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Non-Invasive Prenatal Fetal Blood Group Genotype and Its Application in the Management of Hemolytic Disease of Fetus and Newborn: Systematic Review and Meta-Analysis

Transfus Med Rev. 2021 Apr;35(2):85-94 doi: 10.1016/j.tmrv.2021.02.001.
PICO Summary
POPULATION:

Women whose pregnancy was at risk of haemolytic disease of foetus and new born (HDFN), (19 studies).

INTERVENTION:

Systematic review and meta-analysis on non-invasive prenatal analysis (NIPT) in conjunction with quantitative maternal alloantibody analysis.

COMPARISON:

OUTCOME:

NIPT was estimated highly sensitive/specific for foetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons were optimum to increase accuracy. NIPT permitted cost-effectiveness and was associated with low emotional stress. Knowledge of parental ethnicity was important for correct NIPT result interpretations and quantitative screening. Cut-off titre ≥8-up-to-32 was relevant for anti-D alloantibodies, while, lower titre was for anti-K. Alloimmunisation was influenced by maternal RHD status, gravida status, and history of adverse obstetrics.

Abstract

Hemolytic disease of fetus and newborn (HDFN) imposes great healthcare burden being associated with maternal alloimmunization against parental-inherited fetal red blood cell antigens causing fetal anemia or death. Noninvasive prenatal analysis (NIPT) provides safe fetal RHD genotyping for early identification of risk pregnancies and proper management guidance. We aimed to conduct systematic review and meta-analysis on NIPT's beneficial application, in conjunction with quantitative maternal alloantibody analysis, for early diagnosis of pregnancies at risk. Search for relevant articles was done in; PubMed/Medline, Scopus, and Ovid (January 2006April 2020), including only English-written articles reporting reference tests and accuracy data. Nineteen eligible studies were critically appraised. NIPT was estimated highly sensitive/specific for fetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons are optimum to increase accuracy. NIPT permits cost-effectiveness, precious resources sparing, and low emotional stress. Knowledge of parental ethnicity is important for correct NIPT result interpretations and quantitative screening. Cut-off titer ≥8-up-to-32 is relevant for anti-D alloantibodies, while, lower titer is for anti-K. Alloimmunization is influenced by maternal RHD status, gravida status, and history of adverse obstetrics. In conclusion, NIPT allows evidence-based provision of routine anti-D immunoprophylaxis and estimates potential fetal risks for guiding further interventions. Future large-scale studies investigating NIPT's non-RHD genotyping within different ethnic groups and in presence of clinically significant alloantibodies are needed.

Metadata
KEYWORDS: Fetal genotyping; Maternal blood; NIPT; RHD; Risk pregnancies
MESH HEADINGS: Blood Group Antigens; Female; Fetus; Genotype; Humans; Isoantibodies; Pregnancy; Prenatal Diagnosis; Rh-Hr Blood-Group System
Study Details
Study Design: Systematic Review
Language: eng
Credits: Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine