Breastfeeding, Prepubertal Adiposity, and Development of Precocious Puberty

Abstract

Importance: The incidence of central precocious puberty (CPP) is increasing globally, raising concern about its potential long-term health consequences. However, the association between early-life feeding practices and CPP is poorly understood. Objective: To investigate the association of breastfeeding during the first 4 to 6 months of life with CPP in boys and girls and whether this association is mediated by prepubertal adiposity. Design, Setting, and Participants: This nationwide, retrospective cohort study used health claims data from the South Korean National Health Insurance Service Database between January 1, 2007, and December 31, 2020. Children who underwent routine health checkups at 4 to 6 months (examination 1) and 66 to 71 months (examination 7) were eligible. Children with comorbidities, who died during the follow-up period, who had missing information, or who were diagnosed with CPP before age 6 years were excluded. Data were analyzed between October 9, 2024, and January 14, 2025. Exposure: Feeding practice patterns collected through a primary caregiver-reported questionnaire during examination 1. Main Outcomes and Measures: The primary outcome was the incidence of CPP, defined by International Statistical Classification of Diseases, Tenth Revision diagnostic codes and administration of gonadotropin-releasing hormone agonists. The association between feeding practices and incidence of CPP was assessed using a multivariable Cox proportional hazards model to estimate adjusted hazard ratios (AHRs) and 95% CIs. Causal mediation analysis within a counterfactual framework was conducted to quantify mediation by childhood overweight or obesity. Results: Among 322 731 children (58.1% girls), 46.0% were exclusively breastfed, 34.9% were formula-fed, and 19.1% were mixed-fed. Compared with exclusively breastfed children, formula-fed children had the greatest risk of CPP in boys (AHR, 1.16; 95% CI, 1.10-1.21) and girls (AHR, 1.60; 95% CI, 1.24-2.06), followed by mixed-fed boys (AHR, 1.14; 95% CI, 1.07-1.20) and girls (AHR, 1.45; 95% CI, 1.07-1.97). Mediation through prepubertal adiposity accounted for 7.2% (bootstrap 95% CI, 4.5%-12.1%) and 17.8% (bootstrap 95% CI, 6.6%-30.0%) of the association between formula feeding and CPP in boys and girls, respectively. Conclusions and Relevance: In this nationwide, retrospective cohort study, breastfeeding during the first 4 to 6 months of life was associated with a lower risk of CPP in boys and girls. This association was partially mediated by prepubertal adiposity, highlighting the critical role of early-life nutrition in pubertal timing. This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine