Pregnancy and Connective Tissue Disorders
Doruk Erkan
Lisa R. Sammaritano
KEY POINTS
Pregnancy-induced physiologic changes and the complications in pregnancy may make assessment of connective tissue disorder (CTD) activity during pregnancy difficult.
Most patients with CTD may safely complete pregnancy with good outcome. Both maternal and fetal outcome are better for patients with inactive disease at the time of conception.
Prepregnancy evaluation for patients with CTD should include the following:
Assessment of disease activity and disease-related organ damage.
Serologic assessment for the relevant autoantibodies.
Review of medications, with required adjustments before pregnancy is attempted.
Evaluation and monitoring of the patient with CTD, during pregnancy, requires participation of both a rheumatologist and an obstetrician capable of handling high-risk pregnancies.
Care and follow-up must continue through the postpartum period, as patients are at continued risk for complications, including disease flare or thrombosis.
Treatment with aspirin and heparin can have a profoundly positive effect in patients with prior pregnancy losses due to antiphospholipid (aPL) antibodies.
INTRODUCTION
Pregnancy is an altered physiologic state characterized by particular signs, symptoms, and hormonal changes. Awareness of these changes is critical for appropriate assessment of patients with connective tissue disease (CTD) during pregnancy.
Hemodynamic changes. Intravascular volume increases approximately 30% during pregnancy, which may further stress previously compromised renal or cardiac function.
Skin and musculoskeletal systems. Palmar and facial erythema from increased cutaneous blood flow, generalized edema, and arthralgia are common in late pregnancy, and may mimic inflammatory rash or joint symptoms.
Coagulation. Pregnancy is a prothrombotic state. Fibrinogen, factor II, platelet activation inhibitor-1, prothrombin fragment 1 and 2, D-dimer, and tissue plasminogen
activator levels increase, whereas free and total protein S decrease, during normal pregnancy. As a result of these changes, and in conjunction with the increased venous stasis, the risk of venous thromboembolism increases during pregnancy by a factor of five.
Hematologic changes. Moderate anemia due to hemodilution is frequent during pregnancy. Despite increased platelet production, increased utilization may lead to mild thrombocytopenia in up to 8% of uncomplicated pregnancies.
Erythrocyte sedimentation rate (ESR) increases during normal pregnancy, which makes this test less useful as a gauge of systemic inflammation.
Pregnancy-induced complications are often difficult to distinguish from active CTD due to the similarity in signs and symptoms.
The pre-eclampsia (PEC) syndrome includes hypertension in late pregnancy, (i.e., blood pressure higher than 140/90 mm Hg recorded after 20 weeks’ gestation on at least two occasions), proteinuria (more than 300 mg/day), edema, and hyperuricemia. If seizures occur in this setting, the syndrome is defined as eclampsia.
The HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) may be a severe variant of PEC. Patients with this life-threatening syndrome present with prominent hepatic enzyme abnormalities, fever, thrombocytopenia, and encephalopathy.
Pregnancy loss represents the most extreme pregnancy-related complication and can occur as: pre-embryonic loss (conception through week 4 of gestation); embryonic loss (week 5 through 9); fetal loss (tenth week of gestation until delivery); and neonatal loss. It is critical to differentiate pregnancy loss due to CTD [e.g., antiphospholipid antibody (aPL)-related loss] from other obstetric etiologies.
Data on outcomes of pregnancy in many CTDs are limited due to lack of prospective controlled studies. Maternal and fetal outcomes in selected CTDs will be discussed in the subsequent text.
RHEUMATOID ARTHRITISI. RISK OF DISEASE FLARE
Pregnancy usually has a positive effect on rheumatoid arthritis (RA) symptoms. Up to three-fourths of patients experience some degree of clinical remission during pregnancy, even in the absence of medication.
Almost all patients relapse following delivery by the end of 8 months postpartum; most within the first 6 weeks.
The development of remission during pregnancy has been attributed to maternal-fetal disparity in certain human leukocyte antigen (HLA)-DQ loci.
II. RISK OF DISEASE ONSET
A large case-control study found a decreased risk of development of RA in women who had at any time been through a pregnancy. However, an increased risk of RA onset during the postpartum period has been noted in multiple studies.
III. FETAL AND NEONATAL OUTCOMES
Fertility and parity are not decreased in patients with RA and no conclusive increase in fetal morbidity or mortality has been demonstrated. Intrauterine growth retardation (IUGR) has been described in RA patients with severe disease activity and vasculitis.
IV. MANAGEMENT
Many patients do not require medications during pregnancy. Corticosteroid (CS) may be used for active disease. Most other medications [other than Hydroxychloroquine (HCQ)] are stopped due to safety concerns.
Cervical spine arthritis with atlanto-axial instability dictates careful management of patients under general anesthesia, because manipulation of the unstable spine may produce spinal cord compression.
Severe cricoarytenoid involvement may also be a relative contraindication to intubation with general anesthesia.
Assessment for adequate hip range of motion (native or prosthetic joints) should be done prior to vaginal delivery, especially if epidural anesthesia is planned.
SYSTEMIC LUPUS ERYTHEMATOSUSI. RISK OF DISEASE FLARE
The definition of lupus flare during pregnancy is not uniform. Although recent case-control studies support little or no increased risk for flare during pregnancy, patients with systemic lupus erythematosus (SLE) may flare anytime during pregnancy, most commonly in the latter half and during the postpartum period.
Inactive disease for the 6 months preceding pregnancy is associated with lower risk of disease flare.
Hypertension and active kidney disease preceding pregnancy increase the risk of lupus kidney flare and PEC. Risk of significant decrease in renal function is greatest for patients with a creatinine clearance of less than 60 mL/minute. Assessing the degree of renal dysfunction is of more prognostic value than studying the precise renal histology.
Differentiating lupus flare from PEC can be challenging (Table 38-1). Changes felt to represent SLE activity include an increase in anti–double-stranded DNA antibody level, lymphadenopathy, lupus rash, inflammatory arthritis, fever, and microscopic hematuria with erythrocyte casts. It is not uncommon for patients to have both a lupus flare and PEC—they are not mutually exclusive.
II. RISK OF DISEASE ONSET
The initial presentation of SLE with or without nephritis during pregnancy is rare.
III. FETAL OUTCOMES
Fertility is generally unimpaired unless the patient has been treated with cyclophosphamide. Fetal outcome is related more to the presence of renal involvement and the presence of aPL than the occurrence of lupus flare.
If disease is quiescent for at least 6 months before conception, the pregnancy outcome improves. Pregnancy is inadvisable in the presence of uncontrolled hypertension, progressive renal failure, severe neurologic and cardiopulmonary involvement, severe thrombocytopenia, and during the use of teratogenic medications.
Proteinuria higher than 0.5 g/24 hours is an independent predictor of poor fetal outcome.
aPL, present in approximately 30% of patients with SLE, markedly increases the risk of fetal loss [see antiphospholipid syndrome (APS) section below]. Risk of fetal loss related to aPL appears to be similar for patients with SLE and primary APS.
IV. Neonatal outcomes
depend on several factors: presence of aPL, presence of anti-Ro/SS-A and anti-La/SS-B autoantibodies, and maternal medications. Presence of aPL is associated with increased risk of prematurity and its attendant complications. Offsprings of the 30% of mothers with SLE who are positive for anti-Ro and anti-La are at risk for neonatal lupus erythematosus (NLE), consisting of rash, thrombocytopenia, abnormal liver function tests, and congenital heart block (CHB). The risk for any manifestation of NLE in the offspring of a mother who is positive for anti-Ro is
approximately 25%; however, the risk for cardiac involvement with irreversible CHB and myocarditis is less than 3%. The risk for development of SLE in a child of a mother with SLE is small; the risk for positive autoantibodies in the child is approximately 10%, and the risk for development of SLE is approximately 1%.
approximately 25%; however, the risk for cardiac involvement with irreversible CHB and myocarditis is less than 3%. The risk for development of SLE in a child of a mother with SLE is small; the risk for positive autoantibodies in the child is approximately 10%, and the risk for development of SLE is approximately 1%.
Table 38-1 Helpful and Unhelpful Measures for Defining Systemic Lupus Erythematosus (SLE) Activation during Pregnancy | |||||||||||||||||
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V. MANAGEMENT
Both the rheumatologist and an experienced obstetrician capable of handling high-risk cases should partner throughout the management of patients with SLE during their pregnancy.
Initial evaluation should include an assessment of disease activity and disease-related organ damage, review of current medications, and discussion of specific risks with the patient and her partner.
Laboratory evaluation should include complete blood count, biochemical profile, urinalysis, 24-hour urine for creatinine clearance and total protein, aPL, and anti-Ro and anti-La antibodies. Regular (monthly) follow-up of each of these tests is helpful, with the exception of the aPL and the anti-Ro and anti-La antibodies.
Fetal monitoring
Antepartum monitoring of the fetal heart rate (nonstress test) is often initiated at approximately 26 weeks; a nonreactive test (absence of appropriate heart rate response) is abnormal and may precede a decrease in fetal movement by several weeks. If fetal distress is noted and the fetus is considered viable, early delivery may prevent fetal death.
Fetal echocardiography, generally at weeks 20 through 24, should be performed for evaluation of fetal heart rhythm, pericardial effusion, or myocarditis in mothers who are positive for anti-Ro and anti-La antibodies. More intensive monitoring is indicated for high-risk patients with a previous history of a child with NLE.Related posts:
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