Characterization of the clinical course of early-onset severe hemolytic disease of the fetus and newborn.

Authors

Dick Oepkes, Kenneth J Moise, Enrico Lopriore, Eleonor Tiblad, E J T Joanne Verweij, Rory Windrim, Pranav Pandya, Robert M Silver, Stephen P Emery, John Smoleniec, Olga Ocón-Hernández, Rachel K Morris, Russell S Miller, James B Streisand, Diane D Harrison, Valerie Smith, Lisa B Schwartz, May Lee Tjoa, Leona E Ling, Shumyla Saeed-Khawaja, Yosuke Komatsu

Published in

Pregnancy (Hoboken, N.J.). Volume 2. Issue 4. Pages e70352. Epub Jul 12, 2026.

Abstract

Severe fetal anemia developing at ≤24 weeks gestational age (GA) in pregnancies complicated by early-onset severe hemolytic disease of the fetus and newborn (EOS-HDFN) is managed by intrauterine erythrocyte transfusions (IUTs). Evidence of off-label intravenous immunoglobulin (IVIG) for preventing/reducing fetal hydrops, fetal anemia, and IUT(s) remains limited to retrospective studies and case series. The prospective, global, multicenter, observational CLARITY study characterized standard-of-care management and outcomes for high-risk pregnancies complicated by EOS-HDFN and their offspring at expert referral centers.
CLARITY enrolled individuals with singleton pregnancies at ≥8 weeks GA and high risk for EOS-HDFN, defined by prior severe fetal anemia, fetal hydrops, or stillbirth at ≤24 weeks GA with indicative fetal/placental HDFN pathology, and current titers ≥32 anti-Rhesus D (RhD) or ≥4 anti-Kell with a confirmed antigen-positive fetus.
Of 15 pregnant participants, two (13%) achieved the primary endpoint of a live birth at ≥32 weeks GA without IUT, indicating the absence of clinically relevant fetal anemia and low disease burden. Fourteen (93%) pregnancies resulted in a live birth (median GA, 36^2/7 weeks; range, 31^4/7-38^0/7), including seven (50%) preterm births and 12 (86%) cesarean deliveries. Thirteen (87%) participants required IUTs (median IUTs/pregnancy, 4; range, 1-11), with median GA at first IUT of 24^0/7 weeks (range, 13^0/7-28^2/7). One (7%) fetal death occurred at 16^5/7 weeks, following early IUT (13^0/7 weeks) and serial IVIG treatment (13^1/7-14^6/7 weeks). IUT complications occurred in four (31%) pregnant participants who received IUTs. In an exploratory, post hoc analysis, eight (53%) pregnant participants received IVIG starting between 10^6⁄7 and 19^3⁄7 weeks (median administrations/pregnancy, 12.5; range, 1-20); IVIG-related complications were reported in three (38%), and two (25%) met the primary endpoint. Of 14 live-born neonates followed through 12 weeks of life, three (21%) received exchange transfusion(s), nine (64%) received simple transfusion(s) (one required both types of transfusions), while three (21%) required no transfusions (one required no IUTs during the pregnancy).
Outcomes of this prospective study of high-risk EOS-HDFN pregnant participants and their offspring are consistent with previous retrospective studies, indicating a high risk of early IUT, neonatal transfusions, and fetal/neonatal morbidity and mortality. The results underscore the unmet medical need for effective treatments for EOS-HDFN.
ClinicalTrials.gov Identifier: NCT03755128.

PMID:
42819096
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.