TY - JOUR
T1 - Association of Assisted Reproductive Technology with Offspring Growth and Adiposity from Infancy to Early Adulthood
AU - Elhakeem, Ahmed
AU - Taylor, Amy E.
AU - Inskip, Hazel M.
AU - Huang, Jonathan
AU - Tafflet, Muriel
AU - Vinther, Johan L.
AU - Asta, Federica
AU - Erkamp, Jan S.
AU - Gagliardi, Luigi
AU - Guerlich, Kathrin
AU - Halliday, Jane
AU - Harskamp-Van Ginkel, Margreet W.
AU - He, Jian Rong
AU - Jaddoe, Vincent W.V.
AU - Lewis, Sharon
AU - Maher, Gillian M.
AU - Manios, Yannis
AU - Mansell, Toby
AU - McCarthy, Fergus P.
AU - McDonald, Sheila W.
AU - Medda, Emanuela
AU - Nisticò, Lorenza
AU - De Moira, Angela Pinot
AU - Popovic, Maja
AU - Reiss, Irwin K.M.
AU - Rodrigues, Carina
AU - Salika, Theodosia
AU - Smith, Ash
AU - Stazi, Maria A.
AU - Walker, Caroline
AU - Wu, Muci
AU - Åsvold, Bjørn O.
AU - Barros, Henrique
AU - Brescianini, Sonia
AU - Burgner, David
AU - Chan, Jerry K.Y.
AU - Charles, Marie Aline
AU - Eriksson, Johan G.
AU - Gaillard, Romy
AU - Grote, Veit
AU - Håberg, Siri E.
AU - Heude, Barbara
AU - Koletzko, Berthold
AU - Morton, Susan
AU - Moschonis, George
AU - Murray, Deirdre
AU - O'Mahony, Desmond
AU - Porta, Daniela
AU - Qiu, Xiu
AU - Richiardi, Lorenzo
AU - Rusconi, Franca
AU - Saffery, Richard
AU - Tough, Suzanne C.
AU - Vrijkotte, Tanja G.M.
AU - Nelson, Scott M.
AU - Nybo Andersen, Anne Marie
AU - Magnus, Maria C.
AU - Lawlor, Deborah A.
N1 - Funding/Support: 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).
Publisher Copyright:
© 2022 American Medical Association. All rights reserved.
PY - 2022/7/26
Y1 - 2022/7/26
N2 - 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..
AB - 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..
UR - http://www.scopus.com/inward/record.url?scp=85134916107&partnerID=8YFLogxK
U2 - 10.1001/jamanetworkopen.2022.22106
DO - 10.1001/jamanetworkopen.2022.22106
M3 - Article
C2 - 35881399
AN - SCOPUS:85134916107
SN - 2574-3805
VL - 5
JO - JAMA network open
JF - JAMA network open
IS - 7
M1 - E2222106
ER -