Cerebral palsy in children born after assisted reproductive technology: a meta-analysis

Background Several studies have assessed the association between cerebral palsy (CP) and assisted reproductive technology (ART), but the results remain controversial. We conducted a meta-analysis to evaluate the risk of CP after ART compared with natural conceptions and to examine CP risk separately in ART singletons, multiples and preterm births. Methods Web-based databases (PubMed, Embase, the Cochrane Library, and Web of Science) were searched until November 22, 2020. Studies which compare CP rates after ART with natural conceptions were included. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. Effect estimates were extracted and combined using the fixed-effects or random-effects model depending on the heterogeneity test. Results There were nine studies included in the meta-analysis. The included studies were of moderate or high quality. A significantly higher risk of CP [odds ratio (OR) = 2.17, 95% confidence interval (CI) 1.72-2.74] was found in ART children (n = 89,214) compared with naturally conceived children (n = 4,160,745). The significantly higher risk decreased when data were restricted to singletons (OR = 1.36, 95% CI 1.16-1.59) and disappeared when data were restricted to multiples (OR = 1.05, 95% CI 0.86-1.29) or preterm births (OR = 1.53, 95% CI 0.66-3.56). Subgroup and sensitivity analyses indicated that the overall results were robust. Conclusions The risk of CP is increased more than two-fold after ART. This increased risk is largely due to increased rates of multiple birth and preterm delivery in ART children.