Maternal Smoking During Pregnancy and Timing of Puberty in Sons and Daughters: A Population-Based Cohort Study

Abstract

As early puberty has been linked to diseases later in life, identification of modifiable causes of early puberty is of interest. We explore the possible associations between maternal smoking during pregnancy and pubertal development in sons and daughters. Between 2012 and 2017, 15,819 children from the Danish National Birth Cohort, born during 2000-2003, provided half-yearly information on puberty from the age of 11 years. We estimated adjusted age differences (in months) at attaining various pubertal milestones, including Tanner stages, per 10 daily cigarettes smoked in first trimester. In sons, smoking in pregnancy was associated with earlier genital development (Tanner 2: -1.3, 95% confidence interval (CI): -2.5, 0.0. Tanner 5: -3.7, 95% CI: -5.3, -2.0), pubic hair development (Tanner 2: -1.8, 95% CI: -2.9, -0.6. Tanner 5: -2.9, 95% CI: -4.2, -1.7), and voice break (-2.4, 95% CI: -3.6, -1.3). In daughters, smoking was associated with earlier breast development (Tanner 2: -3.4, 95% CI: -5.3, -1.5. Tanner 5: -4.7, 95% CI: -6.5, -2.9), pubic hair development stage 3 to 5 (Tanner 5: -2.5, 95% CI: -4.1, -1.0), and menarche (-3.1, 95% CI: -4.0, -2.3). Fetal exposure to tobacco smoke may advance timing of puberty in boys and girls.

Risk of selection bias due to non‐participation in a cohort study on pubertal timing

“…(b) We then ran the aetiologic analyses for the entire Puberty Cohort using both bootstrap samples and then for participants only using the bootstrap sample for participants only using fixed sampling weights derived previously. 8 (c) We then saved the difference between the estimates for the two populations. Then, we repeated step 1-3 in 10 000 replications to obtain the 95% CI.…”

“…Sampling weights reflect the inverse probability of being sampled and were included in all analysis to account for the sampling strategy in the Puberty Cohort. 8 Robust SEs were applied to account for clustering of siblings (166 male-male and 136 female-female siblings) and the use of sampling weights. All analyses were performed in stata 15.1 MP software (StataCorp).…”

“…To obtain large exposure contrasts, the Puberty Cohort was sampled independently according to 12 different prenatal exposures hypothesised to be prenatal causes of pubertal timing such as pre-pregnancy obesity, maternal smoking during pregnancy, and alcohol drinking during pregnancy. 8 If a child was sampled more than once (ie from different exposure categories), the child was only included in the analyses once. Based on rules from probability theory and the sampling fractions, we were able to calculate exact sampling probabilities.…”

“…The mathematical derivation of the sampling weights is described in detail previously. 8 In total, 22 439 of 56 641 children were sampled to constitute the Puberty Cohort. These children were invited to provide information on their current pubertal development as part of the 11-year follow-up in the DNBC and as part of…”

GENETICS IN ENDOCRINOLOGY: Genetic etiologies of central precocious puberty and the role of imprinted genes

“…While minor advances in the age of menarche have been observed in the United States and Europe since the 1960s, more dramatic reductions have been observed in countries with improving socioeconomic status such as Indonesia, Brazil, Argentina and China, often in the setting of increased rates of childhood obesity (14,15,16,17,18,19,20). Furthermore, increasing recognition of environmental factors and exposures have been described in association with an earlier age of puberty, such as the effects of maternal smoking during pregnancy, of girls being raised without a father, and of some endocrine-disrupting chemicals (21,22,23).…”