Associations of fetal and infant growth with pubertal timing

Objective: Impaired fetal and infant growth may cause alterations in developmental programming of the hypothalamic-pituitary-gonadal axis and subsequently pubertal development. We aimed to assess associations between fetal and infant growth and pubertal development. Design: Population-based prospective birth cohort. Setting: Rotterdam, the Netherlands. Patients: 5830 singleton born children. Interventions: We estimated fetal weight in second and third trimester by ultrasound. Infant growth measures were gestational age and weight at birth and infant weight at 6, 12 and 24 months. Main outcome measures: Pubertal timing outcomes included difference between chronological and skeletal age assessed using dual-energy X-ray absorptiometry, testicular or ovarian volumes assessed using MRI at 10 years, age at menarche and Tanner staging at 13 years. Results: Among girls, 1-SD scores birth weight increase was associated with larger ovarian volume at 10 years (0.07 SD (95% CI 0.02 to 0.12) and later age at menarche (0.06 (0.02 to 0.11)). Among girls, increased infant growth was associated with an older skeletal age at 10 years (difference 2.67 (95% CI 2.26 to 3.08) months), earlier menarche (difference 0.10 (95% CI -0.14 to -0.06) years) and more advance breast and pubic hair development at 13 years (difference in Tanner stages 0.09 (0.05 to 0.13) and 0.07 (0.03 to 0.12)). In boys, increased infant growth was associated with an older skeletal age (3.13 (95% CI 2.58 to 3.69) months) and a larger testicular volume (0.07 (95% 0.02 to 0.12) SD) at 10 years, and with more advance pubic hair development (0.09 (95% CI 0.05 to 0.14) at 13 years). Conclusion: Birth anthropometrics and early-life growth patterns are associated with altered pubertal development in a sex-specific manner.