Hydroxychloroquine and lupus pregnancy: review of a series of 36 cases.

OBJECTIVE: To study maternal and fetal outcome of pregnancy in patients with lupus who were exposed to hydroxychloroquine (HCQ). METHODS: The case records of women (n = 33) exposed to HCQ during their pregnancies (n = 36) and of 53 control patients from a single lupus pregnancy centre were reviewed to determine lupus activity, obstetric experience, and infant outcome. RESULTS: HCQ was not apparently teratogenic. Lupus activity and obstetric outcome in the two groups were similar. CONCLUSION: HCQ continuation is probably safe during pregnancy in patients with lupus, but there is no obvious advantage in commencing treatment.     

系统性红斑狼疮患者合并妊娠的临床研究

目的 探讨系统性红斑狼疮(SLE)患者妊娠的安全性、妊娠结局及对子代的影响.方法 回顾性分析1999年6月至2009年10月我院收治的SLE合并妊娠的患者的妊娠情况,比较选择性妊娠和非选择性妊娠组患者的SLE疾病活动情况、产科并发症情况、胎儿情况.并对SLE患者的子代进行随访.统计学处理采用x2检验和t检验.结果 SLE合并妊娠的患者共62例,选择性妊娠组43例,非选择性妊娠组19例;选择性妊娠组中10例(23%)患者在妊娠过程中出现疾病活动,8例(19%)流产,35例(81%)活胎分娩,其中低体质量儿7例,早产7例;非选择性妊娠组中16例(84%)出现疾病活动,13例(68%)流产,6例(32%)活胎分娩,均为低体质量儿,4例早产,3例合并胎儿生长受限.选择性妊娠组的妊娠过程中疾病活动率、流产率均显著低于非选择性妊娠组(P＜0.05).22例子代随访未发现SLE患儿.结论 选择性妊娠组与非选择性妊娠组患者均面临妊娠过程中SLE疾病活动及妊娠结局不良的风险,但是选择性妊娠组患者妊娠期间疾病稳定状况、母婴的预后均优于非选择性妊娠组.     

Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of one hundred thirty-three cases compared with a control group

OBJECTIVE: The use of hydroxychloroquine (HCQ) in pregnancy remains controversial. The recent demonstration that HCQ passes across the placenta, with cord blood concentrations nearly identical to those found in maternal blood, emphasizes the need for careful evaluation of pregnancies in women receiving HCQ. However, only small series of HCQ-treated pregnant women have been reported, and most of these studies had no control group. We now report our experience with 133 pregnancies in women being treated with HCQ, resulting in 117 live births. Results in the HCQ group are compared with those in a control group. METHODS: One hundred thirty-three consecutive pregnancies in 90 women treated with 200 mg of HCQ either twice daily (122 pregnancies) or once daily (11 pregnancies) were studied. These pregnancies were compared with 70 consecutive pregnancies in 53 women with similar disorders who did not receive HCQ. Electrocardiography was performed in 47 children of mothers treated with HCQ and in 45 children in the control group. RESULTS: Eighty-eight percent of pregnancies in the HCQ group and 84% of those in the control group ended successfully with a live birth. The outcomes of pregnancy were not statistically different between groups. One child in each group died of causes related to prematurity. Three malformations were observed in the HCQ group (1 hypospadias, 1 craniostenosis, and 1 cardiac malformation) versus 4 in the control group. On the electrocardiograms, the PR interval and the corrected QT interval were not statistically different between groups. No visual, hearing, growth, or developmental abnormalities were reported in any of the children at the last follow-up (ages 12-108 months; mean age 26 months). CONCLUSION: Our findings support preliminary evidence for the safety of HCQ therapy during pregnancy. This treatment probably should be maintained throughout pregnancy in patients with systemic lupus erythematosus.     

系统性红斑狼疮合并妊娠患者孕期病情的变化及其对母儿结局的影响

目的 探讨系统性红斑狼疮(SLE)合并妊娠孕妇孕期病情的变化及其对母儿结局的影响.方法 选择44例合并SLE患者的46次妊娠,分析孕期SLE病情的活动情况及其对母儿结局的影响,找出与母儿不良预后相关的危险因素.采用t检验、X2检验或Fisher精确概率法及多因素非条件Logistic回归分析等方法进行统计学分析.结果 ①孕期出现SLE病情活动19例次(活动组);无SLE活动27例次(稳定组).SLE的活动率在孕前病情稳定的患者中为16％(5/32),在孕前病情不稳定的患者中为100％( 8/8),2组相比差异有统计学意义(P＜0.05).②孕期SLE活动的主要临床表现为:活动性狼疮肾炎(11例)、皮疹(10例)和关节炎(7例);主要并发症为各类感染(11例).③母儿结局:早产、胎儿生长受限( FGR)和胎儿丢失的发生率在活动组分别为42％、47％和26％,在稳定组分别为7％、15％和0,活动组较稳定组明显升高,差异有统计学意义(P＜0.05);子痫前期、胎儿窘迫和新生儿窒息的发生率在活动组分别为16％、16％和5％,在稳定组分别为7％、19％和0,2组相比差异无统计学意义(P＞0.05).11例活动性狼疮肾炎患者的早产和FGR的发生率分别为55％和64％,较无活动性狼疮肾炎者的11％和17％明显升高,差异有统计学意义(P＜0.05).⑤Logistic回归分析显示肾损害、低补体水平、抗磷脂抗体(aPL)阳性和血清尿素氮水平分别是早产、FGR、胎儿丢失和胎儿窘迫的独立危险因素(P＜0.05).结论 ①孕期SLE活动可明显增加早产、FGR和胎儿丢失的发生率;活动性狼疮肾炎可明显增加早产和FGR的发生率;②肾损害、低补体水平、aPL阳性和血清尿素氮水平与不良胎儿结局密切相关.     

Impact of previous lupus nephritis on maternal and fetal outcomes during pregnancy

Previous reports suggest that renal involvement before pregnancy or active renal disease during pregnancy may be associated with poor fetal and maternal outcomes in systemic lupus erythematosus (SLE) women. We report our experience of fetal and maternal complications in pregnant lupus women with and without previous lupus nephritis. We analyzed the clinical records of pregnant SLE patients attended in a tertiary reference center during a 5-year period. Patients were allocated into two groups according to the presence or absence of previous lupus nephritis. Women were evaluated monthly during pregnancy and at least 1 month postpartum. Maternal and fetal outcomes of pregnancy were abstracted. We included 95 pregnancies in 92 patients. Compared with pregnant women without lupus nephritis (n = 60), pregnancies with previous lupus nephritis (n = 35) were associated with a higher risk of maternal complications (88.5% vs. 43.3%, p = 0.00001), higher rate of lupus flares (54.2% vs. 25%, p = 0.004), and renal flares (45.7% vs. 6.6%, p = 0.00001), but most of which in most instances were reversible. On the other hand, fetal outcome was similar in both groups. Multivariate analysis showed that previous lupus nephritis and active lupus at conception were predictors of adverse maternal outcome. Pregnancies in women with previous lupus nephritis had a higher rate of maternal complications in comparison with those without. However, fetal prognosis was similar in both groups.     

Preterm deliveries in women with systemic lupus erythematosus

OBJECTIVE: To compare the clinical, laboratory, and demographic variables of women in our clinic with systemic lupus erythematosus (SLE) who have had a pregnancy resulting in a live birth and identify any correlations with either term or preterm delivery. METHODS: Pregnancies in women with SLE from 1999 to 2001 were retrospectively reviewed. We recorded demographic data, disease activity (SLE Disease Activity Index, SLEDAI), obstetric history, prednisone dosage, other medications taken during pregnancy, history of renal disease, and autoantibody status [including antinuclear antibody, anti-DNA, anticardiolipin IgG (aCL), and lupus anticoagulant (LAC)]. Preterm delivery was defined as gestational age at delivery < 37 weeks. We performed a literature survey using PubMed and the key words SLE, pregnancy, and outcome. RESULTS: Of the 72 pregnancies, 28 (38.9%) resulted in preterm deliveries. There were no significant differences in any demographic or disease variables measured comparing term versus preterm delivery groups. More women in the preterm group were taking > or = 10 mg/day prednisone during their pregnancy (50.0% vs 22.2%; p = 0.028), and the mean dose was significantly higher than the term group taking > or = 10 mg/day (24.8 vs 16.7 mg/day; p = 0.047). There was a higher prevalence of women with aCL IgG in the preterm group (p = 0.023). The mean weeks gestation was shorter for women positive for aCL IgG compared to the group negative for aCL (34.9 +/- 4.4 vs 37.5 +/- 3.2 weeks, respectively; p = 0.032). There was no difference in second trimester disease activity between the term and preterm groups (33.3% and 36.4% of each group had a SLEDAI of 0). However, significantly more women in the term group received no medication during their pregnancies compared to women in the preterm group (20.0% vs 0.0%; p = 0.031). CONCLUSION: The rates of preterm deliveries, premature rupture of membranes, intrauterine growth restriction, and aPL in SLE pregnancies vary considerably in published reports, most of which are retrospective analyses. Our rates closely approximate the median values for all measures. We found preterm deliveries to be associated with disease activity (as determined by the use of any medication throughout pregnancy vs no medication, and prednisone dose > or = 10 mg/day) and the presence of aCL IgG but not LAC. Our results suggest that inactive disease rather than controlled disease at the onset of pregnancy may be the determining factor in extending SLE pregnancies to full term, thereby decreasing maternal and fetal morbidity.     

Pleading to maintain hydroxychloroquine throughout Lupus pregnancies

PURPOSE: The use of Hydroxychloroquine (HCQ) during pregnancy has remained controversial for a long time. However, it is generally agreed that pregnancy per se increases disease activity in patients with systemic lupus erythematosus (SLE) and that withdrawal of HCQ at the onset of pregnancy may result in exacerbation of SLE. Therefore, stopping HCQ at the onset of pregnancy may result in exacerbation of SLE which could be detrimental to both mother and fetus. CURRENT KNOWLEDGE AND KEY POINTS: The available data suggest that HCQ can be continued safely throughout pregnancy. After the first report by Parke of successful continuation of HCQ throughout gestation, more than 250 pregnancies resulting in live births have been reported and no increase in the rate of birth defects have been demonstrated. When studied, no retinal toxicity and ototoxicity have been found in the children. Data concerning lactation and HCQ treatment are rare. However, the amount of HCQ received by children through lactation seems very low. FUTURE PROSPECTS AND PROJECTS: For patients with SLE already taking HCQ, the benefits of continuing treatment with this medication throughout pregnancy seem to outweigh the hypothetical risks associated with its use. HCQ should probably be maintained throughout pregnancy in these patients with SLE and it does not seem necessary to advise against breastfeeding. Further studies with prospective follow-up of children exposed in utero to HCQ remain however needed to provide a definitive answer.     

Pregnancy outcome in 396 pregnancies in patients with SLE in Saudi Arabia

The aim of this study was to examine the pregnancy outcomes in patients with systemic lupus erythematosus (SLE) and the effect of SLE flare and treatment on pregnancy outcomes. We performed a retrospective evaluation of all pregnancies occurring in patients with SLE during the 27-year period from 1980 to 2006. Of the 319 women with SLE planning pregnancy after SLE onset, 176 (55.2%) conceived resulting in 396 pregnancies. Live births were significantly lower in proportion (70.2% vs. 85.7%) and more likely to end in fetal deaths (29.7% vs. 14.2%) and preterm births (26.7% vs. 5.8 %) in pregnancies occurring after SLE onset than in pregnancies occurring before SLE onset (p < 0.0001). With respect to different disease manifestations, we found that fetal loss was significantly higher in patients with antiphospholipid (aPL) antibodies than without (p < 0.001). Preterm deliveries were significantly more frequent in patients with lupus nephritis, anti-Ro/SSA antibodies, hypertension, history of intravenous cyclophosphamide treatment and aPL than those without these features (p < 0.05). Neonates with intrauterine growth retardation (IUGR) neonates were more common in hypertensive and Raynaud's-positive pregnancies (p < 0.05). SLE flares occurred in 30.8% pregnancies. There was increased risk of fetal loss, preterm births and IUGR in pregnancies with SLE exacerbations than without (p < 0.05). Prednisolone was found to improve the rate of live births, although it was also a predictor of prematurity. The predictors of pregnancy loss were lupus nephritis (odds ratio (OR) 7.3), aPL (OR 3.9), and SLE flares in pregnancy (OR 1.9). There was higher risk of preterm deliveries in patients with lupus nephritis (OR 18.9), anti-Ro antibodies (OR 13.9), hypertension (OR 15.7) and SLE flares (OR 2.5). IUGR was found to be associated with hypertension (OR 37.7), Raynaud's (OR 12.3), and SLE flares (OR 4.2). In conclusion, pregnancies in SLE patients with active lupus nephritis, anti-Ro/SSA antibodies, aPL, hypertension, Raynaud's phenomenon, active disease at conception and SLE exacerbations are at a higher risk of adverse pregnancy outcomes. It is important to carefully plan pregnancy, and experienced rheumatologists and obstetricians should monitor SLE patients in pregnancy and postpartum.     

Outcome of lupus pregnancy: a controlled study

OBJECTIVE: The reciprocal relationship between systemic lupus erythematosus (SLE) and pregnancy was investigated in a controlled study. METHOD: The outcome of 47 pregnant SLE patients with 59 pregnancies was compared with that of 57 healthy control women and 59 pregnancies. The results were also compared with those of 59 non-pregnant control SLE patients. RESULTS: All pregnant SLE patients but one were in remission at the onset of pregnancy and were being treated with low doses of prednisone (< or = 10 mg/day, 26 patients), hydroxychloroquine (200 mg/day, eight patients) or azathioprine (100 mg/day, one patient). Sixty-one per cent of SLE pregnancies were delivered at term and 5% had premature deliveries. The rates of spontaneous abortion and total fetal loss were significantly higher in the mothers with SLE than in the control population (P: < 0.001 and P: < 0.01 respectively). None of the 39 neonates from SLE mothers had neonatal lupus, anti-Ro(SSA) or anti-La(SSB) antibodies. Eight out of 59 pregnancies of SLE mothers (13.5%) were characterized by disease exacerbation. Arthralgias or arthritis, fever and skin lesions were observed more frequently in the mothers with SLE than in the non-pregnant group (P: < 0.001). Renal involvement was found in three SLE patients during pregnancy and in three after delivery. CONCLUSIONS: Pregnant women with SLE are at high risk of fetal loss and spontaneous abortion. Pregnancy does not cause life-threatening manifestations of the disease. Thus, for a better outcome of lupus pregnancy, it is essential to control disease activity and to achieve clinical remission.     

妊娠合并系统性红斑狼疮94例临床分析

目的 寻找妊娠合并系统性红斑狼疮(SLE)患者妊娠及产后不良母婴预后的因素.方法 回顾性分析北京协和医院妇产科收治的妊娠合并SLE患者的临床资料,根据SLE活动与否,将患者分为SLE不活动组和SLE活动组.用logistic回归分析影响不良母婴结局的危险因素.结果 妊娠合并SLE者97例,其中3例失访,94例SLE患者共96例次妊娠,96例次妊娠中SLE不活动组36例次,SLE活动组60例次.96例次妊娠中18例次为治疗性引产或人工流产,胎儿丢失7例次,活产71例次,3例新生儿死亡.SLE活动组早产、小于胎龄JD(SGA)、窒息发生率高于SLE不活动组(P＜0.05).logistic回归分析显示,胎儿不良结局与子痫前期/子痫、低血小板血症、SLE活动等因素有关(13值分别为2.463、2.228、2.769,P＜0.05).96例次妊娠中56例次孕前SLE稳定,其中22例次(39.3%)在妊娠期和产后发生SLE活动.共有24例子痫前期,2例子痫.合并狼疮肾炎(LN)者52例次,孕前LN控制稳定者有25例次(48.1%,25/52),其中稳定1年以上者22例次,妊娠期有12例次发生LN活动;而LN稳定短于1年者3例,妊娠期全部发生LN活动.4例产妇死亡,均发生于产后.logistic回归分析显示,子痫前期/子痫与LN活动呈正相关(β值2.658,P＜0.05),而SLE活动与孕前尿蛋白呈正相关(13值3.263,P＜0.05).结论 SLE患者妊娠后胎儿丢失、早产、SGA、新生儿窒息的发生率在SLE活动时显著增加.约1/3的SLE患者在妊娠后出现SLE活动,LN活动时子痫前期、子痫发生率显著升高.     

系统性红斑狼疮合并妊娠145例次母婴结局及临床预测因素

目的 总结系统性红斑狼疮(SEE)合并妊娠的母婴结局,分析妊娠期问SLE病情恶化、胎儿丢失、不良胎儿结局的预测因素.方法 回顾性分析1990年1月至2007年12月在北京协和医院和深圳市人民医院住院的SEE合并妊娠临床资料.结果 120例SEE合并妊娠145例次,妊娠时年龄18～4I岁,平均(28±4)岁,SEE病程0.5～18年,平均(5±4)年.共有46例次(31.7%)妊娠期间SLE病情恶化,主要在妊娠中、晚期,常累及皮肤黏膜及关节肌肉系统.妊娠期间SEE病情恶化与妊娠前病情活动及低补体血症有关(P＜0.05).妊娠前病情活动组子痫前期及子痫的发生率明显高于病情稳定组(P＜0.01).共成功分娩104例次(71.7%,其中双胞胎2例),18例次自然流产(12.4%),10例次死产(6.9%),13例次治疗性流产(9.0%).早产36例次(34.6%),新生儿出现宫内生长迟缓(IUGR)37例次(35.6%).胎儿丢失(包括自然流产及死产)的危险因素有合并抗磷脂综合征(APS)、妊娠前病情活动(P＜0.05);引起不良胎儿结局(包括早产或IUGR)的危险因素有妊娠前抗dsDNA抗体阳性、泼尼松剂量≥10 mg/d及妊娠期间SLE病情恶化(P＜0.05).21例患者行胎盘病理学检查,其中13例发现胎盘组织血管壁纤维素样坏死、梗死表现,该组患者抗磷脂抗体阳性率明显高于胎盘病理基本健康组(P＜0.05).结论 妊娠前SEE病情活动、低补体血症与SEE妊娠期间SEE病情恶化相关.合并APS、妊娠前病情活动使胎儿丢失的危险性增加,而妊娠前抗dsDNA抗体阳性、泼尼松剂量≥10 mg/d及妊娠期间SLE病情恶化使不良胎儿结局的危险性增加.     

The impact of increased lupus activity on obstetric outcomes

OBJECTIVE: Systemic lupus erythematosus is associated with multiple adverse pregnancy outcomes. We examined the impact of disease activity on spontaneous abortions, perinatal mortality, preterm delivery, and birth weight. METHODS: The study was designed to assess all pregnancies in a cohort of lupus patients who were observed prospectively from 1987 to 2002. At each visit, the physician's estimate of lupus activity was determined on a visual analog scale (high-activity lupus defined as a score of >or=2). Disease activity in each trimester was compared. We assessed the impact of high-activity lupus during pregnancy on gestational age, live birth rate, and small for gestational age babies. Potential confounders, including demographics of the women as well as maternal history of lupus, renal lupus, and antiphosphoplipid antibody syndrome, were analyzed through multivariate analysis. RESULTS: Two hundred sixty-seven pregnancies were observed. Of these, 229 (85.8%) resulted in a live birth. High-activity lupus occurred in 57 pregnancies (21%). Fewer pregnancies among women with high-activity lupus ended with live births (77% versus 88% of those with low-activity lupus; P = 0.063). Full-term delivery was achieved in 15 pregnancies (26%) among women with high-activity lupus, compared with 127 pregnancies (61%) achieving full-term in those with no or mild lupus activity (P < 0.001). High-activity lupus in the first and second trimesters led to a 3-fold increase in pregnancy loss (miscarriages and perinatal mortality). CONCLUSION: High-activity lupus during pregnancy leads to increased premature birth and a decrease in live births, with almost one-quarter of these pregnancies resulting in fetal loss. Pregnancies in lupus patients must be closely watched and treated during all trimesters to improve pregnancy outcomes.     

Pregnancy outcomes in women with childhood-onset and adult-onset systemic lupus erythematosus: a comparative study

To compare the maternal and fetal outcomes between childhood-onset and adult-onset systemic lupus erythematosus (SLE), we reviewed the medical records of SLE pregnant women treated from January 2005 to August 2013. For comparison, patients were allocated to one of the two groups, those pregnant patients with SLE onset before 18 years of age (childhood-onset) and ≥18 years (adult-onset). The patients were evaluated at least once in each trimester and postpartum. Relevant maternal and fetal outcomes were extracted, such as lupus flare, preeclampsia/eclampsia, rate of liveborns, fetal loss (spontaneous abortion and stillbirth), term delivery, preterm birth, neonatal death, low birth weight, low birth weight at term, and congenital malformations. We studied 186 pregnancies (in 180 women), 58 of them had childhood-onset SLE, and the remaining 128 had adult-onset SLE. The rate of maternal and fetal complications was similar in both groups. Multivariate analysis showed that active SLE before pregnancy, primigravida, renal flare, preeclampsia, lupus flare, anticardiolipin antibodies, and low serum complement were associated with an increased risk of poor maternal and fetal outcomes. The diagnosis of childhood-onset had no impact on maternal–fetal outcome. The maternal and fetal outcome in women with childhood-onset SLE is similar to that reported in women with adult-onset SLE. Pregnancy in women with childhood-onset SLE should not be contraindicated if the disease is well controlled.     

Could women with systemic lupus erythematosus (SLE) have successful pregnancy outcomes? Prospective observational study

Aim of the workThe aim of this study was to determine the frequencies and predictors of maternal and fetal pregnancy outcomes in women with systemic lupus erythematosus (SLE).Patients and methodsData of 37 pregnancies of 34 patients with systemic lupus erythematosus were collected prospectively from patients at Rheumatology and Rehabilitation department of Cairo University Hospitals from 2007 to 2009. Univariate analysis and logistic regression analysis were used.ResultsThere were five spontaneous miscarriages, and 32 pregnancies resulting in live births. There were 20 full term babies and 12 preterm babies. Eight fetuses were born with intrauterine growth retardation (IUGR) and seven babies were born with low birth weight (LBW). Six babies were incubated at NICU (premature) with four neonatal deaths. Among 37 pregnancies, 32 women (86.5%) were in clinical remission before pregnancy; only five patients (13.5%) were active. There were 21/32 episodes of SLE flare up (65.6%) during pregnancy and eight postpartum flare up (21.6%). Eight women (21.6%) developed preeclampsia during pregnancy. Planned pregnancy and SLEDAI at the beginning of pregnancy were significantly associated with fetal loss at univariate analysis. However, there were no significant predictors of fetal loss at binary logistic regression analysis. There was no maternal mortality reported. Renal lupus disease was found to be a predictor of pre-eclampsia occurrence in univariate analysis (P = 0.04).ConclusionIn general, pregnancies can be successful in most women with SLE with a favorable fetal outcome. SLE tends to flare during pregnancy. Flares are maximal during the second trimester.     

Lupus activity in pregnancy

Pregnancy in a woman with systemic lupus erythematosus (SLE) can be complicated by both lupus activity and pregnancy mishaps. The majority of recent studies found an increase in lupus activity during pregnancy, perhaps exacerbated by hormonal shifts required to maintain pregnancy. Increased lupus activity, in turn, prompts an elevated risk for poor pregnancy outcomes, including stillbirth, preterm birth, low birth weight, and preeclamspsia. Fortunately, the majority of pregnancies in women with SLE are successful. However, the interaction between pregnancy and SLE activity can lead to complications for both mother and baby.     

Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: A study of one hundred thirty‐three cases compared with a control group

Objective

The use of hydroxychloroquine (HCQ) in pregnancy remains controversial. The recent demonstration that HCQ passes across the placenta, with cord blood concentrations nearly identical to those found in maternal blood, emphasizes the need for careful evaluation of pregnancies in women receiving HCQ. However, only small series of HCQ‐treated pregnant women have been reported, and most of these studies had no control group. We now report our experience with 133 pregnancies in women being treated with HCQ, resulting in 117 live births. Results in the HCQ group are compared with those in a control group.

Methods

One hundred thirty‐three consecutive pregnancies in 90 women treated with 200 mg of HCQ either twice daily (122 pregnancies) or once daily (11 pregnancies) were studied. These pregnancies were compared with 70 consecutive pregnancies in 53 women with similar disorders who did not receive HCQ. Electrocardiography was performed in 47 children of mothers treated with HCQ and in 45 children in the control group.

Results

Eighty‐eight percent of pregnancies in the HCQ group and 84% of those in the control group ended successfully with a live birth. The outcomes of pregnancy were not statistically different between groups. One child in each group died of causes related to prematurity. Three malformations were observed in the HCQ group (1 hypospadias, 1 craniostenosis, and 1 cardiac malformation) versus 4 in the control group. On the electrocardiograms, the PR interval and the corrected QT interval were not statistically different between groups. No visual, hearing, growth, or developmental abnormalities were reported in any of the children at the last follow‐up (ages 12–108 months; mean age 26 months).

Conclusion

Our findings support preliminary evidence for the safety of HCQ therapy during pregnancy. This treatment probably should be maintained throughout pregnancy in patients with systemic lupus erythematosus.

     

Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes

Systemic lupus erythematosus (SLE) is a disease of reproductive-age women, and thus questions regarding how disease influences pregnancy outcomes arise. We investigated whether five specific types of SLE activity during the 6 months before conception or during pregnancy (nephritis, cytopenias, skin disease, arthritis, serositis) were associated with adverse pregnancy outcomes. We performed a retrospective cohort study of pregnancy outcomes among women with SLE at the Brigham and Women’s Hospital Lupus Center. Adverse pregnancy outcomes included pre-eclampsia, pre-term delivery, elective termination due to SLE, spontaneous miscarriage at weeks 12–20, and stillbirth. SLE and obstetric history, laboratories, and medications were obtained from electronic medical records. Generalized linear mixed models adjusting for potential confounders were used to identify predictors of any adverse pregnancy outcome. Most pregnancies resulted in a live term delivery (76.5 %). After adjustment for Hispanic ethnicity, prior adverse pregnancy outcome and medication use 6 months before conception, nephritis during pregnancy (odds ratio (OR) 3.6, 95 % confidence interval (CI) 1.0–12.8), cytopenias during pregnancy (OR 3.9, 95 % CI 1.3–11.4), and serositis during pregnancy (OR 5.9, 95 % CI 1.0–34.0) were significantly associated with adverse pregnancy outcome. Specific types of SLE disease activity during pregnancy were related to adverse pregnancy outcome. Nephritis, cytopenias, and serositis carried a higher risk of adverse pregnancy outcome, suggesting that these abnormalities should be carefully monitored during pregnancy.     

Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study.

We conducted a randomized, controlled study to assess the need for hydroxychloroquine (HCQ) during lupus pregnancy and to assess safety. Twenty consecutive pregnant patients with similar characteristics were enrolled. The HCQ group included eight patients with systemic lupus erythematosus (SLE) and two with discoid lupus erythematosus (DLE). The placebo (PL) group included nine patients with SLE and one with DLE. The HCQ group had no flare-ups. SLEPDAI scores were similar at study entry, and at conclusion the placebo group had significantly higher scores. One patient had improvement of skin lesions and another of arthritis, allowing a decrease of prednisone dose. There were no retinal effects. Three patients in the PL group flared up, two with skin rashes, one also with arthritis and uveitis, and one (previously in remission on HCQ) with hemolytic anemia, polyserositis and anti-dsDNA antibody. Toxemia was diagnosed in only three patients in the PL group (one fetal death). Comparing prednisone dosage change, we noted a decrease in the HCQ and an increase in the PL group. Delivery age and Apgar scores were higher in the HCQ group. Neonatal examination did not reveal congenital abnormalities, nor did a neuro-ophthalmological and auditory evaluation at 1.5-3 y of age. In spite of the small number of patients studied, we noted beneficial effects of HCQ during lupus pregnancy, as measured by SLEPDAI and decrease in prednisone dose with no detriment to patients' health.     

Systemic lupus erythematosus. VI. Analysis of the interrelationship with pregnancy

The influence of systemic lupus erythematosus (SLE) on pregnancy and vice versa was examined during 39 pregnancies in 19 patients, and outcome was compared with 24 pregnancies in 18 other patients before SLE was established. No difference in fetal loss or premature birth rate was found, although more babies were born with low birth weight after SLE was diagnosed; there was a preponderance of female babies in both groups. Pregnancy during SLE was accompanied by disease exacerbations in up to 74% of all patients. These exacerbations concerned mostly musculoskeletal (41%) and hematological abnormalities (36%), while organ involvement occurred in 13% of all exacerbations. No differences in pregnancy outcome during SLE were found between patients with active or quiescent disease, as established by the lupus activity criteria count (LACC). The presence of antibodies to SSA in the mother was associated with the occurrence of congenital heart block; no association was found between antiphospholipid antibodies and fetal loss.     

Importance of planning ovulation induction therapy in systemic lupus erythematosus and antiphospholipid syndrome: a single center retrospective study of 21 cases and 114 cycles

OBJECTIVE: To analyze the results and complications of ovulation induction therapy (OIT) in women with systemic lupus erythematosus (SLE) and/or the antiphospholipid syndrome (APS). METHODS: A retrospective study of 21 women followed in a single tertiary-referral French center who underwent 114 OIT cycles with or without in vitro fertilization and embryo transfer (IVFET). RESULTS: Before OIT, SLE was present in 6 women, APS in 3, SLE-related APS in 3, and discoid lupus in 1. Eight women had no identified disease and underwent 36 cycles of OIT. Diagnosis (SLE, n = 3; primary APS, n = 5) was made after OIT complication: spontaneous abortion (n = 5), SLE flare (n = 2), and thrombophlebitis (n = 1). Five women with known disease intentionally concealed their history from their gynecologists and underwent 34 cycles. Forty-four cycles were planned in 11 women, in 3 of them after complications of prior OIT performed without particular therapy and monitoring. Eighteen pregnancies occurred, which ended in 9 live births, 4 fetal deaths, and 5 embryonic losses. The pregnancy rate was higher with gonadotropin and/or gonadotropin-releasing hormone analog (GnRHa) (25% of cycles) than with clomiphene (4% of cycles, P <.0001). When the gynecologists did not know the underlying disease, three-quarters of pregnancies induced by OIT with IVFET ended in embryonic losses or fetal deaths. In contrast, 6 of 7 pregnancies induced by planned OIT with IVFET ended in live births (P <.0001). Phlebothromboses were observed only with gonadotropin treatment. The SLE flare rate was higher with gonadotropin and/or GnRHa (27% of cycle) than with clomiphene (6%, NS). It also was higher (30%) when the gynecologists did not know the underlying disease than in the planned procedures (10%, NS). CONCLUSIONS: The OIT may precipitate SLE or APS. A careful review of the patient's history and appropriate laboratory tests should be undertaken before OIT. Clomiphene complications are rare. When gonadotropins are prescribed, preventive anti-inflammatory therapy should be considered in women with SLE, in addition to heparin and/or anti-aggregant therapy in patients with asymptomatic anti-phospholipid antibodies or prior thrombotic events.