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Association of Assisted Reproductive Technology with Offspring Growth and Adiposity from Infancy to Early Adulthood

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posted on 2022-10-17, 03:41 authored by A Elhakeem, AE Taylor, HM Inskip, J Huang, M Tafflet, JL Vinther, F Asta, JS Erkamp, L Gagliardi, K Guerlich, J Halliday, MW Harskamp-Van Ginkel, JR He, VWV Jaddoe, S Lewis, GM Maher, Y Manios, T Mansell, FP McCarthy, SW McDonald, E Medda, L Nisticò, AP De Moira, M Popovic, IKM Reiss, C Rodrigues, T Salika, A Smith, MA Stazi, C Walker, M Wu, BO Åsvold, H Barros, S Brescianini, D Burgner, JKY Chan, MA Charles, JG Eriksson, R Gaillard, V Grote, SE Håberg, B Heude, B Koletzko, S Morton, George MoschonisGeorge Moschonis, D Murray, D O'Mahony, D Porta, X Qiu, L Richiardi, F Rusconi, R Saffery, SC Tough, TGM Vrijkotte, SM Nelson, AM Nybo Andersen, MC Magnus, DA Lawlor
Importance: People conceived using assisted reproductive technology (ART) make up an increasing proportion of the world's population. Objective: To investigate the association of ART conception with offspring growth and adiposity from infancy to early adulthood in a large multicohort study. Design, Setting, and Participants: This cohort study used a prespecified coordinated analysis across 26 European, Asia-Pacific, and North American population-based cohort studies that included people born between 1984 and 2018, with mean ages at assessment of growth and adiposity outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and February 2022. Exposures: Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer) vs natural conception (NC; without any medically assisted reproduction). Main Outcomes and Measures: The main outcomes were length / height, weight, and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13 age groups. Results: Up to 158066 offspring (4329 conceived by ART) were included in each age-group meta-analysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence, with differences largest at the youngest ages and attenuating with older child age. For example, adjusted mean differences in offspring weight were -0.27 (95% CI, -0.39 to -0.16) SD units at age younger than 3 months, -0.16 (95% CI, -0.22 to -0.09) SD units at age 17 to 23 months, -0.07 (95% CI, -0.10 to -0.04) SD units at age 6 to 9 years, and -0.02 (95% CI, -0.15 to 0.12) SD units at age 14 to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was -0.14 [95% CI, -0.20 to -0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, -0.15 to 0.15] SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat measurements, and there was imprecise evidence that offspring conceived by ART developed greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17 years: 0.23 [95% CI, -0.04 to 0.50] SD units). Conclusions and Relevance: These findings suggest that people conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence..

Funding

This work was funded by the European Research Council under the European Union (EU) Horizon 2020 research and innovation program (agreements No. 101021566 [ART-HEALTH] and 733206 [LifeCycle]), the Medical Research Council (grant No. MC_UU_00011/6), British Heart Foundation (grants No. CH/F/20/90003 and AA/18/7/34219), and Bristol National Institute of Health Research Biomedical Research Centre (grant No. NF-0616-10102).

History

Publication Date

2022-07-26

Journal

JAMA Network Open

Volume

5

Issue

7

Article Number

e2222106

Pagination

16p.

Publisher

American Medical Association

ISSN

2574-3805

Rights Statement

This is an open access article distributed under the terms of the CC-BY License. © 2022 Elhakeem A et al. JAMA Network Open.

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