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Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies

Lookup NU author(s): Dr Demetris AvraamORCiD, Emeritus Professor Paul BurtonORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Copyright: © 2023 Vinther et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. BACKGROUND: Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence. METHODS AND FINDINGS: We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries. CONCLUSIONS: This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.

Publication metadata

Author(s): Vinther JL, Cadman T, Avraam D, Ekstrom CT, I A Sorensen T, Elhakeem A, Santos AC, Pinot de Moira A, Heude B, Iniguez C, Pizzi C, Simons E, Voerman E, Corpeleijn E, Zariouh F, Santorelli G, Inskip HM, Barros H, Carson J, Harris JR, Nader JL, Ronkainen J, Strandberg-Larsen K, Santa-Marina L, Calas L, Cederkvist L, Popovic M, Charles M-A, Welten M, Vrijheid M, Azad M, Subbarao P, Burton P, Mandhane PJ, Huang R-C, Wilson RC, Haakma S, Fernandez-Barres S, Turvey S, Santos S, Tough SC, Sebert S, Moraes TJ, Salika T, Jaddoe VWV, Lawlor DA, Nybo Andersen A-M

Publication type: Article

Publication status: Published

Journal: PLoS medicine

Year: 2023

Volume: 20

Issue: 1

Online publication date: 26/01/2023

Acceptance date: 19/12/2022

Date deposited: 09/02/2023

ISSN (print): 1549-1277

ISSN (electronic): 1549-1676

Publisher: Public Library of Science


DOI: 10.1371/journal.pmed.1004036

PubMed id: 36701266


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Funder referenceFunder name
European Union’s Horizon 2020 research and innovation programme (Grant Agreement No. 733206 LifeCycle
Grant Agreement No. 824989 EUCANConnect