postnatal growth, which may increase the offspring's risk of metabolic diseases.

Objectives To determine whether neonates undergoing major abdominal surgical procedures in the first day of life could achieve a positive protein balance without protein toxicity in the immediate perioperative period by using parenteral amino acids and fentanyl analgesia. Study design Newborns undergoing major surgery for gastroschisis in the first 24 hours of life (n = 13) were alternately allocated to immediate postoperative parenteral administration of 1.5 g/kg −1 /day −1 versus 2.5 g/kg −1 /day −1 amino acids. Protein balance was determined at 1.6 to 2.6 days postoperatively with both nitrogen balance and leucine stable isotope methodology. Statistical analyses were conducted with the unpaired t test and linear regression. Results Protein balance was significantly different in the 2 groups with both nitrogen balance and leucine stable isotope methodology. There was no evidence of protein toxicity as determined with blood urea nitrogen, creatinine, and ammonia concentrations. Conclusions Neonates undergoing the metabolic stress of abdominal surgery shortly after birth are able to achieve a net positive protein balance with parenteral amino acid administration without evidence of protein intolerance.

Our objective was to identify among women with gestational diabetes mellitus (GDM) the patient characteristics that predict treatment failure with glyburide.Historical cohort of 95 GDM women offered glyburide after dietary failure with defined entry criteria.From November 2000 to May 2005, 118 women had 124 pregnancies and were offered glyburide therapy by the 2 codirectors of our Diabetes Clinic. All but 2 women elected glyburide, and 27 pregnancies were excluded due to criteria defined a priori to the study. A cohort of 95 women with 95 pregnancies were included for analysis. Nineteen percent failed glyburide. Significant predictors of failure were maternal age (34 years compared with 29 years, P = .001), earlier diagnosis of GDM (23 weeks compared with 28 weeks, P = .002), higher gravidity (P = .01) and parity (P = .03), and a higher mean fasting blood glucose (112 compared with 100 mg/dL; P = .045) compared with those successfully treated. After adjustment in the multivariable logistic regression analysis, GDM women diagnosed at a gestational age less than 25 weeks were 8.3 times more likely to fail glyburide compared with those diagnosed after 25 weeks. Maternal and fetal outcomes were favorable with a cesarean delivery rate of 25% and macrosomia rate of 7%.Glyburide was more likely to fail in women diagnosed earlier in pregnancy, of older age and multiparity, and with higher fasting glucoses, suggesting that earlier glucose intolerance and a reduced capacity to respond to an insulin secretagogue may distinguish this group. The time for glyburide as an alternative treatment has come; however, it should be prescribed after careful consideration of these patient characteristics to minimize the likelihood of failure.II-2.

To examine associations between pregnancy physical activity and neonatal fat mass and fat-free mass, birth weight, and small for gestational age (SGA).We analyzed 826 mother-neonate pairs (term births) participating in the longitudinal Healthy Start study. The Pregnancy Physical Activity Questionnaire was used to assess total energy expenditure and meeting American College of Obstetricians and Gynecologists (College) guidelines for physical activity during early pregnancy, midpregnancy, and late pregnancy. Models were adjusted for maternal and neonatal characteristics.Neonates had mean fat mass of 292.9 g, fat-free mass of 2,849.8 g, and birth weight of 3,290.7 g. We observed 107 (12.9%) SGA and 30 (3.6%) large-for-gestational age neonates. A significant inverse linear trend between total energy expenditure during late pregnancy and neonatal fat mass (Ptrend=.04) was detected. Neonates of mothers in the highest compared with the lowest quartile of total energy expenditure during late pregnancy had 41.1 g less fat mass (249.4 compared with 290.5 g; P=.03). No significant trend was found with total energy expenditure and neonatal fat-free mass or birth weight. Early-pregnancy and midpregnancy total energy expenditure were not associated with neonatal outcomes. No significant trend was observed between late-pregnancy total energy expenditure and SGA (Ptrend=.07), but neonates of mothers in the highest compared with the lowest quartile had a 3.0 (95% confidence interval 1.4-6.7) higher likelihood of SGA. Meeting the College's physical activity guidelines during pregnancy was not associated with differences in neonatal outcomes.Increasing levels of late-pregnancy total energy expenditure are associated with decreased neonatal adiposity without significantly reduced neonatal fat-free mass.II.

Objective To examine associations between exposure to prenatal smoking and early-life changes in fat mass (FM), fat-free mass (FFM) and anthropometrics. Design and Methods We analyzed 670 mother-offspring pairs in the longitudinal Healthy Start study. Maternal smoking data were collected during prenatal research visits. Offspring body composition and size were measured by air displacement plethysmography at delivery and postnatal follow-up (5 months) visits. Results Comparing exposed and unexposed offspring, exposure to prenatal smoking was significantly associated with reduced neonatal FM (P = 0.007) and FFM (P = 0.02). In contrast, at 5 months, exposed offspring had comparable FM (P = 0.61) and FFM (P = 0.41). After subsequent adjustment for birth weight, offspring exposed to prenatal smoking had significantly greater FFM (154.7 g, 0.5, 309.0; P = 0.049) and sum of skinfolds (2.7 mm: 0.06, 5.3; P = 0.04). From delivery to follow-up, exposed offspring had significantly greater increases in FFM (156.4 g, 2.8, 310.1; P = 0.046) and sum of skinfolds (2.7 mm, 0.06, 5.3; P = 0.04), even after adjustment for respective delivery measures. Conclusions Exposure to prenatal smoking was significantly associated with rapid postnatal growth, which may increase the offspring’s risk of metabolic diseases.

To examine the dose-dependent and time-specific relationships of prenatal smoking with neonatal body mass, fat mass (FM), fat-free mass (FFM), and FM-to-FFM ratio, as measured by air-displacement plethysmography (PEA POD system).We analyzed 916 mother-neonate pairs participating in the longitudinal prebirth cohort Healthy Start study. Maternal prenatal smoking information was collected in early, middle, and late pregnancy by self-report. Neonatal body composition was measured with the PEA POD system after delivery. Multiple general linear regression models were adjusted for maternal and neonatal characteristics.Each additional pack of cigarettes smoked during pregnancy was associated with significant decreases in neonatal body mass (adjusted mean difference, -2.8 g; 95% CI, -3.9 to -1.8 g; P .001), FM (-0.7 g; 95% CI, -1.1 to -0.3 g; P .001), and FFM (-2.1 g; 95% CI, -2.9 to -1.3 g; P .001). Neonates exposed to prenatal smoking throughout pregnancy had significantly lower body mass (P .001), FM (P .001), and FFM (P .001) compared with those not exposed to smoking. However, neonates of mothers who smoked only before late pregnancy had no significant differences in body mass (P = .47), FM (P = .43), or FFM (P = .59) compared with unexposed offspring.Exposure to prenatal smoking leads to systematic growth restriction. Smoking cessation before late pregnancy may reduce the consequences of exposure to prenatal smoking on body composition. Follow-up of this cohort is needed to determine the influence of catch-up growth on early-life body composition and the risk of childhood obesity.

Objectives To assess precision magnetic resonance imaging in the neonate and determine whether there is an early maternal influence on the pattern of neonatal fat deposition in the offspring of mothers with gestational diabetes mellitus (GDM) and obesity compared with the offspring of normal-weight women. Study design A total of 25 neonates born to normal weight mothers (n = 13) and to obese mothers with GDM (n = 12) underwent magnetic resonance imaging for the measurement of subcutaneous and intra-abdominal fat and magnetic resonance spectroscopy for the measurement of intrahepatocellular lipid (IHCL) fat at 1-3 weeks of age. Results Infants born to obese/GDM mothers had a mean 68% increase in IHCL compared with infants born to normal-weight mothers. For all infants, IHCL correlated with maternal prepregnancy body mass index but not with subcutaneous adiposity. Conclusion Deposition of liver fat in the neonate correlates highly with maternal body mass index. This finding may have implications for understanding the developmental origins of childhood nonalcoholic fatty liver disease.

There are many unresolved issues regarding how to feed the extremely-low-birth-weight (ELBW) infant. Trophic feedings of small volumes of breast milk or formula do not appear to increase the incidence of necrotizing enterocolitis (NEC). For prevention of NEC, breast milk, antenatal steroids and fluid restriction each confers a benefit. Because the incidence of NEC is relatively low, to determine if a particular prevention strategy is effective, large numbers of infants would need to be enrolled in a prospective, randomized controlled trial, and such trials are rare. Candidate therapies for NEC prevention that warrant further study include oral immunoglobulins, probiotics, long-chain polyunsaturated fatty acids and arginine. Suboptimal nutrition in ELBW infants is common in the early postnatal period. This is also the most critical time for the development of bronchopulmonary dysplasia, when even brief periods of malnutrition have significant effects on lung development and growth.

Conventional diet therapy in women with gestational diabetes (GDM) has focused on restriction of carbohydrate (CHO), which typically results in greater fat intake. Diets higher in fat are known to promote insulin resistance and thus may increase fetal adiposity.

Background The prevalence of gestational diabetes mellitus (GDM) continues to rise in the face of the obesity epidemic affecting up to 14% of some ethnic populations. Studies have shown that treatment of GDM with insulin decreases serious maternal and fetal morbidity and perinatal mortality. Oral medications are preferred by patients and this could lead to increased compliance. Glyburide remains unapproved for use in GDM. Study This was a retrospective review of 124 women who were offered glyburide therapy between November 2000 and May 2005. A cohort of 101 women was included for analysis, approximately 50% Hispanic, 33% Caucasian, and 3% African American. Neonatal outcomes reviewed included birth weight, macrosomia, weight > 90%, admission to the neonatal intensive care unit, hypoglycemia, evidence of respiratory distress (RDS), and congenital anomalies. Results Eighty percent of the pregnancies were treated successfully with glyburide. There were no reported perinatal deaths. Overall cesarean section rate was 27% and there were no reports of shoulder dystocia. The macrosomia rate was 7% and 27% of the infants were large for gestational age (LGA) with a mean birth weight of 3,307 ± 490 g. Although 21% were admitted to the NICU, only 8% required IV glucose for hypoglycemia and only 8% were treated for RDS. Three congenital anomalies were noted but glyburide was initiated after 22 weeks gestation. Conclusion Although the study was a retrospective retrieval of data, the management of these patients was standardized. Fetal growth was considered in the decisions regarding titration of glyburide and this may have contributed to neonatal outcomes such as weight, shoulder dystocia, and rate of cesarean section. Given that the relative safety of glyburide has been confirmed, outcomes with glyburide are at least comparable to outcomes with insulin, and oral medications are preferred to insulin and this may increase compliance, glyburide would be another option to treat GDM and therefore improve overall fetal morbidity.