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Associations of Assisted Reproductive Technology and Twin Pregnancy With Risk of Congenital Heart Defects

Authors
  • Wen, Shi Wu1, 2, 3,
  • Miao, Qun4, 5
  • Taljaard, Monica2, 3
  • Lougheed, Jane6, 7
  • Gaudet, Laura1, 2, 3
  • Davies, Michael8
  • Lanes, Andrea4
  • Leader, Art2
  • Corsi, Daniel J.1, 2, 3, 4
  • Sprague, Ann E.4, 5
  • Walker, Mark1, 2, 3, 4
  • 1 OMNI Research Group, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
  • 2 Department of Obstetrics and Gynecology, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
  • 3 School of Epidemiology and Public Health, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
  • 4 Better Outcomes Registry & Network (BORN) Ontario, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada
  • 5 Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
  • 6 Division of Cardiology, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada
  • 7 Department of Pediatrics, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
  • 8 Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia
Type
Published Article
Journal
JAMA Pediatrics
Publisher
American Medical Association
Publication Date
Feb 24, 2020
Volume
174
Issue
5
Pages
1–9
Identifiers
DOI: 10.1001/jamapediatrics.2019.6096
PMID: 32091547
PMCID: PMC7042937
Source
PubMed Central
License
Green
External links

Abstract

Importance The extent to which assisted reproductive technology is associated with increased risk of congenital heart defects independent of its known association with twinning remains uncertain. Objective To assess the extent to which assisted pregnancy is associated with increased risk of congenital heart defects independent of its known association with twinning. Design, Setting, and Participants This retrospective cohort study linked records of congenital heart defect diagnoses with assisted reproductive technology cycles in 507 390 singleton or twin pregnancies (10 149 assisted pregnancies and 497 241 nonassisted pregnancies), including singleton and twin early pregnancy losses, stillbirths, and live births (follow-up to 1 year of age) in Ontario, Canada, between April 1, 2012, and October 31, 2015. Statistical analysis was performed from January 1, 2017, to September 9, 2019. Exposures Assisted reproductive technology and its 2 subtypes: intracytoplasmic sperm injection and in vitro fertilization without intracytoplasmic sperm injection. Main Outcomes and Measures The main outcome was congenital heart defects (prevalence and relative risk measured as odds ratios [ORs]). Mediation analysis was performed to assess the extent to which the association between assisted reproductive technology and congenital heart defects was mediated by twinning. Results Of 507 390 mother-infant pairs with singleton or twin pregnancies evaluated, the prevalence of congenital heart defects in assisted pregnancies (223 [2.2%]) was higher than that in nonassisted pregnancies (6057 [1.2%]; crude OR, 1.82; 95% CI, 1.59-2.09). The strength of the association between assisted pregnancy and congenital heart defects decreased after adjusting for several risk factors simultaneously (adjusted OR, 1.70; 95% CI, 1.48-1.95). Further mediation analysis indicated that most of the association between assisted pregnancy and congenital heart defects was mediated by twinning (adjusted OR, 1.68; 95% CI, 1.44-1.92), and the natural direct association of assisted pregnancy with congenital heart defects among singleton pregnancies was 1.09 (95% CI, 0.93-1.25). Mediation of twinning accounted for 87.3% of the association. Conclusions and Relevance Our study results suggest that the association between assisted reproductive technology and congenital heart defects may be mediated by twinning.

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