Background Transplacental fetal treatment of immune-mediated fetal heart disease, including third-degree atrioventricular block (AVB III) and endocardial fibroelastosis, is controversial. Methods and Results To study the impact of routine transplacental fetal treatment, we reviewed 130 consecutive cases, including 108 with AVB III and 22 with other diagnoses (first-degree/second-degree atrioventricular block [n=10]; isolated endocardial fibroelastosis [n=9]; atrial bradycardia [n=3]). Dexamethasone was started at a median of 22.4 gestational weeks. Additional treatment for AVB III included the use of a β-agonist (n=47) and intravenous immune globulin (n=34). Fetal, neonatal, and 1-year survival rates with AVB III were 95%, 93%, and 89%, respectively. Variables present at diagnosis that were associated with perinatal death included an atrial rate <90 beats per minute (odds ratio [OR], 258.4; 95% CI, 11.5-5798.9; P<0.001), endocardial fibroelastosis (OR, 28.9; 95% CI, 1.6-521.7; P<0.001), fetal hydrops (OR, 25.5; 95% CI, 4.4-145.3; P<0.001), ventricular dysfunction (OR, 7.6; 95% CI, 1.5-39.4; P=0.03), and a ventricular rate <45 beats per minute (OR, 12.9; 95% CI, 1.75-95.8; P=0.034). At a median follow-up of 5.9 years, 85 of 100 neonatal survivors were paced, and 1 required a heart transplant for dilated cardiomyopathy. Cotreatment with intravenous immune globulin was used in 16 of 22 fetuses with diagnoses other than AVB III. Neonatal and 1-year survival rates of this cohort were 100% and 95%, respectively. At a median age of 3.1 years, 5 of 21 children were paced, and all had normal ventricular function. Conclusions Our findings reveal a low risk of perinatal mortality and postnatal cardiomyopathy in fetuses that received transplacental dexamethasone±other treatment from the time of a new diagnosis of immune-mediated heart disease.

Patients with early-onset lysosomal storage diseases are ideal candidates for prenatal therapy because organ damage starts in utero. We report the safety and efficacy results of in utero enzyme-replacement therapy (ERT) in a fetus with CRIM (cross-reactive immunologic material)-negative infantile-onset Pompes disease. The family history was positive for infantile-onset Pompes disease with cardiomyopathy in two previously affected deceased siblings. After receiving in utero ERT and standard postnatal therapy, the current patient had normal cardiac and age-appropriate motor function postnatally, was meeting developmental milestones, had normal biomarker levels, and was feeding and growing well at 13 months of age.