The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2026
Assisted reproductive technology and birth defects: analysis of the mediating pathways in twin pregnancies.
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Hu Fengjiao, Zhu Huiyuan, Fang Junqun, Li Bo, Xie Donghua
Аннотация
OBJECTIVE: To systematically evaluate the epidemiological association between ART and the risk of birth defects.
METHODS: Based on the latest provincial monitoring data from a large sample in Hunan Province, China for the period 2023-2024, we conducted a retrospective study comparing baseline characteristics between ART-conceived and naturally-conceived pregnancies. Through multivariable logistic regression, we estimated ART-birth defect associations, with interaction analyses across key subgroups. Besides, we performed mediation analysis to quantify twin pregnancy's role in the ART-birth defect relationship.
RESULTS: A total of 745,671 fetuses were included in this study. Regression analysis showed that assisted reproduction is a risk factor for birth defects, with an adjusted odds ratio(aOR) of 1.84 (1.68-2.01). Compared with infants born through natural conception, infants conceived through ART had a significantly increased risk of birth defects (single fetus: aOR = 1.59, 95% confidence interval [CI]: 1.42-1.77; twin fetus: aOR = 1.83, 95%CI: 1.51-2.21). The risk of specific birth defect subtypes in infants conceived through ART was significantly increased, including: circulatory system defects, musculoskeletal abnormalities, and cleft lip and palate. Subgroup analysis showed that gestational age (p < 0.001) and place of residence (p = 0.007) had significant interaction effects on the association between ART and birth defects. In addition, in the mediation analysis, twin pregnancies could explain 14.33% of the relative impact of ART on birth defects.
CONCLUSIONS: This study has found that the use of ART increases the risk of birth defects. In the association between ART and birth defects, twin pregnancies accounted for 14.33%.
METHODS: Based on the latest provincial monitoring data from a large sample in Hunan Province, China for the period 2023-2024, we conducted a retrospective study comparing baseline characteristics between ART-conceived and naturally-conceived pregnancies. Through multivariable logistic regression, we estimated ART-birth defect associations, with interaction analyses across key subgroups. Besides, we performed mediation analysis to quantify twin pregnancy's role in the ART-birth defect relationship.
RESULTS: A total of 745,671 fetuses were included in this study. Regression analysis showed that assisted reproduction is a risk factor for birth defects, with an adjusted odds ratio(aOR) of 1.84 (1.68-2.01). Compared with infants born through natural conception, infants conceived through ART had a significantly increased risk of birth defects (single fetus: aOR = 1.59, 95% confidence interval [CI]: 1.42-1.77; twin fetus: aOR = 1.83, 95%CI: 1.51-2.21). The risk of specific birth defect subtypes in infants conceived through ART was significantly increased, including: circulatory system defects, musculoskeletal abnormalities, and cleft lip and palate. Subgroup analysis showed that gestational age (p < 0.001) and place of residence (p = 0.007) had significant interaction effects on the association between ART and birth defects. In addition, in the mediation analysis, twin pregnancies could explain 14.33% of the relative impact of ART on birth defects.
CONCLUSIONS: This study has found that the use of ART increases the risk of birth defects. In the association between ART and birth defects, twin pregnancies accounted for 14.33%.