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Division of Rheumatology and Immunology, Duke University Medical Center, Box 3535 Trent Drive, Durham, NC 27710, USA Systemic lupus erythematosus (SLE) primarily affects women in their reproductive years, making the issue of pregnancy important to many pa-tients. There are an estimated 4500 pregnancies in women with SLE eachyear in the United States The impact of pregnancy on SLE activity has been debated in the litera- ture, but the majority of studies endorse an increase in disease activity dur-ing pregnancy. In some patients, this will mean a dramatic worsening ofsymptoms that can be life threatening. Most patients, however, will havea modest increase in symptoms making pregnancy uncomfortable but notaffecting their long-term survival.
Women with SLE have complicated pregnancies: one third will result in a cesarean section, 33% will have preterm birth, and more than 20% will becomplicated by preeclampsia Increased lupus activity, particularly be-fore conception and early in pregnancy, significantly increases the risks forthese complications. For this reason, timing pregnancy to coincide with a pe-riod of SLE quiescence is a worthy goal.
This article will address the impact of pregnancy on SLE activity, of SLE activity on pregnancy outcome, and the treatment of women with SLE tominimize these effects.
Systemic lupus erythematosus activity during pregnancy Whether SLE activity increases during pregnancy has been debated widely in the literature. In murine models, increasing doses of estrogen,like those seen in pregnancy, promote physiologic and immunologic changesassociated with increased lupus activity . Different methods to deter-mine a flare and active lupus were used in many of the cohort studies ofSLE pregnancy in the literature. Therefore, it is difficult to draw clear Megan Clowse is a BIRCWH Scholar: NIH grant number 5K12-HD-043446.
E-mail address: 0889-857X/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.rdc.2007.01.002 conclusions about the impact of pregnancy on SLE activity. Several smallstudies that matched pregnant lupus patients with nonpregnant lupuspatients found no significant increase in SLE activity during pregnancyHowever, more recent studies have found a two- to threefold increasein SLE activity during pregnancy () . Based on these studies, itappears that between 35% and 70% of all pregnancies will have measurableSLE activity, with most studies showing the risk to be between 40% and50% The risk for a moderate to severe flare is lower and rangesbetween 15% and 30% .
The risk of lupus flare is increased drastically if the woman has had active lupus in the 6 months before pregnancy. Two hundred sixty-five pregnanciesto women with lupus were seen in the Hopkins Lupus Pregnancy Cohortbetween 1987 and 2002. In this cohort, the risk for significant SLE activityduring pregnancy was 7.25-fold higher if the patient had recently active lupusbefore conception (58% versus 8%, P!.001) . Other studies have founda twofold increase in risk for lupus flare during pregnancy among womenwith active SLE at conception . Other risk factors for increased lupusactivity in pregnancy include the discontinuation of antimalarial therapyand a history of highly active lupus in the years before pregnancy .
Fortunately, the majority of SLE activity in pregnancy is not severe. In most studies, skin, joint, and constitutional symptoms are most commonly Box 1. Impact of pregnancy on systemic lupus erythematosusactivity Pregnancy probably increases lupus activity: About 50% of women will have measurable SLE activity during Most of the disease activity will be mild to moderate15% to 30% of women will have highly active SLE in pregnancy Most common types of SLE activity in pregnancy: Cutaneous diseaseArthritisHematologic disease Risk factors for increased lupus activity: Active lupus within the 6 months before conceptionMultiple flares in the years before conceptionDiscontinuation of hydroxychloroquine reported. The risk for skin disease ranges from 25% to 90%, depending onthe severity measured . The rates for arthritis during pregnancy aresimilarly disparate between studies, based on the severity measured. How-ever, 2 large cohorts show a 20% risk of significant arthritis, althoughmany more women will have an increase in less-severe joint pain Hema-tologic disease, in particular thrombocytopenia, is also common duringpregnancy, with the risk ranging from 10% to 40% in different cohorts The risk for lupus nephritis during lupus ranges from 4% to 30%, based on the cohort characteristics and the definition of lupus nephritis. Women with a prior history of lupus nephritis have 20% to30% risk of relapse during pregnancy . For women who have worsen-ing renal function because of SLE nephritis during pregnancy, an estimated25% had continuing renal damage after pregnancy, despite aggressive ther-apy . Fortunately, very few women require lifelong dialysis.
Timing of systemic lupus erythematosus flares in pregnancy Lupus flares can occur at any time during pregnancy, as well as in the sev- eral months after delivery. Although several studies have reported on thetiming of activity in trimesters, a consistent pattern is not apparent. It is important to keep in mind, however, that lupus patients re-main at risk of flare in the months after delivery Impact of systemic lupus erythematosus activity on pregnancy outcome Overall, about 20% of pregnancies to women with SLE will end with a miscarriage or stillbirth The risk of miscarriage (a pregnancy loss be-fore 20 weeks gestation) is not markedly elevated over the general popula-tion. The risk of stillbirth (a pregnancy loss after 20 weeks gestation),however, is elevated in several studies. The two most important risk factorsfor pregnancy loss are increased lupus activity and antiphospholipid syn-drome (APS). In a Greek cohort of SLE pregnancies, six of eight (75%)pregnancies with high-activity SLE resulted in a fetal loss, whereas only14% of pregnancies without active lupus and 5% of non-SLE pregnanciesended with a loss In the Hopkins Lupus Pregnancy Cohort, increasedlupus activity did not increase the risk for miscarriage, but the stillbirthrate was threefold higher () The timing of lupus activity affectsthe pregnancy loss rate, with activity early in pregnancy being the mostdangerous. Proteinuria, thrombocytopenia, and hypertension in the firsttrimester are each independent risk factors for pregnancy loss. A womanwith any of these risk factors has a 30% to 40% chance of suffering a preg-nancy loss .
Table 1Increased lupus activity in pregnancy increases pregnancy complications Late preterm (28 to 37 weeks’ gestation) (!10th percentile weightfor gestational age) Data from Clowse MEB, Magder L, Witter F, Petri M. The impact of increased lupus activity on obstetric outcomes. Arthritis Rheum 2005;52(2):514–21.
The risk for preterm birth (delivery before 37 weeks gestation) is estimated to be 33% in all lupus pregnancies In a population-based study of 555lupus deliveries in California, 21% were preterm, which was almost sixfoldhigher than the rate in healthy women . Among cohorts at tertiary referralcenters, however, the rate tends to be higher, ranging from 20% to 54%Preterm premature rupture of membranes (PPROM) isa prominent cause of preterm birth among lupus patients Althoughmost of the preterm births are spontaneous, a significant proportion ofthem are induced to protect the health of either the mother or the baby .
Risk factors for preterm birth include lupus activity before and during pregnancy, higher prednisone dose, and hypertension. In the HopkinsLupus Pregnancy Cohort, 66% of pregnancies with active lupus were deliv-ered preterm versus 32% of pregnancies without active lupus (P!.05) (seeBabies born before 28 weeks’ gestation are at highest risk forlong-term medical complications and neonatal death. Within this cohort,17% of all pregnancies with active SLE were born between 24 and 28 weeks’gestation, but only 6% of those without SLE activity were born during thisrisky period (P ¼ .09) .
In women without SLE, an estimated one third of spontaneous preterm births are associated with infection within the uterus. The inflammation as-sociated with chorioamnitis is postulated to promote dissolution of the am-niotic sac, ripening of the cervix, and uterine contractions, which all lead topreterm birth. Unfortunately, no data have been published about the rate ofchorioamnititis in SLE pregnancies. Placenta studies, however, do not showincreased rates for infection on pathology We can hypothesize that theinflammation seen in active lupus may have a similar effect on the utero-placental unit, thereby increasing preterm labor and rupture of membranes.
Research to study this hypothesis is in its infancy, but in the future we hopethat the role of inflammation in preterm birth will be more clearly elucidated. Once this mechanism is understood, improved methods of ther-apy may be developed.
Any study of low birth weight babies, in particular among lupus pregnan- cies, is complicated by the high rate of preterm birth. Therefore, the correc-tion of the weight by gestational age is generally used. A small forgestational age (SGA) baby weighs less than the tenth percentile based onnational norms On average, 9.4% of all SLE pregnancy cohort birthswere SGA, comparable to what would be expected in the general population. However, some cohorts had significant increases over the expected rate,with some as high as 35% . Given the relatively small risk for SGA,clear risk factors have not been identified. When a pregnancy is complicatedby placental insufficiency, the baby may grow slowly and fail to gainadequate weight. Placental studies report a higher incidence of thrombosisamong pregnancies affected by SLE For this reason, it is not surprisingthat some SLE pregnancies produce growth-restricted infants.
Preeclampsia is characterized as elevated blood pressure and proteinuria starting in the latter half of pregnancy. Preeclampsia places a woman andher fetus at considerable risk for stroke, preterm birth, and even death. Insevere situations, preeclampsia may evolve into eclampsia with the additionof grand mal seizures in the mother. Definitive treatment for preeclampsia isdelivery of the pregnancy; once the fetus (and probably more importantlythe placenta) is removed, the hypertension, proteinuria, and risks subside.
Pregnant women with SLE are at increased risk for preeclampsia. Pre- eclampsia complicates 5% to 8% of pregnancies in the United States. How-ever, among lupus pregnancy cohorts, the rate of preeclampsia ranges from13% to 35% . Preeclampsia is thought to arise from vasculardysfunction in the placenta. Several experimental markers for preeclampsia,including sFlt-1 (soluble FMS-like tyrosine kinase) and PIGF (placentalgrowth factor), have been found to correspond to preeclampsia in lupuspatients as they do in women with SLE . Women at particular risk for pre-eclampsia are in their first pregnancy, have a history of preeclampsia or renaldisease, have active SLE at conception, have positive anti–double-strandedDNA antibody (dsDNA) or antiribonucleoprotein antibodies, have lowcomplement, are obese, and/or have hypertension ( Among cohorts of patients with a history of lupus nephritis before preg- nancy, pregnancy loss rates range from 8% to 36%, excluding pregnanciesthat are electively terminated . In patients with active lupus Table 2Factors that distinguish between preeclampsia and systemic lupus erythematosus activity (white blood cells, redblood cells, casts) Physical findings: signs and symptoms of active SLE nephritis in pregnancy, fetal loss occurs in 36% to 52% of the pregnancies. Among patients with prior lupus nephritis but with stable creatinineand minimal proteinuria during pregnancy, 11% to 13% result in a fetal loss. Prematurity occurs in 16% to 75% of pregnancies, with most seriesreporting around 35% to 40% preterm . Although a historyof lupus nephritis does not preclude pregnancy, it does increase the risks forreactivation of lupus activity, preeclampsia, and pregnancy loss.
Distinguishing lupus activity from the signs and symptoms of pregnancy Systemic lupus erythematosus versus pregnancy: signs and symptoms Many of the signs and symptoms of pregnancy can be easily mistaken for signs of active SLE For this reason, when the SLE disease activity Table 3Symptoms of pregnancy that can mimic lupus activity  Fatigue that can be debilitating throughout entire pregnancy.
 Palmar erythema and a facial blush from increased estrogen.
 Melasma: ‘‘mask of pregnancy.’’ A macular, photosensitive hyperpigmented area over cheeks and forehead.
 Increased hair growth and thickness during pregnancy.
 Hair loss in the weeks to months postpartum.
 Increased respiratory rate early in pregnancy from  Dyspnea from enlarging uterus late in pregnancy.
 Back pain in second and third trimesters.
B Relaxin loosens sacroiliac joint and symphysis pubis B Gravid uterus increases lumbar lordosis.
 Joint effusions: noninflammatory in lower extremities.
 Headache can be part of normal pregnancy or associated  Seizures occur in eclampsia.
 Cerebral vascular accidents can be caused by preeclampsia or From Tsokos GC, Gordon C, Smolen JS, editors. Systemic lupus erythematosusda compan- ion to rheumatology. St. Louis: Mosby; 2007; with permission.
index (SLEDAI) was modified for pregnancy, several caveats were includedto rule out pregnancy-related complications, thus allowing for a clearer mea-sure of true SLE activity Symptoms such as severe fatigue, melasma (the‘‘mask of pregnancy’’), postpartum hair loss, increased shortness of breath,arthralgias, and headaches frequently accompany normal pregnancy.
Arthralgias are common among pregnant women because of increased weight as well as the effect of relaxin on the joints. A study comparingpregnant women with and without rheumatoid arthritis documented thateven women without arthritis have significant pain. The HAQ (Health As-sessment Questionnaire) score for healthy pregnant women increased from0.02 in the first trimester to 0.16 in the second and 0.48 in the third (scoreranges from 0 to 3) Because up to 30% of SLE patients are also affected by fibromyalgia, it is important to distinguish between the aches and pains of fibromyalgia and anarthritis that is accompanied by inflammation. There is very limited pub-lished information about the change in fibromyalgia symptoms in preg-nancy. A single study comparing 22 pregnant women with fibromyalgiaand 22 pregnant women without found a significant worsening of fibromyal-gia symptoms during pregnancy . Because steroids do not have a role intreating fibromyalgia, they should not be given if inflammation is notpresent.
In normal pregnancy, the woman’s blood volume increases by 50%, which alters several laboratory parameters. The hematocrit level frequentlydecreases because of hemodilution. Up to 50% of pregnancies in healthy women may have some degree of anemia. Hemolytic anemia, however, isnot considered normal and could be a sign of a lupus flare or HELLP syn-drome (a severe derivative of preeclampsia with hemolysis, elevated livertests, and low platelets). Mild thrombocytopenia, usually with a plateletcount around 100,000, can occur in up to 8% of healthy pregnancies. Aplatelet count below this, however, is more likely to be from lupus activity,severe preeclampsia, or HELLP syndrome.
The creatinine level normally decreases secondary to the increased glomerular filtration rate required to accommodate the increased blood vol-ume. In fact, a creatinine level that remains stable throughout pregnancyand does not decrease could be a sign of renal insufficiency. In womenwith prior renal damage from lupus nephritis, the degree of urine proteinmay increase. This is, again, secondary to increased blood flow throughthe kidneys, resulting in increased tubular flow. Therefore, alarm shouldnot be raised unless baseline proteinuria doubles. Even in healthy pregnan-cies, a small degree of proteinuria (!300 mg/24 hr) can be considered withinthe normal range.
Complement levels (C3 and C4) may decrease with increased lupus activ- ity, because these proteins are consumed in the inflammatory process Inpregnancy, however, the complement levels may increase 10% to 50% in re-sponse to increased hepatic protein synthesis Therefore, the utility ofcomplement measurement in pregnancy is unclear. In the Hopkins LupusPregnancy Cohort, half of the pregnancies had hypocomplementemia atsome point. Low complement alone was not particularly predictive of eitherlupus activity or pregnancy outcome. However, the combination of lowcomplement and high-activity lupus led to a three- to fivefold increase inpregnancy loss and preterm birth The anti–double-stranded DNA antibody (dsDNA) is very sensitive for the diagnosis of lupus and can be indicative of increased lupus activity, es-pecially in the kidney. A rising level of dsDNA during pregnancy may cor-respond to increasing lupus activity. In the Hopkins Lupus PregnancyCohort, 43% of women had a positive dsDNA during pregnancy. Womenwith a positive dsDNA had a higher incidence of increased lupus activity(28%) than those without this antibody (16%, P!.05) . However, thisantibody did not predict pregnancy outcomes. Instead, the combinationof a positive dsDNA titer and highly active SLE contributed toward afour- to sixfold increase in perinatal mortality and a two- to threefold de-crease in full-term birth .
The erythrocyte sedimentation rate (ESR) is unreliable in pregnancy be- cause it increases significantly in normal pregnancy. The C-reactive protein(CRP), however, may be more useful during pregnancy. In non-SLE preg-nancies, an increased CRP level in the second trimester has been associatedwith preterm birth The CRP does not increase in all pregnancies andmay be more reflective of the degree of overall inflammation during preg-nancy. In nonpregnant SLE patients, the CRP may increase with a lupus flare The use of CRP has not been systematically tested in SLEpregnancies yet.
Distinguishing lupus nephritis from preeclampsia One of the greatest challenges of caring for pregnant SLE patients is dis- tinguishing between preeclampsia and a lupus nephritis flare. Both presentwith proteinuria, hypertension, and lower extremity edema and may havemore systemic effects as well (see The treatment of these two con-ditions is different: preeclampsia will remit with delivery of the fetus, but ac-tive SLE will require immunosuppression.
Preeclampsia is diagnosed when a pregnant woman has a blood pressure O140/90 and proteinuria O0.3 g per 24 hours after 20 weeks’ gestation. Se-vere preeclampsia can be accompanied by severe hypertension (R160/110);microangiopathic hemolytic anemia with thrombocytopenia, anemia, andan elevated lactate dehydrogenase level; liver damage with elevated liver en-zymes and epigastric pain; CNS ischemia causing headache, visual changes,and stroke; and renal pathology with nephrotic range proteinuria and an in-creasing serum creatinine level. Eclampsia is the addition of grand mal sei-zures to preeclampsia.
The breadth of symptoms that can be attributed to severe preeclampsia makes it clear that distinguishing it from active lupus is difficult and, insome situations, impossible. outlines some risk factors, laboratory,and physical findings that may clarify the diagnosis. Prior lupus nephritisincreases the risk for both a renal SLE flare in pregnancy as well aspreeclampsia.
Treatment of systemic lupus erythematosus in pregnancy All pregnant women should take a prenatal multivitamin with at least 400 mg of folic acid each day. Folic acid supplementation is very important forwomen who have taken methotrexate before pregnancy, because folate de-ficiency can lead to neural tube defects ).
Prevention of systemic lupus erythematosus activity The best prevention of SLE flares during pregnancy is the delay of con- ception until a woman has had quiescent SLE for at least 6 months. In manysituations, however, this is not possible. The continuation of medications forSLE during pregnancy helps to prevent SLE flares.
Many women with SLE will be taking hydroxychloroquine (HCQ) (Pla- quenil) before pregnancy. This medication has been proven to decrease therisk of SLE flare, improve the prognosis of SLE nephritis, and prevent death. It is also very well tolerated with arguably the best side-effect profileof any medication available to treat SLE. An expert panel, comprised of 29 Table 4Medications to prevent and treat lupus activity in pregnancy second trimester only.
Discontinue use in thirdtrimester.
pregnancy or to treat mildflares in pregnancy.
a FDA pregnancy risk categories: A, no risk in controlled clinic trials of humans; B, human data reassuring or when absent, animal studies show no risk; C, human data are lacking andanimal studies show risk or are not done; D, positive evidence of risk but the benefit may out-weigh the risks; X, contraindicated in pregnancy.
international leaders in the research and care of women with SLE, recentlyrecommended the continuation of HCQ during pregnancy Amongmore than 300 pregnancies described in the literature that were exposedto HCQ for the treatment of autoimmune disease, there has been no eleva-tion of fetal anomalies identified. When chloroquine is taken at suprathera-peutic doses, there may be ocular or auditory damage. However, no suchchanges were seen among 133 babies exposed to HCQ in utero .
In nonpregnant SLE patients, the cessation of HCQ is associated with a 2-fold risk of SLE flare within the following 6 months Amongpregnant SLE patients, as well, the risk for flare increases when HCQ useis discontinued. In the Hopkins Lupus Pregnancy Cohort, 38 womendiscontinued HCQ use just before or early in pregnancy because of concernabout fetal exposure, and 56 women continued HCQ therapy throughoutpregnancy (. Among women who discontinued the medication,the risk for increased lupus activity, whether measured by absolutephysician’s estimate of activity, change in this scale, or the SLEDAI, was Table 5Lupus activity during pregnancy based on the use of hydroxychloroquine Abbreviation: PEA, physician’s estimate of activity.
Data from Clowse MEB, Magder L, Witter F, Petri M. Hydroxychloroquine in lupus preg- nancy. Arthritis Rheum 2006;54(11):3640–7.
significantly increased. More of these women required corticosteroid ther-apy at higher doses than women who continued taking HCQ. Within thiscohort, as in other reports, there was no increase in fetal abnormalities afterHCQ exposure. The pregnancy outcomes among women who continued anddiscontinued taking HCQ were similar. This likely reflects the type of SLEactivity that women who discontinued taking HCQ suffered: they did nothave increased rates of lupus nephritis, anemia, or thrombocytopenia. In-stead, women who discontinued taking HCQ had increased incidence of fa-tigue and joint symptoms. Although these symptoms are uncomfortable,they are generally not life threatening nor do they require cytotoxic therapy.
They may, however, prompt the institution or increase of corticosteroidtherapy mid-pregnancy.
Azathioprine (Imuran) may be the safest immunosuppressant medication taken during pregnancy. The fetal liver does not have the enzyme requiredto metabolize azathioprine into its active form . A report of three womenwho took azathioprine throughout pregnancy for inflammatory bowel dis-ease or autoimmune hepatitis showed comparable levels of 6-thioguaninenu-cleoties (6-TGN) but no evidence of 6-methylmercaptopurine (6-MMP) infetal blood at the time of delivery . The level of 6-TGN is associatedwith myelosuppression in adults, and may rarely prompt transient myelo-suppression after in utero exposure . Series of pregnancies exposed toazathioprine for inflammatory bowel disease or renal transplants show nosignificant increase in fetal abnormalities Among renal transplant pa-tients, however, up to 40% of the offspring were small for gestational age.
It is not clear if this was a product of the underlying illness, corticosteroids,or azathioprine use .
Little data are available about the use of azathioprine in SLE pregnancy.
In the Hopkins Lupus Pregnancy Cohort, 31 pregnancies were exposed toazathioprine . Among the women who conceived while taking azathio-prine and continued it through pregnancy, 2 of the 13 ended in a pregnancyloss, both in women who had active SLE in pregnancy. Among the 10women who maintained low lupus activity and azathioprine throughout pregnancy, all resulted in live births at greater than 34 weeks’ gestation.
Based on these data, we recommend the continuation of azathioprine treat-ment throughout pregnancy if the woman required it before pregnancy totreat her lupus. We also recommend switching women from mycophenolatemofetil (MMF) to azathioprine therapy before conception to avoid theteratogenic effects of the MMF.
Treatment of systemic lupus erythematosus flares during pregnancy Women without any signs or symptoms of active SLE require no specific treatment during pregnancy. Prior recommendations for prophylactic corti-costeroids have been rescinded because of increased hypertension, pretermbirth, and low birth weight seen with excess use of this medication.
Mild activity can be treated with low-dose prednisone (less than 20 mg/d) as required. The side effects of low-dose corticosteroids include increasedrisk for hypertension and diabetes, just as in a nonpregnant woman. Theremay be a 2-fold increased risk for cleft lip or palate with systemic corticoste-roid use, although the absolute risk for this remains low (about 20 per10,000 babies with corticosteroid exposure) .
Nonsteroidal anti-inflammatory drugs (NSAIDs) can be used during the latter part of the first trimester and during the second trimester. There isevidence in a murine model that COX enzymes are important for embryoimplantation, which may explain the increased risk for early miscarriagein women taking NSAIDs around the time of conception .
NSAIDs are considered fairly safe in the second trimester, although theymay decrease fetal renal excretion and therefore promote oligohydramnios. NSAIDs should be stopped in the third trimester for 2 reasons:they can prolong labor and may promote premature closure of the ductusarteriosis Moderate lupus activity can be treated with higher doses of corticoste- roids, including pulse–dose steroids. Only a small percentage of each doseof prednisone and prednisolone cross the maternal–fetal membranes. How-ever, fluorinated glucocorticoids, such as dexamethasone and betametha-sone, easily transfer to the fetus. These steroids can be helpful in treatingthe fetus, in particular in promoting fetal lung maturity before a preterm de-livery. However, they have also been associated with lasting adverse effectson the offspring. Children exposed to these corticosteroids may have in-creased blood pressure and cognitive deficits Therefore, dexametha-sone and betamethasone should not be used to treat lupus activity duringpregnancy.
The commencement of azathioprine mid-pregnancy for a lupus flare may be risky. In the Hopkins Lupus Pregnancy Cohort there was an increase inpregnancy loss among woman who used azathioprine to treat a moderate tosevere flare: of the 8 pregnancies with moderate to severe flare treated withazathioprine, five (63%) resulted in a pregnancy loss, whereas only 1 of 9 (11%) of those with severe SLE activity but treated without azathioprinewere lost (P ¼ .02) Another option for treatment mid-pregnancy is intravenous immunoglo- bin (IVIg). IVIg can be particularly helpful in controlling hematologic and re-nal disease There are no published series of IVIg use for lupus duringpregnancy; however, there are multiple reports of IVIg use to prevent recur-rent miscarriage. In these cases, the primary outcome is live birth, and there isno change in this rate with the use of IVIg. Little has been published on theeffects of IVIg on the offspring, but cell count levels seem to be stable, andno congenital anomalies have been reported. IVIg that contains sucrosecan prompt renal insufficiency, but this has not hampered the treatment ofnonpregnant women with lupus nephritis Some women will have head-aches, rigors, or fevers with IVIg therapy, but more severe side effects are rare.
Cyclophosphamide (Cytoxan) and MMF (Cellcept) should be avoided during pregnancy. First trimester exposure to cyclophosphamide causes fe-tal abnormalities in a significant minority of patients. Exposure in the sec-ond and third trimesters does not increase the risk for fetal anomaliesamong women treated for breast cancer during pregnancy. Of the threepregnancies women with SLE who had cyclophosphamide treatment duringmid-pregnancy reported in the literature, however, only one resulted ina live birth . Cyclophosphamide should only be used when all otheroptions are exhausted, and a frank a discussion about the risk for pregnancyloss has been discussed with the mother. The data on MMF in pregnancyare scarce but worrisome. There appears to be an elevated risk for both fetalanomalies and pregnancy losses .
The hormonal and physiologic changes that occur in pregnancy can in- duce lupus activity. Likewise, the increased inflammatory response duringa lupus flare can cause significant pregnancy complications. Distinguishingbetween lupus activity and signs of both healthy and pathologic pregnancycan be difficult. A rheumatologist and a high-risk obstetrician are bestequipped to care for women with lupus who become pregnant. Fortunately,most women with lupus remain well throughout pregnancy and deliverhealthy babies. However, careful planning and treatment may be requiredto achieve this success.
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