Prevalence of Ethnic Neutropenia and Duffy Null Phenotype in Neonates

The Prevalence of Ethnic Neutropenia in Neonates

This is a prospective observational study designed to assess the prevalence of the Duffy null phenotype (associated with ethnic neutropenia) in neonates born at Kaplan Medical Center. Blood samples will be collected from umbilical cords (non-invasively) to evaluate Duffy antigen expression. Data on ethnicity, perinatal factors, and routine blood counts at 9-12 months (when available) will also be collected to correlate phenotype with absolute neutrophil count (ANC).

Study Overview

• Status: Recruiting
• Conditions: Neutropenia (Low White Blood Cell Count)
• Intervention / Treatment: Diagnostic test: Cord blood

Detailed Description

This is a prospective, observational cohort study designed to evaluate the prevalence of the Duffy null phenotype (Fya-/Fyb-) and its association with ethnic neutropenia in neonates born at Kaplan Medical Center in Israel. The Duffy null phenotype has been linked to lower peripheral neutrophil counts without increased infection risk in certain ethnic groups, a condition commonly referred to as benign ethnic neutropenia.

Cord blood samples will be collected from approximately 1,000 neonates during routine G6PD testing. An additional 3 mL will be obtained non-invasively from the umbilical cord after labour to determine the expression of Duffy antigens using serologic gel testing. Parental consent will be obtained, and information regarding ethnicity and family history of neutropenia will be collected.

Participants identified with the Duffy null phenotype will be followed through electronic health records to assess their neutrophil counts during routine blood screening at 9-12 months of age. The study will analyze associations between Duffy phenotype, neutropenia prevalence, and parental ethnic origin.

Findings may support improved diagnostic clarity around neonatal neutropenia and help reduce unnecessary interventions in otherwise healthy infants with genetically determined low neutrophil counts.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Tal Ben Ami, M.D; Phone Number: +972-50-7414922; Email: tal.ben.ami11@gmail.com
• Study Contact Backup: Name: Yael Zeitak, PhD; Phone Number: +972-52-627-4987; Email: yaelze4@clalit.org.il

Study Locations

• Israel
  • Rehovot, Israel, 7661041
    • Recruiting
    • Kaplan Medical Center
    • Contact: Yael Zeitak, PhD; Phone Number: +972-52-627-4987; Email: yaelze4@clalit.org.il
    • Contact: Tal Ben Ami, MD; Phone Number: +972-50-7414922; Email: tal.ben.ami11@gmail.com
    • Contact: Tal Ben Ami, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Neonates born at Kaplan Medical Center

Description

Inclusion Criteria:

• Neonates born at Kaplan Medical Center between 1.9.2024 and 31.12.2025
• Parental informed consent obtained
• Umbilical cord blood available for routine testing

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Neonatal birth cohort; Neonates born at Kaplan Medical Center whose cord blood is tested for Duffy antigen status and complete blood count. Follow-up neutrophil data is collected at 9-12 months if available.	Diagnostic test: Cord blood; Cord blood samples will be collected during routine G6PD testing. An additional 3 mL will be obtained non-invasively from the umbilical cord to determine the expression of Duffy antigens using serologic gel testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Duffy null phenotype in neonates	Percentage of neonates born with the Duffy null phenotype (Fya-/Fyb-) as determined by serologic gel-based testing.	At birth (umbilical cord sample)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of neutropenia in infants with Duffy null phenotype	Percentage of Duffy null infants with ANC <1000/µL based on routine CBC performed at at 9-12 months	9-12 months
Association between parental ethnicity and Duffy null phenotype	Distribution of Duffy null phenotype stratified by self-reported parental origin.	At birth

Collaborators and Investigators

• Sponsor: Kaplan Medical Center
• Investigators: Principal Investigator: Tal Ben Ami, MD, Kaplan Medical Center

Publications and helpful links

General Publications

• Gay K, Dulay K, Ravindranath Y, Savasan S. Duffy-Null Phenotype-Associated Neutropenia is the Most Common Etiology for Leukopenia/Neutropenia Referrals to a Tertiary Children's Hospital. J Pediatr. 2023 Nov;262:113608. doi: 10.1016/j.jpeds.2023.113608. Epub 2023 Jul 6.
• Rappoport N, Simon AJ, Lev A, Yacobi M, Kaplinsky C, Weingarten M, Somech R, Amariglio N, Rechavi G. Correlation between 'ACKR1/DARC null' polymorphism and benign neutropenia in Yemenite Jews. Br J Haematol. 2015 Sep;170(6):892-5. doi: 10.1111/bjh.13345. Epub 2015 Mar 26. No abstract available.
• Atallah-Yunes SA, Ready A, Newburger PE. Benign ethnic neutropenia. Blood Rev. 2019 Sep;37:100586. doi: 10.1016/j.blre.2019.06.003. Epub 2019 Jun 21.

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 27, 2025
• First Submitted That Met QC Criteria: March 27, 2025
• First Posted (Actual): April 3, 2025

Study Record Updates

• Last Update Posted (Actual): April 6, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Neonates; Neutropenia; Duffy null associated count
• Additional Relevant MeSH Terms: Cytopenia; Leukocyte Disorders; Hematologic Diseases; Agranulocytosis; Neutropenia; Leukopenia
• Other Study ID Numbers: KMC-24-0090 (Other Identifier: Kaplan Medical Center Ethical Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study involves neonates and is based on anonymized samples; individual-level data will not be shared due to privacy and ethical considerations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No