Histologic features and decreased lung FOXF1 gene expression in severe bronchopulmonary dysplasia without a genetic diagnosis of alveolar capillary dysplasia.

We report the case of a preterm infant who died at 10 months of age with severe bronchopulmonary dysplasia (sBPD) with refractory pulmonary hypertension and respiratory failure who had striking histologic features compatible with the diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) but without genetic confirmation of the diagnosis. We further demonstrate dramatic reductions in lung FOXF1 and TMEM100 content in sBPD, suggesting common mechanistic links between ACDMPV and sBPD with impaired FOXF1 signaling.

A Truncating Variant of CHRNG as a Cause of Escobar Syndrome: A Multiple Pterygium Syndrome Subtype.

Escobar syndrome is a milder variant of multiple pterygium syndrome characterized by pterygia, scoliosis, and multiple congenital contractures. It is most frequently due to a genetic variant in CHRNG , which encodes the γ-subunit of the nicotinic acetylcholine receptor. Though the subunit is considered a "fetal" form and transitions to the "adult" ε-subunit by 33 weeks' gestation, the pathogenic musculoskeletal effects during fetal development render children with this condition permanently affected. We report a neonate with homozygous CHRNG c.117dupC and discuss some of the downstream clinical effects we observed with this variant.

National Trends in Survival and Short-Term Outcomes of Periviable Births ≤24 Weeks Gestation in the United States, 2009 to 2018.

OBJECTIVE: Data from the academic medical centers in the United States showing improvements in survival of periviable infants born at 22 to 24 weeks GA may not be nationally representative since a substantial proportion of preterm infants are cared for in community hospital-based neonatal intensive care units. Our objective was to examine the national trends in survival and other short-term outcomes among preterm infants born at ≤24 weeks gestational age (GA) in the United States from 2009 to 2018. STUDY DESIGN: This was a retrospective, repeated cross-sectional analysis of the National Inpatient Sample for preterm infants ≤24 weeks GA. The primary outcome was the trends in survival to discharge. Secondary outcomes were the trends in the composite outcome of death or one or more major morbidity (bronchopulmonary dysplasia, necrotizing enterocolitis stage ≥2, periventricular leukomalacia, severe intraventricular hemorrhage, and severe retinopathy of prematurity). The Cochran-Armitage trend test was used for trend analysis. p-Value <0.05 was considered significant. RESULTS: Among 71,854 infants born at ≤24 weeks GA, 34,251 (47.6%) survived less than 1 day and were excluded. Almost 93% of those who survived <1 day were of ≤23 weeks GA. Among the 37,603 infants included in the study cohort, 48.1% were born at 24 weeks GA. Survival to discharge at GA ≤ 23 weeks increased from 29.6% in 2009 to 41.7% in 2018 (p < 0.001), while survival to discharge at GA 24 weeks increased from 58.3 to 65.9% (p < 0.001). There was a significant decline in the secondary outcomes among all the periviable infants who survived ≥1 day of life. CONCLUSION: Survival to discharge among preterm infants ≤24 weeks GA significantly increased, while death or major morbidities significantly decreased from 2009 to 2018. The postdischarge survival, health care resource use, and long neurodevelopmental outcomes of these infants need further investigation. KEY POINTS: · Survival increased significantly in infants ≤24 weeks GA in the United States from 2009 to 2018.. · Death or major morbidity in infants ≤24 weeks GA decreased significantly from 2009 to 2018.. · Death or surgical procedures including tracheostomy, VP shunt placement, and PDA surgical closure in infants <=24 weeks GA decreased significantly from 2009 to 2018..

Gastrostomy Tube Placement and Resource Use in Neonatal Hospitalizations With Down Syndrome.

OBJECTIVES: To determine the trends in gastrostomy tube (GT) placement and resource utilization in neonates ≥35 weeks' gestational age with Down syndrome (DS) in the United States from 2006 to 2017. METHODS: This was a serial cross-sectional analysis of neonatal hospitalizations of ≥35 weeks' gestational age with International Classification of Diseases diagnostic codes for DS within the National Inpatient Sample. International Classification of Diseases procedure codes were used to identify those who had GT. The outcomes of interest were the trends in GT and resource utilization and the predictors of GT placement. Cochran-Armitage and Jonckheere-Terpstra trend tests were used for trend analysis of categorical and continuous variables, respectively. Predictors of GT placement were identified using multivariable logistic regression. P value <.05 was considered significant. RESULTS: Overall, 1913 out of 51 473 (3.7%) hospitalizations with DS received GT placement. GT placement increased from 1.7% in 2006 to 5.6% in 2017 (P <.001), whereas the prevalence of DS increased from 10.3 to 12.9 per 10 000 live births (P <.001). Median length of stay significantly increased from 35 to 46 days, whereas median hospital costs increased from $74 214 to $111 360. Multiple comorbidities such as prematurity, sepsis, and severe congenital heart disease were associated with increased odds of GT placement. CONCLUSIONS: There was a significant increase in GT in neonatal hospitalizations with DS, accompanied by a significant increase in resource utilization. Multiple comorbidities were associated with GT placement and the early identification of those who need GT could potentially decrease length of stay and resource use.

H2S mediates the vasodilator effect of endothelin-1 in the cerebral circulation.

H2S is an endogenous gasotransmitter that increases cerebral blood flow. In the cerebral vascular endothelium, H2S is produced by cystathionine δ-lyase (CSE). Endothelin-1 (ET-1) has constrictor and dilator influences on the cerebral circulation. The mechanism of the vasodilation caused by ET-1 may involve endothelium-derived factors. We hypothesize that ET-1-elicited dilation of pial arterioles requires an elevation of H2S production in the cerebral vascular endothelium. We investigated the effects of ET-1 on CSE-catalyzed brain H2S production and pial arteriolar diameter using cranial windows in newborn pigs in vivo. H2S was measured in periarachnoid cerebrospinal fluid. ET-1 (10-12-10-8 M) caused an elevation of H2S that was reduced by the CSE inhibitors propargylglycine (PPG) and ß-cyano-l-alanine (BCA). Low doses of ET-1 (10-12-10-11 M) produced vasodilation of pial arterioles that was blocked PPG and BCA, suggesting the importance of H2S influences. The vasodilator effects of H2S may require activation of smooth muscle cell membrane ATP-sensitive K+ (KATP) channels and large-conductance Ca2+-activated K+ (BK) channels. The KATP inhibitor glibenclamide and the BK inhibitor paxilline blocked CSE/H2S-dependent dilation of pial arterioles to ET-1. In contrast, the vasoconstrictor response of pial arterioles to 10-8 M ET-1 was not modulated by PPG, BCA, glibenclamide, or paxilline and, therefore, was independent of CSE/H2S influences. Pial arteriolar constriction response to higher levels of ET-1 was independent of CSE/H2S and KATP/BKCa channel activation. These data suggest that H2S is an endothelium-derived factor that mediates the vasodilator effects of ET-1 in the cerebral circulation via a mechanism that involves activation of KATP and BK channels in vascular smooth muscle. NEW & NOTEWORTHY Disorders of the cerebral circulation in newborn infants may lead to lifelong neurological disabilities. We report that vasoactive peptide endothelin-1 exhibits vasodilator properties in the neonatal cerebral circulation by stimulating production of H2S, an endothelium-derived messenger with vasodilator properties. The ability of endothelin-1 to stimulate brain production of H2S may counteract the reduction in cerebral blood flow and prevent the cerebral vascular dysfunction caused by stroke, asphyxia, cerebral hypoxia, ischemia, and vasospasm.

Glycerin Suppositories Use in Very Low Birth Weight Infants.

Objective To study the characteristics of very low birth weight (VLBW) infants receiving glycerin suppositories (GS) and evaluate the association of GS use with outcomes. Study Design This is a retrospective study of VLBW infants admitted to a level III neonatal intensive care unit. Infants with birth weight between 500 and 1,499 g were evaluated. We evaluated the frequency of GS use and compared the characteristics and outcomes of the GS group with the no-GS group. Multivariate analyses controlling for gestational age and small for gestational age status were performed to study the effect of GS on outcomes. Results A total of 1,073 infants were included in the study. Out of those, 527 (49.1%) infants received GS. Incidence of necrotizing enterocolitis was not significantly different between the two groups, while days to reach full enteral feeds and length of hospital stay were significantly longer in the GS group. Conclusion Frequent use of GS warrants further prospective studies to evaluate its safety and efficacy in view of our study showing association with longer time to reach full enteral feeds. We speculate that GS use could be a marker for gastrointestinal dysmotility and hence the association with unfavorable clinical outcomes.