Diabetes in Pregnancy, Neonatal Morbidities, and Early Growth in Moderate or Late Preterm Infants.

OBJECTIVES: To compare differences in short term morbidities and early growth among moderate and late preterm infants of mothers with and without diabetes (DM) in pregnancy. METHODS: In a longitudinal analysis using data from the Pediatrix Clinical Data Warehouse of preterm infants (born 32 0/7 to 36 6/7 weeks) discharged from neonatal intensive care units from 2008 to 2019, health characteristics were compared between DM exposure groups. Change in growth from birth to discharge were compared using linear mixed effects modeling. RESULTS: Among 301 499 moderate and late preterm infants in the analysis, 14% (N = 42 519) were exposed to DM in pregnancy. Incidence of congenital anomalies, hypoglycemia, and hyperbilirubinemia were higher in DM-group (P < .001), and DM-group was more likely to need respiratory support in the first postnatal days (P = .02). Percent weight change from birth differed by gestational age, such that 36-week DM-group infants remained on average 2% (95% confidence interval [CI]: 1.57 to 2.41) below birth weight on day 14, whereas 32-week DM-group infants were on average 2.1% (95% CI: 1.69 to 2.51) above birth weight on day 14. In the regression analysis, DM-group had faster weight loss in the first postnatal week when stratified by gestational age. The adjusted difference in weight velocity (g per day) from days 0 to 3 was -4.5 (95% CI: -5.1 to -3.9), -6.5 (95% CI: -7.4 to -5.7), and -7.2 (95% CI: -8.2 to -6.2) for infants born 34-, 35-, and 36-weeks, respectively. CONCLUSIONS: In moderate or late preterm infants, diabetes in pregnancy is associated with common neonatal morbidities. Examination of intensive care nutritional practices may identify reasons for observed differences in weight trajectories by gestational age and diabetes exposure.

Growth patterns among late preterm infants of mothers with diabetes.

OBJECTIVE: Exposure to diabetes mellitus during pregnancy increases the risk of offspring obesity and cardiometabolic disease. Limited information exists regarding growth patterns among preterm infants exposed to maternal diabetes. This study describes growth differences during early childhood among late preterm infants of mothers with and without diabetes during pregnancy. MATERIALS AND METHODS: In a retrospective longitudinal analysis, weight trajectories from birth to age 2 years were compared between diabetes exposure groups (N = 1554) using mixed effects modeling and adjusting for maternal and infant demographic covariates. RESULTS: Overall, 134 (9%) infants were exposed to diabetes (DM-group). DM-group had higher average weight (adjusted difference 300 g [95% CI: 228, 371]) and weight z-score (adjusted difference 0.67 standard deviation scores (SDS) [95% CI: 0.50, 0.84]) compared with unexposed infants. DM-group infants had accelerated weight gain from birth to discharge (adjusted weight difference 31.8 g [95% CI: 12.5, 51.1], adjusted weight z-score difference 0.07 SDS [95% CI: 0.02, 0.11]) compared with unexposed infants, including in the first postnatal week (adjusted weight gain velocity difference, day 0-3: 6.07 g/day [95% CI: 0.88, 11.25]; day 3-7: 8.37 g/day [95% CI: 1.60, 15.13]). Through age two, infants in the DM-group maintained higher average weight (adjusted difference 185.7 g [95% CI: 37.2, 334.3]) and weight z-score (adjusted difference 0.32 SDS [95% CI: 0.09, 0.55]) than unexposed infants, with greater weight gain between 18 and 24 months (adjusted difference 28.5 g/week [95% CI: 2.6, 54.4]). CONCLUSIONS: Maternal diabetes exposed late preterm infants had higher weight from birth to age two and greater weight gain in the first postnatal week than unexposed infants. Long term risk associated with weight trajectories in this population requires further study.

Commentary on "compatibility of rapid enteral feeding advances and noninvasive ventilation in preterm infants-an observational study".

Nutritional support is essential in the critical care of the very preterm infant, however, the study of the potential role of nutrition in the multifactorial pathogenesis of bronchopulmonary dysplasia (BPD) is limited. Achievement of full enteral feeding faster has not been shown to be harmful and may be of benefit in extremely preterm infants. This commentary discusses the studied risk and potential benefits of more rapid enteral feeding advancement in extremely preterm infants.

Neonatal and Adolescent Adipocytokines as Predictors of Adiposity and Cardiometabolic Risk in Adolescence.

OBJECTIVE: This study aimed to examine associations of changes in leptin and adiponectin concentrations from birth to age 12 years with adolescent adiposity and cardiometabolic risk in the Health Outcomes and Measures of Environment (HOME) Study, a prospective birth cohort (Cincinnati, Ohio; N = 166). METHODS: Adiposity and cardiometabolic risk factors were assessed at age 12 years using anthropometry, dual-energy x-ray absorptiometry, and fasting serum biomarkers. Cardiometabolic risk scores were calculated by summing age- and sex- standardized z scores for individual cardiometabolic risk factors. RESULTS: Most serum adipocytokine concentrations at birth were not associated with adiposity or cardiometabolic risk outcomes. Leptin and adiponectin concentrations at age 12 years were associated with all outcomes in the expected direction. Adolescents with increasing (ß: 4.2; 95% CI: 3.2 to 5.2) and stable (ß: 2.2; 95% CI: 1.2 to 3.2) leptin concentrations from birth to age 12 years had higher cardiometabolic risk scores than adolescents with decreasing concentrations (reference group). Adolescents with increasing (e.g., fat mass index = ß: -1.04; 95% CI: -1.27 to -0.80) and stable (ß: 0.66; 95% CI: -0.92 to -0.40) adiponectin/leptin ratios had more favorable adiposity outcomes than adolescents with decreasing ratios. CONCLUSIONS: In this cohort, changes in leptin concentrations and adiponectin/leptin ratios over childhood were associated with adiposity and cardiometabolic risk scores, indicating that adipocytokine concentrations are potential biomarkers for predicting excess adiposity and cardiometabolic risk in adolescence.

NOVEL XRCC4 MUTATIONS IN AN INFANT WITH MICROCEPHALIC PRIMORDIAL DWARFISM, DILATED CARDIOMYOPATHY, SUBCLINICAL HYPOTHYROIDISM, AND EARLY DEATH: EXPANDING THE PHENOTYPE OF XRCC4 MUTATIONS.

OBJECTIVE: Microcephalic primordial dwarfism (MPD) is a group of clinically and genetically heterogeneous disorders which result in severe prenatal and postnatal growth failure. X-ray repair cross-complementing protein 4 (XRCC4) is a causative gene for an autosomal recessive form of MPD. The objective of this report is to describe novel XRCC4 mutations in a female infant with MPD, dilated cardiomyopathy, and subclinical hypothyroidism. METHODS: Genetic testing was performed using a comprehensive next generation sequencing panel for MPD, followed by targeted XRCC4 gene sequencing. RESULTS: We report the case of a 970-gram, 35-cm, female infant (weight z score -5.05, length z score -4.71) born at 36 weeks and 3 days gestation. Physical examination revealed triangular facies, micrognathism, clinodactyly, and second and third toe syndactyly. Initial echocardiogram at birth was normal. Follow-up echocardiogram at 60 days of life revealed dilated cardiomyopathy with moderate left ventricular systolic dysfunction (ejection fraction was 40 to 45%), and anticongestive therapy was initiated. Thyroid testing revealed subclinical hypothyroidism with elevated thyroid-stimulating hormone of 13.0 µIU/mL (reference range is 0.3 to 5.0 µIU/mL) and normal free thyroxine by dialysis of 1.6 ng/dL (reference range is 0.8 to 2.0 ng/dL). Levothyroxine was initiated. Postnatal growth remained poor (weight z score at 3 months -4.93, length z score at 3 months -6.48), including progressive microcephaly (head circumference z score at 3 months -10.94). Genetic testing revealed novel compound heterozygous XRCC4 variants in trans: c.628A>T and c.638+3A>G. The child ultimately had cardiopulmonary arrest and died at 6 months of life. CONCLUSION: Molecular diagnosis in MPD is key to defining the natural history, management, and prognosis for patients with these rare disorders.

Predictors of Parenting Readiness in Fathers of High-Risk Infants in the Neonatal Intensive Care Unit.

To evaluate discharge readiness perceptions among mother-father dyads, parents of infants in the neonatal intensive care unit completed a parenting readiness survey. Fathers had more favorable perceptions than their partners. Maternal perceptions and social risk, but not infant morbidities, predicted paternal perceptions. Discharge support should focus on the mother-father dyad.

Neonatal Adipocytokines and Longitudinal Patterns of Childhood Growth.

OBJECTIVE: Adipocytokines are markers of fetal metabolism, but their association with childhood growth is unclear. This study examined associations of neonatal adipocytokines with longitudinal childhood adiposity measures in a prospective cohort of pregnant women and their children. METHODS: Leptin and adiponectin concentrations at delivery and children's BMI z scores between age 4 weeks and 8 years were measured. Differences in BMI z scores and rates of BMI z score change by leptin (n = 257) and adiponectin (n = 271) terciles were estimated. RESULTS: Children in the middle (mean difference: 0.2; 95% CI: -0.1 to 0.4) and highest (0.4; 95% CI: 0.1 to 0.6) leptin terciles had greater BMI z scores than children in the lowest tercile. Associations were null after adjustment for birth weight z score. Children in the lowest adiponectin tercile had greater gains in BMI z score (change per year: 0.10; 95% CI: 0.08 to 0.13) than children in the middle (0.07; 95% CI: 0.04 to 0.09) and highest terciles (0.04; 95% CI: -0.01 to 0.05) (adiponectin × age interaction P < 0.001). CONCLUSIONS: Lower adiponectin levels were associated with increased rates of BMI gains in the first 8 years of life. Though leptin was positively associated with BMI, this association may be confounded by birth weight.

Prenatal exposure to perfluoroalkyl substances and adipocytokines: the HOME Study.

OBJECTIVE: Gestational perfluoroalkyl substances exposure has been associated with decreased birthweight. We determined if gestational perfluoroalkyl substances exposure was associated with fetal metabolic markers using data from the HOME Study, a prospective birth cohort of pregnant women and their children in Cincinnati, Ohio. METHODS: Maternal serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid, and perfluorohexane sulfonic acid were quantified. We measured neonatal adipocytokine (leptin and adiponectin) concentrations in umbilical cord serum, and estimated percent differences with a 2-fold increase in maternal perfluoroalkyl substances concentrations among 230 mother-infant pairs. RESULTS: Median maternal serum PFOA and PFOS concentrations were 5.6 ng/mL and 14 ng/mL, respectively. Leptin was positively correlated with infant birthweight (p < 0.001). There were no statistically significant associations between maternal perfluoroalkyl substances and neonatal adipocytokine concentrations; each 2-fold increase in PFOA was associated with a non-significant increase in leptin (5%; 95% CI: -10, 22) and adiponectin (7%; 95% CI: -4, 19). CONCLUSION: Despite known associations with reduced birthweight, gestational serum perfluoroalkyl substances concentrations were not associated with neonatal adipocytokine concentrations. Further exploration of pathways of perfluoroalkyl substances associated changes in birthweight may help identify biomarkers that could be used to identify at-risk populations and develop interventions.

Prenatal Exposure to Stressful Life Events and Infant Breastfeeding.

BACKGROUND: Of the various barriers to breastfeeding, limited information is available on the relationship between prenatal stress and breastfeeding. This study investigates the association between prenatal stressful life event (SLE) exposure and breastfeeding initiation postpartum. MATERIALS AND METHODS: Using Rhode Island Pregnancy Risk Assessment Monitoring System data from 2012 to 2014, SLE was defined as self-report of prenatal exposure to 14 predefined life events such as job loss or illness. Exposure to SLE was categorized by number and type of events. Multivariable logistic regression was performed to assess the relationship between SLE and breastfeeding initiation. Results accounted for complex survey design and were adjusted for maternal and infant characteristics (age, race, ethnicity, insurance, delivery type, parity, gestational age, birth weight for gestational age, and neonatal intensive care unit admission). RESULTS: Among 3,353 respondents, 86% reported breastfeeding initiation, 74% reported exposure to ≥1 SLE, and 17% reported exposure to ≥4 SLE. Decreased odds of breastfeeding initiation were associated with prenatal exposure to ≥4 SLE (adjusted odds ratio [aOR] 0.67; 95% confidence interval [CI]: 0.48-0.95), emotional stressors (aOR 0.77; 95% CI: 0.61-0.98), and traumatic stressors (aOR 0.68; 95% CI: 0.50-0.91). CONCLUSION: This study underscores the impact of exposure to prenatal SLE on breastfeeding initiation among postpartum women. Findings may assist providers in identifying at-risk women for anticipatory guidance to improve breastfeeding rates.