Pathophysiology of coarctation of the aorta in dichorionic twins with growth discordance

Coarctation of the aorta (CoA) is an abnormal narrowing of the aorta which can occur as an isolated defect or in association with other intracardiac anomalies, in syndromic and non-syndromic patients, with a prevalence of 4 per 1000 live births1. CoA represents a challenge in prenatal diagnostics, and its pathophysiological mechanisms are not well-understood. We report on four dichorionic diamniotic twin pairs presenting with CoA and fetal growth restriction (FGR) in one twin and a discordant phenotype in the cotwin (Table 1). In all cases, the karyotype was normal and the pregnant woman was not diagnosed with an infection or exposed to any identifiable teratogen or medication. The four cases with CoA were diagnosed on postnatal echocardiography and underwent end-to-end anastomosis after birth. Weight discordance of approximately 20% was noted between neonates with CoA and their cotwins. In the Baltimore-Washington Infant Study2, CoA was present in 3.2% of cases, with a 2-fold higher prevalence in twin compared with singleton pregnancies. All cotwins were unaffected2. Congenital heart diseases have been reported to affect 7% of pregnancies with twin-to-twin transfusion syndrome (TTTS), which represent 10–15% of monochorionic pregnancies3. TTTS is characterized by the presence of placental anastomoses, which result in chronic unbalanced volumes circulating from the donor to the recipient twin4. An increased risk for CoA has been reported in donor twins, whose aortic arch may be underdeveloped due to hypovolemia, reduced placental venous return and decreased cardiac output5. Moreover, increased vascular resistance in donor twins may lead to intrauterine growth restriction. A large study including 103 liveborn singletons diagnosed with isolated CoA reported moderate birth-weight deficiency in this population6. Despite the growing attention to the prevention of complications in newborns with low birth weight and CoA in the literature7, the potential common pathophysiological mechanism has not been explored in detail. In the present dichorionic diamniotic pregnancies, one fetus was affected by CoA, with a discordant cardiac phenotype observed in the cotwin. As in the ‘donor–recipient circulation model’, all cases affected by CoA had FGR, suggesting altered fetal–placental hemodynamics as the mechanism of CoA. Therefore, we postulate that CoA occurs secondary to FGR, which in turn is caused by inadequate perfusion of placental structures, in singleton as well as in twin pregnancies. The higher prevalence of CoA in twin pregnancies could be due to the higher risk of hemodynamic alterations, causing FGR in one of the fetuses. A large multicenter prospective study (Evaluation of Sonographic Predictors of Restricted Growth in Twins (ESPRIT)) demonstrated that a birth-weight discordance of 18% in dichorionic twins represents the cut-off above which the risk for adverse perinatal outcome is increased8. Unequal distribution of uteroplacental blood flow between twins, aberrant placental insertion of the umbilical cord and TTTS represent contributing causes of birth-weight discordance in monochorionic twins. Although the precise mechanism is unknown in dichorionic twins, the presence of discordant cardiac phenotype and growth discordance suggests that both genetic and environmental factors are involved and that a flow-related mechanism may explain both FGR and CoA. In conclusion, in the four dichorionic twin pregnancies described herein, we observed a discordant phenotype characterized by CoA and FGR in one of the twins. These cases suggest that alterations in intrauterine blood flow and fetal–placental hemodynamics, resulting in FGR and an altered flow through the aortic arch, may be one of the mechanisms of CoA development. The data that support the findings of this study are available from the corresponding author upon reasonable request.