148 Discordant congenital heart defects in monochorionic twins: risk factors and proposed pathophysiology

Abstract

There is a six-fold increase in congenital heart defects (CHD) among monochorionic (MC) twins compared to singleton or dichorionic twin pregnancies. Though MC twins share a genotype, discordant phenotypes related to CHD have been described. Our objective was to characterize the spectrum of CHD in MC twins in the context of genetic results and clinical demographics for a modern cohort to provide insight into risk factors and pathophysiology of discordant CHD in MC twins. Retrospective analysis of all twins receiving prenatal fetal echocardiography at a single institution from January 2010 – March 2020 (N=163) yielded 24 MC twin pairs (48 neonates) with CHD (n=6 concordant CHD, n=18 discordant CHD). Descriptive analysis including frequencies, means, and standard deviations were conducted for all maternal, CHD diagnoses, and neonatal variables. Continuous variables were analyzed using the Student t-test and categorical variables were analyzed using the Fisher Exact test. The most common lesions were septal defects (50% and 45% in concordant and discordant cohort) and right heart lesions (33% and 18% in concordant and discordant cohort). Diagnostic genetic testing was abnormal for 17% of the concordant and 6% of the discordant pairs, with no difference between the groups (p=0.45). Six (25%) twin pairs, 2 concordant and 4 discordant, were complicated by twin-to-twin transfusion syndrome, with all recipient twins acquiring diagnosis of CHD and no twins with abnormal genetic testing. No significant association was found between clinical risk factors and development of discordant CHD (p>0.05). This data supports environmental and epigenetic influences versus genotypic factors in the development of discordant CHD, pertinent for early diagnosis and postnatal prognosis. This is illustrated by the higher rates of discordant (75%) versus concordant (25%) CHD in MC twin pairs in this population, low incidence of family history of CHD, and the low incidence of genetic abnormalities (8.3%) in our MC cohort with CHD.