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

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.

Maternal age, paternal age and new-onset hypertension in late pregnancy.

OBJECTIVE: To examine the association between maternal age, paternal age, and new-onset hypertension in late pregnancy. METHODS: We carried out a retrospective cohort study of 9,302,675 pregnant women with live births in the United States between 1995 and 1998. Maternal and paternal ages were analyzed together using "couple age" in multivariate logistic regression models to reduce colinearity between maternal age and paternal age. The effect of paternal age was also analyzed with stratification of maternal age. RESULTS: Compared with couples with both a maternal and paternal age of 20 to 34 years, an older maternal age (above 35 years) was associated with an increased risk for new-onset hypertension, except for couples with a very young father (below 20 years). Younger maternal age (below 20 years) was associated with a decreased risk for new-onset hypertension, except for couples with a very old father (above 45 years). There was no significant association between paternal age and new-onset hypertension with stratification of maternal age. CONCLUSION: Increased risk for new-onset hypertension in late pregnancy is significantly associated with advancing maternal age, whereas there is no association between paternal age and new-onset hypertension in late pregnancy.