Clinical trial NCT04067375: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Fetal and Neonatal Alloimmune Thrombocytopenia
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Sanquin Research & Blood Bank Divisions
name: Landsteiner Foundation for Blood Transfusion
First posted: 2019-08-26
Enrollment: 3660
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant women.

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.

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.

\[ WILSONBEKWAAM EXCLUSIE\]

Primary outcomes:
measure: Clinical relevant FNAIT
timeFrame: Within 7 days after birth.
Secondary outcomes:
measure: Neonatal thrombocytopenia
timeFrame: Within 7 days after birth.
measure: Neonatal infection
timeFrame: Within 7 days after birth.
measure: Chromosomal abnormality
timeFrame: Within 7 days after birth.
Other outcomes:
measure: Maternal age
timeFrame: Measured at 27 weeks gestational age of current pregnancy.
measure: Number of participatnts with idiopathic thrombocytopenic purpura
timeFrame: At inclusion
measure: Spontaneous miscarriage in obstetric history
timeFrame: At inclusion
measure: Intrauterine fetal demise in obstetric history
timeFrame: At inclusion
measure: Number of participants with hypertensive disorder
timeFrame: 3 months after delivery
measure: Prematurity
timeFrame: through study completion, until delivery, an average of 6 months
measure: Apgar Score at 5 minutes after birth
timeFrame: 5 minutes after birth
measure: Small for gestational age
timeFrame: through study completion, until delivery, an average of 6 months
Locations:
city: Amsterdam
country: Netherlands
facility: Stichting Bloedbank Sanquin
Study officials:
affiliation: Department of Obstetrics, Leiden University Medical Centre, Leiden
name: Dick Oepkes, Prof MD PhD
role: STUDY_DIRECTOR
affiliation: Department of Immunohematology Diagnostics, Sanquin Diagnostics, Amsterdam
name: Masja de Haas, Prof MD PhD
role: STUDY_DIRECTOR
affiliation: Department of Experimental Immunohematology, Sanquin Reseach, Amsterdam
name: Ellen vd Schoot, Prof MD PhD
role: STUDY_DIRECTOR
References:
citation: 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.