强烈建议新生儿狼疮综合征婴儿出生3个月时监测临床和实验室指标

作者：A.A. Zuppa et al

翻译：中日友好医院吴东海

摘要：新生儿狼疮综合征（NLS）是母体抗SSA/Ro抗体（Ab）通过胎盘引起的独特临床疾病。母亲可能患有系统性红斑狼疮、干燥综合征或其他结缔组织病，或可能在分娩时是完全健康的。NLS包括几种临床表现：完全先天性心脏阻滞（CCHB）和皮肤狼疮是最常见的，而肝胆疾病、血液学表现和中枢神经系统受累可能发生。

关于NLS不同临床表现发病率的文献数据难以比较，因为它们主要来自回顾性研究或前瞻性研究，但至今未进行系统的随访。我们一项大型前瞻性单中心研究进行了系统的临床和实验室随访长达9个月，以评估NLS特征的发生率和临床影响。

从2004年到2014年，所有在我们中心由抗SSA/Ro Ab阳性母亲所生的婴儿都被入选参加一个特异诊断和随访计划。

50名由抗SSA/Ro Ab阳性母亲生的婴儿在出生时被发现抗SSA/Ro Ab阳性。 在出生3个月时，对婴儿进行抗SSA/Ro Ab测试，如果阳性，在6和9个月时重新测试。在9个月时，10％的儿童抗SSA/Ro Ab阳性。 在两例（4％）中，怀孕期间发现了CCHB，出生时需要植入起搏器。10％的病例在随访期间发现了一过性心电图改变。几例患者在出生和随访期间发现血液学NLS特征（贫血，中性粒细胞减少，血小板减少），在9个月时，所有患者无临床表现，大多数患者完全正常。在3至6个月之间，轻度和短暂血液转换酶升高者分别为56％和40％; 9例患者（18％）出生时有无临床神经系统症状的非特异性超声脑异常，随后正常化。

为了早期发现CCHB，产前母体筛查是非常最重要的，CCHB需要治疗母亲，婴儿出生时植入起搏器。在出生时，对所有抗SSA / Ro Ab阳性母亲所生的婴儿都要监测NLS症状。然而，在出生的头几个月，这些婴儿似乎只出现轻度、短暂和自限性临床表现，在大多数情况下，这些临床表现在9个月的时间里完全消散。这一考虑，连同只有10％的婴儿在9个月时血液中抗SSA / Ro Ab持续存在的证据提示，对这些儿童随访6-9个月，临床上是安全的。另外，强烈建议在3个月时监测临床和实验室指标，这时血液学特征和肝脏检查变化发生率最高。将来，持续抗SSA / Ro阳性的患儿或抗SSA / Ro阳性母亲所生婴儿中是否需要随访到成年期这一问题将会被澄清。

附原文：Abstract Neonatal Lupus Syndrome (NLS) is a distinct clinical entity caused by transplacental passage of maternal anti-SSA/Ro antibodies (Ab).Mothers may have systemic lupus erythematosus, Sj?gren syndrome, or other connective tissue disease, or may be completely healthy at the time of giving birth. NLS includes several clinical manifestations: complete congenital heart block (CCHB) and cutaneous lupus are the most common, while hepatobiliary disease, hematological manifestations and central nervous system involvement may occur.Data from literature on the incidence of the different clinical manifestations of NLS are difficult to compare because they come mostly from retrospective studies or prospective studies, but up to date no systematic follow-up was carried out.We performed a large prospective single-center study with a systematic clinical and instrumental follow-up until 9 months of life, in order to evaluate the incidence and the clinical impact of NLS features.From 2004 to 2014 all infants born in our center to mothers with anti-SSA/Ro Ab were enrolled in a specific diagnostic and follow-up (FU) program. At birth, 50 infants born to mothers with anti-SSA/Ro Ab were found positive for anti-SSA/Ro Ab. Infants were tested for anti SSA/Ro Ab at 3 months of life, if positive they were re-tested at 6 and 9 months. At 9 months anti-SSA/Ro Ab were positive in 10% of children. In two cases (4%) a CCHB was identified during pregnancy and required pacemaker implantation at birth. In 10% of cases a transient ECG alterations was found during follow-up. Hematological NLS features (anemia, neutropenia, thrombocytopenia) were found at birth and during FU in several patients, in all cases without clinical manifestations and in most cases with complete normalization at 9months.Mild and transient elevation of aminotransferases between 3 and 6 months of life were found in 56% and 40% of patient, respectively; non-specific ultrasound cerebral anomalies in absence of clinical neurological signs were found at birth in 9 patients (18%), subsequently normalized.Prenatal maternal screening is of primary importance in order to early detect CCHB, which requires maternal treatment and pacemaker implantation at birth. Infants born to mothers with anti-SSA/Ro Ab should be monitored for all NLS features at birth. However, during the first months of life, these infants seem to develop only mild, transient and self-limited clinical manifestations, which in most cases are completely solved at 9 months of life. This consideration, together with the evidence that only 10% of infants had anti-SSA/Ro Ab persistent in blood at 9months, suggests that follow-up of these children can be performed until 6–9months of life with good clinical safety.Moreover, a clinical and laboratory monitoring at 3 months of life, when the highest incidence of hematological features and liver tests alterations are observed, is strongly recommended. In the future, it would be clarified if a follow-up until adulthood would be indicated in cases with persistent anti SSA/Ro or in all infants born to mother with anti SSA/Ro.

引自：A.A. Zuppa et al.Neonatal lupus: Follow-up in infants with anti-SSA/Ro antibodies and review of the literature. / Autoimmun Rev 16 (