Neonatal alloimmune thrombocytopenia caused by anti-HPA antibodies in pregnant Chinese women: a study protocol for a multicentre, prospective cohort trial

Li Chen,Tiemei Liu,Zhongjun Li,Yonggeng Chen,Yongjun Wang,Jun Zhang,Zhiwei Liu,Xiancang Ma ,Tingting Xie,Yinlan Kang,Bo Sun,Qiushi Wang,Xiaojing Zeng,Beizhan Yan,Meiying Rao,Xiaochuan Song,Jiang Wu,Xiangfu Liu,Lei Zhang,Jun Wen,Yu Guo ,Fenghua Li ,Genling Zhang,Wen Yin,Yurong Huang ,Peng Wang,Xiaojuan Li,Yaming Wei

doi:10.1186/s12884-017-1453-y

Abstract

BackgroundNeonatal alloimmune thrombocytopenia (NAIT), caused by maternal antibodies raised against alloantigens carried on foetal platelets, is a very common haematological abnormality in newborns worldwide. However, baseline data on NAIT in China are lacking. Therefore, this study seeks to explore the incidence of alloantibody against the human platelet antigen (HPA) in pregnant women and its associations with NAIT in China.MethodsA multicentre, prospective cohort study design will be used, and 55,497 pregnant women will be recruited for the first screening of the anti-HPA antibody at 12 to 28 weeks of gestational age. Subjects who are positive in the first screening for the anti-HPA antibody will be included in the exposure group. Re-tests of the antibody titre, antigen-specificity and genotyping of HPA and HLA will be conducted during admission. A ratio of 1:1 paired individuals with the same ethnicity and parity but testing negative for the anti-HPA antibody will be randomly selected to be included in the non-exposure group. NAIT will be diagnosed in the newborns on day one of the birth. The HPA of the neonates in the exposure group will also be genotyped by sequencing. Associations of maternal HLA with the occurrence of the anti-HPA antibody and correlation of the severity of NAIT with the titre of the anti-HPA antibody will be further analysed.DiscussionThe study is expected to provide baseline data on NAIT in China. Besides, we hope to find out a population who expresses particular HLA molecules has significant higher risk of HPA alloimmunization in Chinese individuals. We also hope to find a Chinese-specific cut-off antibody titre for the prediction of the severity of NAIT and to provide a means to evaluate the necessity of antenatal treatment.Trial registrationClinicalTrials.gov: NCT02934906 (date registered: 13.10.2016).

Highlights

Neonatal alloimmune thrombocytopenia (NAIT), caused by maternal antibodies raised against alloantigens carried on foetal platelets, is a very common haematological abnormality in newborns worldwide
human platelet antigen (HPA) antibodies are not routinely screened for in every pregnant woman, and NAIT is always diagnosed after the birth of the first affected child
Antenatal treatment can be offered only in the subsequent pregnancies to avoid the recurrence of severe FNAIT [12]

Summary

Methods

A multicentre, prospective cohort study design will be used, and 55,497 pregnant women will be recruited for the first screening of the anti-HPA antibody at 12 to 28 weeks of gestational age. Subjects who are positive in the first screening for the anti-HPA antibody will be included in the exposure group. Re-tests of the antibody titre, antigenspecificity and genotyping of HPA and HLA will be conducted during admission. A ratio of 1:1 paired individuals with the same ethnicity and parity but testing negative for the anti-HPA antibody will be randomly selected to be included in the non-exposure group. The HPA of the neonates in the exposure group will be genotyped by sequencing. Associations of maternal HLA with the occurrence of the anti-HPA antibody and correlation of the severity of NAIT with the titre of the anti-HPA antibody will be further analysed

Discussion

Background

Findings