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Neonatal and Obstetrical Outcomes of Pregnancies in Systemic Lupus

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Neonatal and Obstetrical Outcomes of Pregnancies in Systemic Lupus original article Oman Medical Journal [2018], Vol. 33, No. 1: 15-21 Neonatal and Obstetrical Outcomes of Pregnancies in Systemic Lupus Erythematosus Reem Abdwani 1*, Laila Al Shaqsi2 and Ibrahim Al-Zakwani3,4 1Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman 2Department of Pediatrics, Al Nahda Hospital, Muscat, Oman 3Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman 4Gulf Health Research, Muscat, Oman ARTICLE INFO ABSTRACT Article history: Objectives: Systemic lupus erythematous (SLE) is a chronic autoimmune disease Received: 30 July 2017 that affects women primarily of childbearing age. The objective of this study was Accepted: 17 October 2017 to determine the neonatal and maternal outcomes of pregnancies in SLE patients Online: compared to pregnancies in healthy controls. Methods: We conducted a retrospective DOI 10.5001/omj.2018.04 cohort study in a tertiary care hospital in Oman between January 2007 and December 2013. We analyzed 147 pregnancies and compared 56 (38.0%) pregnancies in women Keywords: Neonatal Systemic Lupus with SLE with 91 (61.9%) pregnancies in healthy control women. Disease activity was Erythematosus; Premature determined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Infant; Intrauterine Growth Results: The mean age of the cohort was 30.0±5.0 years ranging from 19 to 44 years old. Retardation; Oman. Patients with SLE were treated with hydroxychloroquine (n = 41; 73.2%), prednisolone (n = 38; 67.8%), and azathioprine (n = 17; 30.3%). There was no disease activity in 39.2% (n = 22) of patients while 41.0% (n = 23), 12.5% (n = 7), and 7.1% (n = 4) had mild (SLEDAI 1–5), moderate (SLEDAI 6–10), and severe (SLEDAI ≥ 11) disease activity, respectively, at onset of pregnancy. Pregnancies in patients with SLE were associated with higher abortions (42.8% vs. 15.3%; p < 0.001), gestational diabetes (28.3% vs. 10.2%; p = 0.004), polyhydramnios (7.1% vs. 0.0%; p = 0.020), previous preterm pregnancies (8.9% vs. 1.0%; p = 0.030), and intrauterine growth retardation (21.4% vs. 0.0%; p < 0.001) when compared to pregnancies in healthy control women. Furthermore, the neonates born to mothers with SLE were more likely to be preterm (28.5% vs. 1.0%; p < 0.001), have a low birth weight (< 2 500 g) (32.1% vs. 1.0%; p < 0.001), and were associated with stillbirth (7.1% vs. 0.0%; p = 0.010) when compared to neonates born to healthy control mothers. Conclusions: Pregnancies in women with SLE were associated with higher neonatal and maternal complications. Therefore, pregnant women with SLE should have their pregnancy accurately planned, monitored, and managed according to a multidisciplinary treatment schedule. ystemic lupus erythematosus (SLE) is an disorders, such as Sjögren's syndrome, undifferentiated autoimmune disease with a diverse clinical autoimmune syndrome, or rheumatoid arthritis.1 phenotype characterized by the presence The major clinical manifestations of NSLE include of autoreactive B and T cells, which neonatal heart block and subacute cutaneous lupus Sare responsible for the aberrant production of a lesions. Hepatobiliary and hematological cytopenias heterogeneous group of autoantibodies. Neonatal are also well established, although less common. SLE (NSLE) occurs as a result of the transplacental Rarely, urinary abnormalities and neurological passage of maternal immunoglobulin G (IgG) involvement have been reported.1 autoantibodies against Sjögren's syndrome A-B (SSA There seem to be conflicting results on the (Ro) and SSB (La)), and/or U1 ribonucleoprotein impact of pregnancy on disease activity in patients (U1-RNP). However, only 1–2% of infants with with SLE. While some studies show no change in positive maternal autoantibodies develop NSLE.1 activity, and various other studies have demonstrated Besides SLE, mothers of neonates with NSLE may an increase in lupus activity during pregnancy.2–4 have other defined or undifferentiated autoimmune Furthermore, specific maternal factors in patients *Corresponding author:[email protected] 16 Reem Abdwani, et al. Reem Abdwani, et al. 17 with SLE during pregnancy, such as active disease, gender, birth weight, growth restriction, and Apgar lupus nephritis and specific antibodies such as scores.16 Gestational age was considered preterm antiphospholipid, anti-Ro/SSA, and anti-La/SSB if neonate was born < 37 weeks of gestation and are found to be associated with unfavorable neonatal term if the neonate was born ≥ 37 weeks gestation. outcomes.5 However, other prospective studies have Low birth weight (LBW) was defined as infants not indicated such relationships.6–8 The differences < 2 500 g and intrauterine growth retardation may be explained by the diversity of presentation, (IUGR) was defined as fetal weight < 10th percentile limited number of patients included in the various for gestational age. Apgar scores < 7 at one minute studies, lack of standardized criteria for defining were considered abnormal. The data collected lupus flares, and different treatments used in the from neonates born to mothers with SLE included management of SLE during pregnancy.9 In addition, clinical manifestations of NSLE including skin, several manifestations secondary to pregnancy may cardiac, hematological, and liver involvement in be erroneously attributed to lupus flares, including addition to duration and circulating maternal arthralgia, myalgia, facial rash, and edema in the autoantibody profile. face, hands, and lower limbs. Equally, serological All mothers with a diagnosis of SLE were abnormalities used to define lupus flares may be > 18 years old and fulfilled the American College of physiologically altered during pregnancy, such as Rheumatology (ACR) 1997 revised criteria for the complement levels and inflammatory markers.8 classification of SLE.17 The control group was made Although many studies have been forthcoming up of age- and parity-matched healthy mothers. from Euro-American populations, there are some The data collected from both cohorts of mothers indications in the existing literature that race and included obstetrical complications during pregnancy ethnicities may impact disease susceptibility and such as the occurrence of gestational diabetes, pre- manifestations.10–12 More severe disease occurs in eclampsia, oligohydramnios or polyhydramnios. African Americans and Asians resulting in increased Information on previous obstetric complications morbidity and higher mortality rates in these (i.e., previous abortion, preterm labor, intrauterine groups.13 There are limited studies in SLE patients fetal death (IUFD) or stillbirth) were also collected. emanating from the Arab world; however, it is Gestational diabetes was defined as glucose recognized that Arabs experience a different disease intolerance of variable degree with onset or first burden than those from Europe and North America recognition during pregnancy, and pre-eclampsia with a higher burden of disease and different was defined as hypertension and proteinuria with or frequency of disease manifestation.14,15 without pathological edema. Polyhydramnios and The objective of this study was to describe the oligohydramnios were diagnosed when the amniotic neonatal and obstetrical outcomes of pregnancies in fluid index was < 24 cm and < 5 cm, respectively. SLE patients compared to healthy pregnant controls The data collected from mothers with SLE in an Arab cohort population from Oman. included demographics, clinical features of SLE since onset of diagnosis, disease activity at onset of pregnancy, and disease flares during pregnancy. Other METHODS data collected included immunological parameters This retrospective study was conducted at at onset of pregnancy and medications used during Sultan Qaboos University Hospital, one of the pregnancy. The main SLE clinical manifestations rheumatology referral centers in Oman. The evaluated in this study were defined according to patients treated in the clinics are referred from all the American Rheumatism Association glossary governorates in the country and are representative committee. The immunological parameters recorded of the population as a whole. The study population included antinuclear antibody (ANA) determined included consecutive neonates born to mothers with by immunofluorescence using Hep-2 cells as SLE from January 2007 to December 2013. The substrate. Anti-double stranded DNA antibody control group included consecutive neonates born to (anti-dsDNA), extractable nuclear antigen, and healthy mothers during the same study period. The antiphospholipid antibodies (APLA) were measured data collected from neonates of both cohort groups qualitatively using enzyme-linked immunosorbent included demographic data such as gestational age, assay technique (ELISA). The results were expressed Oman med J, vol 33, no 1, JanuarY 2018 16 Reem Abdwani, et al. Reem Abdwani, et al. 17 in international units. Complement C3 and C4 percentages were reported. Differences between groups levels were measured by nephelometry. In addition, were analyzed using Pearson’s chi-square tests (or Fisher’s SLE disease activity at the onset of pregnancy and exact tests for cells < 5). For continuous variables, mean disease flares during pregnancy were measured using and standard deviation (SD) were used to summarize the the SLE Disease Activity Index (SLEDAI) score. data. Analyses were performed using Student’s t-tests. SLEDAI is a validated and reliable measuring tool.18
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