Assisted reproductive technology and birth defects in a Chinese birth cohort study

Hong Lv; Feiyang Diao; Jiangbo Du; Ting Chen; Qingxia Meng; Xiufeng Ling; Hong Li; Ci Song; Qi Xi; Yangqian Jiang; Yan Xu; Shiyao Tao; Lei Huang; Mingyang Wen; Meijuan Peng; Cong Liu; Qun Lu; Yuanlin He; Yin Yin; Xiaoyu Liu; Bo Xu; Xiumei Han; Kun Zhou; Tao Jiang; Yang Zhao; Hongxia Ma; Guangfu Jin; Yankai Xia; Jiayin Liu; Yuan Lin; Zhibin Hu; Hongbing Shen

doi:10.1016/j.lanwpc.2020.100090

Assisted reproductive technology and birth defects in a Chinese birth cohort study

Lancet Reg Health West Pac. 2021 Jan 22:7:100090. doi: 10.1016/j.lanwpc.2020.100090. eCollection 2021 Feb.

Authors

Hong Lv^{1

2}, Feiyang Diao^{1

3}, Jiangbo Du¹, Ting Chen⁴, Qingxia Meng^{1

5}, Xiufeng Ling^{1

6}, Hong Li^{1

5}, Ci Song¹, Qi Xi⁷, Yangqian Jiang¹, Yan Xu⁸, Shiyao Tao¹, Lei Huang¹, Mingyang Wen¹, Meijuan Peng¹, Cong Liu¹, Qun Lu¹, Yuanlin He¹, Yin Yin^{1

9}, Xiaoyu Liu¹, Bo Xu¹, Xiumei Han¹, Kun Zhou¹, Tao Jiang¹, Yang Zhao¹, Hongxia Ma¹, Guangfu Jin¹, Yankai Xia^{1

10}, Jiayin Liu^{1

2

3}, Yuan Lin^{1

2

11}, Zhibin Hu^{1

2}, Hongbing Shen^{1

2}

Affiliations

¹ State Key Laboratory of Reproductive Medicine, Centre for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
² State Key Laboratory of Reproductive Medicine (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215002, China.
³ Clinical Centre of Reproductive Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing 210029, China.
⁴ Scientific Education Section, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Hospital, Nanjing 210004, China.
⁵ Reproductive Genetic Centre, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215002, China.
⁶ Department of Reproduction, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Hospital, Nanjing 210004, China.
⁷ Department of Obstetrics, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215002, China.
⁸ Department of Maternal and Child Health, Jiangsu Commission of Health, Nanjing 210008, China.
⁹ Department of Obstetrics, First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing 210029, China.
¹⁰ Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
¹¹ Department of Maternal, Child and Adolescent Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.

Abstract

Background: It has been consistently shown in several meta-analyses that infants born after ART have an excess of birth defects compared with those after spontaneous conception, however, the prevalence of birth defects among ART offspring in China is incompletely studied. Moreover, it is unclear to what extent the risk of birth defects is associated with parental infertility characteristics, specific ART procedures and twinning.

Methods: In the prospective cohort study, we included women who participated in the cohort, and had pregnancies of at least 20 gestational weeks between August 2016 and May 2019, and followed them until their children reached 1 year of age. Exposures of interest were ART, as well as infertility-related characteristics, certain ART procedures and specific medication usage. The primary outcome was birth defects including both major and minor defects, which we analysed with logistic generalized estimating equations to investigate the association with ART and certain ART characteristics.

Findings: A total of 1,825 women with ART-pregnancy and 3,483 women with spontaneous-pregnancy were included in the analysis. The prevalence of any defects was significantly higher among ART-births than their non-ART counterparts at each follow-up, specifically at prenatal screening (2•2% vs. 1•2%), at delivery (4•9% vs. 2•9%), at 6 months (10•4% vs. 5•3%) and 1 year of age (13•9% vs. 7•0%), and the associations between ART and increased risk of birth defects at each follow-up were similarly robust. Among ART-births, GnRH antagonist regimen for ovulation induction in women was associated with an increased risk of birth defects in their offspring after taking into account potential influencing factors (Multivariable model: adjusted risk ratio [aRR] 1•47, 1•04-2•07). Additionally, mediation through twinning accounted for 31•1% of the risk of ART-associated birth defects.

Interpretation: The results suggest that ART confers an increased risk for birth defects in offspring. The risk is partly attributable to infertility characteristics, certain ovulation induction regimen, and to some extent mediated by twinning. Our findings highlight the importance of long-term follow-up of children conceived via ART for health conditions.

Funding: National Key Research and Development Program of China, National Natural Science Foundation of China and Natural Science Foundation of Jiangsu Province.