Association between congenital heart disease and parenteral nutrition-associated liver disease in neonates: A retrospective cohort study.

OBJECTIVE: Infants receiving parenteral nutrition (PN) are at increased risk of PN-associated liver disease (PNALD), which can lead to hepatic fibrosis. Congenital heart disease (CHD) represents a risk factor for hepatic fibrosis, so this study sought to better understand whether infants with CHD were at elevated risk of PNALD when receiving long-term PN. STUDY DESIGN: This study includes a retrospective cohort of infants at a level IV neonatal intensive care unit from 2010 to 2020 who received long-term PN during the first 8 weeks of life. A time-varying Cox survival model was used to model risk of PNALD between infants with and without CHD, adjusted for demographics, surgical intervention, and PN exposure, using a 5000-iteration bootstrap estimation. Secondary analyses evaluated risk against discrete CHD diagnoses, and sensitivity analysis was performed on the magnitude and quantity of direct bilirubin laboratory measurements making up the PNALD definition. RESULTS: Neonates with CHD were found to be at higher risk for PNALD during or soon after long-term PN exposure. A pattern of increasing association strength with increasing bilirubin threshold suggests infants with CHD may also experience higher degrees of injury. CONCLUSIONS: This work offers a step in understanding how diagnoses can be factored into neonate PN prescription. Future work will explore modifications in lipid profiles and timing to mitigate risk in patients with CHD.

Gastroschisis with intestinal atresia leads to longer hospitalization and poor feeding outcomes.

OBJECTIVE: Compare in-hospital outcomes in gastroschisis with intestinal atresia versus simple gastroschisis (GS) using a national database. STUDY DESIGN: The Children's Hospitals Neonatal Database identified infants with gastroschisis from 2010 to 2016. RESULTS: 2078 patients with gastroschisis were included: 183 (8.8%) with co-existing intestinal atresia, 1713 (82.4%) with simple gastroschisis, the remainder with complex gastroschisis without atresia. Length of hospitalization was longer for those with atresia, and yielded higher rates of mortality, medical NEC, and intestinal perforation. They began enteral feedings later, were less likely to initiate feeds orally, and reached full feedings later. They were less likely to be receiving any maternal breast milk or breastfeeding at discharge and more likely than simple gastroschisis to be discharged with a feeding tube. CONCLUSION: A large multicenter cohort showed gastroschisis with atresia results in worse outcomes and complications, including necrotizing enterocolitis, feeding delays, and enteral feeding tube dependence.

Extracellular Superoxide Dismutase (EC-SOD) Regulates Gene Methylation and Cardiac Fibrosis During Chronic Hypoxic Stress.

Chronic hypoxic stress induces epigenetic modifications mainly DNA methylation in cardiac fibroblasts, inactivating tumor suppressor genes (RASSF1A) and activating kinases (ERK1/2) leading to fibroblast proliferation and cardiac fibrosis. The Ras/ERK signaling pathway is an intracellular signal transduction critically involved in fibroblast proliferation. RASSF1A functions through its effect on downstream ERK1/2. The antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), decreases oxidative stress from chronic hypoxia, but its effects on these epigenetic changes have not been fully explored. To test our hypothesis, we used an in-vitro model: wild-type C57B6 male mice (WT) and transgenic males with an extra copy of human hEC-SOD (TG). The studied animals were housed in hypoxia (10% O2) for 21 days. The right ventricular tissue was studied for cardiac fibrosis markers using RT-PCR and Western blot analyses. Primary C57BL6 mouse cardiac fibroblast tissue culture was used to study the in-vitro model, the downstream effects of RASSF-1 expression and methylation, and its relation to ERK1/2. Our findings showed a significant increase in cardiac fibrosis markers: Collagen 1, alpha smooth muscle actin (ASMA), and SNAIL, in the WT hypoxic animals as compared to the TG hypoxic group (p < 0.05). The expression of DNA methylation enzymes (DNMT 1&3b) was significantly increased in the WT hypoxic mice as compared to the hypoxic TG mice (p < 0.001). RASSF1A expression was significantly lower and ERK1/2 was significantly higher in hypoxia WT compared to the hypoxic TG group (p < 0.05). Use of SiRNA to block RASSF1A gene expression in murine cardiac fibroblast tissue culture led to increased fibroblast proliferation (p < 0.05). Methylation of the RASSF1A promoter region was significantly reduced in the TG hypoxic group compared to the WT hypoxic group (0.59 vs. 0.75, respectively). Based on our findings, we can speculate that EC-SOD significantly attenuates RASSF1A gene methylation and can alleviate cardiac fibrosis induced by hypoxia.

Bivalirudin and thrombolytic therapy: a novel successful treatment of severe aortic arch thrombosis in a term neonate.

An early-term infant with uncomplicated perinatal history was found to have a large thrombus in the aortic arch after he failed regular newborn critical congenital heart defect screen. He responded well to bivalirudin thrombolytic and tissue-plasminogen activator (tPA) combination therapy, with a significant resolution of the thrombus. The infant tolerated hospital admission well with no significant complications. He was discharged home on daily aspirin at 2 weeks of life. To our knowledge, the combination therapy approach with bivalirudin and tPA is the first one reported in the literature in the neonatal age group.