The estimated effect of season and vitamin D in the first trimester on pubertal timing in girls and boys: a cohort study and an instrumental variable analysis

Abstract

Background Season of birth has been associated with age at menarche. Maternal vitamin D levels in pregnancy may explain this effect. We investigated whether the season of first trimester or maternal 25-hydroxyvitamin D3 [25(OH)D3] levels were associated with pubertal timing in children. Methods We conducted a follow-up study of 15 819 children born in 2000–03 from the Puberty Cohort, nested in the Danish National Birth Cohort (DNBC). Mean differences in attaining numerous pubertal markers, including a combined estimate for the average age at attaining all pubertal markers, were estimated for low (November–April) relative to high (May–October) sunshine exposure season in the first trimester using multivariable interval-censored regression models. Moreover, we conducted a two-sample instrumental variable analysis using season as an instrument for maternal first-trimester 25(OH)D3 plasma levels obtained from a non-overlapping subset (n = 827) in the DNBC. Results For the combined estimate, girls and boys of mothers who had their first trimester during November–April had earlier pubertal timing than girls and boys of mothers whose first trimester occurred during May–October: –1.0 months (95% CI: –1.7 to –0.3) and –0.7 months (95% CI: –1.4 to –0.1), respectively. In the instrumental variable analysis, girls and boys also had earlier pubertal timing: respectively, –1.3 months (95% CI: –2.1 to –0.4) and –1.0 months (95% CI: –1.8 to –0.2) per SD (22 nmol/L) decrease in 25(OH)D3. Conclusions Both first pregnancy trimester during November–April and lower 25(OH)D3 were associated with earlier pubertal timing in girls and boys.

Maternal Intake of Vitamin D Supplements during Pregnancy and Pubertal Timing in Children: A Population-Based Follow-Up Study

“…In another study from the Puberty Cohort, we have previously found an association between maternal 25(OH)D 3 levels predicted based on the season of the first pregnancy trimester and earlier pubertal timing in both boys and girls [ 45 ]. In the study using season of gestational week 8 as an instrumental variable for maternal 25(OH)D 3 levels, we found that boys experienced earlier pubertal timing of −1.0 months (95% CI: −1.8; −0.2 months) per 22 nmol/L lower maternal 25(OH)D 3 levels for the combined estimate for pubertal timing.…”

“…In the study using season of gestational week 8 as an instrumental variable for maternal 25(OH)D 3 levels, we found that boys experienced earlier pubertal timing of −1.0 months (95% CI: −1.8; −0.2 months) per 22 nmol/L lower maternal 25(OH)D 3 levels for the combined estimate for pubertal timing. Girls experienced earlier pubertal timing of −1.3 months (95% CI: −2.1; −0.4 months) per 22 nmol/L lower maternal 25(OH)D 3 levels for the combined estimate for pubertal timing [ 45 ]. This inconsistency warrants further exploration, but could be explained by potential violation of the assumptions underlying the applied methods or may arise due to bias.…”

Minipuberty in Sons of Women with Low Vitamin D Status during Pregnancy

“…Low 25-hydroxyvitamin D levels were also observed in variants of precocious puberty: premature adrenarche [12] and premature menarche [13]. Lastly, first pregnancy trimester between November and April, a period of the year when the sunlight-induced skin synthesis of endogenous calciferol is decreased [14], was associated with earlier pubertal timing both in girls and boys, which was attributed to lower 25-hydroxyvitamin D levels [15]. Vitamin D receptors and enzyme-metabolizing calciferol are expressed in Sertoli cells, Leydig cells, germ cells, spermatozoa, and in the epithelial cells lining the male reproductive tract [16].…”