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- Title
Associations of Assisted Reproductive Technology and Twin Pregnancy With Risk of Congenital Heart Defects.
- Authors
Wen, Shi Wu; Miao, Qun; Taljaard, Monica; Lougheed, Jane; Gaudet, Laura; Davies, Michael; Lanes, Andrea; Leader, Art; Corsi, Daniel J.; Sprague, Ann E.; Walker, Mark
- Abstract
This cohort study assesses the extent of association of assisted reproductive technology with congenital heart defects independent of its known association with twin pregnancies. Key Points: Question: Is assisted reproductive technology associated with increased risk of congenital heart defects independent of its association with twin pregnancies? Findings: In this cohort study of 507 390 singleton or twin pregnancies, the prevalence of congenital heart defects was higher in assisted pregnancies (223 [2.2%]) than in nonassisted pregnancies (6057 [1.2%]). Twinning mediated 87.3% of the association between assisted pregnancy and congenital heart defects. Meaning: The findings suggest the association between assisted reproductive technology and congenital heart defects may be mediated by twinning. 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.
- Subjects
ONTARIO; CONFIDENCE intervals; CONGENITAL heart disease; FERTILIZATION in vitro; HUMAN reproductive technology; LONGITUDINAL method; MULTIPLE pregnancy; HEALTH outcome assessment; PERINATAL death; RELATIVE medical risk; DISEASE prevalence; RETROSPECTIVE studies; DESCRIPTIVE statistics; ODDS ratio; DISEASE risk factors
- Publication
JAMA Pediatrics, 2020, Vol 174, Issue 5, p446
- ISSN
2168-6203
- Publication type
Article
- DOI
10.1001/jamapediatrics.2019.6096