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 - Nybo Andersen, Anne-Marie

AU - Assisted Reproductive Technology and Future Health (ART-Health) Cohort Collaboration

PY - 2022

Y1 - 2022

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 158 066 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 158 066 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.

KW - Adiposity

KW - Adolescent

KW - Adult

KW - Child

KW - Child, Preschool

KW - Cohort Studies

KW - Embryo Transfer/methods

KW - Female

KW - Humans

KW - Infant

KW - Male

KW - Obesity/epidemiology

KW - Pregnancy

KW - Reproductive Techniques, Assisted/adverse effects

KW - Semen

U2 - 10.1001/jamanetworkopen.2022.22106

DO - 10.1001/jamanetworkopen.2022.22106

M3 - Journal article

C2 - 35881399

VL - 5

JO - JAMA network open

JF - JAMA network open

SN - 2574-3805

IS - 7

M1 - e2222106

ER -