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Maternal and Neonatal Outcomes in Pregnancies Complicated by Systemic Lupus Erythematosus: A Population-Based Study
OBSTETRICS
Maternal and Neonatal Outcomes in Pregnancies Complicated by Systemic Lupus Erythematosus: A Population-Based Study Firouzeh Nili, MD,1 Lynne McLeod, MD,2 Colleen O’Connell, PhD,3 Evelyn Sutton, MD,4 Douglas McMillan, MD5 1
Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran
2
Department of Obstetrics and Gynecology, Dalhousie University, Halifax NS
3
Perinatal Epidemiology Research Unit, Dalhousie University, Halifax NS
4
Department of Internal Medicine, Dalhousie University, Halifax NS
5
Department of Pediatrics, Dalhousie University, Halifax NS
Abstract
Résumé
Objective: To determine maternal and neonatal outcomes in pregnancies complicated by systemic lupus erythematosus (SLE).
Objectif : Déterminer les issues maternelles et néonatales dans les cas de grossesse compliquée par le lupus érythémateux disséminé (LED).
Methods: In a retrospective cohort study using the Nova Scotia Atlee Perinatal Database, 97 pregnancies in women with SLE, with 99 live births, were compared with 211 355 pregnancies in women without SLE and their 214 115 babies. All were delivered in Nova Scotia between 1988 and 2008. Results: In women with SLE, gestational age at birth and mean neonatal birth weight were lower (P < 0.001) than in women without SLE. On bivariate analysis, severe preeclampsia, Caesarean section, newborn resuscitation for > 3 minutes, respiratory distress syndrome, assisted ventilation, bronchopulmonary dysplasia, patent ductus arteriosus, mild to moderate intraventricular hemorrhage, retinopathy of prematurity, and congenital heart block in neonates were significantly more frequent in the women with SLE.
Logistic regression analysis identified that having SLE increased the risks of Caesarean section (OR 1.8; 95% CI 1.1 to 2.8, P = 0.005), postpartum hemorrhage (OR 2.4; 95% CI 1.3 to 4.3, P = 0.003), need for blood transfusion (OR 6.9; 95% CI 2.7 to 17, P = 0.001), postpartum fever (OR 3.2; 95% CI 1.7 to 6.1, P = 0.032), small for gestational age babies (OR 1.7; 95% CI 1.005 to 2.9, P = 0.047), and gestational age ≤ 37 weeks (OR 2.1; 95% CI 1.3 to 3.4, P = 0.001). Neonatal death was not shown to be more common in women with SLE (RR 3.05; CI 0.43 to 21.44, P = 0.28).
Conclusion: Mothers with SLE have an increased risk of Caesarean section, postpartum hemorrhage, and blood transfusion. They are more likely to deliver premature babies, smaller babies, and babies with congenital heart block. J Obstet Gynaecol Can 2013;35(4):323–328 Key Words: Systemic lupus erythematosus, pregnancy, newborn, outcome Competing interests: None declared. Received on August 2, 2011 Accepted on November 22, 2012
Méthodes : Dans le cadre d’une étude de cohorte rétrospective menée au moyen de la Nova Scotia Atlee Perinatal Database, 97 grossesses chez des femmes présentant le LED (ayant donné lieu à 99 naissances vivantes) ont été comparées à 211 355 grossesses chez des femmes ne présentant pas le LED (ayant donné lieu à 214 115 naissances vivantes). Toutes ces femmes ont accouché en Nouvelle-Écosse entre 1988 et 2008. Résultats : Chez les femmes présentant le LED, l’âge gestationnel à la naissance et le poids de naissance moyen étaient inférieurs (P < 0,001) à ceux qui ont été constatés chez les femmes ne présentant pas le LED. Dans le cadre de l’analyse bivariée, nous avons constaté que la prééclampsie grave, la césarienne, la réanimation néonatale menée pendant > 3 minutes, le syndrome de détresse respiratoire, la ventilation assistée, la dysplasie bronchopulmonaire, la persistance du canal artériel, l’hémorragie intraventriculaire allant de légère à modérée, la rétinopathie des prématurés et le bloc cardiaque congénital chez les nouveau-nés étaient considérablement plus fréquents chez les femmes présentant le LED.
L’analyse par régression logistique a déterminé que le fait de présenter le LED entraînait une hausse des risques de césarienne (RC, 1,8; IC à 95 %, 1,1 - 2,8, P = 0,005), d’hémorragie postpartum (RC, 2,4; IC à 95 %, 1,3 - 4,3, P = 0,003), de voir une transfusion sanguine s’avérer nécessaire (RC, 6,9; IC à 95 %, 2,7 - 17, P = 0,001), de fièvre puerpérale (RC, 3,2; IC à 95 %, 1,7 - 6,1, P = 0,032), d’hypotrophie fœtale (RC, 1,7; IC à 95 %, 1,005 - 2,9, P = 0,047) et de constater un âge gestationnel ≤ 37 semaines (RC, 2,1; IC à 95 %, 1,3 - 3,4, P = 0,001). Il n’a pas été démontré que le décès néonatal était plus courant chez les femmes présentant le LED (RR, 3,05; IC 0,43 - 21,44, P = 0,28).
Conclusion : Les mères présentant le LED sont exposées à un risque accru de césarienne, d’hémorragie postpartum et de transfusion sanguine. Elles sont plus susceptibles d’accoucher d’enfants prématurés, plus petits que la normale et présentant un bloc cardiaque congénital.
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INTRODUCTION
S
ystemic lupus erythematosus is an autoimmune disease with a lifetime incidence in white women of 1 in 700.1 Specific factors such as active disease during pregnancy, renal involvement, antiphospholipid antibodies, hypertension, and antibodies to Ro/SSA and La/SSB are associated with unfavourable maternal and neonatal outcomes.2,3 Treatment required for SLE such as glucocorticoids may increase the risk of gestational diabetes, preeclampsia, and fetal growth impairment during pregnancy.2,4 Consumption of low-dose acetylsalicylic acid is considered safe in pregnancy and appears to improve fetal outcome, but higher doses of non-steroidal anti-inflammatory drugs have the potential to cause premature closure of the ductus arteriosus, persistent fetal circulation, fetal renal impairment, and necrotizing enterocolitis.2 A review of current literature reveals that pregnancies in women with SLE are associated with increased rates of stillbirth, fetal death prior to 20 weeks’ gestation, prematurity, intrauterine growth retardation, and neonatal complications such as neonatal lupus erythematosus.5 NLE is a rare syndrome characterized by fetal and neonatal congenital heart block that may also occur with subacute lupus erythematosus skin lesions, thrombocytopenia, anemia, hepatitis, glomerulonephritis, and neurologic involvement.6–8 Few studies have focused on neonatal outcomes, such as the effects of SLE and related drug therapy on the rates of respiratory distress syndrome, intraventricular hemorrhage, patent ductus arteriosus, persistent fetal circulation, necrotizing enterocolitis, sepsis, and retinopathy of prematurity. Using the Nova Scotia Atlee Perinatal Database, we compared maternal and neonatal outcomes in pregnancies complicated by clinically diagnosed SLE with those of the remaining Nova Scotia population without the clinical diagnosis of SLE delivered between 1988 and 2008. MATERIAL AND METHODS
Information for the study was obtained from the Nova Scotia Attlee Perinatal Database, which contains detailed ABBREVIATIONS CHB
congenital heart block
ITP
idiopathic thrombocytopenic purpura
NLE
neonatal lupus erythematosus
PIH
pregnancy induced hypertension
SLE
systemic lupus erythematosus
324 l APRIL JOGC AVRIL 2013
information on maternal characteristics, labour and delivery events, neonatal diagnoses, and procedures for all women who give birth in Nova Scotia and, where possible, for those women from Nova Scotia who deliver outside the province. Information in the database was collected from antenatal records and medical charts by trained personnel using standardized forms. An ongoing data quality assurance program, which conducts periodic abstraction and validation studies, has shown that the data are accurate and reliable.9 We used the database to identify pregnancies complicated by SLE for the study group and pregnancies without the diagnosis of SLE for the comparison group. We used codes from the database, version 13.0.0, with the definition of SLE based on documentation in the patient’s record. All women with the diagnosis of SLE were used as the study population. The comparison group included all other pregnant women without identified rheumatologic disease who delivered between January 1, 1988, and December 31, 2008. Analysis of the data was performed using SAS version 8 (SAS Institute, Cary, NC) and SPSS version 15 (IBM Corp., Armonk NY) software. Continuous variables were analyzed using the Student t test, and categorical variables were analyzed using the chi-square test (with Fisher exact test where appropriate). Logistic regression for maternal and neonatal outcome variables included all with a P value < 0.05 on bivariate analysis. A P value of < 0.05 was considered statistically significant. Odds ratios with corresponding 95% confidence intervals were calculated for dichotomous variables. As some women in the cohort had several pregnancies during the study period, the statistical significance of observed differences was assessed using a generalized estimating equations approach. Adjusted estimates of odds ratios were calculated using binary regression with a log link. Ethics approval for the study was provided by the IWK Health Centre Research Ethics Board. RESULTS
Of 211 452 women, there were 97 pregnancies in 77 patients with SLE (the SLE group) during the study period. Among 99 neonates in the SLE group, there were 52 males (52.5%) and 47 females (47.5%), a ratio that was not different from the non-SLE group (P = 0.7). Ninetythree of the 97 pregnancies in the SLE group (96.9 %) were singletons (not different from non-SLE; P = 0.12). Fortyfour women (45.8%) were nulliparous, similar to the 44.7% non-SLE mothers (P = 0. 8). On bivariate analysis, there were differences in mean maternal age (SLE: 29.8 ± 4.9 years, non-SLE: 28.2 ± 5.4 years), median gravidity (SLE 2
Maternal and Neonatal Outcomes in Pregnancies Complicated by Systemic Lupus Erythematosus: A Population-Based Study
Table 1. Complications in previous pregnancies
Low birth weight < 2500 grams Pregnancy loss > 500 g or > 20 weeks
SLE n = 97 n (%)
Non-SLE n = 211 355 n (%)
8 (8.3) < 5 (4.2)
OR (95% CI)
P
8102 (3.9)
2.1 (1.0 to 4.1)
0.025
1728 (0.8)
4.8 (1.8 to 12.7)
0.005
Previous fetal death
< 5 (4.2)
1788 (0.9)
5.0 (1.8 to 13.6)
0.01
Loss of fetus in previous pregnancy
41 (42.7)
54 409 (25.7)
2.1 (1.4 to 3.2)
< 0.001
Non-SLE n = 211 355 n (%)
OR (95% CI)
P 0.072
Table 2. Maternal complications in current pregnancies SLE n = 97 n (%) Chronic hypertension
< 5 (3.1)
2106 (1.0)
3.2 (1.0 to 10.1)
Pregnancy induced hypertension
17 (17.7)
19 081 (9.0)
2.1 (1.2 to 3.6)
0.003
Caesarean section
37 (38.5)
46 201 (21.9)
1.7 (1.3 to 2.2)
< 0.001
Oligohydramnios
6 (6.3)
3967 (1.9)
3.4 (1.5 to 7.9)
0.002
Thromboemboembolic disease
< 5 (2.1)
203 (0.1)
22.13 (5.4 to 90.4)
0.004
Postpartum hemorrhage: > 500 mL after delivery
13 (13.5)
12 732 (6.0)
2.4 (1.3 to 4.3)
0.002
Maternal fever ≥ 38ºC (during the 48 hours after delivery)
13 (13.5)
6717 (3.2)
4.7 (2.6 to 8.5)
< 0.001
[range 1 to 8], non-SLE 1 [range 1 to 21]), mean birth weight (SLE 3117 ± 700 g, non-SLE 3431 ± 62 g), mean gestational age (SLE 38.2 ± 2.6 weeks, non-SLE 39.1 ± 2.1 weeks), median one-minute Apgar score (SLE 9 [range 1 to 9], nonSLE 9 [range 0 to 10]), mean maternal hospital stay (SLE 4.6 ± 3.3 days, non-SLE 3.1 ± 1.6 days), and mean neonatal hospital stay (SLE 8.5 ± 20.0 days, non-SLE 4.0 ± 8.2 days). As shown in Table 1, significant complications in the past history of mothers with SLE included higher rates of pregnancy loss and of low birth weight infants. There was no significant difference in the frequency of infertility, pregnancy induced hypertension, gestational diabetes, or thromboembolic disease in the previous pregnancies in the SLE and non-SLE groups. There were significant differences between the groups in the incidence of ITP (Note this abbreviation has been defined) (SLE 5.2%, non-SLE 0.3%, P < 0.001) and asthma (SLE 8.3%, non-SLE 4.2%, P < 0.04). Eleven women with SLE (11.5%) used corticosteroids during a previous pregnancy, five (5.2%) used low-dose ASA, and one used an anticoagulant (1.3%). Significant differences in maternal outcomes in the most recent pregnancy are shown in Table 2. More women in the SLE group had induction of labour (OR 1.8; 95% CI 1.19 to 2.8, P = 0.005) and delivery by CS (OR 2.24; 95% CI 1.4 to 3.44, P < 0.001). Recorded indications for induction of labour in the SLE group were
elective (1%), fetal growth restriction (1%), premature rupture of membranes (1%), thrombocytopenia (1%), fetal distress (1%), geographic (1%), oligohydramnios (2%), postdates (5.2%), hypertension (5.2%), and unspecified (15%). Indications for CS included breech (9.4%), cephalopelvic disproportion (10.4%), fetal distress (5.2%), previous CS (7.3%), hypertension (2.1%), cord prolapse (3.1%), and other (3.1%). None of these indications were more frequent than in the non-SLE group. Polyhydramnios, premature rupture of membranes, antepartum hemorrhage, preterm premature rupture of membranes, rupture of membranes > 24 hours, and chorio amnionitis were similar in the two groups. None of the women in the SLE group had gestational diabetes, pregestational diabetes, eclampsia, intrapartum hemorrhage, placenta previa, placental abruption, sepsis, or lower urinary tract infection. Neonatal complications with bivariate analysis are shown in Table 3. There were no babies with persistent fetal circulation, necrotizing enterocolitis, or intraventricular hemorrhage grades III and IV in the SLE group. Among the babies with CHB in the SLE group, the clinical manifestations included isolated CHB, CHB with arteriovenous malformation of the lung and polymicrogyria, APRIL JOGC AVRIL 2013 l 325
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Table 3. Neonatal outcomes SLE n (%)
Non-SLE n (%)
OR (95% CI)
P
Small for gestational age (< 10th percentile)
17 (17.5)
21 194 (10.1)
1.8 (1.1 to 3.2)
0.026
Apgar score < 7 (1 minute)
16 (16.2)
22 799 (10.8)
1.6 (0.9 to 2.7)
0.082
Apgar score < 7 (5 minutes)
< 5 (3.0)
2902 (1.4)
2.2 (0.7 to 7.1)
0.155
Resuscitation at delivery > 3 minutes
< 5 (4.0)
2211 (1.0)
4.03 (1.4 to 1.0)
0.020
NICU admission
30 (30.3)
21 802 (10.2)
2.9 (2.2 to 4.0)
< 0.001
Complete congenital heart block
< 5 (4.0)
14 (0.01)
642.5 (179 to 1902)
< 0.001
Congenital anomalies Serum bilirubin > 258 µmol/L Hemoglobin < 140 g/L (in first week of life) Platelet count < 100 000 × 109/L Sepsis
7 (7.1)
7640 (3.6)
2.1 (0.95 to 4.4)
0.060
14 (14.1)
19 867 (9.3)
1.6 (0.9 to 2.8)
0.095
6 (6.1)
4581 (2.1)
2.9 (1.2 to 6.7)
0.007
< 5 (2.0)
1042 (0.5)
4.2 (1.0 to 17.1)
0.085
5 (5.1)
11 805 (5.5)
0.9 (0.3 to 2.2)
0.840
Transient respiratory distress
10 (10.1)
6419 (3.0)
3.6 (1.8 to 6.9)
0.001
Mild respiratory distress syndrome
< 5 (1.0)
1624 (0.8)
1.3 (0.18 to 9.5)
0.500
Moderate to severe respiratory distress syndrome
< 5 (4.0)
2368 (1.1)
3.7 (1.3 to 10.2)
0.025
5 (5.0)
4002 (1.9)
2.7 (1.1 to 6.8)
0.019
Ventilation Intermittent positive pressure ventilation
5 (5.0)
3105 (1.5)
3.6 (1.4 to 8.8)
0.003
Surfactant
< 5 (2.0)
882 (0.4)
4.9 (0.85 to 20.5)
0.063
Patent ductus arteriosus
< 5 (2.0)
604 (0.3)
7.2 (1.7 to 29)
0.032
Intraventricular hemorrhage (I, II)
< 5 (2.0)
616 (0.3)
7.15 (1.76 to 29.0)
0.034
Retinopathy of prematurity
< 5 (2.0)
543 (0.3)
8.1 (1.9 to 32.1)
0.027
Brochopulmonary dysplasia
< 5 (3.0)
794 (0.4)
8.3 (2.6 to 26)
0.006
Catheter related venous/arterial thrombosis
< 5 (1.0)
76 (0.0)
28.7 (3.9 to 208)
0.035
and CHB with aortic stenosis. Other anomalies observed in the SLE group without CHB were inguinal hernia, agenesis and hypoplasia of the kidney, vesicoureteral reflux, bilateral cleft lip and cleft palate, ventricular septal defect, hypoplasia of the diaphragm, and biliary atresia; the incidence of these anomalies was not statistically different from the incidence in the non-SLE group. Neonatal death was not more common in the SLE group (RR 3.05; 95% CI 0.43 to 21.44, P = 0.28). Multivariate logistic regression analysis controlling for SLE, parity, maternal age, asthma, ITP, maternal corticosteroid, thromboembolism, oligohydramnios, CS, gestational age, and birth weight showed that maternal SLE was associated with significant risk only for the factors shown in Table 4. DISCUSSION
According to Statistics Canada (2006), the Nova Scotian population included 24 175 (2.5%) Aboriginal and 878 915 non-Aboriginal people including various ethnic groups. Visible minorities made up 4% of the population, including 2% of Black ancestry.10 326 l APRIL JOGC AVRIL 2013
The prevalence of SLE in women in Nova Scotia whose pregnancies had reached 20 weeks’ gestation during this 20-year period was 0.046%, similar to that reported in a California population in 2001 (0.05%).11 Ethnicity in that population was different from ours; the proportion of Black, Hispanic, and Asian women was higher than in the Nova Scotian population. Our study provides extensive information, especially related to neonatal outcomes. Many differences that appeared on bivariate analysis were no longer evident after multiple logistic regressions. Our 20-year data review has the major strength of being a large population-based study, but each diagnosis of SLE was based on the patient’s record. We were unable to determine specific organ system involvement or the severity of the illness, but the rates of corticosteroid and low-dose ASA use lead us to believe that the majority of women with SLE had mild to moderate disease activity.12 Although almost all women had access to care during pregnancy that included fetal surveillance, it is possible that CHB could have been missed in cases of otherwise unexplained stillbirth. All epidemiologic studies are limited
Maternal and Neonatal Outcomes in Pregnancies Complicated by Systemic Lupus Erythematosus: A Population-Based Study
Table 4. Risk of maternal and neonatal outcomes associated with SLE Maternal and neonatal outcomes
aOR
95% CI
P 0.004
Maternal Caesarean section
1.8
1.2 to 2.8
Postpartum hemorrhage
2.4
1.3 to 4.42
0.003
Need for blood transfusion
7.1
2.8 to 17.6
< 0.001
Fever (postpartum)
3.6
1.9 to 6.8
< 0.001
Small for gestational age <10th percentile
1.8
1.005 to 3.0
0.029
Gestational age ≤ 37 weeks
2.4
1.5 to 3.8
< 0.001
Neonatal
aOR: adjusted odds ratio
in their ability to detect rare adverse events that may not produce another recordable adverse outcome such as death. The higher rate of previous pregnancy loss may explain the higher mean maternal age in women with SLE in our study. A higher mean maternal age in the SLE group than in the non-SLE group is consistent with the findings in the cohort in California,11 although the mean age of the women in that study was lower than in our cohort. In 2007, Clowse indicated that the rate of preeclampsia among pregnant women with SLE ranged from 13% to 35%.3 Our study showed that 17.8% of pregnancies in women with SLE were complicated by PIH. A history of preeclampsia or renal disease, active SLE at conception, first pregnancy, and hypertension are also associated with preeclampsia in pregnancies in women with SLE.3 In our study, first pregnancy, greater maternal age, previous pregnancy loss, and oligohydramnios were associated with preeclampsia. More frequent CS (38.5% in the SLE group vs. 21.9% in the non-SLE group) was associated with SLE, first pregnancy, greater maternal age, ITP, previous pregnancy loss, oligohydramnios, and mild to severe PIH. In another report, one third of pregnancies in women with SLE resulted in delivery by CS.3 The association between SLE and postpartum hemorrhage was reported in the California cohort,11 but was not evaluated by logistic regression analysis. The rate of postpartum hemorrhage in women with SLE in our study was higher than the rate reported in the California cohort (13.5% vs. 5%)11 and its risk was 2.3-fold higher than in the comparison group. The risk factors for postpartum hemorrhage include first pregnancy, obesity, macrosomia, prolonged or augmented labour, antepartum hemorrhage, placental complications, CS, over-distended uterus, multiple pregnancy, PIH, medication, trauma, and blood clotting
disorders.13–15 In our study, SLE, ITP, first pregnancy, higher maternal age, previous pregnancy loss, and oligohydramnios were all found to contribute to the higher rate of postpartum hemorrhage. We found the risk for transfusion of blood and other products was seven times higher in women with SLE than in control subjects. This difference persisted even with adjustment for CS. SLE, first pregnancy, CS, and ITP were associated with an increased rate of blood transfusion. Antiphospholipid antibodies (e.g., lupus anticoagulant) can produce a prolonged partial thromboplastin time that is not corrected with additional normal plasma but is overcome by adding excess phospholipid or platelets.16 A pre-existing coagulopathy could have explained the higher incidence of postpartum hemorrhage and blood transfusion in women with SLE in our study. A greater need for blood transfusion in pregnancies in women with SLE has not been previously reported. Antiphospholipid antibodies, which are frequently found in patients initially diagnosed with ITP, are associated with thrombosis. This may suggest that antiphospholipid antibodies confer a high risk of thrombosis in patients with ITP, or that ITP is a first symptom of SLE.17 ITP, thromboembolism, and previous pregnancy loss were risk factors for many maternal complications in our survey. Maternal fever during the first 48 hours after delivery was more common in women with SLE (3.6 times more than control subjects). Endometritis, wound infection, mastitis, urinary tract infection, and septic thrombophlebitis are the chief causes of puerperal infection.18 Our study indicated that SLE, first pregnancy, CS, previous pregnancy loss, oligohydramnios, and ITP were the risk factors most correlated with postpartum fever. Flares of SLE can occur at any time during pregnancy, as well as in the several months after delivery.3 It is possible that fever was an early sign of flares of SLE in our study. APRIL JOGC AVRIL 2013 l 327
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In pregnancies in women with SLE, the risk for preterm birth (< 37 weeks’ gestation) is estimated to be 33%.3 In our study 31.6% of pregnancies were preterm, which is consistent with other reports. In the Hopkins Lupus Pregnancy Cohort, the rate of prematurity was almost twice as high when the disease was active (66%) as when it was inactive (32%).3 SLE, a history of ITP, higher maternal age, a first pregnancy, previous pregnancy loss, antenatal treatment with corticosteroids, and use of low-dose ASA were associated with preterm deliveries in our study. It is probable that ASA was used in women with a poor pregnancy history; it is an unexpected predictor for many adverse outcomes.19 The use of corticosteroids has also been proposed as a risk factor for preterm delivery and premature rupture of membranes for the same reason.20 The incidence of small for gestational age in pregnancies in women with SLE (9.4%) is comparable to the defined incidence in the general population of 10%. However, a rate of 35% was reported in the Hopkins Lupus Pregnancy Cohort.3 The rate of SGA among the pregnancies in our cohort with a live birth was 17.3%. We found that SLE, ITP, first pregnancy, thromboembolism, and previous pregnancy loss were associated with SGA infants. In the current study, the rate of CHB in the SLE group was 4.1%. CHB is associated with a mortality rate of 20% to 30% in the neonatal period.21 In our cohort, the combination of CHB, polymicrogyria, and arteriovenous malformation of the lung was associated with high mortality. Boros et al.7 suggested that hydrocephalus and macrocephaly are manifestations of NLE and that infants born to mothers with anti-Ro antibodies should be carefully monitored for hydrocephalus as part of their routine physical examination. Among the babies in our SLE group, the occurrence of biliary atresia could have been related to maternal SLE. Hepatobiliary disease is a relatively common finding in NLE and can be the sole clinical manifestation of NLE.8 CONCLUSION
Our population-based study provides information on maternal and neonatal outcomes in pregnancies complicated by SLE to assist antenatal counselling and preparation of parents for the birth of their babies. In addition to increased pregnancy loss, there is an increased risk of earlier delivery, delivery by Caesarean section, postpartum hemorrhage, and postpartum fever, and a greater need for blood transfusion, and. In the absence of congenital heart block, adverse outcomes for babies are related to prematurity and its complications.
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REFERENCES 1. Kotzin BL. Systemic lupus erythematosus. Cell 1996;85:303–6. 2. Silver RM, Branch DW. Autoimmune disease in pregnancy. Clin Perinatol 1997;24:291–320. 3. Clowse ME. Lupus activity in pregnancy. Rheum Dis Clin North Am 2007;33:237–52. 4. Molad Y, Borkowski T, Monselise A, Ben-Haroush A, Sulkes J, Hod M, et al. Maternal and fetal outcome of lupus pregnancy: a prospective study of 29 pregnancies. Lupus 2005;14:145–51. 5. Kim SY, Lee JH. Prognosis of neonates in pregnant women with SLE. Yonsei Med J 2008;49:515–20. 6. Motta M, Ticani A, Lojacono A, Faden D, Gorla R, Airo P, et al. Neonatal outcome in patients with rheumatic disease. Lupus 2004;13:S718–S723. 7. Boros CA, Spence D, Blaser S, Silverman ED. Hydrocephalus and macrocephalus: new manifestations of neonatal lupus erythematosus. Arthritis Rheum 2007;57:261–6. 8. Lee LA, Sokol RJ, Buyon JP. Hepatobiliary disease in neonatal lupus: prevalence and clinical characteristics in cases enrolled in a national registry. Pediatrics 2002;109:1–4. 9. Joseph KS, Fahey J, Dendukur N, Allen VM, O’Campo P, Dodds L, et al. Recent changes in maternal characteristics by socioeconomic status. J Obstet Gynaecol Can 2009;31:422–33. 10. Statistics Canada. Profile of census division and subdivision in Nova Scotia. Catalogue no.95–547-XP8 2006:10–4. 11. Yasmeen S, Wilkins E, Field N, Sheikh R, Gilbert W. Pregnancy outcomes in women with SLE. J Matern Fetal Med 2001;10:91–6. 12. Buyon J, Kalunian K, Ramsey-Goldman R, Petri MA, Lockshin MD, Ruiz-Iraztorza G, et al. Assessing disease activity in SLE patients during pregnancy. Lupus 1999;8:677–84. 13. Mousa HA, Alfirevic Z. Treatment for primary postpartum hemorrhage. Cochrane Libr 2007; issue 4. Available at: http://www.thecochranelibrary.com. Accessed January 21, 2010. 14. Cunningham FG, Leveno KJ, Bloom SL, Hault JC, Rouse DJ, Spongy CY. Obstetrical hemorrhage. In: Cunningham FG, Leveno KJ, Bloom SL, Hault JC, Rouse DJ, Spongy CY, eds. Williams Obstetrics, 23rd ed. NewYork: McGraw-Hill; 2010:759–60. 15. Sosa CG, Alathabe F, Belizan JM, Bueken P. Risk factors for postpartum hemorrhage in vaginal deliveries in a Latin-American population. Obstet Gynecol 2009;113:1313–9. 16. Drews RE. Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients. Clin Chest Med 2003;24:607–22. 17. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome. J Thromb Haemost 2006;4:295–306. 18. Maharaj D. Puerperal pyrexia: a review. Part II. Obstet Gynecol Surv 2007;62:400–6. 19. Carmona F, Font J, Cevera R, Munoz F, Cararach V, Balasch J. Obstetrical outcome of pregnancy in patients with SLE. A study of 60 cases. Eur J Obstet Gynecol Reprod Biol 1999;83:137–42. 20. Cowhock FS, Reece EA, Balaban D, Branch DW, Plouffe L. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol 1992;166:1398–429. 21. Martin RJ, Fanaroff AA, Walsh MC. In: Blickstein I, Friedman S, eds. Fetal effects of autoimmune disease, 8th ed. St. Louis, MO: Mosby; 2006:371.
Maternal and Neonatal Outcomes in Pregnancies Complicated by Systemic Lupus Erythematosus: A Population-Based Study Firouzeh Nili, MD,1 Lynne McLeod, MD,2 Colleen O’Connell, PhD,3 Evelyn Sutton, MD,4 Douglas McMillan, MD5 1
Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran
2
Department of Obstetrics and Gynecology, Dalhousie University, Halifax NS
3
Perinatal Epidemiology Research Unit, Dalhousie University, Halifax NS
4
Department of Internal Medicine, Dalhousie University, Halifax NS
5
Department of Pediatrics, Dalhousie University, Halifax NS
Abstract
Résumé
Objective: To determine maternal and neonatal outcomes in pregnancies complicated by systemic lupus erythematosus (SLE).
Objectif : Déterminer les issues maternelles et néonatales dans les cas de grossesse compliquée par le lupus érythémateux disséminé (LED).
Methods: In a retrospective cohort study using the Nova Scotia Atlee Perinatal Database, 97 pregnancies in women with SLE, with 99 live births, were compared with 211 355 pregnancies in women without SLE and their 214 115 babies. All were delivered in Nova Scotia between 1988 and 2008. Results: In women with SLE, gestational age at birth and mean neonatal birth weight were lower (P < 0.001) than in women without SLE. On bivariate analysis, severe preeclampsia, Caesarean section, newborn resuscitation for > 3 minutes, respiratory distress syndrome, assisted ventilation, bronchopulmonary dysplasia, patent ductus arteriosus, mild to moderate intraventricular hemorrhage, retinopathy of prematurity, and congenital heart block in neonates were significantly more frequent in the women with SLE.
Logistic regression analysis identified that having SLE increased the risks of Caesarean section (OR 1.8; 95% CI 1.1 to 2.8, P = 0.005), postpartum hemorrhage (OR 2.4; 95% CI 1.3 to 4.3, P = 0.003), need for blood transfusion (OR 6.9; 95% CI 2.7 to 17, P = 0.001), postpartum fever (OR 3.2; 95% CI 1.7 to 6.1, P = 0.032), small for gestational age babies (OR 1.7; 95% CI 1.005 to 2.9, P = 0.047), and gestational age ≤ 37 weeks (OR 2.1; 95% CI 1.3 to 3.4, P = 0.001). Neonatal death was not shown to be more common in women with SLE (RR 3.05; CI 0.43 to 21.44, P = 0.28).
Conclusion: Mothers with SLE have an increased risk of Caesarean section, postpartum hemorrhage, and blood transfusion. They are more likely to deliver premature babies, smaller babies, and babies with congenital heart block. J Obstet Gynaecol Can 2013;35(4):323–328 Key Words: Systemic lupus erythematosus, pregnancy, newborn, outcome Competing interests: None declared. Received on August 2, 2011 Accepted on November 22, 2012
Méthodes : Dans le cadre d’une étude de cohorte rétrospective menée au moyen de la Nova Scotia Atlee Perinatal Database, 97 grossesses chez des femmes présentant le LED (ayant donné lieu à 99 naissances vivantes) ont été comparées à 211 355 grossesses chez des femmes ne présentant pas le LED (ayant donné lieu à 214 115 naissances vivantes). Toutes ces femmes ont accouché en Nouvelle-Écosse entre 1988 et 2008. Résultats : Chez les femmes présentant le LED, l’âge gestationnel à la naissance et le poids de naissance moyen étaient inférieurs (P < 0,001) à ceux qui ont été constatés chez les femmes ne présentant pas le LED. Dans le cadre de l’analyse bivariée, nous avons constaté que la prééclampsie grave, la césarienne, la réanimation néonatale menée pendant > 3 minutes, le syndrome de détresse respiratoire, la ventilation assistée, la dysplasie bronchopulmonaire, la persistance du canal artériel, l’hémorragie intraventriculaire allant de légère à modérée, la rétinopathie des prématurés et le bloc cardiaque congénital chez les nouveau-nés étaient considérablement plus fréquents chez les femmes présentant le LED.
L’analyse par régression logistique a déterminé que le fait de présenter le LED entraînait une hausse des risques de césarienne (RC, 1,8; IC à 95 %, 1,1 - 2,8, P = 0,005), d’hémorragie postpartum (RC, 2,4; IC à 95 %, 1,3 - 4,3, P = 0,003), de voir une transfusion sanguine s’avérer nécessaire (RC, 6,9; IC à 95 %, 2,7 - 17, P = 0,001), de fièvre puerpérale (RC, 3,2; IC à 95 %, 1,7 - 6,1, P = 0,032), d’hypotrophie fœtale (RC, 1,7; IC à 95 %, 1,005 - 2,9, P = 0,047) et de constater un âge gestationnel ≤ 37 semaines (RC, 2,1; IC à 95 %, 1,3 - 3,4, P = 0,001). Il n’a pas été démontré que le décès néonatal était plus courant chez les femmes présentant le LED (RR, 3,05; IC 0,43 - 21,44, P = 0,28).
Conclusion : Les mères présentant le LED sont exposées à un risque accru de césarienne, d’hémorragie postpartum et de transfusion sanguine. Elles sont plus susceptibles d’accoucher d’enfants prématurés, plus petits que la normale et présentant un bloc cardiaque congénital.
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INTRODUCTION
S
ystemic lupus erythematosus is an autoimmune disease with a lifetime incidence in white women of 1 in 700.1 Specific factors such as active disease during pregnancy, renal involvement, antiphospholipid antibodies, hypertension, and antibodies to Ro/SSA and La/SSB are associated with unfavourable maternal and neonatal outcomes.2,3 Treatment required for SLE such as glucocorticoids may increase the risk of gestational diabetes, preeclampsia, and fetal growth impairment during pregnancy.2,4 Consumption of low-dose acetylsalicylic acid is considered safe in pregnancy and appears to improve fetal outcome, but higher doses of non-steroidal anti-inflammatory drugs have the potential to cause premature closure of the ductus arteriosus, persistent fetal circulation, fetal renal impairment, and necrotizing enterocolitis.2 A review of current literature reveals that pregnancies in women with SLE are associated with increased rates of stillbirth, fetal death prior to 20 weeks’ gestation, prematurity, intrauterine growth retardation, and neonatal complications such as neonatal lupus erythematosus.5 NLE is a rare syndrome characterized by fetal and neonatal congenital heart block that may also occur with subacute lupus erythematosus skin lesions, thrombocytopenia, anemia, hepatitis, glomerulonephritis, and neurologic involvement.6–8 Few studies have focused on neonatal outcomes, such as the effects of SLE and related drug therapy on the rates of respiratory distress syndrome, intraventricular hemorrhage, patent ductus arteriosus, persistent fetal circulation, necrotizing enterocolitis, sepsis, and retinopathy of prematurity. Using the Nova Scotia Atlee Perinatal Database, we compared maternal and neonatal outcomes in pregnancies complicated by clinically diagnosed SLE with those of the remaining Nova Scotia population without the clinical diagnosis of SLE delivered between 1988 and 2008. MATERIAL AND METHODS
Information for the study was obtained from the Nova Scotia Attlee Perinatal Database, which contains detailed ABBREVIATIONS CHB
congenital heart block
ITP
idiopathic thrombocytopenic purpura
NLE
neonatal lupus erythematosus
PIH
pregnancy induced hypertension
SLE
systemic lupus erythematosus
324 l APRIL JOGC AVRIL 2013
information on maternal characteristics, labour and delivery events, neonatal diagnoses, and procedures for all women who give birth in Nova Scotia and, where possible, for those women from Nova Scotia who deliver outside the province. Information in the database was collected from antenatal records and medical charts by trained personnel using standardized forms. An ongoing data quality assurance program, which conducts periodic abstraction and validation studies, has shown that the data are accurate and reliable.9 We used the database to identify pregnancies complicated by SLE for the study group and pregnancies without the diagnosis of SLE for the comparison group. We used codes from the database, version 13.0.0, with the definition of SLE based on documentation in the patient’s record. All women with the diagnosis of SLE were used as the study population. The comparison group included all other pregnant women without identified rheumatologic disease who delivered between January 1, 1988, and December 31, 2008. Analysis of the data was performed using SAS version 8 (SAS Institute, Cary, NC) and SPSS version 15 (IBM Corp., Armonk NY) software. Continuous variables were analyzed using the Student t test, and categorical variables were analyzed using the chi-square test (with Fisher exact test where appropriate). Logistic regression for maternal and neonatal outcome variables included all with a P value < 0.05 on bivariate analysis. A P value of < 0.05 was considered statistically significant. Odds ratios with corresponding 95% confidence intervals were calculated for dichotomous variables. As some women in the cohort had several pregnancies during the study period, the statistical significance of observed differences was assessed using a generalized estimating equations approach. Adjusted estimates of odds ratios were calculated using binary regression with a log link. Ethics approval for the study was provided by the IWK Health Centre Research Ethics Board. RESULTS
Of 211 452 women, there were 97 pregnancies in 77 patients with SLE (the SLE group) during the study period. Among 99 neonates in the SLE group, there were 52 males (52.5%) and 47 females (47.5%), a ratio that was not different from the non-SLE group (P = 0.7). Ninetythree of the 97 pregnancies in the SLE group (96.9 %) were singletons (not different from non-SLE; P = 0.12). Fortyfour women (45.8%) were nulliparous, similar to the 44.7% non-SLE mothers (P = 0. 8). On bivariate analysis, there were differences in mean maternal age (SLE: 29.8 ± 4.9 years, non-SLE: 28.2 ± 5.4 years), median gravidity (SLE 2
Maternal and Neonatal Outcomes in Pregnancies Complicated by Systemic Lupus Erythematosus: A Population-Based Study
Table 1. Complications in previous pregnancies
Low birth weight < 2500 grams Pregnancy loss > 500 g or > 20 weeks
SLE n = 97 n (%)
Non-SLE n = 211 355 n (%)
8 (8.3) < 5 (4.2)
OR (95% CI)
P
8102 (3.9)
2.1 (1.0 to 4.1)
0.025
1728 (0.8)
4.8 (1.8 to 12.7)
0.005
Previous fetal death
< 5 (4.2)
1788 (0.9)
5.0 (1.8 to 13.6)
0.01
Loss of fetus in previous pregnancy
41 (42.7)
54 409 (25.7)
2.1 (1.4 to 3.2)
< 0.001
Non-SLE n = 211 355 n (%)
OR (95% CI)
P 0.072
Table 2. Maternal complications in current pregnancies SLE n = 97 n (%) Chronic hypertension
< 5 (3.1)
2106 (1.0)
3.2 (1.0 to 10.1)
Pregnancy induced hypertension
17 (17.7)
19 081 (9.0)
2.1 (1.2 to 3.6)
0.003
Caesarean section
37 (38.5)
46 201 (21.9)
1.7 (1.3 to 2.2)
< 0.001
Oligohydramnios
6 (6.3)
3967 (1.9)
3.4 (1.5 to 7.9)
0.002
Thromboemboembolic disease
< 5 (2.1)
203 (0.1)
22.13 (5.4 to 90.4)
0.004
Postpartum hemorrhage: > 500 mL after delivery
13 (13.5)
12 732 (6.0)
2.4 (1.3 to 4.3)
0.002
Maternal fever ≥ 38ºC (during the 48 hours after delivery)
13 (13.5)
6717 (3.2)
4.7 (2.6 to 8.5)
< 0.001
[range 1 to 8], non-SLE 1 [range 1 to 21]), mean birth weight (SLE 3117 ± 700 g, non-SLE 3431 ± 62 g), mean gestational age (SLE 38.2 ± 2.6 weeks, non-SLE 39.1 ± 2.1 weeks), median one-minute Apgar score (SLE 9 [range 1 to 9], nonSLE 9 [range 0 to 10]), mean maternal hospital stay (SLE 4.6 ± 3.3 days, non-SLE 3.1 ± 1.6 days), and mean neonatal hospital stay (SLE 8.5 ± 20.0 days, non-SLE 4.0 ± 8.2 days). As shown in Table 1, significant complications in the past history of mothers with SLE included higher rates of pregnancy loss and of low birth weight infants. There was no significant difference in the frequency of infertility, pregnancy induced hypertension, gestational diabetes, or thromboembolic disease in the previous pregnancies in the SLE and non-SLE groups. There were significant differences between the groups in the incidence of ITP (Note this abbreviation has been defined) (SLE 5.2%, non-SLE 0.3%, P < 0.001) and asthma (SLE 8.3%, non-SLE 4.2%, P < 0.04). Eleven women with SLE (11.5%) used corticosteroids during a previous pregnancy, five (5.2%) used low-dose ASA, and one used an anticoagulant (1.3%). Significant differences in maternal outcomes in the most recent pregnancy are shown in Table 2. More women in the SLE group had induction of labour (OR 1.8; 95% CI 1.19 to 2.8, P = 0.005) and delivery by CS (OR 2.24; 95% CI 1.4 to 3.44, P < 0.001). Recorded indications for induction of labour in the SLE group were
elective (1%), fetal growth restriction (1%), premature rupture of membranes (1%), thrombocytopenia (1%), fetal distress (1%), geographic (1%), oligohydramnios (2%), postdates (5.2%), hypertension (5.2%), and unspecified (15%). Indications for CS included breech (9.4%), cephalopelvic disproportion (10.4%), fetal distress (5.2%), previous CS (7.3%), hypertension (2.1%), cord prolapse (3.1%), and other (3.1%). None of these indications were more frequent than in the non-SLE group. Polyhydramnios, premature rupture of membranes, antepartum hemorrhage, preterm premature rupture of membranes, rupture of membranes > 24 hours, and chorio amnionitis were similar in the two groups. None of the women in the SLE group had gestational diabetes, pregestational diabetes, eclampsia, intrapartum hemorrhage, placenta previa, placental abruption, sepsis, or lower urinary tract infection. Neonatal complications with bivariate analysis are shown in Table 3. There were no babies with persistent fetal circulation, necrotizing enterocolitis, or intraventricular hemorrhage grades III and IV in the SLE group. Among the babies with CHB in the SLE group, the clinical manifestations included isolated CHB, CHB with arteriovenous malformation of the lung and polymicrogyria, APRIL JOGC AVRIL 2013 l 325
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Table 3. Neonatal outcomes SLE n (%)
Non-SLE n (%)
OR (95% CI)
P
Small for gestational age (< 10th percentile)
17 (17.5)
21 194 (10.1)
1.8 (1.1 to 3.2)
0.026
Apgar score < 7 (1 minute)
16 (16.2)
22 799 (10.8)
1.6 (0.9 to 2.7)
0.082
Apgar score < 7 (5 minutes)
< 5 (3.0)
2902 (1.4)
2.2 (0.7 to 7.1)
0.155
Resuscitation at delivery > 3 minutes
< 5 (4.0)
2211 (1.0)
4.03 (1.4 to 1.0)
0.020
NICU admission
30 (30.3)
21 802 (10.2)
2.9 (2.2 to 4.0)
< 0.001
Complete congenital heart block
< 5 (4.0)
14 (0.01)
642.5 (179 to 1902)
< 0.001
Congenital anomalies Serum bilirubin > 258 µmol/L Hemoglobin < 140 g/L (in first week of life) Platelet count < 100 000 × 109/L Sepsis
7 (7.1)
7640 (3.6)
2.1 (0.95 to 4.4)
0.060
14 (14.1)
19 867 (9.3)
1.6 (0.9 to 2.8)
0.095
6 (6.1)
4581 (2.1)
2.9 (1.2 to 6.7)
0.007
< 5 (2.0)
1042 (0.5)
4.2 (1.0 to 17.1)
0.085
5 (5.1)
11 805 (5.5)
0.9 (0.3 to 2.2)
0.840
Transient respiratory distress
10 (10.1)
6419 (3.0)
3.6 (1.8 to 6.9)
0.001
Mild respiratory distress syndrome
< 5 (1.0)
1624 (0.8)
1.3 (0.18 to 9.5)
0.500
Moderate to severe respiratory distress syndrome
< 5 (4.0)
2368 (1.1)
3.7 (1.3 to 10.2)
0.025
5 (5.0)
4002 (1.9)
2.7 (1.1 to 6.8)
0.019
Ventilation Intermittent positive pressure ventilation
5 (5.0)
3105 (1.5)
3.6 (1.4 to 8.8)
0.003
Surfactant
< 5 (2.0)
882 (0.4)
4.9 (0.85 to 20.5)
0.063
Patent ductus arteriosus
< 5 (2.0)
604 (0.3)
7.2 (1.7 to 29)
0.032
Intraventricular hemorrhage (I, II)
< 5 (2.0)
616 (0.3)
7.15 (1.76 to 29.0)
0.034
Retinopathy of prematurity
< 5 (2.0)
543 (0.3)
8.1 (1.9 to 32.1)
0.027
Brochopulmonary dysplasia
< 5 (3.0)
794 (0.4)
8.3 (2.6 to 26)
0.006
Catheter related venous/arterial thrombosis
< 5 (1.0)
76 (0.0)
28.7 (3.9 to 208)
0.035
and CHB with aortic stenosis. Other anomalies observed in the SLE group without CHB were inguinal hernia, agenesis and hypoplasia of the kidney, vesicoureteral reflux, bilateral cleft lip and cleft palate, ventricular septal defect, hypoplasia of the diaphragm, and biliary atresia; the incidence of these anomalies was not statistically different from the incidence in the non-SLE group. Neonatal death was not more common in the SLE group (RR 3.05; 95% CI 0.43 to 21.44, P = 0.28). Multivariate logistic regression analysis controlling for SLE, parity, maternal age, asthma, ITP, maternal corticosteroid, thromboembolism, oligohydramnios, CS, gestational age, and birth weight showed that maternal SLE was associated with significant risk only for the factors shown in Table 4. DISCUSSION
According to Statistics Canada (2006), the Nova Scotian population included 24 175 (2.5%) Aboriginal and 878 915 non-Aboriginal people including various ethnic groups. Visible minorities made up 4% of the population, including 2% of Black ancestry.10 326 l APRIL JOGC AVRIL 2013
The prevalence of SLE in women in Nova Scotia whose pregnancies had reached 20 weeks’ gestation during this 20-year period was 0.046%, similar to that reported in a California population in 2001 (0.05%).11 Ethnicity in that population was different from ours; the proportion of Black, Hispanic, and Asian women was higher than in the Nova Scotian population. Our study provides extensive information, especially related to neonatal outcomes. Many differences that appeared on bivariate analysis were no longer evident after multiple logistic regressions. Our 20-year data review has the major strength of being a large population-based study, but each diagnosis of SLE was based on the patient’s record. We were unable to determine specific organ system involvement or the severity of the illness, but the rates of corticosteroid and low-dose ASA use lead us to believe that the majority of women with SLE had mild to moderate disease activity.12 Although almost all women had access to care during pregnancy that included fetal surveillance, it is possible that CHB could have been missed in cases of otherwise unexplained stillbirth. All epidemiologic studies are limited
Maternal and Neonatal Outcomes in Pregnancies Complicated by Systemic Lupus Erythematosus: A Population-Based Study
Table 4. Risk of maternal and neonatal outcomes associated with SLE Maternal and neonatal outcomes
aOR
95% CI
P 0.004
Maternal Caesarean section
1.8
1.2 to 2.8
Postpartum hemorrhage
2.4
1.3 to 4.42
0.003
Need for blood transfusion
7.1
2.8 to 17.6
< 0.001
Fever (postpartum)
3.6
1.9 to 6.8
< 0.001
Small for gestational age <10th percentile
1.8
1.005 to 3.0
0.029
Gestational age ≤ 37 weeks
2.4
1.5 to 3.8
< 0.001
Neonatal
aOR: adjusted odds ratio
in their ability to detect rare adverse events that may not produce another recordable adverse outcome such as death. The higher rate of previous pregnancy loss may explain the higher mean maternal age in women with SLE in our study. A higher mean maternal age in the SLE group than in the non-SLE group is consistent with the findings in the cohort in California,11 although the mean age of the women in that study was lower than in our cohort. In 2007, Clowse indicated that the rate of preeclampsia among pregnant women with SLE ranged from 13% to 35%.3 Our study showed that 17.8% of pregnancies in women with SLE were complicated by PIH. A history of preeclampsia or renal disease, active SLE at conception, first pregnancy, and hypertension are also associated with preeclampsia in pregnancies in women with SLE.3 In our study, first pregnancy, greater maternal age, previous pregnancy loss, and oligohydramnios were associated with preeclampsia. More frequent CS (38.5% in the SLE group vs. 21.9% in the non-SLE group) was associated with SLE, first pregnancy, greater maternal age, ITP, previous pregnancy loss, oligohydramnios, and mild to severe PIH. In another report, one third of pregnancies in women with SLE resulted in delivery by CS.3 The association between SLE and postpartum hemorrhage was reported in the California cohort,11 but was not evaluated by logistic regression analysis. The rate of postpartum hemorrhage in women with SLE in our study was higher than the rate reported in the California cohort (13.5% vs. 5%)11 and its risk was 2.3-fold higher than in the comparison group. The risk factors for postpartum hemorrhage include first pregnancy, obesity, macrosomia, prolonged or augmented labour, antepartum hemorrhage, placental complications, CS, over-distended uterus, multiple pregnancy, PIH, medication, trauma, and blood clotting
disorders.13–15 In our study, SLE, ITP, first pregnancy, higher maternal age, previous pregnancy loss, and oligohydramnios were all found to contribute to the higher rate of postpartum hemorrhage. We found the risk for transfusion of blood and other products was seven times higher in women with SLE than in control subjects. This difference persisted even with adjustment for CS. SLE, first pregnancy, CS, and ITP were associated with an increased rate of blood transfusion. Antiphospholipid antibodies (e.g., lupus anticoagulant) can produce a prolonged partial thromboplastin time that is not corrected with additional normal plasma but is overcome by adding excess phospholipid or platelets.16 A pre-existing coagulopathy could have explained the higher incidence of postpartum hemorrhage and blood transfusion in women with SLE in our study. A greater need for blood transfusion in pregnancies in women with SLE has not been previously reported. Antiphospholipid antibodies, which are frequently found in patients initially diagnosed with ITP, are associated with thrombosis. This may suggest that antiphospholipid antibodies confer a high risk of thrombosis in patients with ITP, or that ITP is a first symptom of SLE.17 ITP, thromboembolism, and previous pregnancy loss were risk factors for many maternal complications in our survey. Maternal fever during the first 48 hours after delivery was more common in women with SLE (3.6 times more than control subjects). Endometritis, wound infection, mastitis, urinary tract infection, and septic thrombophlebitis are the chief causes of puerperal infection.18 Our study indicated that SLE, first pregnancy, CS, previous pregnancy loss, oligohydramnios, and ITP were the risk factors most correlated with postpartum fever. Flares of SLE can occur at any time during pregnancy, as well as in the several months after delivery.3 It is possible that fever was an early sign of flares of SLE in our study. APRIL JOGC AVRIL 2013 l 327
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In pregnancies in women with SLE, the risk for preterm birth (< 37 weeks’ gestation) is estimated to be 33%.3 In our study 31.6% of pregnancies were preterm, which is consistent with other reports. In the Hopkins Lupus Pregnancy Cohort, the rate of prematurity was almost twice as high when the disease was active (66%) as when it was inactive (32%).3 SLE, a history of ITP, higher maternal age, a first pregnancy, previous pregnancy loss, antenatal treatment with corticosteroids, and use of low-dose ASA were associated with preterm deliveries in our study. It is probable that ASA was used in women with a poor pregnancy history; it is an unexpected predictor for many adverse outcomes.19 The use of corticosteroids has also been proposed as a risk factor for preterm delivery and premature rupture of membranes for the same reason.20 The incidence of small for gestational age in pregnancies in women with SLE (9.4%) is comparable to the defined incidence in the general population of 10%. However, a rate of 35% was reported in the Hopkins Lupus Pregnancy Cohort.3 The rate of SGA among the pregnancies in our cohort with a live birth was 17.3%. We found that SLE, ITP, first pregnancy, thromboembolism, and previous pregnancy loss were associated with SGA infants. In the current study, the rate of CHB in the SLE group was 4.1%. CHB is associated with a mortality rate of 20% to 30% in the neonatal period.21 In our cohort, the combination of CHB, polymicrogyria, and arteriovenous malformation of the lung was associated with high mortality. Boros et al.7 suggested that hydrocephalus and macrocephaly are manifestations of NLE and that infants born to mothers with anti-Ro antibodies should be carefully monitored for hydrocephalus as part of their routine physical examination. Among the babies in our SLE group, the occurrence of biliary atresia could have been related to maternal SLE. Hepatobiliary disease is a relatively common finding in NLE and can be the sole clinical manifestation of NLE.8 CONCLUSION
Our population-based study provides information on maternal and neonatal outcomes in pregnancies complicated by SLE to assist antenatal counselling and preparation of parents for the birth of their babies. In addition to increased pregnancy loss, there is an increased risk of earlier delivery, delivery by Caesarean section, postpartum hemorrhage, and postpartum fever, and a greater need for blood transfusion, and. In the absence of congenital heart block, adverse outcomes for babies are related to prematurity and its complications.
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