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中国人群母红细胞抗体分布与胎儿严重同种免疫性溶血病风险:产前管理的队列研究。

Distribution of maternal red cell antibodies and the risk of severe alloimmune haemolytic disease of the foetus in a Chinese population: a cohort study on prenatal management.

机构信息

Department of Obstetrics, the Sixth Affiliated Hospital of Sun Yat-sen University, 510655, Guangzhou, Guangdong, China.

Foetal Medicine Centre, Department of Obstetrics and Gynaecology, the First Affiliated Hospital of Sun Yat-sen University, Guangdong, 51000, Guangzhou, China.

出版信息

BMC Pregnancy Childbirth. 2020 Sep 16;20(1):539. doi: 10.1186/s12884-020-03235-w.

Abstract

BACKGROUND

Haemolytic disease of the foetus and newborn (HDFN) is the most common aetiology of haemolytic anaemia and hyperbilirubinaemia in foetuses and neonates. Studies on the distribution of antibodies that cause haemolytic disease of the foetus (HDF) in China are limited, and the effects of multiple antibodies on the severity of HDF need further evaluation.

METHODS

An observational cohort study from January 2005 to December 2019 was conducted in two hospitals affiliated with Sun Yat-sen University. Maternal red cell alloimmunization was identified by the Guangzhou Blood Centre. In total, 268 pregnant woman-foetus pairs were divided into four groups according to the type of maternal alloantibodies: anti-D, anti-D combined with other antibodies, other single-antibody and other multiple antibodies. The obstetric history, antibody characteristics, incidence of severe HDF and foetal outcomes were collected and compared. Logistic regression analysis of the risk factors for HDF and survival analysis of the severe HDF-free interval were conducted.

RESULTS

Anti-D was the most common cause of HDF, followed by anti-M. No anti-K- or isolated anti-c-associated HDF was found. The incidence of severe HDF was higher in the group with anti-D combined with other antibodies than in the group with anti-D alone (P = 0.025), but no significant difference was found in haemoglobin level and reticulocyte count in the anaemic foetuses between these two groups. Foetuses in the other single-antibody group had a lower reticulocyte count (P = 0.007), more IUTs (P = 0.007) and an earlier onset of severe HDF (P = 0.012). The maximum antibody titre was significantly lower in the other single-antibody group than in the anti-D group (P < 0.001). A high maternal antibody titre (P < 0.001), multiple affected pregnancies (P < 0.001) and other single-antibody (P = 0.042) were independent risk factors for HDF. A higher reticulocyte count (P = 0.041) was an independent risk factor for severe HDF in anaemia foetuses affected by Rh(D) alloimmunization.

CONCLUSIONS

The distribution of HDF-associated antibodies in China is different from that in Western countries. Other single non-Rh(D) antibodies could increase the risk of HDF, and anti-D combined with other antibodies would not influence the severity of foetal anaemia compared with anti-D alone.

摘要

背景

胎儿和新生儿溶血病(HDFN)是胎儿和新生儿溶血性贫血和高胆红素血症最常见的病因。在中国,关于引起胎儿溶血病(HDF)的抗体分布的研究有限,需要进一步评估多种抗体对 HDF 严重程度的影响。

方法

本研究为 2005 年 1 月至 2019 年 12 月在中山大学附属的两家医院进行的观察性队列研究。采用广州血液中心鉴定母体红细胞同种免疫。共纳入 268 例孕妇-胎儿对,根据母体同种抗体类型分为四组:抗-D、抗-D 合并其他抗体、其他单抗体和其他多抗体。收集并比较了产科病史、抗体特征、严重 HDF 的发生率和胎儿结局。采用 logistic 回归分析 HDF 的危险因素,并进行严重 HDF 无间隔的生存分析。

结果

抗-D 是 HDF 最常见的原因,其次是抗-M。未发现抗-K-或孤立的抗-c 相关 HDF。抗-D 合并其他抗体组的严重 HDF 发生率高于抗-D 组(P=0.025),但两组贫血胎儿的血红蛋白水平和网织红细胞计数无显著差异。其他单抗体组的网织红细胞计数较低(P=0.007),宫内输血(IUT)较多(P=0.007),严重 HDF 发病较早(P=0.012)。其他单抗体组的最大抗体效价明显低于抗-D 组(P<0.001)。母体高抗体效价(P<0.001)、多次妊娠(P<0.001)和其他单抗体(P=0.042)是 HDF 的独立危险因素。网织红细胞计数升高(P=0.041)是 Rh(D)同种免疫所致贫血胎儿发生严重 HDF 的独立危险因素。

结论

中国 HDF 相关抗体的分布与西方国家不同。其他非 Rh(D)单抗体可增加 HDF 的风险,抗-D 合并其他抗体与抗-D 单独相比不会影响胎儿贫血的严重程度。

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