This chapter focuses on aspects of pregnancy related to anti-Ro/SSA antibody-associated fetal cardiac diseases collectively known as cardiac neonatal lupus erythematosus (NLE). The cardiac manifestations include fetal atrioventricular (AV) block and myocardial disease.

The population prevalence of fetal AV block is approximately 1:15,000 live births.¹,² Fetal AV block, a disease of the second trimester, develops in 2% to 3% of mothers who carry anti-Ro/SSA antibodies.³,⁴,⁵,⁶,⁷ Although anti-Ro/SSA antibodies are present in various rheumatologic disorders including Sjogren syndrome and systemic lupus erythematosus, many of the mothers whose fetuses develop AV block are clinically asymptomatic.⁸,⁹ Furthermore, in rheumatologic disorders, the risk of fetal AV block is independent of maternal disease severity.

Although rare, the burden of anti-Ro/SSA antibody-mediated fetal AV block is considerable as the perinatal mortality of 17% exceeds that for all noncardiac congenital anomalies combined. Furthermore, almost all survivors require lifelong cardiac pacing with its associated complications.¹⁰ In addition, dilated cardiomyopathy, which occurs in 7% to 19% of AV block cases and can present in the perinatal period or in childhood, has a very poor prognosis¹¹,¹²,¹³,¹⁴,¹⁵,¹⁶ (see Part 3, Chapter 5).

It has been hypothesized that 3° AV block is the endpoint of sequential progression from normal rhythm to 1° then 2° AV block and culminating in 3° AV block (FIG. 5.2.1). Once 3° AV block occurs, it is irreversible and normal rhythm cannot be restored. However, anti-inflammatory treatment during 1° or 2° AV block has, in some cases, restored normal rhythm.¹²,¹⁷,¹⁸,¹⁹,²⁰,²¹,²²,²³

These findings have formed the basis for the multidisciplinary care of the anti-Ro/SSA antibody positive pregnant woman. Such care begins with the rheumatologist identifying mothers with anti-Ro/SSA antibodies and referring them to an obstetrician or maternal fetal medicine specialist for prenatal counseling. The goal of prenatal counseling is first, to identify mothers at high risk for fetal cardiac NLE either by anti-Ro/SSA antibody titers (see below) or by history of a previously affected fetus or child, and second, to formulate a surveillance plan with a maternal fetal medicine specialist or pediatric cardiologist that is cost-effective and clinically effective and identifies a window of opportunity for treatment that can be effective.

While the risk of fetal anti-Ro/SSA-mediated disease increases after one affected child, the risk does not decrease after an unaffected child. Published recommendation for fetal surveillance is weekly or biweekly echoes on all anti-Ro/SSA antibody positive pregnancies from 17 to 26 weeks, in order to detect 1° or 2° AV block or early myocardial dysfunction (endocardial fibroelastosis or atrioventricular valve insufficiency).²⁴ However, recent fetal echo guidelines from the American Institute of Ultrasound in Medicine recommend fetal echo surveillance to be “considered” in anti-Ro/SSA positive pregnancies, and “indicated” only with a history of a cardiac NLE in a previous offspring.²⁵ In reality, clinical practice varies widely. Some obstetricians and pediatric cardiologist will not begin surveillance until after 18 weeks (when 3° AV block may already be established), some will perform weekly or biweekly ultrasounds/echoes, and some combine ultrasounds with home or office Doppler monitoring, while others have concluded surveillance is not helpful in preventing AV block and do nothing at all.²⁶

The risk of recurrence with one affected child with either cardiac or cutaneous manifestations of NLE is as high as 18%.³,⁴,¹⁰,²⁷ Hydroxychloroquine has shown great promise in reducing the recurrence of fetal AV block²⁸ and is used by rheumatologists to prevent disease flare-up during pregnancy in women with systemic lupus erythematosus. It was recognized that women given this drug (400 mg/d) before 10 gestational weeks had a 10-fold reduction in recurrence of offspring affected with 3° AV block and zero fetal and childhood mortality compared to the 22% in those untreated.²⁹ A beneficial
effect is supported by a lower prevalence of 3° AV block in current prospective studies in populations where this drug is in routine clinical use³⁰ and safety demonstrated in a histological report showing no cardiotoxicity in the fetal myocardium following its early administration.³¹ These findings are encouraging and suggest prophylaxis with hydroxychloroquine may be the most effective drug with the lowest risk-benefit ratio to date.