Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape

Derek P de Winter; Allysen Kaminski; May Lee Tjoa; Dick Oepkes

doi:10.1186/s12884-022-05329-z

Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape

BMC Pregnancy Childbirth. 2023 Jan 7;23(1):12. doi: 10.1186/s12884-022-05329-z.

Authors

Derek P de Winter^{1

2}, Allysen Kaminski^{3

4}, May Lee Tjoa⁵, Dick Oepkes⁶

Affiliations

¹ Department of Pediatrics, Division of Neonatology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands.
² Department of Immunohematology Diagnostic Services, Sanquin Diagnostic Services, Amsterdam, The Netherlands.
³ OPEN Health, Bethesda, MD, USA.
⁴ Present address: The George Washington University, Washington, DC, USA.
⁵ Janssen Pharmaceuticals, Raritan, NJ, USA.
⁶ Division of Fetal Medicine, Department of Obstetrics, Leiden University Medical Center, K-06-35, PO Box 9600, Leiden, 2300 RC, The Netherlands. D.Oepkes@lumc.nl.

Abstract

Background: Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past decades. Considering improvements in HDFN care, the objectives of this systematic literature review were to assess the prenatal treatment landscape and outcomes of Rh(D)- and K-mediated HDFN in mothers and fetuses, to identify the burden of disease, to identify evidence gaps in the literature, and to provide recommendations for future research.

Methods: We performed a systematic search on MEDLINE, EMBASE and clinicaltrials.gov. Observational studies, trials, modelling studies, systematic reviews of cohort studies, and case reports and series of women and/or their fetus with HDFN caused by Rhesus (Rh)D or Kell alloimmunization. Extracted data included prevalence; treatment patterns; clinical outcomes; treatment efficacy; and mortality.

Results: We identified 2,541 articles. After excluding 2,482 articles and adding 1 article from screening systematic reviews, 60 articles were selected. Most abstracted data were from case reports and case series. Prevalence was 0.047% and 0.006% for Rh(D)- and K-mediated HDFN, respectively. Most commonly reported antenatal treatment was intrauterine transfusion (IUT; median frequency [interquartile range]: 13.0% [7.2-66.0]). Average gestational age at first IUT ranged between 25 and 27 weeks. weeks. This timing is early and carries risks, which were observed in outcomes associated with IUTs. The rate of hydrops fetalis among pregnancies with Rh(D)-mediated HDFN treated with IUT was 14.8% (range, 0-50%) and 39.2% in K-mediated HDFN. Overall mean ± SD fetal mortality rate that was found to be 19.8%±29.4% across 19 studies. Mean gestational age at birth ranged between 34 and 36 weeks.

Conclusion: These findings corroborate the rareness of HDFN and frequently needed intrauterine transfusion with inherent risks, and most births occur at a late preterm gestational age. We identified several evidence gaps providing opportunities for future studies.

Keywords: Fetal anemia; Fetal therapy; Hemolytic disease of the fetus and newborn; Intrauterine transfusion.

Publication types

Systematic Review

MeSH terms

Blood Transfusion, Intrauterine
Erythroblastosis, Fetal* / epidemiology
Erythroblastosis, Fetal* / therapy
Female
Fetus
Hemolysis
Humans
Hydrops Fetalis
Pregnancy