General Health in a cohort of children conceived after assisted reproductive technology in the UK: a population-based record-linkage study

Background: Assisted reproductive technology usage is increasing annually; however, data on long-term child health outcomes including hospital admissions is limited. Objectives: To examine the potential effects of assisted reproductive technology on any and cause-specific hospital admissions not related to perinatal diagnoses. Study design: Population-based record-linkage study utilizing a previously established cohort of children born after assisted reproductive technology in the United Kingdom between 1997 and 2009 (n=63877), their naturally conceived siblings (n=11343), and matched naturally conceived population (n=127544) controls linked to their postnatal health outcomes up to 31st March 2016 to provide robust risk estimates of the potential effects of assisted reproductive technology on any and cause-specific hospital admissions not related to perinatal diagnoses. Additionally, comparison of hospital admissions by type of treatment was performed. Cox regression was used to estimate the risk of hospital admissions and negative binomial regression was used to compare the number of hospital admissions per year. Results: This study had 1.6-million-person years of follow-up [mean: 12.9 years; range 0 to 19 years], and the mean age at the time of first hospital admission was 6.5 years [range 0 to 19 years]. Singletons born after assisted reproductive technology had increased risk of any hospital admission compared to naturally conceived population controls [Hazard ratio: 1.08; 95% CI: 1.05 to 1.10] but not naturally conceived siblings [Hazard ratio: 1.01; 95% CI: 0.94 to 1.09]. We observed increased risk for diagnoses related to neoplasms and diseases of the respiratory, musculoskeletal, digestive, and genitourinary systems, and lower risk of injury, poisoning, and consequences of external causes compared to naturally conceived population controls. Children born after intracytoplasmic sperm injection had a lower risk of hospital admission compared to those born after in-vitro fertilization, although no such differences were observed between children born after fresh and frozen embryo transfers. Conclusions: Children born after assisted reproductive technology showed greater numbers of hospital admissions compared to naturally conceived population controls. Attenuation of these differences in relation to their naturally conceived siblings suggests that this could be partially attributed to the influence of parental subfertility on child health or increased parental concerns as well as an actual increase in morbidity in children born after assisted conception