Towards Routine HPA-screening In Pregnancy to Prevent FNAIT

Brief Title

Towards Routine HPA-screening In Pregnancy to Prevent FNAIT

Official Title

Towards Routine HPA-screening in Pregnancy to Prevent FNAIT: Assessing Disease Burden and Optimising Risk Group Selection

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.
    


Study Type

Observational


Primary Outcome

Clinical relevant FNAIT

Secondary Outcome

 Neonatal thrombocytopenia

Condition

Fetal and Neonatal Alloimmune Thrombocytopenia

Intervention

Clinical data collection.

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Other

Estimated Enrollment

3660

Start Date

March 1, 2017

Completion Date

April 1, 2020

Primary Completion Date

April 1, 2020

Eligibility Criteria

        Inclusion Criteria:

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

        Exclusion Criteria:

          -  There are no predefined exclusion criteria, since we are aiming to determine the
             incidence in the complete pregnant population in the Netherlands.

        [ WILSONBEKWAAM EXCLUSIE]
      

Gender

Female

Ages

N/A - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Dick Oepkes, Prof MD PhD, , 

Location Countries

Netherlands

Location Countries

Netherlands

Administrative Informations


NCT ID

NCT04067375

Organization ID

P16.002


Responsible Party

Principal Investigator

Study Sponsor

Leiden University Medical Center

Collaborators

 Sanquin Research & Blood Bank Divisions

Study Sponsor

Dick Oepkes, Prof MD PhD, Study Director, Department of Obstetrics, Leiden University Medical Centre, Leiden


Verification Date

September 2020