Analysis of Early-Life Growth and Age at Pubertal Onset in US Children

Izzuddin M Aris,Johnnye Lewis,Catherine Karr,Clancy Blair,Sean Deoni,Thomas O’Connor,James Gern,Leonardo Trasande,Cynthia Mcevoy,Assiamira Ferrara,Joseph B Stanford ,Nicole L Mihalopoulos,Xiangrong Kong,Margaret R Karagas ,Chang Liu,Julie B Herbstman ,Alison E Hipwell ,Irva Hertz‐Picciotto ,Craig J Newschaffer ,Cristiane S Duarte ,Christine W Hockett,Elizabeth T Jensen,Akram N Alshawabkeh ,Carlos Eduardo Camargo ,Scott T Weiss ,Judy L Aschner ,T Michael Oʼshea ,Wei Perng,Jean M Kerver ,Megan M Herting,Dana Dabelea,Susan L Schantz ,Amy J Elliott ,Olivia Robertson ,Emily Oken,Leslie D Leve ,Anne L Dunlop ,Jody M Ganiban,Carrie V Breton ,Barry M Lester ,Kristine Marceau,Marie‐France Hivert ,Rosalind J Wright

doi:10.1001/jamanetworkopen.2021.46873

Abstract

Earlier pubertal onset may be associated with an increased risk of chronic diseases. However, the extent to which growth in the first 5 years of life-an important developmental life stage that lays the foundation for later health outcomes-is associated with pubertal onset remains understudied. To assess whether changes in weight, length or height, and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) during the first 5 years of life are associated with earlier pubertal onset. This cohort study used data from 36 cohorts participating in the Environmental Influences on Child Health Outcomes program from January 1, 1986, to December 31, 2015. Participant inclusion required at least 1 anthropometric measure in the first 5 years of life and at least 1 measure of pubertal onset. Data were analyzed from January 1 to June 30, 2021. Standardized velocities of weight, length or height, and BMI gain in early infancy (0-0.5 years), late infancy (0.5-2 years), and early childhood (2-5 years). Markers of pubertal onset for boys and girls, including age at peak height velocity (APHV), time to puberty score greater than 1, time to Tanner pubic hair stage greater than 1, and time to menarche. Multivariable regression models were used to estimate mean differences in APHV by growth periods. Of 7495 children included in the study, 3772 (50.3%) were girls, 4505 (60.1%) were White individuals, and 6307 (84.1%) were born during or after the year 2000. Girls had a younger APHV (10.8 vs 12.9 years) than boys. In boys, faster weight gain (per 1-SD increase) in early infancy (β, -0.08 years; 95% CI, -0.10 to -0.06), late infancy (β, -0.10 years; 95% CI, -0.12 to -0.08), and early childhood (β, -0.07 years; 95% CI, -0.08 to -0.05) was associated with younger APHV after adjusting for the child's birth year, race, and Hispanic ethnicity as well as maternal age at delivery; educational level during pregnancy; annual household income during pregnancy; prenatal cigarette smoking; whether the mother was nulliparous; whether the mother had gestational diabetes, hypertension, or preeclampsia; mode of delivery; prepregnancy BMI; gestational weight gain; and gestational age at delivery. Similar associations were observed for length or height and BMI gains during the same age periods. In girls, faster gains (per 1-SD increase) in weight (β, -0.03 years; 95% CI, -0.05 to -0.01) and height (β, -0.02 years; 95% CI, -0.04 to 0.00) in early childhood were associated with younger APHV. Faster BMI gain in late infancy was associated with earlier time to menarche, whereas faster BMI gain in early childhood was associated with earlier time to Tanner pubic hair stage greater than 1. This cohort study found that faster gains in weight, length or height, or BMI in early life were associated with earlier pubertal onset. The results suggest that children who experience faster early growth should be monitored closely for earlier onset of puberty and referred as appropriate for supportive services.

Highlights

Puberty is a key physiological milestone, characterized by maturation of the reproductive, musculoskeletal, neurodevelopmental, and cardiometabolic systems via distinct processes in boys and girls.[1]
Faster weight gain in early infancy (β, −0.08 years; 95% CI, −0.10 to −0.06), late infancy (β, −0.10 years; 95% CI, −0.12 to −0.08), and early childhood (β, −0.07 years; 95% CI, −0.08 to −0.05) was associated with younger at peak height velocity (APHV) after adjusting for the child’s birth year, race, and Hispanic ethnicity as well as maternal age at delivery; educational level during pregnancy; annual household income during pregnancy; prenatal cigarette smoking; whether the mother was nulliparous; whether the mother had gestational diabetes, hypertension, or preeclampsia; mode of delivery; prepregnancy BMI; gestational weight gain; and gestational age at delivery
Faster gains in weight (β, −0.03 years; 95% CI, −0.05 to −0.01) and height (β, −0.02 years; 95% CI, −0.04 to 0.00) in early childhood were associated with younger APHV

Summary

Introduction

Puberty is a key physiological milestone, characterized by maturation of the reproductive, musculoskeletal, neurodevelopmental, and cardiometabolic systems via distinct processes in boys and girls.[1] During the past few decades, substantial concern has been raised about children entering puberty at younger ages in the United States and other countries.[2,3,4] These observations have important clinical implications for children and their families that may necessitate counseling and intervention.[5] children with earlier pubertal onset may be at increased risk for long-term chronic diseases[6] and may experience adverse consequences during adolescence, including psychosocial difficulties and dysmetabolism.[7] A clearer understanding of the early life factors associated with pubertal onset is important to develop intervention strategies to prevent earlier pubertal onset. Previous research on pubertal onset has been limited by small sample sizes[16] and inclusion of only girls or homogeneous populations[17,18] and often examined only 1 marker of pubertal timing (ie, age at menarche[19])

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