Transplacental non‐steroidal anti‐inflammatory drugs versus expectant management in fetal Ebstein anomaly with circular shunt: Systematic review and meta‐analysis

• Published in: Prenatal diagnosis Vol. 44; no. 6-7; pp. 773 - 782
• Main Authors: Mustafa, Hiba J., Aghajani, Faezeh, Bairmani, Zinah A., Khalil, Asma
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-06-2024
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Drugs; Ebstein Anomaly; Edema; Effusion; Female; Fetuses; Heterogeneity; Humans; Inflammation; Meta-analysis; Nonsteroidal anti-inflammatory drugs; Pregnancy; Regurgitation; Shunts; Systematic review; Therapy; Tricuspid valve; Ultrasonography, Prenatal; Watchful Waiting - statistics & numerical data
• ISSN: 0197-3851; 1097-0223; 1097-0223
• DOI: 10.1002/pd.6446

Ebstein anomaly (EA) is a rare congenital cardiac malformation associated with high perinatal mortality. In this systematic review and meta‐analysis, we aimed to investigate the outcomes of pregnancies affected by EA or tricuspid valve dysplasia (TVD) with circular shunt, focusing on two prenatal management approaches: (1) expectant management (EM) and (2) transplacental non‐steroidal anti‐inflammatory drugs (NSAID) therapy. We searched PubMed, Scopus, and Web of Science systematically from its inception until June 2023. The random‐effect model was used to pool the data. Heterogeneity was assessed using the I2 value. Twenty‐one studies with a total of 610 fetuses with EA/TVD with circular shunt were included in the synthesis, of which 17 studies (583 fetuses) were on EM and 4 studies (27 fetuses) used transplacental NSAID therapy. The NSAID group had higher rates of moderate to severe tricuspid regurgitation, hydrops, and pericardial effusion on prenatal ultrasound compared with the EM group. However, ductal constriction was achieved in 81% of NSAID cases, mitigating the disease pathophysiology, although 65% of them experienced oligohydramnios. Notably, the NSAID group showed significantly higher rates of live birth (86%) and survival to hospital discharge (89%) compared with the EM group (67% and 43%, respectively). Despite these promising results, it's important to acknowledge that the number of cases treated with NSAIDs was small, with limited safety data. Therefore, caution is advised in interpreting these findings, and patients considering NSAID therapy should be informed about these limitations. Future multicenter studies are necessary to further explore the safety and effectiveness of NSAID therapy in this particular population.
Key points
What's already known about this topic?
Ebstein anomaly (EA) and tricuspid valve dysplasia (TVD) are associated with severe tricuspid regurgitation (TR) and pulmonary regurgitation (PR).
When PR is present, a circular shunt ensues with ineffective systemic blood flow leading to perinatal mortality.
Transplacental administration of non‐steroidal anti‐inflammatory drugs (NSAIDs) may result in a narrowing of the fetal ductus arteriosus (DA) and PR improvement in fetuses with severe EA/TVD.
What does this review add?
This is the first systematic review and meta‐analysis that comprehensively compares expectant management (EM) versus treatment with NSAIDs in fetal EA/TVD with a circular shunt.
Among fetuses with EA/TVD with circular shunt with EM, only 43% survived to hospital discharge versus 89% of those treated with NSAIDs.