Systemic lupus erythematosus (SLE) In Pregnancy

In short: Lupus does not prevent pregnancy, but the disease should be stable for at least 6 months beforehand, with coordination between the rheumatologist and the obstetrician. Some lupus drugs, such as methotrexate, are forbidden in pregnancy. Lupus raises the risk of pre-eclampsia, miscarriage and preterm birth, so blood pressure, urine protein and the baby’s growth need close monitoring. Breastfeeding is not ruled out.

Systemic lupus erythematosus (SLE) is a chronic inflammatory, autoimmune disease that can affect various organs of the body. Characterized by production of antibodies to components of cell nucleus.

• Who’s affected:
• Young women, peak incidence age 15-40 years with female: male ratio 5:1

• African Americans have higher lupus mortality risk compared to Hispanics and Caucasians
• Causes Of Systemic lupus erythematosus (SLE)
• Unknown
• Genetic factors
• Environmental factors, which may include:
• Sunlight (UV rays)
• Stress
• Viral or other type of infection
• Drugs
• There are drugs that cause Drug Induced Lupus
• Most common : Hydralazine, Procainamide, and Isoniazid
• Pathogenesis Of Systemic lupus erythematosus (SLE)
• central immunologic disturbance is autoantibody production
• Antinuclear antibodies (ANA) found in >95% :
• anti-SSA (anti-Ro)
• anti-dsDNA and anti-Sm specific to SLE
• anti-ssDNA
• Others: anti-histones (H1, H2A, H2B, H3),anti-U1RNP,anti-SS-B
• Organs involved
• 90% joints
• 80% skin, serous membranes, lungs
• 67% kidneys, heart
• 25% CNS, small vessels
• Risk factors of Systemic lupus erythematosus (SLE)
• Genetic predisposition (i.e. black race, 25-50% monozygotic twin concordance, 5% dizygotic twin concordance)
• Postmenopausal hormone replacement therapy increases the risk for developing SLE
• Smoking increases the risk for SLE and ex-smokers have an increased risk for SLE
• Diagnosis of Systemic lupus erythematosus (SLE)
• Diagnosis is clinical

• Doctors use the 2019 EULAR/ACR criteria: a positive ANA test (titre 1:80 or higher) is required, then clinical and immunological findings are scored, and a total score of 10 or more supports the diagnosis
• Examples of findings that are scored:
• Malar rash, fixed erythema, flat or raised.
• Discoid lupus , erythematous raised patches with adherent keratotic scaling .
• Painless oral or nasopharyngeal ulcers.
• Non-erosive arthritis , involving 2 or more peripheral joints
• Serositis , pleuritis or pericarditis
• Renal involvement include persistent proteinuria or cellular casts
• Seizures or psychosis without other organic cause
• Hematologic disorder
• Hemolytic anemia with reticulocytosis
• WBC < 4,000 at least 2 times
• Absolute lymphocyte count < 1,500/mm3 at least 2 times
• Platelet count < 100,000/mm3 without thrombocytopenic drugs
• Immunologic disorder
• Anti-DNA, in abnormal titer
• Anti-Smith antibody
• Positive finding of antiphospholipid antibodies based on
• Abnormal serum level of IgG or IgM anticardiolipin antibodies
• Positive lupus anticoagulant
• Low complement (C3/C4)
• Treatment of Systemic lupus erythematosus (SLE)
• Prompt evaluation of unexplained fever
• Lifestyle measures
• Medications guided by specific symptoms
• Nonsteroidal anti-inflammatory drugs
• For constitutional symptoms, musculoskeletal symptoms and mild serositis
• Caution regarding renal toxicity
• Antimalarials
• For skin manifestations and for musculoskeletal symptoms unresponsive to NSAIDs
• Ophthalmologic monitoring recommended every 6-12 months
• Corticosteroids
• Topical steroids useful for skin manifestations
• Systemic steroids may be needed for severe symptoms in any organ system
• Immunosuppressive agents
• Used alone or with steroids
• Particularly effective for renal and CNS symptoms
• Low-dose methotrexate is effective for arthritis
• Omega-3 fatty acids may be effective for SLE
• Based on small randomized trial
• Omega-3 fatty acid group had significant reductions from baseline in disease activity measures

Systemic lupus erythematosus (SLE) in Pregnancy

• There is no increase in infertility
• Outcome is best for mother and child when SLE has been controlled for at least 6 months prior to pregnancy
• Flares during pregnancy occur in 7-33%

Pregnancy Complications with Systemic lupus erythematosus (SLE)

• Preeclampsia
• Fetal Loss: Women with persistent high titers of antiphospholipid antibodies are at increased risk

Women with lupus nephritis have increased risk of fetal loss by 75%

• Preterm Delivery
• Low Birth Weight Infant :Infant less than 2500g
• Deep Vein Thrombosis/Pulmonary Embolism :Risk of DVT and PE increases dramatically with SLEInfant less than 2500g

Neonatal Lupus

• Occurs in about 2% of babies born to mothers with anti-Ro/SSA and or anti-La/SSB antibodies
• Caused by passage of the antibodies across the placenta to the developing baby after about 20 weeks
• Signs of neonatal lupus includes skin manifestations red, raised rash on the scalp and around the eyes that resolves by 6-8 months
• Complete heart block and learning disabilities
• Risk of neonatal lupus in subsequent pregnancy is 17%

Mothers with anti-Ro/SSA or anti-La/SSB antibodies are offered regular checks of the baby’s heart rhythm (fetal echocardiography), usually between 16 and 26 weeks, and hydroxychloroquine is advised because it lowers the risk of heart block.

Preparing for Pregnancy with Systemic lupus erythematosus (SLE)

• Discuss desire to have child with rheumatologist and Obstetrical doctor
• Follow-up with prenatal visits
• After 28 weeks, visits will be weekly to asses fetal condition (. Biophysical profile and NST)
• Women with lupus nephritis should delay pregnancy until their disease is inactive for at least 6 months
• Discuss medication effects
• Women with SLE may need anticoagulation
• Used in women with antiphospholipid syndrome
• Low dose aspirin is safe

Low-dose aspirin (75–150 mg once daily, started from 12 weeks until delivery) is recommended for all pregnant women with lupus, because it lowers the risk of pre-eclampsia. Women with antiphospholipid syndrome may also need heparin injections.

• Increased rates of stillbirth has been shown with aspirin doses greater than 325 mg/day

Medications during Pregnancy for Systemic lupus erythematosus (SLE)

• Drugs to avoid immunosuppressant therapy
• Mycophenolate mofetil
• Cyclophosphamide
• Methotrexate
• Biologic medicines to avoid: anakinra
• Medicines that can be continued when needed: TNF inhibitors such as certolizumab, and infliximab or etanercept in early pregnancy; the choice should be made with your rheumatologist before pregnancy
• Drugs with small risk of harm
• Aspirin
• Prednisone/Glucocorticoids
• Azathioprine
• NSAIDs
• Drugs that are probably safe
• Antimalarials (Hydroxychloroquine)
• No evidence that antimalarials increases risk of miscarriages or birth defects at normal doses

Hydroxychloroquine should be continued throughout pregnancy and breastfeeding: stopping it increases the risk of lupus flares, and in mothers with anti-Ro/SSA antibodies it may reduce the risk of heart block in the baby.

• Delivery in cases of Systemic lupus erythematosus (SLE):
• Women who take long-term steroid tablets (such as prednisolone) during pregnancy will need an extra ‘stress dose’ of steroids during labour or caesarean section
• Breastfeeding in cases of Systemic lupus erythematosus (SLE):
• Is recommended even for women with SLE
• Birth control in cases of Systemic lupus erythematosus (SLE):
• IUD is effective
• OCP can be used but should be avoided in women with the following:
• Migraine with aura
• Raynaud Phenomenon
• Past history DVT
• Presence of antiphospholipid antibodies
• Kidney disease and active SLE

Dr Najeeb Layyous F.R.C.O.G

Consultant Obstetrician, Gynecologist and Infertility Specialist