Maternal Smoking Exposure and Newborn Outcomes: Study Using Urinary Cotinine

Overview

Prenatal exposure to tobacco smoke-whether from active maternal smoking or secondhand exposure-has been linked to adverse neonatal adaptation and metabolic stress. This single-center prospective observational cohort will quantify maternal smoking exposure using maternal urinary cotinine around delivery and examine its association with early neonatal physiologic and biochemical outcomes within the first 24 hours of life. Participants will be pregnant individuals delivering at a tertiary academic hospital and their newborns. After consent, mothers will provide a urine sample for cotinine measurement. Based on pre-specified cotinine thresholds and maternal history, dyads will be classified into three exposure groups: Active smoker, Passive exposure, or No exposure. No experimental intervention is administered; all neonatal assessments are part of routine peripartum care. Neonatal data collected (per standard practice) will include: umbilical cord blood gas parameters (pH, base excess, lactate) and fetal carboxyhemoglobin (FCOHb); birthweight; vital signs/blood pressure at \~6 hours; routine laboratory indices (e.g., hemogram, lipids such as HDL/LDL where available per unit protocol); heel-prick TSH from the standard newborn screen; and hearing screening result prior to discharge. Additional maternal and perinatal covariates (e.g., age, parity, gestational age, delivery mode, intrapartum events) will be recorded to support adjusted analyses. No extra phlebotomy beyond standard care will be performed; the study leverages existing clinical samples and measurements. Primary objective is to determine whether higher maternal cotinine-defined exposure is associated with greater metabolic stress at birth (indexed by cord lactate and related gas parameters) and higher FCOHb. Key secondary objectives include evaluating associations with birthweight, early blood pressure, TSH, hearing screen outcomes, and routine laboratory markers. Prespecified subgroup and sensitivity analyses (e.g., by gestational age strata or delivery mode) will be conducted as feasible. The planned sample includes approximately three cotinine-stratified cohorts recruited consecutively. Statistical analyses will follow a pre-registered plan using multivariable regression to adjust for confounders; ROC analyses may be used to explore cotinine thresholds predictive of adverse neonatal indices. Enrollment is anticipated to start October 13, 2025, with primary data collection completed within 2-3 months of recruitment initiation. This study will provide pragmatic, prospectively collected evidence on how biochemically verified maternal tobacco exposure relates to immediate neonatal metabolic, cardiovascular, endocrine, and auditory outcomes, using measurements obtainable in routine care.