Association of Preimplantation Genetic Testing and Twin Pregnancy with Prenatally Diagnosed Congenital Heart Defects Among High-Risk Pregnant Women

Background: It has been shown that the use of preimplantation genetic testing (PGT) may come with health concerns, such as adverse pregnancy outcomes. However, no research was conducted to explore the association between PGT and fetal CHDs. And what role twin pregnancy plays in PGT and CHDs needs to be studied. Methods: Data from 36,899 high-risk pregnant women who underwent fetal echocardiography were analyzed. Fetal CHDs diagnosed by fetal echocardiography was the outcome of interest, with exposure or mediator being PGT and twin pregnancy respectively. Logistic regression was performed to access associations of PGT and twin pregnancy with fetal CHDs, and mediation analysis conducted to explore the potential mediation of twinning. Findings: A total of 111 (28·0%) and 6421 (17·6%) fetal CHDs were diagnosed in PGT and natural pregnancy respectively. Parental unemployment and paternal engagement in smoking and drinking were strongly associated with increased risk of fetal CHDs. PGT and twin pregnancy were high risk factors for CHDs than natural pregnancy, with twinning account for 14·8% of the association between PGT and CHDs. However, PGT-Twin pregnancies were not associated with fetal CHDs compared to Natural-Singletons. Interpretation: Despite initial screening for abnormal embryos by PGT, couples conceived by PGT or with twin pregnancies were advised to conduct fetal echocardiography to promote prenatal diagnosis of fetal CHDs. Tobacco and alcohol control were also suggested for fathers during maternal pregnancy. Funding: The National Natural Science Foundation of China and Beijing Key Laboratory of Maternal-Fetal Medicine in Fetal Heart Disease.