Abstract Background We evaluated the inter-rater agreement between self-assessed Tanner staging and clinical examination and the intra-individual agreement of self-assessed information on various puberty markers in late adolescents from the longitudinal nationwide Puberty Cohort, a sub-cohort of the Danish National Birth Cohort (DNBC). Methods We invited 715 children from the ongoing Puberty Cohort between June 2016 and January 2017. In total, 366 children (51%) returned an add-on questionnaire identical to the questionnaire used to collect information on puberty markers, including Tanner staging, in the Puberty Cohort. Of these, 197 (54%) also participated in a clinical examination with Tanner staging. We used percentage agreement and weighted kappa statistics to evaluate the inter-rater and intra-individual agreement. Results Due to late entry, more than 75% of children were Tanner stage 4 or above at clinical examination. In girls, the inter-rater agreement for pubic hair and breast staging was 54% and 52%, respectively, yielding weighted kappas of fair strength. In boys, pubic hair and genital staging agreed in 55% and 33%, respectively, corresponding to weighted kappas of fair to moderate strength. Boys tended to underestimate genitalia staging consistently. The intra-individual agreement on Tanner staging was 75–77% in girls and 69% in boys, whereas the intra-individual agreement on axillary hair and acne was above 92%. Conclusions Self-assessment of late stages of pubertal development may be misclassified, leading to random errors in studies of puberty timing. However, self-assessment continues to serve as an important time- and cost-saving tool in large prospective puberty cohorts.
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.
Abstract 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.
Is maternal age at menarche associated with pubertal development in sons and daughters? Maternal age at menarche was associated with pubertal development in both sons and daughters. Studies have shown that age at menarche is greatly inherited from mother to daughter, but it remains largely unknown to what extent age at menarche in mothers is associated with timing of puberty in sons. In this population-based study we used data from the Puberty Cohort nested within the Danish National Birth Cohort. Live-born singletons aged 11 were followed from 2012 to 2016. In total, 15 822 children (7697 sons and 8125 daughters) gave half-yearly information on puberty from the age of 11 years until full sexual maturity or 18 years of age through self-administrated questionnaires (participation rate 71%). Information on maternal age at menarche was reported by the mothers during pregnancy. Maternal age at menarche was used both as a continuous and as a categorical variable (earlier, same time or later than peers). A multivariable regression model for interval-censored data was used. Maternal age at menarche was positively associated with timing of genital development, pubic hair development, first ejaculation of semen, voice break, axillary hair development and acne in sons, and with timing of breast development, pubic hair development, menarche, axillary hair development and acne in daughters. In sons, the associations were of similar strength for all pubertal markers, whereas in daughters, the associations were strongest for breast development and menarche. Age at menarche was recalled during pregnancy. However, studies indicate that age at menarche is recalled moderately in adulthood. Information on puberty was self-reported, but inaccuracy of data would probably cause non-differential misclassification. Early maternal age at menarche was associated with earlier pubertal development, and late maternal age at menarche was associated with later pubertal development in both sons and daughters. The largest effect-estimates were for the associations between maternal age at menarche and the daughters' age at menarche and age at breast development. The study was funded by the Danish Council for Independent Research (4183-00152). There are no competing interests. N/A
This study investigated whether size at birth and infant growth were associated with age of indicators of pubertal development in boys and girls. We hypothesized that restricted fetal growth and accelerated infant growth lead to earlier pubertal age.In total, 15,822 boys and girls answered questionnaires half-yearly with information on pubertal development: age at menarche, first ejaculation, voice break, Tanner stages, axillary hair, and acne. Birth weight and gestational age were used to calculate birth weight Z-scores. Changes in infant weight Z-score from 0 to 5, 5 to 12, and 0 to 12 months were estimated. We estimated the mean monthly difference in timing of puberty between children born small-for-gestational age (SGA) and large-for-gestational age (LGA) with children born appropriate-for-gestational age (AGA) as reference. We further investigated whether increasing infant weight Z-scores were associated with age at attaining indicators of pubertal development.Girls born SGA reached all pubertal markers at an earlier mean age than girls born AGA, as indicated by mean age differences below zero (eg, age at menarche: -2.3 months, 95% CI: -3.4, -1.2), except for breast development. Girls born LGA reached pubertal markers later than girls born AGA (eg, age at menarche: 1.7 months, 95% CI 0.5, 2.9). Boys born SGA and LGA achieved puberty earlier than boys born AGA, though with CIs crossing zero (eg, age at voice break for SGA: -0.7 months, 95% CI -2.1, 0.7 and for LGA: -0.7 months, 95% CI -2.1, 0.8). A 1-unit increase in weight Z-score from 0 to 12 months was associated with a mean age difference of -1.7 to -0.3 months for pubertal development in both sexes.Small size at birth and rapid infant growth were associated with early pubertal age, most consistent and pronounced in girls.