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Association of Assisted Reproductive Technology With Offspring Growth and Adiposity From Infancy to Early Adulthood.

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom. Population Health Science, Bristol Medical School, University of Bristol, Bristol, United Kingdom. National Institute for Health Research Bristol Biomedical Research Centre, Bristol, United Kingdom. MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, United Kingdom. National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom. Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, Singapore. Academic Clinical Program in Obstetrics and Gynaecology, Duke-NUS Medical School, Singapore. Université de Paris, National Institute for Health and Medical Research, National Research Institute for Agriculture, Food and Environment, Centre for Research in Epidemiology and Statistics, Paris, France. Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. Department of Epidemiology, Lazio Regional Health Service, Rome, Italy. The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. Department of Paediatrics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. Department of Mother and Child Health, Ospedale Versilia, Viareggio, Azienda Usl Toscana Nord Ovest, Pisa, Italy. Division of Metabolic and Nutritional Medicine, Department of Pediatrics, Dr von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany. Murdoch Children's Research Institute, Parkville, Australia. University of Melbourne, Parkville, Australia. Amsterdam University Medical Centers, University of Amsterdam, Department of Public and Occupational Health, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands. Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. School of Public Health, University College Cork, Cork, Ireland. The Irish Centre for Maternal and Child Health Research, University College Cork, Cork, Ireland. Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece. Institute of Agri-Food and Life Sciences, Hellenic Mediterranean University Research Centre, Heraklion, Greece. Department of Obstetrics and Gynaecology, University College Cork, Cork, Ireland. Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Canada. Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Canada. Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy. Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Reference Centre for Epidemiology and Cancer Prevention Piemonte, Turin, Italy. Epidemiology Research Unit, Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal. Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional, Porto, Portugal. Centre for Longitudinal Research, He Ara ki Mua, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway. HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Levanger, Norway. Department of Endocrinology, Clinic of Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway. Department of Paediatrics, University of Melbourne, Parkville, Australia. Department of Paediatrics, Monash University, Clayton, Australia. Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore. National Institute for Demographic Studies, National Institute for Health and Medical Research, National Blood Service Joint Unit Elfe, Paris, France. Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Folkhälsan Research Center, Helsinki, Finland. Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway. Department of Food, Nutrition and Dietetics, School of Allied Health, Human Services and Sport, La Trobe University, Melbourne, Australia. Department of Pediatrics and Child Health, University College Cork, Cork, Ireland. National Longitudinal Study of Children in Ireland, Economic and Social Research Institute, Dublin, Ireland. School of Medicine, University of Glasgow, Glasgow, United Kingdom.

JAMA network open. 2022;(7):e2222106
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Abstract

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.

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Publication Type : Meta-Analysis

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