Management of Rheumatologic Diseases in Pregnancy

Oier Ateka-Barrutia; Catherine Nelson-Piercy


Int J Clin Rheumatol. 2012;7(5):541-558. 

In This Article

Neonatal Lupus Syndromes

Anti-Ro and/or anti-La antibodies may be found in patients with SLE, SS, RA, UCTD and healthy asymptomatic carriers.[92] The prevalence of these antibodies in the general population may be up to 1–3%.[93] These antibodies cross the placenta by active transport between the 16th and 30th weeks of gestation, and may cause several clinical syndromes in the fetus and neonate known as neonatal lupus syndrome (NNLS), involving skin, heart, liver and/or cytopenias.[94,95] Although no specific antibody profile for NNLS has so far been detected, high levels of anti-Ro/La have been described as a risk factor for NNLS.[96]

Cutaneous neonatal lupus is the most common manifestation, and the risk of an affected child amongst anti-Ro/La-positive mothers is approximately 5%.[94] It generally presents within the first 2 weeks of life as erythematous geographical lesions in light-exposed areas (generally face and scalp) that resemble those seen in subacute cutaneous lupus. The rash may worsen with ultraviolet light exposure and usually disappears within 3–6 months without residual scarring, when maternal antibodies are cleared from the baby's circulation.[94]

Congenital heart block (CHB) is the most severe form of NNLS and affects approximately 2% of babies born to anti-Ro/La-positive mothers.[97] This risk increases six- to ten-fold to 18% if the mother has already had a child affected by CHB, and up to 50% if she has had two affected children.[94,97] Interestingly, in the majority of children with CHB the mother will have anti-Ro and/or anti-La antibodies.[94] CHB normally develops during 16 and 24 weeks of gestation and presents with a fetal bradycardia (<60 beats per minute).[94] The risk of perinatal death amongst affected children is approximately one in five, and most surviving children need a permanent pacemaker.[94] Incomplete forms such as first- or second-degree heart block may be present, which can progress to complete forms during childhood.[94] Regardless of the underlying disease, there is no correlation between the severity of the mother's illness and the risk or degree of NNLS in the offspring.

Other less frequent cardiac manifestations have also been described as part of NNLS, such as cardiomyopathy[98] and endocardial fibroelastosis.[99] Early diagnosis is crucial in CHB, and fetal cardiac ultrasound is the accepted technique.[100] Current recommendations include serial weekly fetal echocardiograms between 16 and 26 weeks of gestation, and fortnightly between 26 and 32 weeks to pregnant women with anti-Ro and/or anti-La antibodies, although some centers may prefer to offer to listen to fetal heart rate at each visit and perform a fetal cardiology scan at 20 and 28 weeks.[94,100]

Different treatment regimens for CHB have been attempted. Fluorinated steroids (betamethasone and dexamethasone), because they are less extensively metabolized by the placenta, are generally reserved for cases with myocarditis, hydrops or incomplete heart block, as a chance for reversibility has been described.[94,101] The use of steroids should be reserved for incomplete heart block to prevent progression and not used as prophylactic treatment, as the high doses that are usually administered (dexamethasone 4–8 mg/day until the end of the pregnancy) have important side effects for both the mother (i.e., diabetes, hypertension, osteoporosis and infections) and the fetus (i.e., oligohydramnios, IUGR and adrenal suppression).[94]

IVIG treatment has been shown to inhibit placental transfer of anti-Ro/La antibodies and consequent fetal heart damage in a murine model.[102] Nevertheless, two multicenter prospective studies failed to demonstrate a reduced risk of CHB in women with previous affected children treated with IVIG during pregnancy.[103,104] In a different study, plasmapheresis also failed to prevent CHB.[105]

Two recent case–control studies suggest that, in mothers with SLE with anti-Ro/La, exposure to HCQ during pregnancy may decrease the risk of fetal CHB.[106,107]