http://www.hopkins-arthritis.som.jhmi.edu/other/lupus_pregnancy.html

Introduction
Because lupus is a disease that strikes predominantly young women in the
reproductive years, pregnancy is both a practical and a research issue.
For most women with lupus, a successful pregnancy is possible. This is
an immense change from the 1970's, when most women with lupus were
counseled not to become pregnant. Studies of the immune system in
pregnancy are of interest for what they have taught us about the effect
of hormones on lupus flares.

Risk of Miscarriage
First, the risks of pregnancy in lupus patients are real and involve
both the mother and the fetus. About ten percent of pregnancies
currently end in miscarriage. The first trimester losses appear either
to have no known cause or to associate with signs of active lupus. Later
losses occur primarily due to the antiphospholipid antibody syndrome,
inspite of treatment with heparin and aspirin. All women with lupus,
even if they do not have a previous history of miscarriage, should be
screened for antiphospholipid antibodies, both the lupus anticoagulant
(the RVVT and sensitive PTT are the best screening battery) and
anticardiolipin antibody.
The classification criteria for the antiphospholipid antibody syndrome
were revised last year. There are now two major criteria--vascular
thrombosis and pregnancy morbidity. A woman who has had a past venous or
arterial thrombosis should be therapeutically anticoagulated during the
next pregnancy. A woman who has pregnancy morbidity--one or more late
losses, three or more first trimester losses, or severe pre-eclampsia or
placental insufficiency--should be treated with prophylactic doses of
heparin and a baby aspirin during the next pregnancy. Several clinical
trials have indicated that the combination of heparin and aspirin is
likely preferable to aspirin alone, although some women do have
successful pregnancies on aspirin alone. These pregnancies should be
considered high risk, with appropriate fetal monitoring, including
ultrasounds to monitor growth and placental development, and biophysical
profiles, usually from the 26th week onwards. Many of these babies can
be rescued by early C-section when there are signs of severe placental
insufficiency. There is no consensus on whether treatment is indicated
for the woman with lupus who has antiphospholipid antibodies in her
first pregnancy. Many authorities in the field would use a baby aspirin
in this situation.

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Risk of Preterm Birth and Intrauterine Growth Retardation
An equal, if not more important risk is the risk of preterm birth.
Preterm birth in lupus is usually not due to antiphospholipid
antibodies, but due to pre-eclampsia and premature rupture of membranes.
Risk factors for preterm birth in general include active lupus, high
dose prednisone, and renal disease. Maternal hypertension in the second
trimester is a good predictor. Overzealous treatment of maternal blood
pressure could reduce placental blood flow, and is not recommended. We
have not found any risk factors that predict premature rupture of
membranes. In addition to being preterm, the baby is also at risk for
intrauterine growth retardation (IUGR). We have not found a clinical
variable that is predictive of IUGR. In fact, lupus activity,
prednisone, and antiphospholipid antibodies are not predictive of IUGR.
The best predictor using ultrasound monitoring is an abdominal
circumference below the 10th percentile and an estimated fetal weight
below the 50th percentile.
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Maternal Risks
The most important maternal risk, that of a lupus flare, is actually the
most controversial. In prospective studies at both Hopkins and in
London, the risk of flare is greater in a pregnant than a non-pregnant
woman. However, other centers have not confirmed this. There may be
differences in patient selection that account for the different
findings. We have found that the hormone prolactin, which rises during
pregnancy, is associated with lupus activity during pregnancy. Likely
other hormonal influences, especially estrogen, changes in cytokines are
involved as well, although these have not been studied. We have found
that the type of organ system involvement is different in pregnant vs.
non-pregnant patients. In pregnancy we have found an excess of renal and
hematologic flares, and fewer arthritis flares.
Some of the risk to the mother is not directly due to lupus. In a
case-control study we found that women with lupus were more likely to
have multiple complications of pregnancy, including diabetes, urinary
tract infections, and pre-eclampsia. For this reason, referral to a
high-risk obstetrician is always appropriate. Women on prednisone were
more likely to have hypertension and diabetes, as would be expected. The
physician caring for a woman with lupus who wishes to become pregnant
must review her medications. Prednisone is largely metabolized by the
placenta, and is unlikely to cause any fetal malformations, but will
increase the risk of diabetes and hypertension in the mother. Some
immunosuppressives, such as imuran (azathioprine) have been continued
during lupus pregnancy when necessary to control maternal lupus.
Cyclophosphamide should never be used during pregnancy because of the
high risk of important birth defects. Because of potential
teratogenicity, Coumadin should be switched to heparin as soon as the
woman knows she is pregnant. ACE-inhibitors, because of effects on fetal
kidney development, should be stopped as soon as the woman knows she is
pregnant. NSAIDs are usually allowed during the first trimester only,
because of potential adverse effects on the fetal ductus arteriosus.
Plaquenil (hydroxychloroquine) has a good safety record in lupus
pregnancy, and is usually continued if needed to control maternal lupus.

Management and Monitoring
Lupus pregnancy should be timed to coincide with a period of good
disease control if at all possible. It does not make sense to taper
medication simply because a woman desires pregnancy, because of the
likelihood of inducing a flare if medications are reduced too low.
General screening tests should include the antiphospholipid antibodies,
and also anti-Ro and anti-La. A woman who is positive for these
antibodies is at increased risk of congenital heart block in the baby,
and monitoring of the fetal cardiac conduction system by 4-chamber fetal
cardiac echo should be instituted. We generally monitor the mother
monthly during pregnancy and obviously more often if disease activity
warrants it. Laboratory monitoring done monthly includes the complete
blood count, creatinine, liver function tests, urinalysis, and a 24 hour
urine for creatinine clearance and total protein. It is controversial
whether serologic tests are helpful during pregnancy. In normal
pregnancy the C3 and C4 should rise.

Summary
We are lucky to have a long-term collaboration between our high-risk
obstetricians and the Lupus Center at Hopkins that has allowed not only
for superb clinical care of the mothers and babies, but also for the
prospective database that has led to the studies summarized above. For
nearly all mothers, a happy outcome is possible, but we must not forget
that we have had one maternal death in our 150 pregnancies and that 7%
of the pregnancies are characterized by a severe maternal complication.
This is our impetus to continue our research into lupus and its
interactions with pregnancy.

Selected Reference
Petri M. Systemic lupus erythematosus and pregnancy. Rheum Dis Clin
North America 20:87117, 1994.
Fine LG, Barnett EV, Danovitch GM, et al. Systemic lupus erythematosus
in pregnancy. Ann Intern Med 94:667-677, 1981.

Cowchock FS, Reece EA, Balaban D, et al. Repeated fetal losses
associated with antiphospholipid antibodies: A collaborative randomized
trial comparing prednisone with low dose heparin treatment. Am J Obstet
Gynecon 166:1318-23, 1992.