Prenatal features, associated co-morbidities and clinical course of agenesis of the ductus venosus in the current era
McBrien A, Caluseriu O, Niederhoffer KY, Hornberger LK.
Prenat Diagn. 2020 Sep 13. doi: 10.1002/pd.5827. Online ahead of print.
Take Home Points:
- Agenesis of the ductus venosus (ADV) is rare and nearly always associated with genetic or other associated anomalies.
- While increased cardiac output, especially in late gestation, is common, the risk of hydrops and mortality is lower than previously suspected.
Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch: Evaluation of the ductus venosus (DV) is a routine part of the pediatric echocardiogram and risk scoring. The DV is necessary for placental blood regulation, allowing the higher oxygen concentrated blood flow to stream towards the PFO to allow for more oxygen delivery to the coronary arteries and cerebral circulation. Abnormal flow patterns of the DV have been associated with chromosomal abnormalities and absence has been associated with a wide variety of genetic, cardiac, and non-cardiac associated abnormalities, with about ⅓ having a genetic diagnosis and up to about 40% with cardiac or non-cardiac anomalies.
Due to the common association with an extrahepatic connection of the umbilical vein, there is an increased risk of high output cardiac failure, with resulting hydrops or fetal demise. With a significant improvement and availability of genetic testing and imaging, the authors hypothesized that there may be a higher incidence of genetic and structural abnormalities than previously reported, and possibly better outcomes during pregnancy and postnatally.
A retrospective review of patients with ADV was done between 2007-2018. Clinical records, including fetal echocardiograms, prenatal ultrasounds, and postnatal echocardiograms were reviewed. Fetal echo included any structural or functional cardiac abnormalities, combined cardiac output (CCO) measurement, and presence of hydrops. Results of genetic testing (pre and postnatal) and pregnancy outcomes were recorded. 14 cases of ADV were found, with a mean GA of 23.9 weeks. None of the cases were isolated (ADV only). 9/14 (64%) had cardiac abnormalities with 2 patients having bilateral SVC as the only cardiac diagnosis (considered to be a non-pathologic variant). 13/14 (93%) had a non-cardiac abnormality with cystic hygroma being the most frequent diagnosis (29%).
7/14 (50%) had prenatal genetic testing and an additional patient had postnatal testing. Only 14% had aneuploidy, suggesting that more robust genetic testing is necessary to obtain a genetic diagnosis. There were two postnatal deaths. See table 1. There were no terminations of pregnancy and only 1 fetal demise (hydrops at presentation). Mean GA at delivery was 36.4 weeks. Cardiac output was measured in 10 patients and 6 had CCO above a z-score of +2 with only 2 patients developing hydrops (Figure 1). 12/14 had extrahepatic connection of the umbilical vein; the 2 with intrahepatic connection did not have hydrops.
The authors discuss the specific genetic diagnoses (previously reported in Turner and Noonan Syndrome) and speculate the association with PHACE and RASA1 mutations. Additionally, they discuss the CCO elevations that were more common in the 3rd trimester/later gestation as compared to other high output conditions such as TTTS or sacrococcygeal teratoma that are more common mid-gestation, which could possibly explain why hydrops was less likely. They also speculate that longer term neurodevelopmental data may be useful given the pathophysiology of decreased oxygenated blood to the fetal cerebral circulation in those with ADV.