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抗Ro/SSA阳性孕妇的产科和围产期结局:一项前瞻性队列研究。

Obstetric and perinatal outcome in anti-Ro/SSA-positive pregnant women: a prospective cohort study.

作者信息

Martínez-Sánchez Nuria, Pérez-Pinto Sergio, Robles-Marhuenda Ángel, Arnalich-Fernández Francisco, Martín Cameán María, Hueso Zalvide Edurne, Bartha Jose Luis

机构信息

Obstetric and Gynecology Department, High Risk Pregnancy Unit, Autoimmune diseases and pregnancy clinic, University Hospital La Paz, Paseo de la Castella 261, 28046, Madrid, Spain.

Calle Villanueva nº2, escalera 3, 7ºB, 28001, Madrid, Spain.

出版信息

Immunol Res. 2017 Apr;65(2):487-494. doi: 10.1007/s12026-016-8888-5.

Abstract

UNLABELLED

Anti-Ro/SS-A is one specific type of antinuclear antibodies. They are in the majority of cases associated with primary Sjögren syndrome (SS) but also in Systemic Lupus Erythematosus (SLE), rheumatoid arthritis (RA), and in healthy people. During pregnancy, they are mainly associated to congenital heart block (CHB) and neonatal lupus (NL). The aim of this study was to compare the rate of maternal and fetal complications between a series of anti-Ro/SS-A positive pregnant women prospectively followed. Forty-two anti-Ro/SSA antibodies positive pregnant women that were referred to our hospital between 2011 and 2015. Data about pregnancy follow-up and outcomes were prospectively recorded from electronic databases. Data included demographic characteristics of the patients and their diseases (type, treatments, profile of anti-Ro/SSA, and antiphospholipid antibodies), pregnancy complications (CHB, preeclampsia, preterm delivery), ultrasound examinations and conditions, and mode of delivery. Maternal age was 35.22 ± 3.42 years and most of them were either SLE (n = 16, 40%) or Sjögren syndrome (n = 15, 37.5%). The rest of them were asymptomatic carriers (n = 8; 20%), and there was only one case of rheumatoid arthritis (n = 1; 2.5%). The incidence of anti-Ro52 and anti-Ro60 positive was n = 13, 82.4% and n = 16, 100%, respectively. Anti-La/SSB antibodies were present in n = 17, 48,6% of the patients. Half of the patients were taking hydroxycloroquine (n = 18, 45%). Seven pregnancies were complicated by fetal anti-Ro-related cardiac disease (17.9%) including four cases (57.1%) of second-degree heart block, two cases of third degree heart block (28.6%) and one case (14.3%) of intense and diffuse hyperechogenicity in atrioventricular valves without heart block. Gestational age at diagnosis of these conditions was 23.2 ± 3.5 weeks. One of the 18 patients having hydroxychloroquine (5.6%) compared with the six of them in women not having this medication (6/22, 27.3%) (p = 0.10). Concerning about Doppler evaluation, the Z score of umbilical pulsatility index (PI) was significantly higher in the SLE patients (p = 0.02). There were no cases of preeclampsia. Labor was induced in 21 cases (52.5%) and cesarean section rate was 45%. Gestational age at birth was 39 (37-40) weeks, and the general prematurity rate was 20% (n = 8). Birthweight was 2985 g (2425-3185 g) and 2850 (12.25-52.50) centiles for gestational age. The rate of small for gestational age (SGA) infants was 31.3% for SLE patients (5/16), 13.3% for Sjögren syndrome (2/15), and 12.5% for asymptomatic women (1/8). The rate of neonatal acidosis (pH < 7.20) was 20% (8/34) and it was higher in the SLE cases (6/15, 40%) when delivered after 38 weeks. The main pregnancy complication associated to anti-Ro/SS-A antibodies is CHB. The prevalence of CHB in patients taking hydroxychloriquine is lower without distinguishing between high or low risk patients. Preterm delivery occurs in anti-Ro/SS-A patients at the same rate as in the general population if no complications such as CHB or intrauterine growth restriction (IUGR) occur. The SGA rate also is higher probably because of SLE not because anti-Ro/SS-A antibodies. Finally, the finding of high umbilical artery PI will allow to predict fetus at risk of adverse pregnancy outcomes.

HIGHLIGHTS

•Anti-Ro/SS-A and anti-La/SS-B are clinically very relevant during pregnancy mainly because of their association to congenital heart block and neonatal lupus. •In our cohort, the prevalence of congenital heart block detected in patients taking hydroxycloroquine is much lower than in patients not taking it without distinguishing between high and low risk patients. •High umbilical artery pulsatility index in Doppler scans studies has been detected in our anti-Ro/SSA population (basely in SLE patients) demonstrated this measurement as a predictor of SGA and adverse pregnancy outcomes in general population such as cesarean section for fetal distress. The small for gestational age rate is higher probably because of SLE not because anti-Ro/SS-A •Preterm delivery happens in anti-Ro/SS-A patients at the same rate as in the general population if no complications such as congenital heart block or intrauterine growth restriction occur.

摘要

未标注

抗Ro/SS-A是一种特定类型的抗核抗体。在大多数情况下,它们与原发性干燥综合征(SS)相关,但也见于系统性红斑狼疮(SLE)、类风湿关节炎(RA)以及健康人群。在孕期,它们主要与先天性心脏传导阻滞(CHB)和新生儿狼疮(NL)相关。本研究的目的是比较一系列前瞻性随访的抗Ro/SS-A阳性孕妇的母婴并发症发生率。2011年至2015年间,42例抗Ro/SSA抗体阳性孕妇转诊至我院。从电子数据库中前瞻性记录妊娠随访及结局的数据。数据包括患者的人口统计学特征及其疾病(类型、治疗、抗Ro/SSA及抗磷脂抗体谱)、妊娠并发症(CHB、先兆子痫、早产)、超声检查及情况以及分娩方式。产妇年龄为35.22±3.42岁,其中大多数为SLE患者(n = 16,40%)或干燥综合征患者(n = 15,37.5%)。其余为无症状携带者(n = 8;20%),仅有1例类风湿关节炎患者(n = 1;2.5%)。抗Ro52和抗Ro60阳性的发生率分别为n = 13,82.4%和n = 16,100%。17例患者(48.6%)存在抗La/SSB抗体。一半患者服用羟氯喹(n = 18,45%)。7例妊娠合并胎儿抗Ro相关心脏病(17.9%),包括4例二度心脏传导阻滞(57.1%)、2例三度心脏传导阻滞(28.6%)和1例房室瓣强烈弥漫性高回声但无心脏传导阻滞(14.3%)。诊断这些情况时的孕周为23.2±3.5周。服用羟氯喹的18例患者中有1例(5.6%)出现相关情况,而未服用该药物的女性中有6例(6/22,27.3%)出现相关情况(p = 0.10)。关于多普勒评估,SLE患者脐动脉搏动指数(PI)的Z评分显著更高(p = 0.02)。无先兆子痫病例。21例(52.5%)引产,剖宫产率为45%。出生时孕周为39(37 - 40)周,总体早产率为20%(n = 8)。出生体重为2985 g(2425 - 3185 g),对应孕周的百分位数为2850(12.25 - 52.50)。SLE患者小于胎龄儿(SGA)发生率为31.3%(5/16),干燥综合征患者为13.3%(2/15),无症状女性为12.5%(1/8)。新生儿酸中毒(pH < 7.20)发生率为20%(8/34),38周后分娩的SLE病例中更高(6/15,40%)。与抗Ro/SS-A抗体相关的主要妊娠并发症是CHB。服用羟氯喹的患者中CHB的患病率较低,且未区分高风险或低风险患者。如果未发生如CHB或胎儿生长受限(IUGR)等并发症,抗Ro/SS-A患者的早产发生率与一般人群相同。SGA发生率也可能较高,原因可能是SLE而非抗Ro/SS-A抗体。最后,脐动脉PI升高的发现将有助于预测有不良妊娠结局风险的胎儿。

要点

•抗Ro/SS-A和抗La/SS-B在孕期具有非常重要的临床意义,主要是因为它们与先天性心脏传导阻滞和新生儿狼疮相关。

•在我们的队列中,服用羟氯喹的患者中检测到的先天性心脏传导阻滞患病率远低于未服用者,且未区分高风险和低风险患者。

•在我们的抗Ro/SSA人群(主要是SLE患者)的多普勒扫描研究中检测到脐动脉搏动指数升高,这表明该测量可作为一般人群中SGA及不良妊娠结局(如因胎儿窘迫行剖宫产)的预测指标。小于胎龄儿发生率较高可能是因为SLE而非抗Ro/SS-A

•如果未发生如先天性心脏传导阻滞或胎儿生长受限等并发症,抗Ro/SS-A患者的早产发生率与一般人群相同。

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