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

Because early puberty has been linked to diseases later in life, identification of modifiable causes of early puberty is of interest. We explored 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 the first trimester of gestation. In sons, exposure to smoking in utero was associated with earlier genital development (Tanner 2, -1.3 months, 95% confidence interval (CI): -2.5, 0.0; Tanner 5, -3.7 months, 95% CI: -5.3, -2.0), pubic hair development (Tanner 2, -1.8 months, 95% CI: -2.9, -0.6; Tanner 5, -2.9 months, 95% CI: -4.2, -1.7), and voice break (-2.4 months, 95% CI: -3.6, -1.3). In daughters, maternal smoking was associated with earlier breast development (Tanner 2, -3.4 months, 95% CI: -5.3, -1.5; Tanner 5, -4.7 months, 95% CI: -6.5, -2.9), pubic hair development stages 3-5 (Tanner 5, -2.5 months, 95% CI: -4.1, -1.0), and menarche (-3.1 months, 95% CI: -4.0, -2.3). Fetal exposure to tobacco smoke might advance timing of puberty in boys and girls.

Acetaminophen (Paracetamol) Exposure During Pregnancy and Pubertal Development in Boys and Girls From a Nationwide Puberty Cohort.

This study explored the association between exposure to acetaminophen during pregnancy and pubertal development using data from 15,822 boys and girls in the longitudinal Puberty Cohort, nested within the Danish National Birth Cohort. Use of acetaminophen was reported 3 times during pregnancy and 6 months postpartum. In total, 54% of mothers indicated use at least once during pregnancy. Between 2012 and 2017, sons and daughters provided information on a wide range of pubertal milestones-including Tanner stages, axillary hair growth, and age at menarche or voice break and first ejaculation-every 6 months from 11 years of age until full sexual maturation. Data were analyzed using a regression model for interval-censored data, providing adjusted mean monthly differences in age at attaining the pubertal milestones according to intrauterine cumulative (weeks) and trimester-specific acetaminophen exposure. Our results suggested a tendency towards slightly earlier attainment of almost all studied markers of female pubertal development with increasing number of weeks of exposure (i.e., about 1.5-3 months earlier age at pubic hair, axillary hair, and acne development comparing unexposed with those prenatally exposed for more than 12 weeks). Male pubertal development had no strong association with acetaminophen exposure.

Alcohol intake during pregnancy and timing of puberty in sons and daughters: A nationwide cohort study.

We explored whether maternal alcohol intake in early pregnancy is associated with pubertal timing in sons and daughters. In total, 15,819 children, born 2000-2003 within the Danish National Birth Cohort, gave half-yearly, self-reported information on pubertal development (Tanner stages, voice break, first ejaculation, menarche, acne, and axillary hair) from 11 years during 2012-2018. Information on maternal average alcohol intake in first trimester and binge drinking episodes (intake of ≥5 drinks on the same occasion) in first trimester was self-reported by mothers during pregnancy. Average alcohol intake of 5+ weekly drinks in first trimester was not associated with pubertal timing in sons (with no alcohol intake as the reference). A tendency towards earlier pubertal timing was observed in daughters (-2.0 (95 % confidence interval: -4.2, 0.3) months) when combining the estimates for all pubertal milestones. Binge drinking was not associated with pubertal timing in neither sons nor daughters.

Pubertal development after unintended intrauterine exposure to oral contraceptives: a nationwide cohort study.

OBJECTIVE: To study the associations between exposure to oral contraceptives before conception and early in pregnancy and pubertal timing in boys and girls. DESIGN: Population-based cohort study. SETTING: Not applicable. PATIENT(S): Overall, 15,800 children (70%) born during 2000-2003 into the Danish National Birth Cohort were categorized according to maternal use of combined oral contraceptive pills or progestin-only pills reported around gestational week 17: no exposure (reference), exposure 4 months before conception, and exposure in early pregnancy. Children self-assessed pubertal status using Web-based questionnaires from 11 years and biannually throughout puberty. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Adjusted mean age differences (months) for attaining individual pubertal milestones and overall pubertal timing. Proportion mediated by prepubertal body mass index. RESULT(S): In boys, intrauterine exposure to oral contraceptives showed a tendency toward slightly earlier mean age for voice break (months, -3.8; 95% confidence interval [CI] -6.5, -1.0) and first ejaculation (months, -2.9; 95% CI -5.9, 0.1) and a mean difference of -1.4 months (95% CI -3.3, 0.4) for overall pubertal timing. Girls with intrauterine exposure tended to have slightly earlier age at menarche (months, -1.9; 95% CI -4.0, 0.3) and Tanner breast stages and had a mean difference of -0.9 months (95% CI -2.7, 1.0) for overall pubertal timing. Exposure before conception was not associated with pubertal timing. Prepubertal body mass index did not play a mediating role. CONCLUSION(S): This study shows some evidence that intrauterine exposure to oral contraceptives might slightly affect pubertal timing.

Maternal pre-pregnancy obesity and timing of puberty in sons and daughters: a population-based cohort study.

BACKGROUND: In many countries, an increased prevalence of obesity in pregnancy has coincided with a declining pubertal age. We aimed to explore the potential effect of maternal pre-pregnancy overweight and obesity on timing of puberty in sons and daughters. METHODS: Between 2012 and 2018, 15 819 of 22 439 invited children from the Danish National Birth Cohort, born 2000-03, provided half-yearly information from the age of 11 years on the pubertal milestones: Tanner stages, voice break, first ejaculation, menarche, acne and axillary hair. We estimated adjusted mean monthly differences (with 95% confidence intervals) in age at attaining the pubertal milestones for children exposed to maternal pre-pregnancy obesity [body mass index (BMI) ≥30.0 kg/m2] or overweight (BMI 25.0 to 29.9 kg/m2) with normal weight (BMI 18.5 to 24.9 kg/m2) as reference. In mediation analysis, we explored whether childhood BMI at age 7 years mediated the associations. RESULTS: Maternal pre-pregnancy obesity was associated with earlier age at attaining most pubertal milestones in sons, and pre-pregnancy overweight and obesity were associated with earlier age at attaining all pubertal milestones in daughters. When combining all pubertal milestones, pre-pregnancy obesity [sons: -1.5 (-2.5, -0.4) months; daughters: -3.2 (-4.2, -2.1) months] and overweight [daughters only: -2.6 (-3.3, -1.8) months] were associated with earlier timing of puberty. The associations in sons were completely mediated by higher childhood BMI and partly so in daughters. CONCLUSIONS: Maternal pre-pregnancy obesity appears to lower timing of puberty through childhood obesity in sons and mainly through other mechanisms in daughters.

Maternal diabetes mellitus and timing of pubertal development in daughters and sons: a nationwide cohort study.

OBJECTIVE: To study the association between maternal diabetes and timing of pubertal development in daughters and sons. DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 15,822 mother-child pairs included in the Danish National Birth Cohort and the Puberty Cohort with prospectively collected, register-based and self-reported information on maternal diabetes and self-reported information on pubertal development. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Adjusted mean monthly difference in age at attaining pubertal milestones in children born of mothers with diabetes compared with children born of mothers without diabetes. RESULT(S): A total of 502 children were born of mothers with diabetes during pregnancy. In daughters exposed to gestational diabetes mellitus, we observed advanced onset in all pubertal milestones. The associations were statistically significant with regard to pubic hair Tanner stage 2 (-4.8 months) (95% confidence interval [CI] -7.7, -2.0), pubic hair Tanner stage 3 (-2.2 months) (95 % CI -4.4, 0.0), pubic hair Tanner stage 5 (-6.0 months) (95% CI -10.8, -1.2), and menarche (-2.5 months) (95 % CI -4.9, 0.0). We observed no tendencies between maternal type 1 or type 2 diabetes mellitus and pubertal development in daughters. We observed no associations between maternal diabetes and pubertal development in sons. CONCLUSION(S): Our findings suggest that gestational diabetes mellitus may accelerate the pubertal development in daughters. Our results did not support an association between type 1 or type 2 diabetes mellitus and daughters' pubertal development, as well as between any type of maternal diabetes and sons' pubertal development.