Edward F. Bell

Background: Preterm birth is associated with an increased rate of serious maternal complication compared with those who deliver at term. However, data are limited on risk factors for maternal morbidity and mortality specifically in the setting of preterm birth. Improved understanding of risk factors for morbidity in patients with preterm birth can help optimize interventions to best support patients experiencing preterm birth. Objective: To assess associations between obstetric factors and maternal morbidities and mortality among patients who gave birth less than 35 weeks’ gestation. Study design: This is a secondary analysis of a multicenter registry of gravidas carrying singletons or twins who gave birth at 16 0/7 to 34 6/7 weeks’ gestation January through August 2019. The primary outcome was a maternal morbidity and mortality composite (blood transfusion, postpartum hemorrhage, maternal sepsis, stroke, thromboembolism, intensive care unit admission, or death) during the delivery hospitalization. Factors were compared between those with and without the composite outcome to identify statistically significant variables. Those factors were then used to create a parsimonious multivariable logistic regression model with adjusted odds ratio (aOR) and 95% confidence intervals (CIs) using a backward strategy. We estimated area under the curve to quantify the predictive ability of these factors for the primary outcome. Results: The analysis was based on 6660 patients, of whom 15.1% experienced the primary composite outcome. Factors associated with increased odds of the outcome included increasing maternal age, use of assisted reproductive technology, twin gestation, preeclampsia, placental abruption and cesarean delivery—aOR ranged from 1.02 [1.01–1.04] for maternal age (continuous) to 2.55 [2.08–3.14] for abruption. In contrast, nulliparity, gestational diabetes, preterm prelabor rupture of membranes (PPROM), and later birth gestational age were associated with decreased odds of the primary outcome—aOR ranging from 0.96 [0.95–0.98] for gestational age (continuous) to 0.54 [0.44–0.66] for PPROM. The model with these factors had low to moderate predictive ability (AUC 0.68 [0.66–0.69]). Conclusion: Among individuals who experienced preterm birth before 35 weeks, multiple factors were associated with maternal morbidity and mortality. The factors together modestly discriminate maternal morbidity or mortality.

Among the most pressing topics in neonatal-perinatal medicine today is intensive care for infants born at ≤24 weeks’ gestation. Infants born at 22–24 weeks comprise ~1 in 500 live births, with ~7500 liveborn infants annually in the U.S.—more common than Down syndrome or critical congenital heart disease—and make up 1 in 5 U.S. infant deaths. Major uncertainties exist about clinical decisions, including regarding obstetric care, delivery room procedures, incubator management, nutrition, respiratory support, and the optimal developmental environment. Partnering with families, we can develop a sound basis for safe and effective medical care of pregnant women and infants affected by birth at ≤24 weeks.

Background: There is a paucity of data on neurodevelopmental outcomes in preterm infants who undergo transcatheter patent ductus arteriosus (PDA) closure (TCPC). Objective: To evaluate neurodevelopmental impairment (NDI) or death at 2 years among preterm infants treated with TCPC compared to surgical ligation. Methods: Retrospective cohort study of infants born at <27 weeks’ gestation at NICHD NRN sites. Comparisons were made between infants who underwent TCPC and PDA ligation. Results: TCPC and surgical ligation were performed on 99 and 279 infants, respectively. Death or severe NDI occurred in 49% of infants with TCPC and 40% with surgical ligation. There was no difference in odds of death or severe NDI between the two groups [aOR 1.12 95% CI: 0.55–2.26)]. Conclusion: TCPC had similar odds of death or severe NDI compared to surgical ligation. These findings need to be evaluated in large prospective studies as the management practice around the TCPC evolves. Clinical trial registration: ClinicalTrials.gov ID: Generic Database: NCT00063063.

As neonatal care has advanced and more immature infants are admitted to the neonatal intensive care unit, we must reevaluate fundamental management practices originally developed for infants born at later gestational ages. Studies have investigated the use of various incubator humidification levels in the care of preterm infants of older gestational ages, but evidence regarding management of ambient humidity for infants born at <25 weeks’ gestation using contemporary technology is limited. Uncertainty about the best approach to incubator humidification is reflected in major variation in practice around the world. This article summarizes existing evidence about the use of humidity in incubators and its relationship with neonatal skin maturation, fluid management, temperature regulation, and morbidities. It also describes approaches to starting humidification, duration of humidification, and reducing humidification over time. It concludes with a list of important questions requiring future research.

Objective To examine whether changes in survival without moderate or severe neurodevelopmental impairment (NDI) at 18–26 months’ corrected age from 1999 to 2018 differed between male and female infants. Design This retrospective cohort study used data from the NICHD Neonatal Research Network hospitals. Robust Poisson regression models were used to estimate adjusted relative risks (aRRs) and 95% CIs for survival without moderate or severe NDI between males and females. Interactions between sex and time were assessed to evaluate temporal differences in the outcome by sex. Variables adjusted for included centre, maternal age, ethnicity/race, gestational age and small for gestational age. Patients Inborn infants with gestational age of 22–26 weeks at NICHD Neonatal Research Network hospitals from 1999 to 2018. Main outcome measure Change over time in survival without moderate or severe NDI at 18–26 months’ corrected age between male and female infants. Results Of 26 307 infants, 13 045 (49.6%) were male. Survival without moderate or severe NDI declined for both sexes over time, from 32.9% to 30.6% for males and from 47.4% to 40.0% for females, between 1999–2003 and 2014–2018. Males were less likely than females to survive without moderate or severe NDI (aRR=0.80; 95% CI 0.78 to 0.83). Changes in survival without moderate or severe NDI did not differ between males and females. Conclusion There were no differential changes in survival without moderate or severe NDI between male and female infants.

Objective To compare the rates of death or survival with severe neurodevelopmental impairment (sNDI) at 2 years among extremely preterm infants in relation to pre-pregnancy or first-trimester maternal body mass index (BMI). Methods This retrospective cohort study included extremely preterm infants (gestational age 22^0/7–26^6/7 weeks). The study was conducted at National Institute of Child Health and Human Development Neonatal Research Network sites. The primary outcome was death or sNDI at 2 years. Results Data on the primary outcome were available for 1208 children. Death or sNDI was not different among the three groups: 54.9% in normal, 56.1% in overweight, and 53.4% in obese group (p = 0.39). There was no significant difference in mortality, sNDI, moderate/severe cerebral palsy, Bayley Scales of Infant Development (BSID)-III cognitive composite score <70, BSID-III language composite score <70 in adjusted models. Conclusion Neurodevelopmental outcome was not significantly associated with maternal pre-pregnancy BMI among extreme preterm infants.

Hypothesis: Increased social distancing was associated with a lower incidence of extremely preterm live births (EPLB) during the initial COVID-19 pandemic period. Study design: Prospective study at the NICHD Neonatal Research Network sites comparing EPLB (22^0/7–28^6/7 weeks) and extremely preterm intrapartum stillbirths (EPIS) rates during the pandemic period (March-July, weeks 9–30 of 2020) with the reference period (same weeks in 2018 and 2019), correlating with state-specific social distancing index (SDI). Results: EPLB and EPIS percentages did not significantly decrease (1.58–1.45%, p = 0.07, and 0.08–0.06%, p = 0.14, respectively). SDI was not significantly correlated with percent change of EPLB (CC = 0.29, 95% CI = −0.12, 0.71) or EPIS (CC = −0.23, 95% CI = −0.65, 0.18). Percent change in mean gestational age was positively correlated with SDI (CC = 0.49, 95% CI = 0.07, 0.91). Conclusions: Increased social distancing was not associated with change in incidence of EPLB but was associated with a higher gestational age of extremely preterm births. ClinicalTrials.gov ID: Generic Database: NCT00063063.

Objectives To compare serum ferritin and RET-He values among extremely low gestational age neonates ELGANs with other markers of iron-deficient erythropoiesis. Study Design This is a secondary analysis of the NICHD Darbepoetin Trial. Study data from placebo recipients who had a serum ferritin, a RET-He, and a mean corpuscular volume (MCV) measurement within a 24-hour period were analyzed for correlation. Results Mixed linear regression models showed no association between ferritin and RET-He at both early (β = 0.0016, p = 0.40) and late (β = −0.0001, p = 0.96) time points. Positive associations were observed between RET-He and MCV at baseline, early, and late time points (p < 0.01, =0.01, <0.001, respectively), while ferritin was not associated with MCV at any time point. Conclusions Our study shows that RET-He is better correlated with MCV as a marker of iron-limited erythropoiesis than ferritin. The results suggest that ferritin is limited as a marker of iron sufficiency in premature infants. Study Identification FDA IND Number 100138; ClinicalTrials.gov number NCT03169881; NRN ID number NICHD-NRN-0058 (Darbe).

Objective: To compare the rates of death or survival with severe neurodevelopmental impairment (sNDI) at 2 years among extremely preterm infants in relation to pre-pregnancy or first trimester maternal body mass index (BMI). Methods: This retrospective cohort study included extremely preterm infants (gestational age 22^0/7-26^6/7 weeks). The study was conducted at National Institute of Child Health and Human Development Neonatal Research Network sites. The primary outcome was death or sNDI at 2 years. Results: Data on the primary outcome were available for 1,208 children. Death or sNDI was not different among the three groups: 54.9% in normal, 56.1% in overweight, and 53.4% in obese group (p=0.39). There was no significant difference in mortality, sNDI, moderate/severe cerebral palsy, Bayley Scales of Infant Development (BSID)-III cognitive composite score Conclusion: Neurodevelopmental outcome was not significantly associated with maternal pre-pregnancy BMI among extreme preterm infants.