Association of assisted reproductive technology with offspring growth and adiposity from infancy to early adulthood

ABSTRACT Importance People conceived using assisted reproductive technology (ART) make up an increasing proportion of the world’s population, and their numbers are expected to continue rising. Objective Investigate association of ART conception with growth and adiposity outcomes from infancy to early adulthood in offspring from a large multinational multi-cohort study. Design 26 population-based cohort studies. Setting Europe, Asia-Pacific, and North America Participants Infants, 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. Exposures Conception by ART (conventional in vitro fertilisation and intracytoplasmic sperm injection) versus natural conception (NC). Main Outcomes and Measures Length/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. Results Up 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 Relevance 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. KEY POINTS Question Is conception by assisted reproductive technology associated with growth and adiposity from infancy to early adulthood? Findings In 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. Meaning Parents 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.