Ignite Creation Date:
2024-05-06 @ 3:06 PM
Last Modification Date:
2024-10-26 @ 1:43 PM
Study NCT ID:
NCT04529382
Status:
UNKNOWN
Last Update Posted:
2020-08-27
First Post:
2020-07-15
Brief Title:
Neurodevelopmental Outcome After Fetal Neonatal AlloImmune Thrombocytopenia
Sponsor:
Leiden University Medical Center
Organization:
Leiden University Medical Center
Study Overview
Official Title:
Neurodevelopmental Outcome After Fetal Neonatal AlloImmune Thrombocytopenia
Status:
UNKNOWN
Status Verified Date:
2020-08
Last Known Status:
ENROLLING_BY_INVITATION
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NOFNAIT
Brief Summary:
Fetal and neonatal alloimmune thrombocytopenia FNAIT is a disease caused by allo-immunisation during pregnancy If left untreated FNAIT can lead to severe fetal intracranial haemorrhage This complication can be prevented by weekly administration of intravenous immunoglobulin IVIg to the mother during pregnancy Knowledge on long-term development of FNAIT survivors with or without IVIg treatment is very limited but an important subject in the counselling of parents of newly diagnosed cases To evaluate the long-term neurodevelopmental outcome in two groups of children with FNAIT will be asked to participate in our study in an outpatient clinic setting
Detailed Description:
INTRODUCTION AND RATIONALE Fetal and neonatal alloimmune thrombocytopenia FNAIT is the most common cause of thrombocytopenia in otherwise healthy term-born neonates FNAIT is a rare disease with an incidence estimated around 1 per 1000 live newborns During pregnancy alloimmunization can occur due to incompatibility of the Human Platelet Antigens HPA on the maternal and fetal platelets Alloimmunization and maternal production of antibodies directed against the HPA-positive fetal platelets leads to thrombocytopenia and an increased risk of intracranial hemorrhages ICH in the fetus Clinical presentation can vary from skin bleedings to severe ICH leading to lifelong neurologic sequelae or intrauterine death
In the past FNAIT was managed with invasive and high-risk interventions including intrauterine platelet transfusion IUPT Since the end of the 20th century invasive intrauterine transfusions IUT were replaced by a new non-invasive therapy maternal administration of intravenous immunoglobulin IVIg This novel therapy resulted in a significant lower risk of intrauterine fetal death and ICH Intervention with immune modulation in the semi -allogenic environment of the fetus by administration of immunoglobulins Ig is successful especially in preventing ICH However antenatal treatment with IVIg has been implemented as standard of care without strong methodological follow-up research of children from mothers treated with IVIg To date only two follow-up studies have been published in children with anticipated FNAIT cases The first study of a FNAIT cohort treated with IVIg was done by Ward et al in 2006 They concluded that development of children treated for FNAIT was better compared to their non-treated siblings Their conclusions were based on non-validated questionnaires taken by telephone assessing the behavioral outcome of the children and were limited by a 40 lost-to-follow-up rate A second follow-up study including 39 children was published by a research group from our center in 2004 This research stated that the outcome in children with FNAIT and exposed to maternal IVIg treatment was similar to the normal population However this study included a heterogenic group of children with different treatment strategies including IUT hampering definitive conclusions and substantiating the need for more research
No long-term standardized follow-up studies were performed on FNAIT cases without antenatal treatment andor ICH The natural course of the disease and long-term effects of thrombocytopenia on the developing fetus and newborn are unknown FNAIT is defined as a disease caused by alloantibodies resulting in thrombocytopenia and a risk of bleeding in the neonate In the last years evidence is increasing that the maternal alloantibodies can also bind to the fetal endothelium and may impair angiogenesis in the developing fetuses It is not known at which moment in pregnancy the developing brain is most vulnerable for damage induced by these kind of alloantibodies The timing in fetal life FNAIT associated ICH ranges from 23 to 42 weeks but small bleeding may not be diagnosed It may also be that these type of alloantibodies not lead to ICH but to other type of cerebral damage These lesions can remain subclinical directly after birth but lead to developmental delay on the long term This knowledge can be of great interest when counseling parents with a risk of FNAIT or in writing guidelines
For 3 decades a nationwide screening on FNAIT to detect pregnancies with alloantibodies in time and start treatment to prevent bleedings is being discussed If alloantibodies lead to cerebral damage on the long term also in patients without large ICH this might have large implications in the debate on the introduction of a national screening programme Therefore the investigators want to underline that more knowledge about the long-term development of FNAIT survivors is required
The Leiden University Medical Center LUMC a national fetal therapy center in The Netherlands has a close and long-lasting collaboration with Sanquin This collaboration offers a unique opportunity to evaluate a large and complete cohort of children with FNAIT LUMC and Sanquin are both nationwide referral centers for FNAIT and committed to improve timely detection of high-risk cases who need intra-uterine therapy This research group from the national expertise centers are designated to assess long-term outcome in children with FNAIT and describe the natural history of children affected by FNAIT and the long term effects of a given therapy
OBJECTIVE The primary objective is to determine the cognitive test score of children diagnosed with FNAIT without and with antenatal treatment
STUDY DESIGN The investigators will perform an observational cohort study The long-term neurodevelopmental outcome of children affected by FNAIT will be evaluated All children born between 2002 and 2017 and diagnosed with FNAIT are eligible for follow-up assessment and will be invited for an assessment at our outpatient clinic The FNAIT survivors will be collected in two cohorts cohort 1 will consist of FNAIT survivors without antenatal treatment cohort 2 will consist of FNAIT survivors that were antenatally anticipated and therefore IVIg treatment to the mother was given
Enrollment in this study will take place via the LUMC and Stichting Sanquin Bloedvoorziening The LUMC is national referral center for intrauterine therapy and Sanquin is national reference laboratory to diagnose FNAIT Retrospectively FNAIT cases will be collected and asked for permission directly or via referring specialist
After informed consent child cognitive functioning will be assessed with a formal psychological test of cognitive functioning According to age the parents will complete a standardized behavioral and HRQoL questionnaire Academic performance will be assessed by collecting the most recent CITO test scores from the Dutch Pupil monitoring system developed by the National Institute for Educational Measurement Assessment of the prevalence of possible late effects of IVIg on the immune system will be assessed by questionnaires about the prevalence of allergies astma eczema and course of infections by questionnaires Parents and children when 12 years old or older are asked for consent to request the medical letters from the maternity or neonatology ward to obtain perinatal and neonatal data
No laboratory tests will be performed in this study however data of the laboratory tests that were performed at timepoint of diagnosing FNAIT will be involved in this study
After assessment a report will be made from the observations and test results this report will be sent to the parents
In the past FNAIT was managed with invasive and high-risk interventions including intrauterine platelet transfusion IUPT Since the end of the 20th century invasive intrauterine transfusions IUT were replaced by a new non-invasive therapy maternal administration of intravenous immunoglobulin IVIg This novel therapy resulted in a significant lower risk of intrauterine fetal death and ICH Intervention with immune modulation in the semi -allogenic environment of the fetus by administration of immunoglobulins Ig is successful especially in preventing ICH However antenatal treatment with IVIg has been implemented as standard of care without strong methodological follow-up research of children from mothers treated with IVIg To date only two follow-up studies have been published in children with anticipated FNAIT cases The first study of a FNAIT cohort treated with IVIg was done by Ward et al in 2006 They concluded that development of children treated for FNAIT was better compared to their non-treated siblings Their conclusions were based on non-validated questionnaires taken by telephone assessing the behavioral outcome of the children and were limited by a 40 lost-to-follow-up rate A second follow-up study including 39 children was published by a research group from our center in 2004 This research stated that the outcome in children with FNAIT and exposed to maternal IVIg treatment was similar to the normal population However this study included a heterogenic group of children with different treatment strategies including IUT hampering definitive conclusions and substantiating the need for more research
No long-term standardized follow-up studies were performed on FNAIT cases without antenatal treatment andor ICH The natural course of the disease and long-term effects of thrombocytopenia on the developing fetus and newborn are unknown FNAIT is defined as a disease caused by alloantibodies resulting in thrombocytopenia and a risk of bleeding in the neonate In the last years evidence is increasing that the maternal alloantibodies can also bind to the fetal endothelium and may impair angiogenesis in the developing fetuses It is not known at which moment in pregnancy the developing brain is most vulnerable for damage induced by these kind of alloantibodies The timing in fetal life FNAIT associated ICH ranges from 23 to 42 weeks but small bleeding may not be diagnosed It may also be that these type of alloantibodies not lead to ICH but to other type of cerebral damage These lesions can remain subclinical directly after birth but lead to developmental delay on the long term This knowledge can be of great interest when counseling parents with a risk of FNAIT or in writing guidelines
For 3 decades a nationwide screening on FNAIT to detect pregnancies with alloantibodies in time and start treatment to prevent bleedings is being discussed If alloantibodies lead to cerebral damage on the long term also in patients without large ICH this might have large implications in the debate on the introduction of a national screening programme Therefore the investigators want to underline that more knowledge about the long-term development of FNAIT survivors is required
The Leiden University Medical Center LUMC a national fetal therapy center in The Netherlands has a close and long-lasting collaboration with Sanquin This collaboration offers a unique opportunity to evaluate a large and complete cohort of children with FNAIT LUMC and Sanquin are both nationwide referral centers for FNAIT and committed to improve timely detection of high-risk cases who need intra-uterine therapy This research group from the national expertise centers are designated to assess long-term outcome in children with FNAIT and describe the natural history of children affected by FNAIT and the long term effects of a given therapy
OBJECTIVE The primary objective is to determine the cognitive test score of children diagnosed with FNAIT without and with antenatal treatment
STUDY DESIGN The investigators will perform an observational cohort study The long-term neurodevelopmental outcome of children affected by FNAIT will be evaluated All children born between 2002 and 2017 and diagnosed with FNAIT are eligible for follow-up assessment and will be invited for an assessment at our outpatient clinic The FNAIT survivors will be collected in two cohorts cohort 1 will consist of FNAIT survivors without antenatal treatment cohort 2 will consist of FNAIT survivors that were antenatally anticipated and therefore IVIg treatment to the mother was given
Enrollment in this study will take place via the LUMC and Stichting Sanquin Bloedvoorziening The LUMC is national referral center for intrauterine therapy and Sanquin is national reference laboratory to diagnose FNAIT Retrospectively FNAIT cases will be collected and asked for permission directly or via referring specialist
After informed consent child cognitive functioning will be assessed with a formal psychological test of cognitive functioning According to age the parents will complete a standardized behavioral and HRQoL questionnaire Academic performance will be assessed by collecting the most recent CITO test scores from the Dutch Pupil monitoring system developed by the National Institute for Educational Measurement Assessment of the prevalence of possible late effects of IVIg on the immune system will be assessed by questionnaires about the prevalence of allergies astma eczema and course of infections by questionnaires Parents and children when 12 years old or older are asked for consent to request the medical letters from the maternity or neonatology ward to obtain perinatal and neonatal data
No laboratory tests will be performed in this study however data of the laboratory tests that were performed at timepoint of diagnosing FNAIT will be involved in this study
After assessment a report will be made from the observations and test results this report will be sent to the parents
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None