Assisted reproductive technology and childhood morbidity: a longitudinal cohort study

To evaluate the association between assisted reproductive technology (ART) and offspring morbidity in the first decade of life.

Longitudinal cohort study.

Provincial health registry in Quebec, Canada.

A total of 797,654 singleton children born between 2008 and 2019, followed up to 2020.

Retrospective, noninterventional study of any ART procedure vs. no ART.

Childhood morbidity, including hospitalization for infectious, allergic, malignant, and other diseases, assessed using adjusted Cox proportional hazards regression to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association with ART. We controlled for unmeasured family-level confounders that were shared among siblings through stratified Cox regression. To do so, we restricted the analysis to 10,097 siblings with discordant exposure to ART and compared the risk of outcomes in exposed vs. unexposed siblings.

Compared with no ART, ART was associated with 1.23 times the risk of any hospitalization (95% CI 1.19-1.27), 1.25 times the risk of infectious disease hospitalization (95% CI 1.21-1.29), and 1.25 times the risk of allergy hospitalization (95% CI 1.14-1.38). When we used a sibling design to control for shared genetic and environmental confounders, ART was not associated with a greater risk of childhood hospitalization (HR 0.92, 95% CI 0.78-1.08).

ART is associated with an elevated risk of hospitalization up to 11 years of age, but discordant sibling analysis suggests that the association may be due to genetic, environmental, or other shared familial confounders.