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Objective: Hemolytic disease of the fetus and newborn is characterized by fetal anemia, secondary to maternal alloantibody-mediated fetal erythrocyte destruction. Despite our reliance on intrauterine blood transfusion (IUT) to maintain severely affected pregnancies, it remains difficult to predict the fetal response to an infusion of donor blood. Our objective was to determine the daily rate of decline in fetal hemoglobin following one, two, and three transfusions. We also evaluated the relationship between the fetal hemoglobin level and the corresponding doppler measurement of the fetal middle cerebral artery peak systolic velocity (MCA-PSV).Study Design: A prospective observational study of all singleton pregnancies treated with intrauterine transfusion for fetal anemia secondary to maternal alloimmunization at the National Maternity Hospital, a tertiary referral centre, was conducted over a 10-year period (2011-2020). Demographic and clinical data was obtained from the electronic patient records. Ethical approval was granted by the Ethics and Research Committee of the National Maternity Hospital.Results: A total of 90 intrauterine blood transfusions were performed in 41 fetuses affected by maternal alloimmunization, of which 70% (n = 29), 34% (n = 14) and 15% (n = 6) required a 2nd, 3rd, and 4th transfusion, respectively. The mean rate of decline in fetal hemoglobin following the first transfusion was 0.4 g/dl/day (range, 0.12-0.64 g/dl/day). The mean rate of decline was lower after repeat transfusions at 0.27 g/dl/day (range, 0.16-0.45 g/dl/day). The sensitivity of MCA-PSV threshold of 1.5 Multiples of the Median (MoM) to detect moderate-severe anaemia declined with rank of IUT, from 82% after one previous transfusion, to 75% after two or more previous transfusions. No fetal mortality was seen in our series.Conclusion: Knowledge of the expected rate of decline in fetal hemoglobin following an IUT aids in the determination of appropriate timing of subsequent transfusions in a fetus affected by red cell alloimmunization. We observed a reducing rate of daily decline in hemoglobin in fetuses requiring successive transfusions. Our findings suggest a reduced accuracy of the MCA-PSV threshold of 1.5 MoM in determining the optimal timing of 2nd, 3rd, and 4th transfusions. [ABSTRACT FROM AUTHOR]

The introduction of anti‐Rh(D) immunoglobulin more than 50 years ago has resulted in only a 50% decrease in Rhesus disease globally owing to a low uptake of this prophylactic approach. The International Federation of Gynecology and Obstetrics, International Confederation of Midwives, and Worldwide Initiative for Rhesus Disease Eradication have reviewed current evidence regarding the utility of anti‐Rh(D) immunoglobulin. Taking into account the effectiveness anti‐Rh(D), the new guidelines propose adjusting the dose for different indications and prioritizing its administration by indication. These FIGO/ICM guidelines review the evidence regarding the usefulness of anti‐Rh(D) immunoglobulin, prioritizing its administration by indication. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a policy of offering cffDNA testing to all RhD-negative women at about 16 weeks' gestation to avoid anti-D administration when the fetus is RhD-negative could be implemented successfully in the NHS without additional funding.Design: Prospectively planned observational service implementation pilot and notes audit.Setting: Three maternity services in the South West of England.Population: All RhD-negative women in a 6-month period.Methods: Prospective, intervention, cross-sectional observational study, using pre-intervention data as controls.Main Outcome Measures: Proportion of suitable women who offered and accepted the test. Accuracy of the cffDNA result as assessed by cord blood group result. Fall in anti-D doses administered.Results: 529 samples were received; three were unsuitable. The results were reported as RhD-positive (n = 278), RhD-negative (n = 185) or inconclusive, treat as positive (n = 63). Cord blood results were available in 502 (95%) and the only incorrect result was one case of a false positive (cffDNA reported as positive, cord blood negative - and so given anti-D unnecessarily). The notes audit showed that women who declined this service were correctly managed and that anti-D was not given when the fetus was predicted to be RhD-negative. The total use of anti-D doses fell by about 29% which equated to about 35% of RhD-negative women not receiving anti-D in their pregnancy unnecessarily.Conclusions: We recommend this service is extended to all UK NHS services. [ABSTRACT FROM AUTHOR]

We describe two infants with severe hemolytic disease of the fetus and newborn (HDFN) with hepatosplenomegaly treated with intravenous immunoglobulin. Packed red blood cells (PRBC) were transfused resulting in an acute disproportionate increase in hemoglobin with clinical consequences in one case. These cases appear to highlight previously unreported sequelae. We discuss a hypothetical mechanism and suggest that the effect warrants further research as a possible way to decrease the need for and risks of PRBC transfusion in HDFN. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the optimal interval between middle cerebral artery (MCA) Doppler measurements when monitoring pregnancies complicated by red cell alloimmunization. Methods: Thirty-nine fetal blood samplings (FBS) performed on 24 pregnant women with red blood cell alloimmunization followed up using both MCA peak systolic velocity and time-averaged mean velocity measurements on weekly basis. Results: In total, 65.5 and 37.5% of women with moderate or severe fetal anemia had abnormal MCA Doppler values 1 and 2 weeks, respectively, before FBS was performed. Conclusions: A weekly assessment of women at risk for fetal anemia is optimal in most of the cases even though 35.5% of cases of moderate or severe fetal anemia are expected to have normal Doppler measurements the week before the decision of doing an FBS is made. [ABSTRACT FROM AUTHOR]

Objectives To compare different normal reference ranges of fetal blood flow velocity in the middle cerebral artery for predicting fetal anemia. Methods Eight reference ranges of either middle cerebral artery peak or time-averaged mean velocities were compared using the area under the receiver-operating characteristics (ROC) curve for 113 fetal blood samples from 60 women at risk of fetal red blood cell alloinimunization. Results The areas under the ROC curves of the different ranges were not significantly different but there were marked differences in sensitivity(range, 7.14–91.78%) and specificity (range, 31.25–96.88%) with the currently used cut-offs. Except for Man's range, the best theoretical cut-offs, defined as those having the best sensitivity with the best specificity, differed from those in current use, especially when using time-averaged mean velocity. Conclusions Any of the previously reported reference ranges perform well in the non-invasive prediction of fetal anemia. However, with the exception of Man's curve, the currently employed cut-offs for predicting fetal anemia should be changed, some of them markedly, in order to provide reliable support for clinical decisions. [ABSTRACT FROM AUTHOR]

Objective To compare the accuracy of Doppler velocimetry (middle cerebral artery peak systolic velocity, MCA- PSV) and amniocentesis (amniotic fluid delta optical density 450 (OD450)) for the detection of fetal anemia against the gold standard of fetal blood sampling (FBS). Methods Thirty-eight pregnancies were identified to be at risk of fetal anemia from immune causes between January 2000 and May 2002. In a cross-sectional diagnostic accuracy study, MCA-PSV and amniotic fluid delta OD450 values were plotted on reference charts and compared to an FBS obtained within the subsequent 7 days. Receiver-operating characteristics (ROC) curves were used and the area under the curve (A UC) calculated to compare the overall accuracy of the two tests. Sensitivity, specificity and likelihood ratios for positive (LR+) and negative (LR-) test results were generated for specific thresholds of MCA-PSV and delta 0D450. Results For MCA-PSV (n = 38), the AUG was 0.71 (95% Cl 0.57–0.85) and for amniotic fluid delta OD450 (n = 22) it was 0.68 (95% Cl 0.49–0.87) compared with FBS within 7 days. Sensitivity, specificity and LR+, LR- for MGA-PSV were 64%, 81%, 3.4 and 0.5, respectively, and 53%, 71%, 1.9 and 0.7 for amniotic fluid OD450, respectively. Conclusion MCA-PSV and OD450 have similar test accuracy in detecting fetal anemia. MGA-PSV is non- invasive and therefore presents no risk of miscarriage or preterm labor and thus is a preferable method of screening for fetal anemia. [ABSTRACT FROM AUTHOR]

Placental abruption is an unpredictable severe complication in pregnancy. In order to investigate the possibility that the activation of the fetal nonadaptive immune system may be involved in the pathogenesis of this disease, IL-6 release from cord blood monocytes was examined by intracellular cytokine staining and flow cytometric analysis. Our results demonstrate that preterm placental abruption (n = 15) in contrast to uncontrollable preterm labor (n = 33) is associated with significantly (P < 0.001) increased release of IL-6 from the fetal monocytes. The same holds true for rhesus disease (n = 9, P < 0.001) that is characterized by a maternal production of antibodies against the rhesus-D antigen expressed by the fetal erythrocytes. This suggests that during rhesus disease, IL-6 release of monocytes is induced by antibody-mediated cross-linking of these cells to the erythrocytes in the fetal circulation. Hence, this assumption favors the idea that also in case of placental abruption, an increased maternal antibody production against paternal antigens leads to an elevated IL-6 release by the fetal monocytes. To elucidate this potential mechanism, the presence of anti-HLA-antibodies was assessed in the maternal circulation of patients with placental abruption (n = 17) and patients with uncontrollable preterm labor (n = 29). The percentage of women producing anti-paternal HLA-antibodies was significantly (P < 0.01) increased in the group of women with preterm placental abruption (47%) in comparison to women with uncontrollable preterm labor (14%). Therefore, our results suggest that an increased humoral immune response of the mother against the fetus may be decisively involved in the pathogenesis of placental abruption. [Copyright &y& Elsevier]