In a structurally normal heart, 85 percent of atrioventricular block cases develop secondary to transplacental passage of maternal anti-SSA/Ro or anti-SSB/La antibodies (Buyon, 2009). Many of these women have, or subsequently develop, systemic lupus erythematosus or other connective tissue disease (Chap. 59, p. 1142). he risk of third-degree heart block with these antibodies is small-only about 2 percent. But, the risk may reach 20 percent if a prior infant has been afected. Immune-mediated congenital heart block confers a mortality rate of 20 to 30 percent, requires permanent pacing in two thirds of surviving children, and also poses a risk for cardiomyopathy (Buyon, 2009). If associated with efusions, bradyarrhythmias, or endocardial ibroelastosis, neonatal status may progressively worsen after birth (Cuneo, 2007).
Initial research eforts focused on maternal corticosteroid therapy to potentially reverse fetal heart block or forestall it.
Friedman and colleagues (2008, 2009) conducted a prospective multicenter trial of pregnancies with anti-SSA/Ro antibodies the PR Interval and Dexamethasone (PRIDE) study. Weekly sonographic surveillance was performed, and heart block was treated with maternal oral dexamethasone 4 mg daily. Unfortu nately, progression from second-to third-degree block was not prevented with maternal dexamethasone therapy, and third degree atrioventricular block was irreversible. In rare cases, there block. However, irst-degree block did not generally progress even without treatment. In a subsequent review of 156 preg nancies with isolated second-or third-degree fetal heart block, sion, need for pacemaker in the neonatal period, or overall sur vival rates (Izmirly, 2016). hus, dexamethasone use cannot be recommended for this indication.
More recent eforts have turned to potential therapy with hydroxychloroquine (Plaquenil), a mainstay of treatment for systemic lupus erythematosus (Chap. 59, p. 1142). In a multi center review of more than 250 pregnancies in women whose prior pregnancies had been complicated by neonatal lupus, recurrence of congenital heart block was signiicantly lower if the woman had been treated with hydroxychloroquine during pregnancy (Izmirly, 2012). Research in this area is ongoing.
Maternal terbutaline has also been given to increase the fetal heart rate in cases with sustained bradycardia of any cause in which the fetal heart rate is below 55 bpm. Reversal of hydrops with this therapy has been reported (Cuneo, 2007, 2010).
Several autosomal recessive enzyme deiciencies cause impaired fetal synthesis of cortisol from cholesterol by the adrenal cortex. his results in congenital adrenal hyperplasia (CAH). CAH is the most common etiology of androgen excess in females with 46,X disorders of sex development, formerly female pseudohermaphroditism (Chap. 3, p. 41). Lack of cortisol stimulates adrenocorticotrophic hormone (ACTH) secretion by the anterior pituitary, and the resulting androstenedione and testosterone overproduction leads to virilization of female fetuses. Sequelae may include formation of labioscrotal folds, persistence of a urogenital sinus, or even creation of a penile urethra and scrotal sac.