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Middle cerebral artery pulsatility index as possible predictive marker for neonatal death in fetuses with tricuspid valve malformation

Tricuspid valve malformations (TVMs) account for approximately 1% of all congenital heart defects (CHDs)1. Tricuspid valve leaflets are deformed in TVM, with apical displacement in Ebstein’s anomaly (EA) and deficient coaptation in tricuspid valve dysplasia (TVD). Intrauterine/neonatal death is a possible consequence in the management of TVM and, thus, prediction of prognosis is crucial. Other than echocardiographic criteria2, no individual fetal Doppler parameter has been proposed as a possible predictor of neonatal death in affected fetuses. Cerebrovascular resistance may be affected in utero in the presence of CHD, which is evaluated easily by fetal middle cerebral artery (MCA) pulsatility index (PI). We aimed to investigate whether MCA-PI assessment has additional value in predicting neonatal death in fetuses with TVM. We analyzed retrospectively 15 fetuses diagnosed with TVM at the University of Maryland Fetal Heart Program, Baltimore, MD, USA from 2007 to 2018. All diagnoses were confirmed by an expert (S.T.) in fetal echocardiography and later by pediatric cardiologists. Fetal echocardiographic and Doppler variables obtained at both diagnosis and final examination were MCA, umbilical artery and ductus venosus Doppler, and Simpson– Andrews–Sharland (SAS) score parameters, including cardiothoracic ratio, Celermajer index, pulmonary valve flow, arterial duct flow and right–left ventricular diameter ratio (Table S1)2. Celermajer index was calculated as follows: (right atrial area + atrialized right ventricular area)/(functional right ventricular area + left atrial area + left ventricular area). Neonates were divided into survivors and non-survivors (at 2 months after birth). The Shapiro–Wilk test was used to assess the distribution of data for normality. Groups were compared using the Student’s t-test, Mann–Whitney U-test, Fisher’s exact test or chi-square test, as appropriate. The Kendall correlation test was used to determine the degree of correlation in SAS score between diagnosis and final examination. Statistical analyses were performed using SPSS software version 21.0 (IBM Corp., Armonk, NY, USA). P < 0.05 was considered statistically significant. Of the 15 cases, 10 had EA and five had TVD. Data from 14 cases were included, as one EA case was terminated at 23 weeks’ gestation due to intrauterine fetal loss secondary to fetal hydrops. Survivors and non-survivors did not differ according to maternal age, birth weight or gestational age at diagnosis, final examination or delivery (Table 1). There were three fetuses with a chromosomal anomaly. One of the survivors had a gain of 5q21 and a loss of Table 1 Characteristics of 14 pregnancies with fetal tricuspid valve malformation, according to survival at 2 months after birth