Immunoglobulins in Neonates with Rhesus Hemolytic Disease of the Fetus and Newborn: Long-Term Outcome in a Randomized Trial

Klink, Jeanine M.M. van; Veen, Suzanne J van; Smits-Wintjens, Vivianne E.H.J.; Lindenburg, Irene T.M.; Rijken, Monique; Oepkes, Dick; Lopriore, Enrico

doi:10.1159/000434718

Cited by 11 publications

(5 citation statements)

References 7 publications

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“…In a follow-up study of a randomized controlled trial conducted at our center, we found that the neurodevelopmental outcome in children treated with intravenous immunoglobulins for HDFN was not different from children treated with placebo [32,99]. At a median age of 4 years, NDI was detected in 3% in both the IVIG (1/34) and placebo (1/32) group.…”

Section: Long-term Outcome After Immunoglobulinsmentioning

confidence: 82%

Neonatal management and outcome in alloimmune hemolytic disease

Ree

Smits-Wintjens

Bom

et al. 2017

Expert Review of Hematology

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103

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Introduction: Hemolytic disease of the fetus and newborn (HDFN) occurs when fetal and neonatal erythroid cells are destroyed by maternal erythrocyte alloantibodies, it leads to anemia and hydrops in the fetus, and hyperbilirubinemia and kernicterus in the newborn. Postnatal care consists of intensive phototherapy and exchange transfusions to treat severe hyperbilirubinemia and top-up transfusions to treat early and late anemia. Other postnatal complications have been reported such as thrombocytopenia, iron overload and cholestasis requiring specific management. Areas covered: This review focusses on the current neonatal management and outcome of hemolytic disease and discusses postnatal treatment options as well as literature on long-term neurodevelopmental outcome. Expert commentary: Despite major advances in neonatal management, multiple issues have to be addressed to optimize postnatal management and completely eradicate kernicterus. Except for strict adherence to guidelines, improvement could be achieved by clarifying the epidemiology and pathophysiology of HDFN. Several pharmacotherapeutic agents should be further researched as alternative treatment options in hyperbilirubinemia, including immunoglobulins, albumin, phenobarbital, metalloporphyrins, zinc, clofibrate and prebiotics. Larger trials are warranted to evaluate EPO, folate and vitamin E in neonates. Long-term follow-up studies are needed in HDFN, especially on thrombocytopenia, iron overload and cholestasis.ARTICLE HISTORY

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Section: Long-term Outcome After Immunoglobulinsmentioning

confidence: 82%

Neonatal management and outcome in alloimmune hemolytic disease

Ree

Smits-Wintjens

Bom

et al. 2017

Expert Review of Hematology

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103

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“…Lastly, developmental outcomes of children treated with IUTs that were included in a randomized controlled trial to evaluate the effectiveness of IVIG to prevent exchange transfusions were assessed. No difference in the rate of neurodevelopmental adverse outcomes was found between the placebo and interventional group [102].…”

Section: Neurodevelopmental Outcomesmentioning

confidence: 79%

History and current standard of postnatal management in hemolytic disease of the fetus and newborn

et al. 2022

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Since the discovery of the Rh blood group system in 1940, a greater understanding of hemolytic disease of the fetus and newborn (HDFN) was gained. In the years thereafter, researchers and clinicians came to the current understanding that fetal and neonatal red blood cells (RBC) are hemolyzed by maternal alloantibodies directed against RBC antigens potentially leading to severe disease. Preventative measures, such as Rhesus(D) immunoprophylaxis (RhIG), have greatly decreased the prevalence of Rh(D)-mediated HDFN, although a gap between high-income countries and middle-to low-income countries was created largely due to a lack in availability and high costs of RhIG. Other important developments in the past decades have improved the identification, monitoring, and care of pregnancies, fetuses, and neonates with HDFN. Prenatally, fetal anemia may occur and intrauterine transfusions may be needed. Postnatally, pediatricians should be aware of the (antenatally determined) risk of hemolysis in RBC alloimmunization and should provide treatment for hyperbilirubinemia in the early phase and monitor for anemia in the late phase of the disease. Through this review, we aim to provide an overview of important historic events and to provide hands-on guidelines for the delivery and postnatal management of neonates with HDFN. Secondarily, we aim to describe recent scientific findings and evidence gaps.Conclusion: Multiple developments have improved the identification, monitoring, and care of pregnancies and neonates with HDFN throughout the centuries. Pediatricians should be aware of the (antenatally determined) risk of hemolysis in RBC alloimmunization and should provide treatment for hyperbilirubinemia in the early phase and monitor for late anemia in the late phase of the disease. Future studies should be set in an international setting and ultimately aim to eradicate HDFN on a global scale. What is Known:• Developments have led to a greater understanding of the pathophysiology, an improved serological identification and monitoring of at-risk cases and the current pre-and postnatal treatment. What is New:• This review provides the pediatrician with hands-on guidelines for the delivery and postnatal management of neonates with HDFN.• Future studies should be set in an international setting with the ultimate aim of eradicating HDFN.

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“…We were unable to stratify the data per alloimmunization type with the data provided in these articles. One of these studies represented the only prospective study with long-term outcomes [ 89 ], thereby also indicating the lack of data on long-term outcomes and the need for further research on the topic.…”

Section: Discussionmentioning

confidence: 99%

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

Winter

Kaminski

Tjoa

et al. 2023

BMC Pregnancy Childbirth

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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.

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Immunoglobulins in Neonates with Rhesus Hemolytic Disease of the Fetus and Newborn: Long-Term Outcome in a Randomized Trial

Cited by 11 publications

References 7 publications

Neonatal management and outcome in alloimmune hemolytic disease

Neonatal management and outcome in alloimmune hemolytic disease

History and current standard of postnatal management in hemolytic disease of the fetus and newborn

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

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