Maternal cigarette smoking before or during pregnancy increases the risk of birth congenital anomalies: a population-based retrospective cohort study of 12 million mother-infant pairs
Authors: Yang Lili , Wang Huan , Yang Liu , Zhao Min , Guo Yajun , Bovet Pascal , Xi Bo 
Published: January 2022

Abstract
Background
The associations of maternal cigarette smoking with congenital anomalies in offspring have been inconsistent. This study aimed to clarify the associations of the timing and intensity of maternal cigarette smoking with 12 subtypes of birth congenital anomalies based on a nationwide large birth cohort in the USA.

Methods
We used nationwide birth certificate data from the US National Vital Statistics System during 2016–2019. Women reported the average daily number of cigarettes they consumed 3 months before pregnancy and in each subsequent trimester during pregnancy. Twelve subtypes of congenital anomalies were identified in medical records. Poisson regression analysis was used to estimate the risk ratios (RRs) with 95% confidence intervals (CIs) for 12 subtypes of congenital anomalies associated with the timing (i.e., before pregnancy, and during three different trimesters of pregnancy) and intensity (i.e., number of cigarettes consumed per day) of maternal cigarette smoking.

Results
Among the 12,144,972 women included, 9.3% smoked before pregnancy and 7.0%, 6.0%, and 5.7% in the first, second, and third trimester, respectively. Maternal smoking before or during pregnancy significantly increased the risk of six subtypes of birth congenital anomalies (i.e., congenital diaphragmatic hernia, gastroschisis, limb reduction defect, cleft lip with or without cleft palate, cleft palate alone, and hypospadias), even as low as 1–5 cigarettes per day. The adjusted RRs (95% CIs) for overall birth congenital anomalies (defined as having any one of the congenital malformations above significantly associated with maternal cigarette smoking) among women who smoked 1–5, 6–10, and ≥ 11 cigarettes per day before pregnancy were 1.31 (1.22–1.41), 1.25 (1.17–1.33), and 1.35 (1.28–1.43), respectively. Corresponding values were 1.23 (1.14–1.33), 1.33 (1.24–1.42), 1.33 (1.23–1.43), respectively, for women who smoked cigarettes in the first trimester; 1.32 (1.21–1.44), 1.36 (1.26–1.47), and 1.38 (1.23–1.54), respectively, for women who smoked cigarettes in the second trimester; and 1.33 (1.22–1.44), 1.35 (1.24–1.47), and 1.35 (1.19–1.52), respectively, for women who smoked cigarettes in the third trimester. Compared with women who kept smoking before and throughout pregnancy, women who never smoked had significantly lower risk of congenital anomalies (RR 0.77, 95% CI 0.73–0.81), but women who smoked before pregnancy and quitted during each trimester of pregnancy had no reduced risk (all P > 0.05).

Conclusions
Maternal smoking before or during pregnancy increased the risk of several birth congenital anomalies, even as low as 1–5 cigarettes per day. Maternal smokers who stopped smoking in the subsequent trimesters of pregnancy were still at an increased risk of birth congenital anomalies. Our findings highlighted that smoking cessation interventions should be implemented before pregnancy.