Epidemiology, Genetics and Epigenetics of Congenital Heart Diseases in Twins

Congenital heart defects (CHDs) refer to abnormalities in the heart function that arise at the fetal stages. It is the most common birth defect that affects 0.8% of all liveborn infants. There is an increase in the incidence of congenital heart disease in monochorionic twin gestation. A six-fold increase in CHDs exists among monochorionic twins especially in association with twin-twin transfusion syndrome (TTTS) compared to dichorionic twin pregnancy. In this review article, we discussed the epidemiology, the role of genetics like protein-coding genes, epigenetics, placenta, hemodynamics and environmental factors in the etiology of CHD in twins. We conducted a literature search in PubMed indexed journals using the medical terms "twin pregnancy" and "congenital heart defect" to provide an overview of the uptrend in CHD in twin pregnancies, primarily due to assisted reproductive technologies (ARTs) and multiple other factors. Both the heart and placenta are vascular and share a common development window; therefore, CHD can develop secondary to placental pathologies. Among environmental factors, the strongest association of maternal smoking with CHD has been seen. We studied the causative factors to suggest improvement in echocardiographic skills in case of abnormal findings in twin gestations to decrease the CHD-associated morbidity and mortality, as early diagnosis allows doctors to precisely determine the risk of CHD. Systemic ultrasound scanning with five transverse views is very effective in diagnosing fetal CHD in twin pregnancy. In the case of genetics, prenatal counseling allows the expectant to understand the full ramifications of possible events after the pregnancy. The pathological basis of malformations specific to conjoined twinning and twin reversed arterial perfusion sequence is addressed. Also, there is evidence that folate supplementation may be protective against CHD but more research is needed to clarify the mechanisms. We concluded from the literature that monochorionic twins are at high risk of CHD. Chorionicity seems to play a more vital role than zygosity. Even the type of heart defect in monochorial twin pregnancies was unique from single, dizygotic, or dichorionic twin pregnancies. We also emphasize improving echocardiographic skills of technicians in referring ART dichorionic twin fetuses with suspicious findings to fetal cardiologists and performing postnatal scans in the case of TTTS. To understand the role of the placenta, making use of newer technologies and examining the placenta both during pregnancy and beyond delivery will play a vital role in understanding the etiology. Even identifying early signals impacting the heart and placental vasculature and correcting them using advanced technology could downtrend the incidence in coming years. Increased maternal age as well as multiple pregnancies increasing the risk of CHD has also been implicated. For more clarity on the role of genetics, the cost of DNA sequencing needs to decrease. This will enable whole-genome sequencing in the future thus helping to discover the gene responsible for CHD ultimately proving beneficial for future generations. For environmental factors, we have to rely on observational studies to assess the risk to the unborn child. There is difficulty in studying natural factors due to the unreliability of exposure to contaminants like pesticides and air pollution.