Since systemic lupus erythematosus (SLE) primarily affects women of childbearing age, therefore pregnancy assumes great importance for these patients. Accordingly, proper pre-conception counselling is highly relevant to management and can set the stage for a more favourable outcome.

Women of childbearing age with SLE should be advised of medications safe to continue during pregnancy and told that disease should be in remission or at least not acutely active. Hydroxychloroquine is strongly recommended for all women during pregnancy despite a concern raised regarding a very slight increase in malformations, which was not confirmed in a subsequent study. Low dose aspirin to prevent pre-eclampsia should be highly reinforced. The issues related to pregnancy outcome for the maternal-fetal dyad comprise three components, maternal, placental and fetal with the latter clearly influenced by the two former. With the completion of a large prospective US based study,¹ factors associated with poor pregnancy outcomes in patients who are generally stable at the time of conception have emerged and include being Hispanic or non-white, taking blood pressure medications, low platelet counts, active disease even if stable, and the presence of a lupus anticoagulant. In the absence of these factors, pre-eclampsia still occurs at a greater frequency than in the otherwise healthy population, with estimates of about 9%, as does small for gestational age at about 10%. In patients with no risk factors at baseline, the adverse pregnancy outcome rate is about 8% and fetal/neonatal mortality 3.9%. In patients who are either lupus anticoagulant (LAC) positive, or LAC negative but non-white and treated with anti-hypertensives, the adverse pregnancy outcome rate approaches 60%; fetal/neonatal mortality at 22%. In general, patients with prior kidney disease but in remission do well without an increased risk of flare with de novo kidney disease being quite uncommon with risk under 3%. Severe flares in patients stable at conception approach less than 3% at any time during pregnancy and postpartum, and approximately 10% intrapartum and 25% postpartum for mild/moderate flares (most not requiring intervention).²

Promising biomarkers, which may identify women early in pregnancy at risk for poor outcomes, include angiogenic factors and alternative and terminal complement activation factors. Turning to neonatal lupus, newer research supports the contribution of Type I interferon in the pathogenesis. A prospective study supports the use of hydroxychloroquine to decrease the recurrence of congenital heart block in half.³ Data suggest that low titre anti-SSA/Ro antibodies do not confer risk of fetal cardiac injury but defining low and high titres in commercial laboratories is not well established since many do not provide a broad range of values. New approaches to surveillance are being addressed leveraging home heart rate and rhythm monitoring by the mothers.⁴ The NIH has launched a recent US and Canada based study to evaluate whether the titre of anti-SSA/Ro 60 or 52 antibodies confers higher risk and if home Doppler monitoring can identify a transition period of conduction slowing that is reversible with dexamethasone and IVIG if administered within 12 hours of a Doppler abnormality confirmed by echocardiogram. Overall, the landscape for women with lupus contemplating pregnancy is favourable after achievement of stability or remission prior to conception. Prevention of reversible cardiac damage in those women with SLE and anti-SSA/Ro antibodies may be on the horizon.

References

1. Buyon JP, et al. Predictors of pregnancy outcomes in patients with lupus: a cohort study. Ann Intern Med 2015 Aug 4;163(3):153–163.

2. Davis-Porada J, et al. Low frequency of flares during pregnancy and post-partum in stable lupus patients. Arthritis Res Ther 2020 Mar 19;22(1):52.

3. Izmirly P, et al. Hydroxychloroquine to prevent recurrent congenital heart block in fetuses of anti-SSA/Ro-positive mothers. J Am Coll Cardiol 2020 Jul 21;76(3):292–302.

4. Cuneo BF, et al. Home monitoring for fetal heart rhythm during anti-Ro pregnancies. J Am Coll Cardiol 2018 Oct 16;72(16):1940–1951.

References Case 1: A 36-year-old-white female

A 36-year-old white female who has occasional dry eyes, no dry mouth, and no other symptoms was tested for anti-SSA/Ro antibodies, given the dry eyes and a family history of lupus, and found to be positive with a titre done by a commercial lab as >8 EU. Anti-SSB/La antibodies, anti-RNP and anti-dsDNA were negative. Her complements were normal. She was otherwise well and was told she did not meet criteria for SLE or Sjögren’s Syndrome.

The patient became pregnant a year later and returned to the rheumatologist who had initially diagnosed her has having an undifferentiated autoimmune syndrome. She had no new symptoms and in fact her dry eyes were now much improved, and she could even wear contact lenses. This was her first pregnancy and she was not placed on any medications. She was again tested for anti-SSA/Ro and SSB/La antibodies and the former was again positive at >8 EU; no evaluation was done specifically for anti-Ro60kD or Ro52kD. The mother was told to have fetal echocardiograms weekly from 17 to 26 weeks. The weekly echo was normal at 17 and 18 weeks but at 19 weeks the fetus was bradycardic at 65 bpm with third degree block confirmed. There were no signs of valvular dysfunction, no endocardial fibroelastosis and no evidence of cardiomyopathy. The mother was treated with 8 mg dexamethasone, which was tapered to 4 mg by Week 25 and then 2 mg by Week 30 with no emergence of endocardial fibroelastosis or deterioration in cardiac function. The baby was growing well but at 35 weeks oligohydramnios developed. Dexamethasone was discontinued. The amniotic fluid increased and the fetal heart rate remained at 60–65 beats per minutes. The baby was delivered at 38 weeks by C-section and did not require a pacemaker at birth. The mother breastfed the baby and no further issues ensued, no rashes. By age 5 years the baby’s heart rate had dropped to 50 bpm and a biventricular pacemaker was placed. The child is now 20-years-old and working in a biology lab during college and participates in sports. Her mother has developed lupus but symptoms are mild with a positive, ANA, low WBC, a malar rash and joint swelling of her PIPs for which she takes hydroxychloroquine and is doing well.

Learning Objectives

• Explain clinical and laboratory risk factors for adverse pregnancy outcomes in women with SLE

• Assess flare rates in pregnancies of women with SLE

• Manage SLE pregnancies complicated by anti-SSA/Ro antibodies