“… Fig. 2 Prevalence of Rh(D)-mediated HDFN (Requiring a Form of Treatment) Among All Referred Pregnancies [ 18 , 24 , 40 , 42 , 49 ]. D, Rh(D); HDFN, hemolytic disease of the fetus and newborn; Rh, Rhesus; SD, standard deviation …”
Section: Resultsmentioning
confidence: 99%
“…Antenatal treatment data were available for 24 studies (Table S 8 ) [ 24 , 25 , 29 , 30 , 33 – 37 , 42 , 43 , 48 , 51 , 52 , 56 , 58 – 63 , 65 , 71 , 80 ]. The most commonly reported antenatal treatment across these studies was IUT ( n = 9 with representative data [ 25 , 29 , 33 , 36 , 37 , 56 , 59 , 60 , 65 ]; n = 3 with nonrepresentative data [ 35 , 58 , 62 ].…”
Section: Resultsmentioning
confidence: 99%
“…Use of other treatments (therapeutic plasma exchange [TPE]; maternal plasma exchange ± high-dose IVIG; TPE + IVIG + IUT; TPE + immunoadsorption + IVIG + IUT; plasmapheresis + IUT; and plasmapheresis + IVIG + IUT) were reported in 10 studies with a total of 38 cases [ 24 , 30 , 34 , 36 , 43 , 51 , 52 , 63 , 71 , 80 ]. Plasmapheresis + IVIG + IUT was the most commonly reported treatment regimen across these 10 studies.Two of these studies did not report gestational age at start of the treatment, at first IUT (if applicable) and at birth [ 36 , 80 ].…”
Section: Resultsmentioning
confidence: 99%
“…The most commonly reported maternal/fetal clinical outcome across studies was hydrops fetalis ( n = 19 with representative data [ 23 , 28 , 31 , 32 , 41 , 42 , 47 , 49 , 51 , 53 , 59 , 64 , 66 , 67 , 69 , 75 , 76 , 79 , 80 ] (Table S 8 ); n = 10 with nonrepresentative data [ 24 , 39 , 40 , 44 , 46 , 52 , 55 , 68 , 70 , 74 ]). The rate of hydrops fetalis among pregnancies with Rh(D)-mediated HDFN treated with IUT was 14.9% (range, 0–50%) in 72/483 reported cases [ 31 , 32 , 49 , 53 , 66 , 76 , 79 ].…”
Section: Resultsmentioning
confidence: 99%
“…Assessment of IVIG efficacy in women and fetuses affected by HDFN was based on treatment response in 6 studies [ 24 , 30 , 34 , 48 , 62 , 80 ] and associated mortality in 3 studies [ 35 , 42 , 63 ] (Table S 8 ). Collectively, findings indicate that IVIG delayed or prevented IUT.…”
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.
“… Fig. 2 Prevalence of Rh(D)-mediated HDFN (Requiring a Form of Treatment) Among All Referred Pregnancies [ 18 , 24 , 40 , 42 , 49 ]. D, Rh(D); HDFN, hemolytic disease of the fetus and newborn; Rh, Rhesus; SD, standard deviation …”
Section: Resultsmentioning
confidence: 99%
“…Antenatal treatment data were available for 24 studies (Table S 8 ) [ 24 , 25 , 29 , 30 , 33 – 37 , 42 , 43 , 48 , 51 , 52 , 56 , 58 – 63 , 65 , 71 , 80 ]. The most commonly reported antenatal treatment across these studies was IUT ( n = 9 with representative data [ 25 , 29 , 33 , 36 , 37 , 56 , 59 , 60 , 65 ]; n = 3 with nonrepresentative data [ 35 , 58 , 62 ].…”
Section: Resultsmentioning
confidence: 99%
“…Use of other treatments (therapeutic plasma exchange [TPE]; maternal plasma exchange ± high-dose IVIG; TPE + IVIG + IUT; TPE + immunoadsorption + IVIG + IUT; plasmapheresis + IUT; and plasmapheresis + IVIG + IUT) were reported in 10 studies with a total of 38 cases [ 24 , 30 , 34 , 36 , 43 , 51 , 52 , 63 , 71 , 80 ]. Plasmapheresis + IVIG + IUT was the most commonly reported treatment regimen across these 10 studies.Two of these studies did not report gestational age at start of the treatment, at first IUT (if applicable) and at birth [ 36 , 80 ].…”
Section: Resultsmentioning
confidence: 99%
“…The most commonly reported maternal/fetal clinical outcome across studies was hydrops fetalis ( n = 19 with representative data [ 23 , 28 , 31 , 32 , 41 , 42 , 47 , 49 , 51 , 53 , 59 , 64 , 66 , 67 , 69 , 75 , 76 , 79 , 80 ] (Table S 8 ); n = 10 with nonrepresentative data [ 24 , 39 , 40 , 44 , 46 , 52 , 55 , 68 , 70 , 74 ]). The rate of hydrops fetalis among pregnancies with Rh(D)-mediated HDFN treated with IUT was 14.9% (range, 0–50%) in 72/483 reported cases [ 31 , 32 , 49 , 53 , 66 , 76 , 79 ].…”
Section: Resultsmentioning
confidence: 99%
“…Assessment of IVIG efficacy in women and fetuses affected by HDFN was based on treatment response in 6 studies [ 24 , 30 , 34 , 48 , 62 , 80 ] and associated mortality in 3 studies [ 35 , 42 , 63 ] (Table S 8 ). Collectively, findings indicate that IVIG delayed or prevented IUT.…”
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.
Background
Advances in postnatal care for hemolytic disease of the fetus and newborn (HDFN) have occurred over the past decades, but little is known regarding the frequency of postnatal treatment and the clinical outcomes of affected neonates. Most studies reporting on HDFN originate from high-income countries or relatively large centers, but important differences between centers and countries may exist due to differences in prevalence and available treatment options. We therefore aimed to evaluate the postnatal treatment landscape and clinical outcomes in neonates with Rhesus factor D (Rh(D))- and/or K-mediated HDFN and to provide recommendations for future research.
Methods
We conducted a rapid literature review of case reports and series, observational retrospective and prospective cohort studies, and trials describing pregnancies or children affected by Rh(D)- or K-mediated HDFN published between 2005 and 2021. Information relevant to the treatment of HDFN and clinical outcomes was extracted. Medline, ClinicalTrials.gov and EMBASE were searched for relevant studies by two independent reviewers through title/abstract and full-text screening. Two independent reviewers extracted data and assessed methodological quality of included studies.
Results
Forty-three studies reporting postnatal data were included. The median frequency of exchange transfusions was 6.0% [interquartile range (IQR): 0.0–20.0] in K-mediated HDFN and 26.5% [IQR: 18.0–42.9] in Rh(D)-mediated HDFN. The median use of simple red blood cell transfusions in K-mediated HDFN was 50.0% [IQR: 25.0–56.0] and 60.0% [IQR: 20.0–72.0] in Rh(D)-mediated HDFN. Large differences in transfusion rates were found between centers. Neonatal mortality amongst cases treated with intrauterine transfusion(s) was 1.2% [IQR: 0–4.4]. Guidelines and thresholds for exchange transfusions and simple RBC transfusions were reported in 50% of studies.
Conclusion
Most included studies were from middle- to high-income countries. No studies with a higher level of evidence from centers in low-income countries were available. We noted a shortage and inconsistency in the reporting of relevant data and provide recommendations for future reports. Although large variations between studies was found and information was often missing, analysis showed that the postnatal burden of HDFN, including need for neonatal interventions, remains high.
Systematic review registration
PROSPERO 2021 CRD42021234940. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021234940.
Maternal erythrocyte alloimmunization is one of the most important causes of fetal anemia. The standard treatment for anemic fetuses is intrauterine blood transfusion (IUT). However, IUT may have adverse effects, particularly before 20 weeks of gestation. In this report, two women who had previously had severely affected alloimmunized pregnancy developed high titers of anti-D antibodies before 20 weeks of gestation. Ultrasound Doppler showed severe fetal anemia, and intrauterine transfusion was expected to be unavoidable. To prolong pregnancy to a gestation in which intravascular IUT was possible, we used repeated double filtration plasmapheresis (DFPP) as a rescue therapy. The titers of IgG-D, IgG-A, and IgG-B decreased after DFPP treatment. One woman successfully prolonged pregnancy until 20 weeks of gestation. Subsequently, she underwent four cycles of IUTs and delivered at 30 weeks of gestation by emergency cesarean section due to fetal bradycardia during the fifth intrauterine transfusion. The other woman successfully delayed intrauterine transfusion until 26 weeks of gestation. The favorable results of the two patients indicate that DFPP may be an effective and safe treatment modality for RhD immunity in pregnant women. Moreover, DFPP is potentially helpful for reducing the occurrence of ABO hemolytic disease in neonates due to the clearance of IgG-A and IgG-B antibodies (e.g., O pregnant women harbored A/B/AB neonates). However, more clinical trials are needed to verify the results.
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