zyxwvutsrqponmlkji zyxwvutsrqpon zyxwvutsrqp Aust NZ J Obstet Gynaecol 1999; 39: 1: 28 zyxwvuts zyxw zyx Pregnancy in Patients With Systemic Lupus Erythematosus Neelam Aggarwal’ ‘ MD, Harjeet SawhneyZhMD, Kala Vasi~hta’.~ MD, Seema C h ~ p r aMD ~.~ and Pardeep Bambery’ MD Departments of Obstetrics and GynaecologyO and Internal Medicine; Nehru Hospital Postgraduate Institute of Medical Education and Research, Chandigarh, India Summary: We reviewed the obstetrical performance and outcome of 15 pregnancies in patients with systemic lupus erythematosus (SLE) (study group) and compared them with 45 age and parity-matched normal pregnancies (control group). Eleven women (73.8%) were in remission phase and 4 (26.7%) had active disease at the time of conception. The time interval between disease diagnosis and the index pregnancy was 4 . 2 f 2 . 5 years. Two patients with renal involvement had lupus flare-up during the antenatal period. There was no case of lupus flare-up in the postpartum period. Gestational age at delivery was significantly lower in SLE patients (35.9 f2.5 weeks) compared to the control group (37.4 f2.2 weeks). The incidence of intrauterine growth retardation was significantly higher in the SLE patients (40%). There was no case of neonatal lupus or congenital heart block. Systemic lupus erythematosus (SLE) is an autoimmune disease which has a predilection for women in the childbearing age. The effect of pregnancy on the course of maternal disease is controversial, especially in regard to the incidence of lupus flare-ups throughout gestation (1-5). The impact of systemic lupus erythematosus on the course of pregnancy is perhaps better understood, although dependent on many factors. Most series report increased rates of spontaneous abortion, prematurity, perinatal mortality and intrauterine growth retardation (2,6,7). Poor pregnancy outcome in women with SLE has been principally ascribed to the presence of renal involvement (6). The unpredictable course of the disease makes it difficult to evaluate the risk for any one pregnancy. To assess the impact of systemic lupus erythematosus on the outcome of pregnancy and the course of disease during pregnancy, we reviewed our experience with 15 patients with this disease. MATERIAL AND METHODS During the 13 year-period from 1985 to 1997, 15 patients with SLE were registered in our special Medical and Surgical Disorders Clinic at the Nehru Hospital, Chandigarh. During this period 43,47 1 1. Assistant Professor. 2. Associate Professor. 3. Professor. 4.Senior Resident. 5. Additional Professor. Address for correspondence: Dr Harjeet Sawhney, Department of Obstetrics and Gynaecology, Postgraduate Institute of Medical Education and Research, Chandigarh- 160012, India. deliveries took place in this hospital. In our hospital the incidence of small for gestational age fetuses is 12.3% and the perinatal mortality rate is 122.3/1,000 deliveries. The diagnosis of SLE was made by a rheumatologist according to the criteria of the American Rheumatism Association for SLE (8). The patient’s age, parity, height and weight at the time of antenatal booking were recorded. The medical history was recorded in detail regarding age at diagnosis of SLE, duration of the disease, medication received for the treatment, disease activity at the time of pregnancy and the organ-system involvement. Their obstetric histories, if any, were reviewed in detail to evaluate the previous obstetrical performance and outcome. A complete physical examination was performed and the patients were followed up 3weekly until the sixth month of pregnancy and then 2weekly until the eighth month and weekly thereafter. The same dose of steroids or immunosuppressives as before pregnancy was continued unless relapse occurred. The criteria for relapse of the disease included evidence of acute synovitis, pruritus, pericarditis, new neurological or psychiatric symptoms, haematological parameters revealing leucopenia, thrombocytopenia or active kidney disease. The dose of steroids or immunosuppressives was increased in case of relapse and the patient was hospitalized. Pregnancies were allowed to continue until term and induction of labour was done for obstetrical indications. Peripartum steroids (injection of hydrocortisone 100 mg 8-hourly) were given to all patients. Antenatal complications, incidence and timing of flare-up of SLE, intrapartum maternal fetal events, mode of delivery and perinatal outcome were noted. All neonates less than 1 standard deviation from the NEELAM ACCARWAL ET AL mean birth-weight for gestational age as compared to our institute reference intrauterine growth curve were classified as small for gestational age and pregnancies terminated between 28-37 weeks were considered premature. Any deterioration of the disease activity in the puerperium was also looked for. For each case 3 age and parity-matched healthy controls (45) were chosen who delivered within 48 hours of each study case. Statistical analysis was performed by x' and t-test. 29 Table 2. Disease Characteristics at Onset of Pregnancy Number of patients ( n = 15) Parameters zyxwvuts zyxwvuts zy RESULTS The mean maternal age at diagnosis of disease (SLE) was 22.9 k 4.3 years. Maternal age and parity were similar in both the groups. Patients with SLE had bad obstetrical histories compared to the control group but the difference between the 2 groups was not statistically significant (p<0.05) (table 1). Eleven patients (73.3%) were in remission at the time of conception and 4 (26.7%) had active disease. The time interval between diagnosis of disease and the present pregnancy was 4 . 2 f 2 . 5 years. Three patients had 'overlap syndrome' (SLE with polymyositis (l), SLE with dermatomyositis (2)) (table 2). The majority of the patients had arthritis (9 of 15), 2 had evidence of renal involvement and 1 had multiorgan involvement (predominantly central nervous system and lungs): I. Clinical manifestations (a) SLE i) Renal + arthritis ii) Arthritis iii) Arthritis + LAC +ve iv) Arthritis + hypothyroidism v) Arthritis + cutaneous disease vi) Cutaneous disease vii) Multiorgan involvement (b) SLE dermatomyositis (c) SLE + polymyositis + Raynaud disease 11. State of disease Active Remission 12 2+ 4 1+ 1 1 2 1+ 2 1 4 11 111. Time interval (years) diagnosis-pregnancy mean f SD 4.2 k 2.5 LAC = lupus anticoagulant; SLE = systemic lupus erythematosus; + = active disease at time of conception Table 3. Treatment of SLE Affected Pregnancies No. of oatients DNSS Topical steroids Prednisolone only Prednisolone plus chloroquinine Prednisolone plus thyroxine Prednisolone plus LMWH Prednisolone plus azathioprine+ 1 10 1 zyxwvutsrqpo Table 1. Maternal Profile of the Study group (n = 15) Study and Control Groups Control t/x2 p value group (n = 45) 1 1 1 LMWH = low molecular weight heparin; + = discontinued at 12 weeks' gestation zyxwvutsr zyxwvutsr i) -Maternal age (years) (mean f SD) (a) At diagnosis of disease 22.9 f 4.3 (b) At pregnancy 27.1 f 3.8 25.3 f 3.2 t = 1.755 >0.05 ii) Parity (Mean k SD) 0.7 f 0.9 0.6 f 0.7 t = 0.020 >0.05 iii) Primigravidas 7 (46.7%) 18 (40%) x2=0.206 20.05 iv) Previous obstetric outcome 47 No. of pregnancies 23 Abortions 3 (39.1%) 9 (19.1%) x2 = 3.228 >0.05 Preterm 3 (13.0%) 5 (10.6%) x2y= 0.011 >0.05 Stillbirth 4 of 14* 4 of 38* (10.5%) X'Y = 1.360 >0.05 (28.6%) 2 of 34 Neonatal death 2 of 10 (20.0%) (5.9%) X'Y = 0.363 >0.05 6 of 38 Perinatal death 6 of 14 (15.7%) X'Y = 2.815 >0.05 (42.8%) * = Number of deliveries All of the patients were taking prednisolone during pregnancy. One patient was taking an immunosuppressive drug at the time of conception, which was discontinued at 12 weeks of gestation (table 3). Two patients had a flare-up of SLE during the antenatal period and their dose of steroids was increased. Both patients had active disease with renal involvement at the onset of pregnancy. Table 4. Perinatal Outcome in the Study (SLE) and Control Groups Study Control t/x' p value group group (n = 45) (n = 15) Intranatal events i) Gestational age at delivery (weeks) 35.9 f 2.5 37.4f 2.2 t = 2.119 >0.05 (mean k SD) ii) Preterm delivery 5 (33.3%) 15 (33.3%) x*= 0 >0.05 iii) Premature rupture 3 x2y = 5.73 <0.025 of the membranes iv) NVD 10 29 X' = 0.024 >0.05 1 5 x'y= 0.0 >0.05 v) Forceps vi) Caesarean section 4 11 x2y = 0.03 >0.05 Neonatal i) Birth-weight (g) Mean f SD ii) Stillbirth iii) SGA 2,308 k 701 2,660 f472 t = 2.20 <0.05 2 (13.3%) 1 (2.2%) X'Y = 1.053 >0.05 6 (40%) 9 (20%) x2= 2.4 >0.05 NVD = normal vaginal delivery; SGA = small for gestational age Two (13.3%) patients in the study group and 3 (6.9%) in the control group had pregnancy-induced hypertension. Gestational age at delivery was significantly lower in the study group (table 4). The incidence of preterm delivery and mode of delivery was comparable in both groups. The mean birthweight was 2,308 f 0.701 g in the study group and 30 zyxwvutsrqpo zyxwvuts zyxwvutsrq zy AUSTA N D NZ JOURNAL OF OBSTETKICS A N D GYXAECOLOGY 2,660 & 0.472 g in the control group; the difference between the 2 groups was statistically significant (p<0.05). There were 2 stillbirths in the study group. One was associated with a flare-up of the disease activity in a patient with renal involvement and the other was due to hyperpyrexia due to malaria infection in a patient whose SLE was in remission. The incidence of small for gestational age fetuses was significantly higher in the study group. No patient had a flare-up of SLE activity in the postpartum period. There was no congenital malformation in the newborns of either of the groups. There were no specific complications noted in the liveborn infants that could be related to maternal medications or disease in the study group. DISCUSSION The impact of pregnancy on the course of systemic lupus erythematosus is still controversial, especially in regard to the incidence of lupus flares or exacerbations throughout gestation. In our study the course of the disease did not alter during pregnancy. Two of the 15 patients had flare-ups of the disease in the third trimester. Both patients had active disease with renal involvement at conception. The results of the present study are in accordance with prior studies (1,2) where pregnancy did not predispose to exacerbation of maternal disease. Locksin (1) documented exacerbation of disease in 1 of 9 pregnancies. Nicklin (2) also reported a low incidence (4 of 42) of disease flare-up in pregnancy. In contrast, Petri et a1 (4) and Irastorza et a1 (5) reported higher incidences of disease flare-up during pregnancy. Petri et a1 (4) observed flare-up of disease in 24 of 40 (60%) pregnancies. They did not observe any increase in the frequency of postpartum or third trimester flares compared with flares occumng in the first 2 trimesters. The pregnancy flare rate (1.6 k 0.3) was significantly higher than both the after delivery flare rate (0.63 k 0.15; p<O.OOl) and the rate in nonpregnant patients (0.65f 0.05; p<O.OOOl). Similar observations were made by Irastorza et a1 (5). They reported a flare-up rate of 65% during pregnancy andor the puerperium and 42% in control nonpregnant patients. Patients with SLE have been reported to have an increased risk of intrauterine death, prematurity, intrauterine growth retardation, as well as babies with complete heart block and neonatal systemic lupus erythematosus (2,6,7). Two of the pregnancies reported in the present study resulted in antepartum stillbirths, 1 in a patient with disease flare-up with evidence of renal involvement and other stillbirth was due to incidental malarial infection and hyperpyrexia. The incidence of intrauterine growth retardation was higher in our study group (6 or 15, 40%) than the control group (9 of 45, 20%) although the difference was not statistically significant (table 4). Wong et a1 (3) did not observe any adverse perinatal outcome in SLE patients. In their study, the incidences of threatened abortion, preeclampsia and intrauterine growth retardation were low and comparable with the rate in the general population. Varner et a1 (7) also reported a low incidence of growth retarded fetuses ( 3 of 30) in their series. The mechanisms by which SLE affects the outcome of pregnancy have not been elucidated. Abramowsky et a1 (9) have studied the placentas of women with SLE and found evidence of avascular lesions of the placenta of a similar nature to the vasculitis seen with other clinical manifestations of the disease. Another possible explanation regarding the impaired outcome of these pregnancies is a direct effect of the disease (12). Neonatal lupus is a rare but serious complication of pregnancies complicated by SLE. No case of neonatal lupus was found in the present study and this is consistent with the low incidence quoted in the world literature. We conclude from our study that pregnancyinduced SLE flare-up is uncommon but SLE is associated with an increased incidence of intrauterine growth retardation. The majority of our patients were on corticosteroid therapy during pregnancy and it is possible that steroid therapy may have contributed to the low flare-up rate. References 1. Lockshin MD. Pregnancy does not cause systemic lupus erythematosus to worsen. Arthritis Rheum 1989; 32: 665-670. 2. Nicklin JL. Systemic Lupus Erythematosus and Pregnancy at the Royal Women’s Hospital, Brisbane 1979-1989.Aust NZ J Obstet Gynaecol 1991; 31: 128-133. 3. Wong IL, Chan FY, Lee CP. Outcome of pregnancy in patients with systemic lupus erythematosus. Arch Intern Med 1991: 151: 269-273. 4. Petri M, Howard D, Repke J. Frequency of Lupus flare in pregnancy - The Hopkins Lupus pregnancy center experience. Arthritis and Rheumatism 1991; 34: 1538-1545. 5. Irastorza GR. Lima F, Khamashta MA, Simpson J, Hughes GRV, Buchanan NMN. Increased rate of lupus flare during pregnancy and puerperium: A prospective study of 78 pregnancies. Br J Rheumatol 1996; 35: 133-138. 6. Gimovsky ML, Montoro M, Paul RH. Pregnancy outcome in women with systemic lupus erythematosus. Obstet Gynecol 1984: 63: 686-692. 7. Varner MW, Mechan RT, Syrop CH, Strottmann MP, Goplerud CP. Pregnancy in patients with systemic lupus erythematosus. Am J Obstet Gynecol 1983; 145: 1025-1037. 8. Tan EM, Cohen AS, Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-1277. 9. Absramowsky CR, Vegas ME, Swinehart G. Decidual Vasculopathy of the placenta in lupus erythematosus. N Eng J Med 1980: 303: 668-672. zyxwvut