Connective tissue disease in pregnancy

Published on 09/03/2015 by admin

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Chapter 49 Connective tissue disease in pregnancy

Amy Mellor

Systemic lupus erythematosus (SLE)

SLE is a multisystem autoimmune disease, involving direct attack by autoantibodies and deposition of immune complexes. It mainly affects women in the reproductive age group, making it a frequently encountered condition in obstetric practice. SLE has a prevalence of 1 in 5000–10,000 women, with a female to male ratio of 9:1. SLE is thought not to impair fertility. Pregnancy outcome for mother and offspring is best when the disease has been quiescent for at least 6 months prior to conception, and renal function is stable.

Pregnancy probably does not increase the rate of SLE exacerbation compared with the non-pregnant population. Flares occur equally across the trimesters, and are common in the immediate postpartum period. They present most commonly as fever, lymphadenopathy, skin and joint involvement, and renal impairment. Neurological, cardiovascular and respiratory manifestations may also occur. Exacerbation is more common when disease is active at the time of conception. Flare is associated with hypocomplementaemia and an increase in anti-double stranded DNA titres. One-third to one-half of SLE patients have antiphospholipid antibodies (aPL), and one-third have anti-Ro/SSA or anti-La/SSB antibodies.

Maternal effects

• pre-eclampsia: occurs in around 13% of patients with SLE, is much more frequent in women with preexisting renal disease and aPL, and can be difficult to distinguish from lupus nephritis
• lupus nephritis: associated with an increased risk of fetal loss and worsening of renal and extra-renal manifestations
• venous thromboembolism
• postpartum haemorrhage

Fetal effects

• intrauterine growth restriction (IUGR)
• intrauterine fetal death: risk is higher in women with active disease at conception, hypertension, renal disease, aPL, hypocomplementaemia, elevated anti-DNA antibodies and thrombocytopenia
• preterm birth: three times more common than in women without SLE

Neonatal lupus

• results from passive transfer of anti-Ro/SSA or anti-La/SSB antibodies
• causes complete heart block in the fetus/neonate in 2% of cases
• other features include rash, thrombocytopenia, hepatitis and haemolytic anaemia
• no congenital anomalies associated with SLE

Management

Pregnancy in women with SLE should be managed in a high-risk setting by an obstetrician and physician. Ideally, medication should be reviewed and disease management optimised preconceptually.

Initial investigations

• full blood count, renal function tests (including urinalysis, protein/creatinine ratio)
• aPL assays
• anti-Ro/SSA and anti-La/SSB antibodies
• C3 and C4 titres
• anti-double stranded DNA antibody titres

Ongoing management

• frequent auscultation of fetal heart with or without echocardiogram if heart block suspected
• monthly platelet count
• repeat aPL, complement, anti-double stranded DNA antibodies and renal function tests each trimester
• surveillance for exacerbation of disease, pre-eclampsia and IUGR
• regular surveillance of fetal wellbeing if complications arise
• delivery timed according to complications/fetal condition

Drug therapy

• The potential for medication to cross the placenta and cause fetal harm must be weighed against the risks of active disease to the mother and fetus.
• Low-dose aspirin with or without heparin should be considered in women with aPL.
• Non-steroidal anti-inflammatory drugs (NSAIDs) and azathrioprine should be used with caution.
• Glucocorticoids at the lowest possible dose to control disease activity are recommended for management of disease exacerbation. These increase the risk of gestational diabetes and adrenal suppression, necessitating hydrocortisone in labour.
• The safety of antimalarial drugs is uncertain.
• Cytotoxic agents are contraindicated in pregnancy.

Antiphospholipid syndrome (APS)

APS is characterised by arterial or venous thrombosis and specific pregnancy complications, in association with laboratory evidence of aPL.

Antiphospholipid antibodies (aPL)

The diagnosis of APS requires the presence of anticardiolipin antibody (aCL), lupus anticoagulant (LA) or antibody to B2-glycoprotein 1 on two occasions at least 12 weeks apart. Antibodies are present in 2% of the pregnant population.

Pregnancy complications

• complications are thought to arise primarily due to antibody-induced thrombosis in the uteroplacental circulation; antibodies also have a direct effect on placental trophoblast, resulting in reduced trophoblast invasion and human chorionic gonadotrophin (hCG) production
• intrauterine fetal death
• recurrent miscarriage after 10 weeks gestation (correlates with level of aCL immunoglobulin G (IgG))
• IUGR occurs in 30% of women with APS
• early, severe pre-eclampsia (stronger association with aCL than LA)
• maternal thromboembolic disease: 5% risk in women with APS

Management

• There is a paucity of data from large, well-designed trials into the management of pregnant women with APS.
• Women with known APS should be managed in a high-risk setting by an obstetrician and physician. Additional surveillance includes baseline renal and liver function tests, and serial growth and wellbeing ultrasounds.
• Low-dose aspirin has been associated with an increase in successful pregnancy outcome in some studies. It should be commenced as soon as possible from conception, and ceased at 36 weeks gestation.
• Heparin enhances the effects of antithrombin and other antithrombotic factors, and may also bind aPL to render them inactive. Meta-analysis shows the combination of heparin and aspirin significantly reduces the incidence of pregnancy loss compared with aspirin alone.
• Women with a history of thrombosis and aPL should receive thromboprophylaxis antenatally and in the postpartum period. These women are at high risk for recurrence and are generally on lifelong anticoagulation.
• Women with a history of early, severe pre-eclampsia or IUGR in a previous pregnancy can be recommended low-dose aspirin in the second and third trimesters.

Rheumatoid arthritis

Rheumatoid arthritis occurs predominantly in females, many of whom are in the reproductive age group.

Pregnancy

• About 75% of women experience improvement in rheumatoid arthritis symptoms. This is likely due to the immunological changes of pregnancy, resulting in a less inflammatory state.
• About 90% of women experience exacerbation of disease within the first 3 months after delivery.
• Reintroduction of medication in the immediate postpartum period is recommended.
• Pregnancy is generally uneventful, with no evidence of increased adverse outcome.
• Medication may need to be continued, or reintroduced if flare occurs.
• NSAIDs should be avoided in the third trimester to avoid premature closure of the ductus arteriosus.
• Prednisone at the lowest possible dose to control disease is the safest option.
• Sulfasalazine, azathioprine and hydroxychloroquine may be used in refractory cases.
• Elective caesarean section may occasionally be necessary where joint disease precludes vaginal delivery.

Further reading

Bermas B.L. Rheumatoid arthritis and pregnancy. Up To Date.. 2007. September

Lockshin M.D., Salmon J.E., Erkan D. Pregnancy and rheumatic diseases. In: Creasy R.J., Resnik R., editors. Maternal–fetal medicine: principles and practice. 6th edn. Philadelphia: Saunders Elsevier; 2009:1079-1087.

Lockwood C.J., Schur P.H. Management of pregnant women with antiphospholipid antibodies or the antiphospholipid syndrome. Up To Date,. 2008. November

Lockwood C.J., Schur P.H. Obstetrical manifestations of the antiphospholipid syndrome. Up To Date,. 2008. October

Schur P.H., Bermas B.L. Pregnancy in women with systemic lupus erythematosus. Up To Date,. 2008. October

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