Effect of In Utero Non-Steroidal Anti-Inflammatory Drug Therapy for Severe Ebstein Anomaly or Tricuspid Valve Dysplasia (NSAID Therapy for Fetal Ebstein anomaly)
Freud LR, Wilkins-Haug LE, Beroukhim RS, LaFranchi T, Phoon CK, Glickstein JS, Cumbermack KM, Makhoul M, Morris SA, Sun HY, Ferrer Q, Pedra SR, Tworetzky W.Am J Cardiol. 2021 Feb 15;141:106-112. doi: 10.1016/j.amjcard.2020.11.013. Epub 2020 Nov 18.PMID: 33217351
Take Home Points:
- Ebstein anomaly (EA) and tricuspid valve dysplasia (TVD) often produce severe tricuspid regurgitation (TR) in the fetus and in some cases; pulmonary regurgitation (PR) and circular shunting ensue. Since the ductus arteriosus (DA) plays a critical role in the circular shunt and may be constricted by transplacental nonsteroidal anti-inflammatory drugs (NSAIDs)
- 12 of 15 (80%) achieved DA constriction after a median of 2.0 days. (All fetuses with DA constriction had improved PR; 92% had improved Doppler patterns.
- Eleven of 12 patients (92%) with DA constriction survived to live-birth, whereas 4 of 9 patients (44%) who did not receive NSAIDs or achieve DA constriction survived (p = 0.046)
Commentary from Dr. Manoj Gupta (New York, USA), section editor of Pediatric & Fetal Cardiology Journal Watch: This is a retrospective case series, which included mothers of second- and third-trimester fetuses with severe EA/TVD and circular shunting who were offered NSAID therapy at multiple international centers from 2010 to 2018. All fetuses had severe EA/TVD with severe TR and circular shunting with at least moderate PR.
High-dose indomethacin (100 mg 2 to 4 times daily) was typically administered as initial therapy to achieve DA constriction. Fetal echocardiograms were performed approximately every 24 to 48 hours to assess whether DA constriction was achieved. If DA constriction was achieved, then therapy was commonly transitioned to maintenance ibuprofen (200 to 600 mg 3 to 4 times daily), throughout the remainder of gestation.
All 12 fetuses with DA constriction had improved PR, with 1 having complete resolution, and half achieved antegrade pulmonary blood flow.
With regard to safety, 1 fetus developed complete DA constriction after 6 days of indomethacin therapy; this fetus had resolution of hydrops and normalization of the extracardiac Dopplers and was delivered at 38.0 weeks. Ten patients (67%) developed oligohydramnios, ranging from 3 to 42 days after initiation of indomethacin and/or ibuprofen therapy. In 5 cases, therapy was transitioned from indomethacin to ibuprofen or briefly stopped with resumption of normal amniotic fluid volume. In 2 cases that developed oligohydramnios at 33.6 and 35.7 weeks, the decision was made to proceed with delivery at 34.1 and 35.9 weeks, respectively. The remainder was monitored without intervention until delivery. Postnatally, 2 neonates had renal failure requiring peritoneal dialysis.