Low birthweight in term singletons mediates the association between maternal smoking intensity exposure status and immediate neonatal intensive care unit admission: The E-value assessment

Abstract

Background: Research investigating the wellbeing of term neonates in the United States is scarce. The objectives of this study were to estimate the prevalence of low birthweight (LBW) and neonatal intensive care unit (NICU) admission among term singletons in association with maternal smoking intensity exposure status, to explore LBW as a mediator linking smoking to immediate newborn NICU transfer/admission, and to assess the potential impact of unmeasured confounding in effect estimates. Methods: The Natality File of live births registered in the United States in 2016, the first year that all 50 states implemented the revised 2003 standard birth certificate, was restricted to singleton term births (37-41 completed weeks gestation). The prevalence of LBW (< 2500 g) and NICU transfer/admission was estimated across maternal demographic characteristics and smoking intensity status in early and in late pregnancy. Mediation analyses, based on the counterfactual approach, were conducted to examine the total effect (TE), controlled direct effect (CDE), natural direct (NDE) and indirect effects (NIE), and the percentage mediated through LBW. The E-values based on effect size estimates and on lower-bounds of 95% confidence intervals (CIs) assessed the potential impact of unmeasured confounding. Results: Nearly 6.8% of women smoked in early and in late pregnancy, most (36.4%) smoked at high intensity (≥ 10 cigarettes /day) and had the highest prevalence of LBW (6.7%) and NICU transfer/admission (7.0%). For the largest smoking intensity exposure category, the estimate of the TE was 1.68 (95% CI: 1.63, 1.73), of the NDE was 1.56 (95% CI: 1.51, 1.61), of the NIE was 1.08 (95% CI:1.07, 1.09), and the percentage mediated by LBW was 17.6%. The E-values for association estimates and for the lower-bounds of 95% CIs demonstrated the minimum strength of the potential unmeasured confounding necessary to explain away observed associations. Conclusions: These findings fill a gap on the prevalence of LBW and NICU transfer/admission in term neonates of mothers who smoke and on the role of LBW linking to NICU placement, which could be used to update practitioners, to implement smoking cessation interventions, monitor trends, and to inform planning and allocation of healthcare resources.