Placental weight Z-score and pubertal timing: A population-based cohort study.

Abstract

The placenta provides nutrients, oxygen, and hormonal support for adequate fetal growth and development of the hormonal axes, which are important for pubertal timing later in life. We investigated if an indicator of poor placental function, low gestational age-specific Z-score for placental weight at birth, was associated with earlier pubertal timing. The study is based on a population-based cohort of 15195 singleton boys and girls (68% of 22439 invited) born 20 to 43weeks of gestation (2000-2003) nested within the Danish National Birth Cohort. Placental Z-score was estimated from data collected at birth. Between 2012 and 2018, the children returned half-yearly web-based questionnaires from age of 11years on status of the pubertal milestones: Tanner stages, voice break, first ejaculation, menarche, acne, and axillary hair. We estimated adjusted monthly differences in mean age at attaining the pubertal milestones and pubertal timing overall with placental Z-score continuously and as restricted cubic splines. Further, we explored whether growth by birthweight Z-score and body mass index Z-score around 7years mediated the associations. Placental Z-score was positively associated with age at attaining most of the pubertal milestones in girls, particularly for age at menarche, but not in boys. Effect sizes were modest, and when combining all pubertal milestones, one standard deviation increase in placental Z-score was associated with 0.5months (95% confidence interval [CI] 0.2, 0.9) later pubertal timing overall in girls. The associations in girls were largely mediated through fetal growth. Assuming that placental Z-score correlates with placental function, these findings suggest that placental dysfunction (low placental Z-score) advances pubertal timing in girls slightly by reducing fetal growth. Future studies need to evaluate whether placental weight sufficiently captures intrauterine growth of importance for pubertal development and search for other potential candidates reflecting placental function.