Towards Routine HPA-screening In Pregnancy to Prevent FNAIT

Fetal and Neonatal Alloimmune Thrombocytopenia Clinical Trial

— HIP  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04067375
• Other study ID #: P16.002
• Status: Completed
• Start date: March 1, 2017
• Est. completion date: April 1, 2020

Study information

• Verified date: September 2020
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3660
• Est. completion date: April 1, 2020
• Est. primary completion date: April 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

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]

Related Conditions & MeSH terms

• Fetal and Neonatal Alloimmune Thrombocytopenia
• Thrombocytopenia

Intervention

Other:
• Clinical data collection.
The following clinical data will be collected; maternal baseline characteristics, delivery related data, neonatal outcome, neonatal bleeding signs.

Locations

Country	Name	City	State
Netherlands	Stichting Bloedbank Sanquin	Amsterdam

Sponsors (3)

Lead Sponsor	Collaborator
Leiden University Medical Center	Landsteiner Foundation for Blood Transfusion, Sanquin Research & Blood Bank Divisions

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maternal age	Maternal age in years	Measured at 27 weeks gestational age of current pregnancy.
Other	Number of participatnts with idiopathic thrombocytopenic purpura	Idiopathic thrombocytopenic purpura defined as thrombocytopenia in presence of autoantibodies.	At inclusion
Other	Spontaneous miscarriage in obstetric history	Number of previous spontaneous miscarriage before 12 weeks' gestation	At inclusion
Other	Intrauterine fetal demise in obstetric history	Number of previous IUFD after 12 weeks' gestation	At inclusion
Other	Number of participants with hypertensive disorder	Pre-eclamspsia or pregnancy induced hypertension	3 months after delivery
Other	Prematurity	Gestational age at delivery below 37 weeks (premature) Or below 34 weeks gestation (very premature)	through study completion, until delivery, an average of 6 months
Other	Apgar Score at 5 minutes after birth	Measured as Apgar Score below 7 at 5 minutes after birth	5 minutes after birth
Other	Small for gestational age	Birth weight (in grams) below the 10th percentile for the corresponding estational age at delivery	through study completion, until delivery, an average of 6 months
Primary	Clinical relevant FNAIT	Incidence of HPA-1a mediated FNAIT. defined as severe or mild FNAIT; Severe: Intracranial haemorrhage or Internal organ haemorrhage Mild: petechiae, hematoma, purpura or mucosal bleeding.Thrombocytopenia for platelet transfusion, IVIg or clinical observation.	Within 7 days after birth.
Secondary	Neonatal thrombocytopenia	Thrombocytopenia: platelet count <150 x10^9/L Moderate thrombocytopenia: platelet count <100 x10^9/L Severe thrombocytopenia: platelet count <50 x10^9/L Extremely severe thrombocytopenia: platelet count <20 x10^9/L	Within 7 days after birth.
Secondary	Neonatal infection	CRP >10 and positive blood culture, for which antibiotics are administerd	Within 7 days after birth.
Secondary	Chromosomal abnormality	Chromosomal abnormalities as measured by DNA assessment (karyotyping, array, WGS/WES)	Within 7 days after birth.