Autoimmune, Neurologic & Cardiac Disease in Pregnancy
Which chronic diseases pregnancy calms, which it inflames, and which it can make lethal
Systemic lupus erythematosus
Planning. Pregnancy goes best after at least 6 months of quiescence on pregnancy-compatible drugs: hydroxychloroquine, azathioprine, low-dose prednisone, tacrolimus or cyclosporine. Mycophenolate, methotrexate and cyclophosphamide are stopped or switched beforehand. Active disease at conception, especially nephritis, raises the risks of flares, preeclampsia, fetal loss, growth restriction and preterm birth, and low-dose aspirin starts at 12 weeks because lupus is a major preeclampsia risk factor.
Never stop hydroxychloroquine in pregnancy: withdrawal provokes flares, the drug is compatible with breastfeeding, and continuing it may lower the risk of congenital heart block in anti-Ro–positive mothers.
Nephritis flare or preeclampsia. Both present with hypertension, proteinuria, edema and sometimes thrombocytopenia, but treatment differs: immunosuppression for lupus, delivery for preeclampsia.
| Feature | Lupus nephritis flare | Preeclampsia |
|---|---|---|
| Complement (C3, C4) | Low | Normal or high (rises in pregnancy) |
| Anti-dsDNA | Rising titer | Stable |
| Urine sediment | Active: RBC casts, dysmorphic RBCs | Bland |
| Other clues | Rash, arthritis, serositis; any gestational age | After 20 weeks; raised transaminases, headache |
| Treatment | Steroids ± azathioprine | Delivery; magnesium if severe |
Neonatal lupus. Maternal anti-Ro/SSA (± anti-La/SSB) IgG crosses the placenta and can inflame the fetal AV node, causing congenital heart block in about 2% of exposed pregnancies and roughly 15–20% after a previously affected child. The block is often complete and irreversible, and many infants need a pacemaker, so the fetal mechanical PR interval is measured by serial echocardiography from 16 to 26 weeks. Neonatal lupus can also cause a transient annular rash and cytopenias, and many mothers have Sjögren syndrome or no symptoms.
Antiphospholipid syndrome
Diagnosis. APS requires a clinical event (vascular thrombosis, a fetal death at ≥10 weeks, delivery before 34 weeks for severe preeclampsia or placental insufficiency, or ≥3 consecutive losses before 10 weeks) plus lupus anticoagulant, anticardiolipin or anti-β2-glycoprotein I antibodies positive on two occasions ≥12 weeks apart.
| Situation | During pregnancy | Postpartum |
|---|---|---|
| Obstetric APS, no thrombosis | Prophylactic LMWH + low-dose aspirin | Prophylactic LMWH for 6 weeks |
| APS with prior thrombosis | Therapeutic LMWH + low-dose aspirin | Resume long-term warfarin (compatible with breastfeeding) |
Why heparin. Heparins do not cross the placenta, and LMWH causes less heparin-induced thrombocytopenia and osteoporosis than unfractionated heparin. Warfarin crosses the placenta, causing embryopathy with exposure at 6–12 weeks and fetal bleeding later, so a woman on warfarin switches to LMWH as soon as pregnancy is confirmed, ideally before 6 weeks. DOACs are avoided in pregnancy and are inferior to warfarin in high-risk APS.
Epilepsy and multiple sclerosis
Epilepsy. Keep the lowest effective dose of a single drug, preferably lamotrigine or levetiracetam, together with folic acid. Valproate carries the highest risk of neural tube defects, lower IQ and autism, and topiramate (cleft lip and palate) and phenytoin are also best avoided. Uncontrolled convulsions cause maternal hypoxia, injury, placental abruption and sudden unexpected death in epilepsy (SUDEP), so drugs are never stopped abruptly.
Falling levels. Rising clearance and volume of distribution lower drug levels; estrogen-induced glucuronidation can double or triple lamotrigine clearance. Levels are checked each trimester (monthly for lamotrigine) and doses raised, then tapered back within weeks after delivery to avoid toxicity.
A first seizure after 20 weeks is eclampsia until proven otherwise: give magnesium sulfate.
Multiple sclerosis. The relapse rate falls during pregnancy, most in the third trimester, and rebounds in the first 3 months postpartum; pregnancy does not worsen long-term disability. Most disease-modifying drugs are stopped before conception (interferon-β and glatiramer acetate may continue), relapses are treated with IV methylprednisolone, and epidural anesthesia and breastfeeding are allowed.
Heart disease
Physiology. Plasma volume rises about 40–50% and cardiac output 30–50%, nearing its peak in the late second trimester, while systemic vascular resistance falls. Stenotic lesions therefore fare poorly and regurgitant lesions well.
- Late second trimesterVolume load and cardiac output near peak
- LaborPain and tachycardia; each contraction autotransfuses about 300–500 mL
- Immediately postpartumUterine autotransfusion and relief of caval compression push preload highest: peak risk of pulmonary edema
| Lesion | Why it is dangerous | Approach |
|---|---|---|
| Pulmonary arterial hypertension, Eisenmenger | Very high maternal mortality from right heart failure and sudden death, mostly around delivery and postpartum | Advise against pregnancy with reliable contraception; discuss termination if pregnant |
| Severe mitral stenosis | Tachycardia shortens diastolic filling → pulmonary edema, AF | β-blocker, diuretic; balloon valvotomy if refractory; ideally fix before conception |
| Marfan, aortic root >4.5 cm | Dissection in late pregnancy or postpartum | Repair before pregnancy; β-blocker and serial echo if pregnant |
| Mitral or aortic regurgitation | Falling SVR reduces regurgitant flow | Usually well tolerated |
Mitral stenosis. β-blockers slow the rate and lengthen diastole, diuretics relieve congestion, and percutaneous balloon valvotomy is done during pregnancy for refractory severe disease. Labor uses an epidural and an assisted second stage to limit tachycardia and pushing.
Marfan syndrome. This autosomal dominant FBN1 disorder passes to half of offspring. The hyperdynamic circulation and hormonal weakening of the aortic media raise dissection risk. Pregnant women take a β-blocker (never losartan) with serial echocardiography, and delivery uses an epidural with a shortened second stage, or cesarean when the aorta is dilated.
Mechanical valves. Warfarin prevents valve thrombosis best but causes embryopathy (nasal hypoplasia, stippled epiphyses) with exposure at 6–12 weeks, a risk that is lower at doses ≤5 mg/day. LMWH spares the fetus but must be titrated to anti-Xa levels, because rising clearance leaves fixed doses subtherapeutic and under-dosing causes valve thrombosis. Heparin replaces warfarin by about 36 weeks so that delivery can be planned.
Asthma
Keep controllers going. Asthma improves, worsens or stays unchanged in roughly equal thirds of pregnancies. Poor control, with maternal hypoxia, threatens the fetus far more than the drugs, so inhaled corticosteroids (budesonide has the most data), albuterol and long-acting β-agonists continue, and oral steroids are used for exacerbations.
Pregnancy normally lowers PaCO2 to about 30 mm Hg, so a PaCO2 of 40 during an attack signals fatigue and impending respiratory failure. For postpartum hemorrhage in an asthmatic, avoid carboprost, a PGF2α analog that causes bronchospasm.