Pregnancy and Rheumatic Diseases

M. Gayed; C. Gordon

Disclosures

Rheumatology. 2007;46(11):1634-1640. 

In This Article

Effect of Pregnancy on Autoimmune Diseases in the Mother

SLE

(a) Flares. There is no consensus on whether or not pregnancy increases the risk of lupus flares in pregnancy, but until recently pregnancy was considered to aggravate lupus disease activity. However, in the past, many patients used to stop all their therapy upon discovering that they were pregnant, which may have contributed to an increased risk of flare in pregnancy.

Appropriate counselling on treatment regimens, prior to conception and during pregnancy is essential. Studies have produced contradictory results as to whether lupus flare is more common in pregnancy than in non-pregnant state or not. This may be explained by differences in the definition of lupus flare, assessment of disease activity, and differentiation between lupus flare and pregnancy associated complications or physiological changes of pregnancy.[14,15] In order to overcome this situation, recent research has been directed at developing standardized methods of assessing disease activity in pregnancy.[16] The lupus activity index in pregnancy (LAI-P) has been validated[17] and a version of BILAG-2004[18] for use in pregnancy is currently being developed. Studies demonstrating an increase in flares during pregnancy and 3 months postpartum when compared with non-pregnant lupus patients in a 12-month period, showed that most flares were mild and responsive to low dose steroids, hydroxychloroquine and or azathioprine.[14,15] SLE can flare at any point in the pregnancy or postpartum period. It has demonstrated that if the disease is inactive at conception then the risk of flares is reduced, in comparison with both those who had active disease at conception and the non-pregnant controls.[19] It is important to be aware of the risk of pulmonary hypertension in lupus as, despite it being rare, there is a 50% mortality rate in pregnancy.[20]

Cortico-steroids are used to control active lupus during pregnancy. Prednisolone is mainly metabolized, meaning that very little crosses the placenta in doses up to 20 mg daily so that adrenal neonatal suppression is rare. In severe cases methylprednisolone pulses may be given. However, it is important to maintain the minimum possible dose as, with doses above 10 mg daily, steroids can associated with an increased risk of pre-eclampsia, pregnancy induced hypertension, gestational diabetes, infection and possible premature rupture of membranes.[14] Further discussion about the safety of drugs used to control disease activity in pregnancy can be found in the comprehensive review by Ostensen et al.[1]

(b) Hypertension. A higher rate of adverse obstetric outcome has been demonstrated in women with SLE and hypertension. For example in hypertensive patients, there is a three-fold higher rate of intra-uterine growth restriction (IUGR). Nearly 25% of pregnancies in women with SLE are complicated by hypertensive disorders and there is also a higher rate of caesarean sections than in the control population.[21] Hypertension is more common in pregnant patients on corticosteroids and in patients with a history of lupus nephritis than in controls.

(c) Renal Lupus. Renal involvement in SLE is an important aspect of managing all SLE patients as the kidney is one of the major target organs and up to 60% of patients experience focal or diffuse renal involvement at some point in the disease course.[22] Renal lupus is characterized by the following features: proteinuria greater than 500 mg/24 h, haematuria, red cell casts and hypertension. Proteinuria without the presence of red cells or casts in the urine can be difficult to distinguish from pre-eclampsia. There is usually extra-renal active disease at the same time and the laboratory tests show increasing anti-dsDNA antibodies and falling complement C3 and C4 levels with active lupus nephritis. Active lupus nephritis is a contraindication for pregnancy as it is associated with poor fetal outcome as well as maternal complications. It is recommended that that conception should be planned at least 6 months after induction of remission to reduce the risk of pregnancy exacerbating lupus nephritis. Remission in lupus nephritis has been defined as stable renal function, a serum creatinine within the normal range, urinary red cells below 5/high power field, proteinuria below 0.5 g/day and ideally normal serum C3 levels for 12–18 months.[3,23,24] Once pregnancy has occurred, patients should be followed up by a multi-disciplinary team, so that all aspects of the disease and the pregnancy can be managed most efficiently and safely for the mother and baby.

(d) Pre-eclampsia. Although pre-eclampsia and lupus nephritis may co-exist in pregnancy, it is essential to differentiate isolated pre-eclampsia from renal lupus during pregnancy, as management will be very different depending on the diagnosis. Pre-eclampsia can be defined as blood pressure over 140/90 or the rise of 30 mmHg systolic or 15 mmHg diastolic in combination with proteinuria (>300 mg/24 h) and oedema at greater than 20 weeks gestation. Serologically the complement levels C3 and C4, will characteristically fall by 25% with active renal involvement, in contrast to the 10–15% rise seen in normal pregnancy and pre-eclampsia.[14,16,25] If the proteinuria is of recent onset and associated with hypertension, or there is a previous history of pre-eclampsia, hypertension or antiphospholipid syndrome, proteinuria is more likely to be due to pre-eclampsia than lupus nephritis.[3,14,16] Lupus nephritis is more likely if there is a positive urinary sediment (cells and/or casts in the urine in the absence of other causes of red or white cells). Pre-eclampsia is also more likely if associated with features of the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome, but again it is important to differentiate this from active lupus nephritis, as steroids are necessary to treat lupus nephritis but will aggravate pre-eclampsia. The ultimate treatment for pre-eclampsia is delivery of the fetus, although anti-hypertensives may be tried initially.

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