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, 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

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.

Conflict of interest statement

We declare no competing interests.

© 2020 The Author(s). Published by Elsevier Ltd.

Figures

Fig. 1
Fig. 1
Cumulative prevalence of birth defects according to age at diagnosis.
Fig. 2
Fig. 2
Analysis of assisted reproductive technology and birth defects association with twin pregnancy as a mediator.

References

    1. Yang X., Li Y., Li C., Zhang W. Current overview of pregnancy complications and live-birth outcome of assisted reproductive technology in mainland China. Fertil Steril. 2014;101(2):385–391.
    1. Hansen M., Kurinczuk J.J., Milne E., de Klerk N., Bower C. Assisted reproductive technology and birth defects: a systematic review and meta-analysis. Hum Reprod Update. 2013;19(4):330–353.
    1. Qin J., Wang H., Sheng X., Liang D., Tan H., Xia J. Pregnancy-related complications and adverse pregnancy outcomes in multiple pregnancies resulting from assisted reproductive technology: a meta-analysis of cohort studies. Fertil Steril. 2015;103(6) 1492-508 e1-7.
    1. Giorgione V., Parazzini F., Fesslova V. Congenital heart defects in IVF/ICSI pregnancy: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018;51(1):33–42.
    1. Wen J., Jiang J., Ding C. Birth defects in children conceived by in vitro fertilization and intracytoplasmic sperm injection: a meta-analysis. Fertil Steril. 2012;97(6) 1331-7 e1-4.
    1. Hansen M., Kurinczuk J.J., Bower C., Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med. 2002;346(10):725–730.
    1. Tararbit K., Houyel L., Bonnet D. Risk of congenital heart defects associated with assisted reproductive technologies: a population-based evaluation. Eur Heart J. 2011;32(4):500–508.
    1. Tararbit K., Lelong N., Thieulin A.C. The risk for four specific congenital heart defects associated with assisted reproductive techniques: a population-based evaluation. Hum Reprod. 2013;28(2):367–374.
    1. Pinborg A., Henningsen A.K., Malchau S.S., Loft A. Congenital anomalies after assisted reproductive technology. Fertil Steril. 2013;99(2):327–332.
    1. Boulet S.L., Kirby R.S., Reefhuis J. Assisted reproductive technology and birth defects among live born infants in Florida, Massachusetts, and Michigan, 2000-2010. JAMA Pediatr. 2016;170(6)
    1. Halliday J.L., Ukoumunne O.C., Baker H.W. Increased risk of blastogenesis birth defects, arising in the first 4 weeks of pregnancy, after assisted reproductive technologies. Hum Reprod. 2010;25(1):59–65.
    1. Davies M.J., Moore V.M., Willson K.J. Reproductive technologies and the risk of birth defects. N Engl J Med. 2012;366(19):1803–1813.
    1. Wen S.W., Miao Q., Taljaard M. Associations of assisted reproductive technology and twin pregnancy with risk of congenital heart defects. JAMA Pediatr. 2020
    1. Lambert R.D. Safety issues in assisted reproduction technology: the children of assisted reproduction confront the responsible conduct of assisted reproductive technologies. Hum Reprod. 2002;17(12):3011–3015.
    1. Reefhuis J., Honein M.A., Schieve L.A. Assisted reproductive technology and major structural birth defects in the United States. Hum Reprod. 2009;24(2):360–366.
    1. Ericson A., Kallen B. Congenital malformations in infants born after IVF: a population-based study. Hum Reprod. 2001;16(3):504–509.
    1. Sobel M.E. Asymptotic confidence intervals for indirect effects in structural equation models. Sociol Methodol. 1982;13:290–312.
    1. Valeri L., Vanderweele T.J. Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros. Psychol Methods. 2013;18(2):137–150.
    1. Hansen M., Bower C., Milne E., de Klerk N., Kurinczuk J.J. Assisted reproductive technologies and the risk of birth defects–a systematic review. Hum Reprod. 2005;20(2):328–338.
    1. McDonald S.D., Murphy K., Beyene J., Ohlsson A. Perinatel outcomes of singleton pregnancies achieved by in vitro fertilization: a systematic review and meta-analysis. J Obstet Gynaecol Can. 2005;27(5):449–459.
    1. El-Chaar D., Yang Q., Gao J. Risk of birth defects increased in pregnancies conceived by assisted human reproduction. Fertil Steril. 2009;92(5):1557–1561.
    1. Anthony S., Buitendijk S.E., Dorrepaal C.A., Lindner K., Braat D.D., den Ouden A.L. Congenital malformations in 4224 children conceived after IVF. Hum Reprod. 2002;17(8):2089–2095.
    1. Hansen M., Kurinczuk J.J., de Klerk N., Burton P., Bower C. Assisted reproductive technology and major birth defects in Western Australia. Obstet Gynecol. 2012;120(4):852–863.
    1. Yu H.T., Yang Q., Sun X.X. Association of birth defects with the mode of assisted reproductive technology in a Chinese data-linkage cohort. Fertil Steril. 2018;109(5):849–856.
    1. Yin L., Hang F., Gu L.J., Xu B., Ma D., Zhu G.J. Analysis of birth defects among children 3 years after conception through assisted reproductive technology in China. Birth Defects Res A Clin Mol Teratol. 2013;97(11):744–749.
    1. Zhu J.L., Basso O., Obel C., Bille C., Olsen J. Infertility, infertility treatment, and congenital malformations: danish national birth cohort. BMJ. 2006;333(7570):679.
    1. Bloise E., Feuer S.K., Rinaudo P.F. Comparative intrauterine development and placental function of ART concepti: implications for human reproductive medicine and animal breeding. Hum Reprod Update. 2014;20(6):822–839.
    1. Massaro P.A., MacLellan D.L., Anderson P.A., Romao R.L. Does intracytoplasmic sperm injection pose an increased risk of genitourinary congenital malformations in offspring compared to in vitro fertilization? A systematic review and meta-analysis. J Urol. 2015;193(5 Suppl):1837–1842.
    1. Dar S., Lazer T., Shah P.S., Librach C.L. Neonatal outcomes among singleton births after blastocyst versus cleavage stage embryo transfer: a systematic review and meta-analysis. Hum Reprod Update. 2014;20(3):439–448.
    1. Parazzini F., Cipriani S., Bulfoni G. The risk of birth defects after assisted reproduction. J Assist Reprod Genet. 2015;32(3):379–385.
    1. Ludwig M., Riethmuller-Winzen H., Felberbaum R.E. Health of 227 children born after controlled ovarian stimulation for in vitro fertilization using the luteinizing hormone-releasing hormone antagonist cetrorelix. Fertil Steril. 2001;75(1):18–22.
    1. Thurin A., Hausken J., Hillensjo T. Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization. N Engl J Med. 2004;351(23):2392–2402.
    1. Toner J.P., Coddington C.C., Doody K. Society for assisted reproductive technology and assisted reproductive technology in the United States: a 2016 update. Fertil Steril. 2016;106(3):541–546.
    1. Dawson A.L., Tinker S.C., Jamieson D.J. Twinning and major birth defects, national birth defects prevention study, 1997-2007. J Epidemiol Community Health. 2016;70(11):1114–1121.
    1. Hardin J., Carmichael S.L., Selvin S., Lammer E.J., Shaw G.M. Increased prevalence of cardiovascular defects among 56,709 California twin pairs. Am J Med Genet A. 2009;149A(5):877–886.
    1. Liberman R.F., Getz K.D., Heinke D. Assisted reproductive technology and birth defects: effects of subfertility and multiple births. Birth Defects Res. 2017;109(14):1144–1153.
    1. Kawwass J.F., Badell M.L. Maternal and fetal risk associated with assisted reproductive technology. Obstet Gynecol. 2018;132(3):763–772.

Source: PubMed

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