What are the implications of low Complement 4 (C4) levels in a patient with Systemic Lupus Erythematosus (SLE) during the third trimester of pregnancy?

From the Guidelines

Low C4 complement levels in a pregnant lupus patient in the third trimester requires immediate evaluation and monitoring to prevent adverse maternal and fetal outcomes, as recommended by the 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases 1.

Key Considerations

• The patient should contact their rheumatologist and obstetrician promptly for assessment, which will likely include blood pressure measurement, urine protein testing, complete blood count, and additional complement studies.
• Treatment depends on the underlying cause - if it's active lupus, medications like hydroxychloroquine (200-400mg daily), low-dose prednisone (5-10mg daily), or azathioprine (50-150mg daily) may be adjusted, as these are generally considered safe in pregnancy, according to the EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome 1.
• If preeclampsia is suspected, delivery may be necessary depending on gestational age and maternal/fetal status.
• Regular monitoring should include weekly or biweekly visits with blood pressure checks, laboratory tests, and fetal assessment, including ultrasonographic fetal surveillance, as recommended by the EULAR guidelines 1.

Management of SLE Flares During Pregnancy

• Hydroxychloroquine is recommended during pregnancy if possible, and low-dose aspirin (81 or 100 mg daily) is conditionally recommended, beginning in the first trimester, as stated in the 2020 American College of Rheumatology guideline 1.
• Active disease affects maternal and pregnancy outcome, and monitoring SLE disease activity with clinical history, examination, and laboratory tests at least once per trimester is strongly suggested, as good practice, according to the 2020 American College of Rheumatology guideline 1.

Fetal Surveillance

• Supplementary fetal surveillance in the third trimester at monthly intervals, including Doppler sonography of the umbilical artery, uterine arteries, ductus venosus, and middle cerebral artery, is recommended, as stated in the EULAR guidelines 1.
• In cases of late intrauterine growth restriction (IUGR), reduced abdominal circumference growth velocity, and/or a reduced cerebroplacental ratio at Doppler investigation, may identify fetuses at higher risk of poor perinatal outcome, according to the EULAR guidelines 1.

From the Research

Low C4 in Pregnancy with Known Lupus

In a patient with known lupus in their 3rd trimester, a low C4 level can be an indicator of several potential issues.

• Low C4 levels are often associated with increased disease activity in systemic lupus erythematosus (SLE) 2.
• It is essential to differentiate between an exacerbation of SLE and pre-eclampsia, as both conditions can present with similar symptoms such as proteinuria and hypertension 3, 2.
• Studies have shown that serum C3 and C4 values can help distinguish between SLE activity and pre-eclampsia, with lower levels of C3 and C4 indicating SLE activity 2.
• In pregnant women with SLE, low C4 levels can be a predictor of disease flare-ups and other adverse pregnancy outcomes 4, 5.
• The use of hydroxychloroquine (HCQ) has been shown to improve pregnancy outcomes in women with SLE, including reducing the risk of preeclampsia 4, 6.

Management and Monitoring

• Close monitoring by a multidisciplinary team, including obstetricians, nephrologists, and rheumatologists, is crucial for optimal outcomes in pregnant women with SLE 3, 5.
• Regular measurements of serum C3 and C4 levels, as well as other biomarkers, can help identify potential issues and guide treatment decisions 2.
• The management of SLE during pregnancy requires a coordinated approach, weighing the benefits of treatment against the potential risks to the fetus 5.