Association Between Assisted Reproductive Technology and Cerebral Palsy: A Meta-Analysis

Abstract

Background: Since 1978 many children are born thanks to assisted reproductive technology (ART). However, the long-term effects of these therapies are still not fully known. Our objective is to evaluate the risk of cerebral palsy (CP) after ART compared with that in those spontaneously conceived (SC) and to examine this risk in single, multiple, and preterm births and the evolution of the risk over the years.

Methods: PubMed, Embase, and Web of Science databases were searched until December 2022. Studies were included if they studied CP cases in children born through ART. 16 studies were finally selected. Quality of studies was assessed using Newcastle Ottawa Scale. Pooled OR was estimated by weighting individual OR/RR by the inverse of their variance. A random-effect model was applied. To assess the causes of heterogeneity, we performed meta-regression analyses.

Results: A significantly high risk of CP was found (OR = 1.27; 95% CI 1.12 to 1.43) in children born through ART compared with those SC. This risk increased in singletons (OR = 1.48; 95% CI 1.23 to 1.79) but disappeared in multiple (OR = 1.05; 95% CI 0.93 to 1.18) and preterm births (OR = 1.09; 95% CI 0.87 to 1.37). We found a higher risk of CP in children born before the year 2000 (OR = 3.40; 95% CI 2.49 to 4.63).

Conclusions: ARTs slightly increase the risk of CP once the effect of multiple gestation is controlled. Further studies are needed to clarify whether the techniques themselves, fertility problems, or associated maternal comorbidities are responsible for this risk.

Keywords: Assisted reproduction techniques; Assisted reproductive technologies; Brain damage; Cerebral palsy; Intracytoplasmic sperm injection; In vitro fertilization; Neurodevelopment.