Risk Of Birth Defects In Children Conceived With Assisted Reproductive Technology:a Meta-analysis

Objective: Although assisted reproductive technology(ART)has been widely used in couples with fertility problems,the safety of offspring is still a concern.Therefore,in order to more accurately assess the risk of birth defects in offspring after ART treatment,this study conducted a meta-analysis of available cohort studies to explore the impact of ART on birth defects in offspring.Methods: We used an established strategy to search the databases of PUBMED,EMBASE,COCHRANE,WEB OF SCIENCE,CNKI,CBM,VIP and Wanfang for studies published from establish to 2020.Pooled relative risks(RRs)or odds ratios(ORs)were calculated using fixed effects model or random effects models.Subgroup analyses and sensitivity analyses were used to examine sources of heterogeneity.Rev Man5.3 was used to draw a forest plot,and Stata14.0 was used to test for publication bias.Results: This study included 15 cohort studies from different countries.The infants conceived with ART had a 1.36-fold higher likelihood of birth defects than children born after natural pregnancy(RR = 1.36,95% CI[1.20-1.54],P<0.05).A subgroup analysis of singletons,twins and multiple births revealed that ART was positively correlated with birth defects in singletons(RR = 1.30,95% CI [1.19-1.42],P<0.05),and ART did not increase the incidence of twins The risk of birth defects(RR = 0.95,95%CI[0.90-1.02],P>0.05),ART is also positively correlated with multiple births(RR = 1.17,95%CI [1.01-1.36,P<0.05),In a meta-analysis of data from 6studies,ART increased the risk of cardiovascular defects,musculoskeletal defects,genitourinary defects,central nervous system defects and orofacial defects in offspring.The relationship between ART and specific organ defects of the offspring is as follows: cardiovascular defects,RR = 1.51,95% CI [1.34-1.69],P <0.05;musculoskeletal defects,RR = 1.09,95% CI[1.03-1.15],P <0.05;urogenital defects,RR = 1.24,95% CI [1.11-1.38 ],P<0.05;central nervous system defect,RR = 1.33,95% CI [1.14-1.55],P<0.05;oral defect,RR = 1.45,95% CI [1.15-1.83],P <0.05.Conclusion: ART increases the risk of birth defects in offspring.When distinguishing single births,twins and multiple births,ART is positively correlated with NP singleton and multiple births.ART does not increase the risk of birth defects in twins.ART increases the risk of cardiovascular defects,musculoskeletal defects,genitourinary defects,central nervous system defects and orofacial defects in the offspring,with the offspring having the highest risk of cardiovascular defects.