An Unusual Case of Fetal Myocardial Injury Leading to Intrauterine Fetal Demise: A Possible Sequela of Maternal COVID Infection?

ABSTRACT

Background. Intrauterine myocardial injury/infarction (MI) is exceedingly uncommon and the few reported cases occur most commonly with congenital cardiac anomalies, particularly anomalous coronary arteries. Here we present a case of MI in a fetus resulting in intrauterine fetal demise (IUFD). A 36-year-old G3 P1011 mother with a history of methylenetetrahydrofolate reductase (MTHFR) mutation (double heterozygote;may lead to a procoagulable state) on prophylactic aspirin and recent COVID-19 infection during pregnancy (5 weeks prior, recovered) presented at 28 weeks gestational age with one day of decreased fetal movement, at which time IUFD was diagnosed. Method(s) Induction of labor with misoprostol was performed, and the fetus was delivered stillborn vaginally without complications. A full autopsy including histologic examination (including placental histopathology and immunohistochemistry) was performed. Result(s) Autopsy examination of the fetus revealed normal development, including a structurally normal heart. However, histologic examination of the heart demonstrated a discrete region of intramyocardial fibrosis, dystrophic calcification, and giant cell reaction involving a large portion of one ventricle, consistent with MI (Fig 1). Immunostains for infectious causes of myocarditis (including COVID, cytomegalovirus, herpes simplex virus, parvovirus, adenovirus, and toxoplasmosis) were negative. Histologic examination of all other organs was unremarkable. Gross examination of the placenta was remarkable for a hypercoiled umbilical cord, and histologic examination revealed a hypoplastic umbilical artery with partial smooth muscle necrosis as well as a single, nonoccluding stem villus thrombus, without histologic evidence of downstream fetal vascular malperfusion. Conclusion(s) The cause of demise was concluded to most likely be due to fetal myocardial injury, but the etiology is unclear. The differential diagnosis includes a thromboembolic phenomenon possibly leading to infarction (given maternal history of MTHFR mutation and recent COVID infection), myocarditis (possibly burned- out phase), coronary artery abnormalities that were not appreciated on fresh dissection of the heart, and ventricular dysplasia/aneurysm (least likely given histologically normal surrounding myocardium). This rare case is an example of a lethal myocardial injury in an otherwise structurally normal fetal heart.