Towards Routine HPA-screening In Pregnancy to Prevent FNAIT

NCT ID: NCT04067375

Last Updated: 2020-09-02

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 3660 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-03-01
• Study Completion Date: 2020-04-01

Brief Summary

Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) is the most common cause of severe thrombocytopenia in otherwise healthy born neonates. FNAIT results in a risk of bleeding the most severe complication being intracranial haemorraghes (ICH). Bleedings can be prevented by effective antental treatment. In the absence of screening programs this treatment is too late to prevent the first affected child. The investigators aim to identify the pregnancies at risk and describe the incidence and natural course of this disease. In this way fetuses at risk can be identified in the future and timely antenatal treatment can be initiated.

Detailed Description

Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) is the most common cause of severe thrombocytopenia in neonates. It is an immunological process, in which Human Platelet Antigen (HPA) alloantibodies produced by the mother can cross the placenta and target fetal platelets. The most frequent alloantigen to elicit platelet-reactive antibody responses is HPA-1a. The resulting low platelet count in the fetus or neonate correlates with an increased risk of bleeding complications and severe adverse outcome, defined as perinatal death or intracranial haemorrhage (ICH). This can lead to life-long handicaps, cerebral palsy, cortical blindness and mental retardation. One in 50 pregnancies is at risk for FNAIT, since 2,1% of the Caucasian population is HPA-1a negative. Alloantibodies are calculated to be present in 1:400 pregnancies, leading to FNAIT-related severe adverse outcome in at least 1:1300 fetuses or neonates, and this is likely an underestimation. There is a highly effective antenatal treatment available for preventing these severe adverse outcomes, consisting of weekly injection of intravenous immunoglobulins (IvIG). Unfortunately, in the current practice, this treatment can only be applied in subsequent pregnancies with known alloimmunization, after a symptomatic sibling leading to diagnosis of the disease. In potential future antenatal screening for HPA-alloantibodies, all pregnancies at risk can be identified in time, to start antenatal treatment and reduce severe adverse outcomes. However, before such a program can be realised, detailed information about incidence and natural course of the disease is needed. Furthermore, laboratory tests to identify fetuses at high risk to prevent overtreatment are needed, since approximately 10-30% of the HPA alloimmunized cases result in severe thrombocytopenia and clinically relevant disease.

Objectives:

1. The main objective of this study is to assess the incidence and severity of FNAIT and bleeding complications (including ICH) among neonates.

2. To develop a screening platform, including diagnostic assay(s) to identify fetuses at high risk for bleeding complications due to FNAIT.

Study design: Prospective observational cohort

Study population: Pregnant women

Main study parameters/endpoints: The main study parameters are HPA-1a alloantibodies, clinically relevant FNAIT. Secondary parameters include: neonatal outcome (bleeding signs other than ICH, treatment for thrombocytopenia, morbidity).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: These pregnant women participate in the national antenatal screening programme for Prevention and Screening of Infectious diseases and Erythrocyte Immunisation (PSIE) and have a routine blood sampling at 27th week of gestation. This blood sample will be used this to perform all necessary tests, so no additional (medical) procedures will be performed. Additionally, after delivery clinical data concerning the pregnancy, delivery and the health of the child in the first postnatal period are collected by questioning the obstetric health care provider.

Conditions

Fetal and Neonatal Alloimmune Thrombocytopenia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Pregnant women, HPA-1a positive

RhD or Rhc negative women, identified through prenatal screening for red cell alloimmunization, that are typed as HPA-1a positive.

Clinical data collection.

Intervention Type: OTHER

The following clinical data will be collected; maternal baseline characteristics, delivery related data, neonatal outcome, neonatal bleeding signs.

Pregnant women, HPA-1a negative with HPA-1a alloantibodies

RhD or Rhc negative women, identified through prenatal screening for red cell alloimmunization, that are typed as HPA-1a negative and have formed anti-HPA-1a alloantibodies.

Clinical data collection.

Intervention Type: OTHER

The following clinical data will be collected; maternal baseline characteristics, delivery related data, neonatal outcome, neonatal bleeding signs.

Pregnant women, HPA-1a negative without HPA-1a alloantibodies

RhD or Rhc negative women, identified through prenatal screening for red cell alloimmunization, that are typed as HPA-1a negative and did not have formed anti-HPA-1a alloantibodies.

Clinical data collection.

Intervention Type: OTHER

The following clinical data will be collected; maternal baseline characteristics, delivery related data, neonatal outcome, neonatal bleeding signs.

Interventions

Clinical data collection.

The following clinical data will be collected; maternal baseline characteristics, delivery related data, neonatal outcome, neonatal bleeding signs.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• All pregnant women, of whom routine blood samples are taken at 27 weeks gestational age (GA).

Exclusion Criteria

[ WILSONBEKWAAM EXCLUSIE]

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Sanquin Research & Blood Bank Divisions

OTHER

Sponsor Role: collaborator

Landsteiner Foundation for Blood Transfusion

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

DickOepkes

Professor of Obstetrics and Fetal Therapy. Head of the section Fetal Medicine.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dick Oepkes, Prof MD PhD

Role: STUDY_DIRECTOR

Department of Obstetrics, Leiden University Medical Centre, Leiden

Masja de Haas, Prof MD PhD

Role: STUDY_DIRECTOR

Department of Immunohematology Diagnostics, Sanquin Diagnostics, Amsterdam

Ellen vd Schoot, Prof MD PhD

Role: STUDY_DIRECTOR

Department of Experimental Immunohematology, Sanquin Reseach, Amsterdam

Locations

Stichting Bloedbank Sanquin

Amsterdam, , Netherlands

Countries

Netherlands

References

de Vos TW, Winkelhorst D, Porcelijn L, Beaufort M, Oldert G, van der Bom JG, Lopriore E, Oepkes D, de Haas M, van der Schoot E. Natural history of human platelet antigen 1a-alloimmunised pregnancies: a prospective observational cohort study. Lancet Haematol. 2023 Dec;10(12):e985-e993. doi: 10.1016/S2352-3026(23)00271-5. Epub 2023 Oct 27.

Reference Type: DERIVED

PMID: 38407610 (View on PubMed)

Winkelhorst D, de Vos TW, Kamphuis MM, Porcelijn L, Lopriore E, Oepkes D, van der Schoot CE, de Haas M. HIP (HPA-screening in pregnancy) study: protocol of a nationwide, prospective and observational study to assess incidence and natural history of fetal/neonatal alloimmune thrombocytopenia and identifying pregnancies at risk. BMJ Open. 2020 Jul 20;10(7):e034071. doi: 10.1136/bmjopen-2019-034071.

Reference Type: DERIVED

PMID: 32690731 (View on PubMed)

Other Identifiers

P16.002

Identifier Type: -

Identifier Source: org_study_id