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Fetal and neonatal alloimmune thrombocytopenia (FNAIT) risk across racial and ethnic populations: interim data from an international, prospective natural history study

Sitras, V ; Vander Haar, E ; Bussel, JB ; Abshier-Ware, C ; Allen, GM ; Alson, Sara LU orcid ; Black, D. ; Dhanraj, D ; Gupta, A and Hart, LA , et al. (2025) 22nd World Congress in Fetal Medicine 2025
Abstract (Swedish)

Objective



Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a
rare disease that can result in severe bleeding in a fetus or newborn,
including intracranial hemorrhage. Maternal-fetal human platelet antigen
(HPA)-1a incompatibility is a prerequisite to maternal HPA-1a alloimmunization,
which may result in FNAIT. The risk of HPA-1a alloimmunization is approximately
25-times higher in HPA-1a negative (HPA-1b/b) women who are also positive for
the HLA-DRB3*01: 01 allele. To date, studies characterizing the frequency of
HPA-1a negative women (~2%) who are also positive for HLA-DRB3*01: 01 (~27%)
have predominantly been conducted in White European... (More)

Objective



Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a
rare disease that can result in severe bleeding in a fetus or newborn,
including intracranial hemorrhage. Maternal-fetal human platelet antigen
(HPA)-1a incompatibility is a prerequisite to maternal HPA-1a alloimmunization,
which may result in FNAIT. The risk of HPA-1a alloimmunization is approximately
25-times higher in HPA-1a negative (HPA-1b/b) women who are also positive for
the HLA-DRB3*01: 01 allele. To date, studies characterizing the frequency of
HPA-1a negative women (~2%) who are also positive for HLA-DRB3*01: 01 (~27%)
have predominantly been conducted in White European populations. The primary
objective of this longitudinal, prospective, non-interventional, natural
history study (IPA2002/NCT05345561) is to determine the frequency of higher
risk for HPA-1a alloimmunization and subsequent development of FNAIT among a
racially and ethnically diverse cohort of pregnant women. Herein we report
interim data.



Methods



Pregnant women aged ≥18 years with no history of FNAIT were
enrolled across 28 sites in the United States of America (19), Europe (8), and
Canada (1). Blood samples were collected at gestational weeks 10-14 and studied
using four sequentially-performed screening tests to identify women at higher
risk for HPA-1a alloimmunization: 1. HPA-1b/b genotype (HPA-1a negative); 2.
HLA-DRB3*01: 01 allele positive; 3. Anti-HPA-1a-specific antibody test negative
(demonstrating no pre-existing HPA-1a alloimmunization); and 4. carrying an
HPA-1a positive fetus (cell-free fetal DNA). The proportion of women who were
HPA-1a negative and those who were also HLA-DRB3*01: 01 positive were analyzed
by region (Europe and North America), race (American Indian or Alaska Native, Asian,
Black or African American, Native Hawaiian or Other Pacific Islander, White),
and ethnicity (Hispanic/Latino, not Hispanic/Latino). Race and ethnicity were
self-reported.



Results



In total, 14,038 pregnant women provided informed consent,
of whom 13,773 (98.1%) had completed all required screening laboratory tests as
of December 2024; 30.4% lived in Europe and 69.6% in North America. The
screened population was also predominantly White (71.3%), Black or African
American (14.9%), or Asian (11.5%); 22.4% were Hispanic/Latino. The frequency
of HPA-1a negative pregnant women was 1.7% (233/13,773); 1.9% (78/4,181) in
Europe and 1.6% (155/9,592) in North America. The frequency of HLA-DRB3*01: 01
positivity among those women who were HPA-1a negative was 19.7% (46/233); 21.8%
(17/78) in Europe and 18.7% (29/155) in North America. HPA-1a negative
frequency by race and ethnicity was: White 2.0% (197/9,826); Black or African
American 1.0% (21/2,054); Asian 0.7% (11/1,579); American Indian or Alaska
Native 2.7% (3/110); and Native Hawaiian/Other Pacific Islander 2.2% (3/132).
HPA-1a negative frequency among Hispanic/Latino women was 1.3% (39/3,088) and
among non-Hispanic/Latino women it was 1.8% (194/10,685). The frequency by race
and ethnicity of HLA-DRB3*01: 01 positive women among those HPA-1a negative
was: White 20.3% (40/197); Black or African American 19.1% (4/21); Asian 0%
(0/11); American Indian or Alaska Native 0% (0/3); Native Hawaiian/Other
Pacific Islander 33.3% (1/3). Among Hispanic/Latino women it was 23.1% (9/39);
among non Hispanic/Latino women it was 19.1% (37/194).



Conclusion



This natural history study is unique in identifying rates of
HPA-1a negative FNAIT risk in a racially and ethnically diverse international
population of pregnant women. Estimates of HPA-1a negative, and HPA-1a
negative/HLA-DRB3*01: 01 positive higher-risk groups in the White population
were consistent with previously reported estimates. While differences among
groups were observed, the non-White population and the Hispanic/Latino
population also included women who were HPA-1a negative and HPA-1a negative/HLA-DRB3*01:
01 positive. These results suggest that screening strategies to assess risk of
HPA-1a alloimmunization and FNAIT should include pregnant women of all races
and ethnicities. (Less)

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organization
publishing date
type
Contribution to conference
publication status
published
subject
keywords
Fetal and neonatal alloimmune thrombocytopenia
conference name
22nd World Congress in Fetal Medicine 2025
conference location
Prague, Czech Republic
conference dates
2025-06-29 - 2025-07-03
project
A prospective, natural history study to assess the occurrence of HPA-1a alloimmunization in women identified at higher risk for Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)
language
English
LU publication?
yes
id
552a3422-caf9-4bb0-86ea-1c8d774cc4d1
alternative location
https://www.fetalmedicine.org/abstracts/2025/var/pdf/abstracts/2025/07547.pdf
date added to LUP
2025-08-15 20:31:26
date last changed
2025-08-19 15:18:42
@misc{552a3422-caf9-4bb0-86ea-1c8d774cc4d1,
  abstract     = {{<p class="MsoNormal">Objective </p><br>
<br>
<p class="MsoNormal">Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a<br>
rare disease that can result in severe bleeding in a fetus or newborn,<br>
including intracranial hemorrhage. Maternal-fetal human platelet antigen<br>
(HPA)-1a incompatibility is a prerequisite to maternal HPA-1a alloimmunization,<br>
which may result in FNAIT. The risk of HPA-1a alloimmunization is approximately<br>
25-times higher in HPA-1a negative (HPA-1b/b) women who are also positive for<br>
the HLA-DRB3*01: 01 allele. To date, studies characterizing the frequency of<br>
HPA-1a negative women (~2%) who are also positive for HLA-DRB3*01: 01 (~27%)<br>
have predominantly been conducted in White European populations. The primary<br>
objective of this longitudinal, prospective, non-interventional, natural<br>
history study (IPA2002/NCT05345561) is to determine the frequency of higher<br>
risk for HPA-1a alloimmunization and subsequent development of FNAIT among a<br>
racially and ethnically diverse cohort of pregnant women. Herein we report<br>
interim data. </p><br>
<br>
<p class="MsoNormal">Methods </p><br>
<br>
<p class="MsoNormal">Pregnant women aged ≥18 years with no history of FNAIT were<br>
enrolled across 28 sites in the United States of America (19), Europe (8), and<br>
Canada (1). Blood samples were collected at gestational weeks 10-14 and studied<br>
using four sequentially-performed screening tests to identify women at higher<br>
risk for HPA-1a alloimmunization: 1. HPA-1b/b genotype (HPA-1a negative); 2.<br>
HLA-DRB3*01: 01 allele positive; 3. Anti-HPA-1a-specific antibody test negative<br>
(demonstrating no pre-existing HPA-1a alloimmunization); and 4. carrying an<br>
HPA-1a positive fetus (cell-free fetal DNA). The proportion of women who were<br>
HPA-1a negative and those who were also HLA-DRB3*01: 01 positive were analyzed<br>
by region (Europe and North America), race (American Indian or Alaska Native, Asian,<br>
Black or African American, Native Hawaiian or Other Pacific Islander, White),<br>
and ethnicity (Hispanic/Latino, not Hispanic/Latino). Race and ethnicity were<br>
self-reported. </p><br>
<br>
<p class="MsoNormal">Results </p><br>
<br>
<p class="MsoNormal">In total, 14,038 pregnant women provided informed consent,<br>
of whom 13,773 (98.1%) had completed all required screening laboratory tests as<br>
of December 2024; 30.4% lived in Europe and 69.6% in North America. The<br>
screened population was also predominantly White (71.3%), Black or African<br>
American (14.9%), or Asian (11.5%); 22.4% were Hispanic/Latino. The frequency<br>
of HPA-1a negative pregnant women was 1.7% (233/13,773); 1.9% (78/4,181) in<br>
Europe and 1.6% (155/9,592) in North America. The frequency of HLA-DRB3*01: 01<br>
positivity among those women who were HPA-1a negative was 19.7% (46/233); 21.8%<br>
(17/78) in Europe and 18.7% (29/155) in North America. HPA-1a negative<br>
frequency by race and ethnicity was: White 2.0% (197/9,826); Black or African<br>
American 1.0% (21/2,054); Asian 0.7% (11/1,579); American Indian or Alaska<br>
Native 2.7% (3/110); and Native Hawaiian/Other Pacific Islander 2.2% (3/132).<br>
HPA-1a negative frequency among Hispanic/Latino women was 1.3% (39/3,088) and<br>
among non-Hispanic/Latino women it was 1.8% (194/10,685). The frequency by race<br>
and ethnicity of HLA-DRB3*01: 01 positive women among those HPA-1a negative<br>
was: White 20.3% (40/197); Black or African American 19.1% (4/21); Asian 0%<br>
(0/11); American Indian or Alaska Native 0% (0/3); Native Hawaiian/Other<br>
Pacific Islander 33.3% (1/3). Among Hispanic/Latino women it was 23.1% (9/39);<br>
among non Hispanic/Latino women it was 19.1% (37/194). </p><br>
<br>
<p class="MsoNormal">Conclusion </p><br>
<br>
<p class="MsoNormal"/>This natural history study is unique in identifying rates of<br>
HPA-1a negative FNAIT risk in a racially and ethnically diverse international<br>
population of pregnant women. Estimates of HPA-1a negative, and HPA-1a<br>
negative/HLA-DRB3*01: 01 positive higher-risk groups in the White population<br>
were consistent with previously reported estimates. While differences among<br>
groups were observed, the non-White population and the Hispanic/Latino<br>
population also included women who were HPA-1a negative and HPA-1a negative/HLA-DRB3*01:<br>
01 positive. These results suggest that screening strategies to assess risk of<br>
HPA-1a alloimmunization and FNAIT should include pregnant women of all races<br>
and ethnicities.}},
  author       = {{Sitras, V and Vander Haar, E and Bussel, JB and Abshier-Ware, C and Allen, GM and Alson, Sara and Black, D. and Dhanraj, D and Gupta, A and Hart, LA and Kohari, K and Lambert, C and Litorp, H and Mendez-Figueroa, H and McFarland, EA and Nanda, S and Paidas, MJ and Perry, R and Pothof, R and Schleussner, E and Skupski, DW and Swarup, M and Tiller, H and Thorp, J and Wiberg-Itzel, E. and Williams, S and Lawrence, L and Bombara, M and Armstrong, R. and Verweij, EJT and Miller, R.}},
  keywords     = {{Fetal and neonatal alloimmune thrombocytopenia}},
  language     = {{eng}},
  month        = {{06}},
  title        = {{Fetal and neonatal alloimmune thrombocytopenia (FNAIT) risk across racial and ethnic populations: interim data from an international, prospective natural history study}},
  url          = {{https://www.fetalmedicine.org/abstracts/2025/var/pdf/abstracts/2025/07547.pdf}},
  year         = {{2025}},
}