Association of assisted reproductive technology with offspring growth and adiposity from infancy to early adulthood
Authors: Elhakeem Ahmed , Taylor Amy E. , Inskip Hazel M. , Huang Jonathan , Tafflet Muriel , Vinther Johan L. , Asta Federica , Erkamp Jan S. , Gagliardi Luigi , Guerlich Kathrin , Halliday Jane , Harskamp-van Ginkel Margreet W. , He Jian-Rong , Jaddoe Vincent WV. , Lewis Sharon , Maher Gillian M. , Manios Yannis , Mansell Toby , McCarthy Fergus P , McDonald Sheila W. , Medda Emanuela , Nisticò Lorenza , de Moira Angela Pinot , Popovic Maja , Reiss Irwin KM. , Rodrigues Carina , Salika Theodosia , Smith Ash , Stazi Maria A. , Walker Caroline , Wu Muci , Åsvold Bjørn A. , Barros Henrique , Brescianini Sonia , Burgner David , Chan Jerry KY. , Charles Marie-Aline , Eriksson Johan G. , Gaillard Romy , Grote Veit , HÅberg Siri E. , Heude Barbara , Koletzko Berthold , Morton Susan , Moschonis George , Murray Deirdre , O’ Mahony Desmond , Porta Daniela , Qiu Xiu , Richiardi Lorenzo , Rusconi Franca , Saffery Richard , Tough Suzanne C. , Vrijkotte Tanja GM. , Nelson Scott M. , Andersen Anne-Marie Nybo , Magnus Maria C. ,   ART-Health Cohort Collaboration, Lawlor Deborah A. 
Published: March 2022

ABSTRACTImportancePeople conceived using assisted reproductive technology (ART) make up an increasing proportion of the world’s population, and their numbers are expected to continue rising.ObjectiveInvestigate association of ART conception with growth and adiposity outcomes from infancy to early adulthood in offspring from a large multinational multi-cohort study.Design26 population-based cohort studies.SettingEurope, Asia-Pacific, and North AmericaParticipantsInfants, children, adolescents, and young adults born from 1984 to 2018, with mean ages at assessment of growth/adiposity outcomes ranging from 0.6 month to 27.4 years.ExposuresConception by ART (conventional in vitro fertilisation and intracytoplasmic sperm injection) versus natural conception (NC).Main Outcomes and MeasuresLength/height, weight, and body mass index (BMI). Each cohort was analysed separately with adjustment for maternal BMI, age, smoking, education, parity, ethnicity, and offspring sex and age. Cohort results were combined in random effects meta-analysis for thirteen age groups.ResultsUp to 158,066 offspring (4,329 conceived by ART) were included in each age-group meta-analysis; 47.6% to 60.6% were female. Compared with NC, ART-conceived offspring were slightly shorter, lighter, and thinner from infancy to early adolescence. The differences in growth/adiposity outcomes were largest at the youngest ages and attenuated with older child age, e.g., adjusted standardised mean differences (95% confidence intervals) in offspring weight at age ‘<3 months’, ‘17 to 23 months’, ‘6 to 9 years’, and ‘14 to 17 years’ were -0.27 standard deviation (SD) units (−0.39 to -0.16), -0.16SD (−0.22 to -0.09), -0.07SD (−0.10 to -0.04), and -0.02SD (−0.15 to 0.12), respectively. There was no evidence that results were driven by parental subfertility or of difference between conventional in vitro fertilisation and intracytoplasmic sperm injection however, smaller offspring size appeared to be limited to offspring conceived by fresh but not frozen embryo transfer, compared with NC. More marked but less precise differences were observed for body fat measurements. There was imprecise evidence that offspring conceived by ART may develop greater adiposity by early adulthood.Conclusions and RelevancePeople conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.KEY POINTSQuestionIs conception by assisted reproductive technology associated with growth and adiposity from infancy to early adulthood?FindingsIn this multi-cohort study of up to 158,066 European, Asian-Pacific, and Canadian infants, children, adolescents, and young adults, those conceived using assisted reproductive technology were on average shorter, lighter, and thinner from infancy up to early adolescence when compared with their naturally conceived peers though differences were small across all ages and reduced with older age.MeaningParents conceiving or hoping to conceive through assisted reproductive technology and their offspring should be reassured that differences in early life growth and adiposity are small and no longer apparent by late adolescence.