The rate of decline in fetal hemoglobin following intrauterine blood transfusion in the management of red cell alloimmunization.

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.

Transient congenital hyperinsulinism and hemolytic disease of a newborn despite rhesus D prophylaxis: a case report.

BACKGROUND: In neonates, rhesus D alloimmunization despite anti-D immunoglobulin prophylaxis is rare and often unexplained. Rhesus D alloimmunization can lead to hemolytic disease of the newborn with anemia and unconjugated hyperbilirubinemia. In past reports, transient congenital hyperinsulinism has been described as a rare complication of rhesus D alloimmunization. Our case report illustrates that rhesus D alloimmunization can result in a pseudosyndrome with severe congenital hyperinsulinism, anemia, and conjugated hyperbilirubinemia, despite correctly administered anti-D immunoglobulin prophylaxis. CASE PRESENTATION: We report of a 36-year-old, Caucasian gravida 1, para 1 mother with A RhD negative blood type who received routine antenatal anti-D immunoglobulin prophylaxis. Her full term newborn boy presented with severe congenital hyperinsulinism, anemia, and conjugated hyperbilirubinemia up to 295 µmol/L (ref. < 9), accounting for 64% of the total bilirubin. Syndromic congenital hyperinsulinism was suspected. Examinations showed a positive direct antiglobulin test, initially interpreted as caused by irregular antibodies; diffuse congenital hyperinsulinism by 18F-DOPA positron emission tomography/computed tomography scan; normal genetic analyses for congenital hyperinsulinism; mildly elevated liver enzymes; delayed, but present bile excretion by Tc99m-hepatobiliary iminodiacetic acid scintigraphy; and cholestasis and mild fibrosis by liver biopsy. The maternal anti-D titer was 1:16,000 day 20 postpartum. Y-chromosome material in the mother's blood could not be identified. This could, however, not exclude late intrapartum fetomaternal hemorrhage as the cause of immunization. No causative genetic findings were deetrmined by trio whole exome sequencing. The child went into clinical remission after 5.5 months. CONCLUSION: Our case demonstrates that rhesus D alloimmunization may present as a pseudosyndrome with transient congenital hyperinsulinism, anemia, and inspissated bile syndrome with conjugated hyperbilirubinaemia, despite anti-D immunoglobulin prophylaxis, possibly due to late fetomaternal hemorrhage.

Perinatal outcomes and survival predictors of severe red-cell alloimmunization treated by intrauterine transfusion.

OBJECTIVE: To evaluate perinatal survival rates and predictors in severely anemic fetuses that underwent intrauterine transfusion (IUT). METHOD: This was a retrospective study of both Turkish and Syrian patients who underwent IUT for fetal anemia due to Rh alloimmunization between 2015 and 2019. The association between pretransfusion factors and perinatal survival was evaluated by multivariate logistic regression. Receiver operating characteristics (ROC) curves were used to identify the level of fetal hemoglobin deficits that predict perinatal survival. RESULTS: Eighty-seven IUTs were performed in 42 pregnancies. Approximately 75% of fetuses were severely anemic and the overall perinatal survival rate was 50%. The survival rate was better in Syrian refugees compared to Turkish patients (71.4% vs. 39.3%, p < 0.05). In univariate analysis, hydrops presence (odds ratio [OR] = 0.2; 95% confidence interval [CI] = 0.05-0.7; p < 0.05), first IUT week (OR = 1.4; 95% CI = 1.1-1.8; p < 0.05), pretransfusion hemoglobin level (OR = 1.99; 95% CI = 1.22-3.27; p < 0.05), hemoglobin deficit (OR = 0.5; 95% CI = 0.3-0.8; p < 0.05), and birth week (OR = 2.3; 95% CI = 1.3-3.9; p < 0.05) were associated with survival. However in a multivariate analysis, only hemoglobin deficit (OR = 0.47; 95% CI = 0.22-0.99; p < 0.05) and birth week (OR = 3.3; 95% CI = 1.1-10.3; p < 0.05) were found to be associated with survival. On ROC analysis, a hemoglobin deficit of ≤6.25 g/dl showed a sensitivity of 0.95 and specificity of 0.62 for predicting perinatal survival. CONCLUSION: Despite the improvement in the treatment of fetal anemia, perinatal survival rate remains extremely low in severely anemic cases. Among pretransfusion factors, hemoglobin deficit seemed to be most important in predicting survival during fetal anemia.

[Severe neonatal thrombocytopenia due to maternal alloimmunization: case report and literature review]. / Allo-immunisation fœto-maternelle sévère: à propos d´un cas et revue de la littérature.

Prior to 1970, maternal alloimmunization was the leading cause of perinatal death. Currently, it has become rarer thanks to screening and monitoring in high-risk pregnancies. The advent of transcranial doppler has been a turning point in the monitoring of these pregnancies, as it is a reliable, non-invasive method for the diagnosis of fetal anemia. This helps clinicians decide whether or not to perform intrauterine transfusion. Anti-D immunoprophylaxis has also played an important role in preventing fetal and neonatal hemolytic anemia and its administration is currently well codified. Adequate management helps to avoid the effects of alloimmunization on the fetus and newborn as well as to reduce the risks of alloimmunization in subsequent pregnancies. We here report a case of severe fetomaternal rhesus (Rh) alloimmunization during unmonitored pregnancy complicated by fetoplacental anasarca.

Peak systolic velocity of fetal middle cerebral artery to predict anemia in Red Cell Alloimmunization in un-transfused and transfused fetuses.

OBJECTIVE: To assess the accuracy of middle cerebral artery peak systolic velocity (MCA-PSV) in prediction of severe fetal anemia resulting from Red Cell Alloimmunization (Anti-D) in un-transfused and transfused fetuses. In addition to comparing the accuracy of MCA-PSV and the estimation of the daily decline of fetal hemoglobin (Hb), to determine the appropriate time of subsequent transfusions. STUDY DESIGN: This was a retrospective study of a series of 84 anaemic fetuses due to Red Cell alloimmunization. During each in-utero transfusion session, measurements of (1)MCA-PSV, (2)pre- and (3)post-transfusion Hb levels were recorded. Receiveroperating characteristics (ROC) curves, negative and positive predictive values of MCA-PSV in predicting severe fetal anemia were calculated. Regression analysis assesses the correlation between fetal HB and MCA-PSV, and between observed and expected fetal hemoglobin levels. RESULTS: Eighty four anemic fetuses were included in the study and had an in-utero transfusion. The positive predictive value (PPV) of MCAPSV decreased sharply from 86.0 % at the first IUT, to 52.0 % and 52.1 % at the second and third IUTs respectively. According to the ROC curves, setting the cut-off at 1.70 MoM would provide the best performance of MCA-PSV with respect to the timing of the second and third IUT. Setting a higher threshold of 1.70 MoM for the 2nd and 3rd transfusions would increase the PPV from 52.0 % to 96.4 % at the second IUT, and from 52.1%-99.8 % at the third IUT. CONCLUSION: In this study we suggest that a higher MCA-PSV (MoM 1.7 in compared to 1.5MOM) can accurately predict the recurrence of severe fetal anemia requiring serial IUTs. In transfused fetuses, MCAPSV accuracy to detect severe anemia decline slightly with increase number of IUT. In addition to that, the mean projected daily decrease in fetal hemoglobin has a similar accuracy to MCA-PSV in predicting moderate to severe fetal anemia.

Assessment of fetal right ventricular myocardial performance index changes following intrauterine transfusion.

INTRODUCTION: Severe fetal anemia may cause cardiac ischemia, reduced contractility, and dysfunction. The purpose of our study is to evaluate right ventricular myocardial performance index (MPI) before and after intrauterine transfusion (IUT) in patients who underwent this procedure because of fetal anemia due to Rh-D alloimmunization. MATERIALS AND METHODS: This prospective cohort study was conducted between January 2018 and June 2019 at Kanuni Sultan Suleyman Research and Training Hospital, Istanbul, Turkey. The pregnant women who were applied IUT because of fetal anemia due to Rh-D alloimmunization in our perinatology clinic were included in the study. Fetal right ventricular MPI before and 24 h after IUT were evaluated. RESULTS: A total of 28 IUTs were performed in 17 pregnant women during the study period. The isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) values measured before IUT, were found to be significantly longer compared to the ICT and IRT values measured after IUT. The MPI values measured after transfusion was found to be higher than before transfusion. CONCLUSIONS: The fetal right ventricular MPI increases 24 h after IUT. This increase in the right ventricular MPI might be used as a marker for predicting adverse fetal outcomes following IUT.

Prediction of Fetal Anemia in Subsequent Transfusions: Is There a Need to Change the Threshold of the Peak Systolic Velocity of the Middle Cerebral Artery?

INTRODUCTION: Peak systolic velocity (PSV) of the middle cerebral artery (MCA) shows 100% sensitivity for predicting fetal anemia before the first intrauterine transfusion (IUT). However, its ability to predict subsequent transfusions has remained mostly controversial. OBJECTIVES: To assess if there is a need to change the threshold of MCA-PSV from 1.5 to 1.69 multiples of the median (MoM) to predict fetal anemia and the need for subsequent IUT. METHODS: This is a retrospective audit, wherein case records of mothers who underwent IUT at the Bangalore Fetal Medicine Centre between April 2008 and May 2017 were reviewed; 86 cases were included, and the data were analyzed using MS Excel. The MCA-PSV and pretransfusion Hb were converted into MoM. 40 fetuses that had more than 1 IUT were included in the analysis. -Results: 31/40 fetuses that had >1 IUT had an MCA-PSV >1.5 MoM, of which 29 were anemic according to the post-IUT Hb MoM. 20/29 (69%) had an MCA-PSV >1.69, whereas 9/29 (31%) had an MCA-PSV between 1.5 and 1.69 MoM. Our study shows that changing the MCA-PSV threshold from 1.5 to 1.69 MoM will reduce the detection of fetal anemia and hence the need for repeat IUT by 31%. CONCLUSIONS: Increasing the fetal MCA-PSV threshold from 1.5 to 1.69 will miss out one-third of the fetuses that will require a 2nd, 3rd, or 4th IUT. This is more relevant in geographical areas where the parents must travel long distances for IUTs, which are performed in tertiary fetal care centers.

Delayed cord clamping in Rh-alloimmunised infants: a randomised controlled trial.

Despite advancement in medical care, Rh alloimmunisation remains a major cause of neonatal hyperbilirubinaemia, neuro-morbidity, and late-onset anaemia. Delayed cord clamping (DCC), a standard care now-a-days, is yet not performed in Rh-alloimmunised infants due to paucity of evidence. Hence, we randomised these infants of 28- to 41-week gestation to delayed cord clamping (N = 36) or early cord clamping (N = 34) groups. The primary outcome variable was venous packed cell volume (PCV) at 2 h of birth. The secondary outcomes were incidence of double volume exchange transfusion (DVET) and partial exchange transfusion (PET), duration of phototherapy (PT), functional echocardiography (parameters measured: superior vena cava flow, M-mode fractional shortening, left ventricular output, myocardial perfusion index, and inferior vena cava collapsibility) during hospital stay, and blood transfusion (BT) until 14 weeks of life. Neonates were managed as per unit protocol. The baseline characteristics of enrolled infants were comparable between the groups. The median (IQR) gestation and mean (SD) birth weight of enrolled infants were 35 (33-37) weeks and 2440 (542) g, respectively. The DCC group had a higher mean PCV at 2 h of life (48.4 ± 9.2 vs. 43.5 ± 8.7, mean difference 4.9% (95% CI 0.6-9.1), p = 0.03). However, incidence of DVET and PET, duration of PT, echocardiography parameters, and BT until 14 weeks of postnatal age were similar between the groups.Conclusion: DCC in Rh-alloimmunised infants improved PCV at 2 h of age without significant adverse effects.Trial registration: Clinical Trial Registry of India (CTRI), Ref/2016/11/012572 http://ctri.nic.in/Clinicaltrials, date of trial registration 19.12.2016, date of first patient enrolment 1 January 2017.What is Known:•Delayed cord clamping improves haematocrit, results in better haemodynamic stability, and decreases the need of transfusion in early infancy.•However, due to lack of evidence, potential risk of hyperbilirubinaemia, and exacerbation of anaemia (following delayed cord clamping), early cord clamping is the usual norm in Rh-alloimmunised infantsinfants.What is New:•Delayed cord clamping in Rh-alloimmunised infants improves haematocrit at 2 h of life without any increase in incidence of serious adverse effects.

Perinatal outcomes of intrauterine transfusion for foetal anaemia due to red blood cell alloimmunisation.

The aim of this study was to evaluate the maternal and neonatal outcomes of patients who underwent intrauterine transfusion (IUT) for foetal anaemia due to red blood cell alloimmunisation and to determine the factors that affected the outcomes. All pregnancies that were treated with IUT due to Rh immunisation between January 2015 and June 2018 in the Kanuni Sultan Süleyman Training and Research Hospital, Department of Obstetrics and Gynaecology, were evaluated retrospectively. IUT due to non-Rh alloimmunisation, parvovirus B19 infection, chronic fetomaternal haemorrhage and foetal anaemia due to homozygous alpha-thalassemia were not included in the study. The perinatal and neonatal outcomes of the patients were retrospectively analysed. The gestational age, ultrasonography findings before and after IUT, laboratory results, complications related to IUT, and data on the newborns were recorded. The cases were divided into two groups, those with complication and those without complications, and their perinatal outcomes were compared. A total of 110 IUTs were performed in 42 foetuses. The survival rate after transfusion was 80.95%. Procedure-related complications were found in 12.7% of cases. There were no significant differences between the demographic and clinical characteristics of the patients with and without complications. The survival rate was lower and perinatal mortality was higher in foetuses with hydrops fetalis. IUT is a safe and effective procedure that can be used in the treatment of foetal anaemia in experienced centres. Survival rates can be increased by referring patients to experienced perinatology centres, by improving the IUT technique, and by reducing technique-related complications.Impact statementWhat is already known on this subject? The predominant use of IUT is to treat foetal anaemia due to red blood cell alloimmunisation. Despite the decrease after anti-D immune globulin prophylaxis, Rh immunisation is still a major cause of foetal anaemia. However, foetal survival rates have increased with the use of IUT.What do the results of this study add? The survival rates were increased after the development of a high-resolution ultrasound. Because foetal monitoring can be performed by ultrasonography, cord accidents and overload findings can be detected during transfusion, which allows for early interventions and increases survival rates.What are the implications of these findings for clinical practice and/or further research? The IUT procedure can be used in the treatment of foetal anaemia in experienced centres. After the technique was improved, the complication rates related to the procedure were decreased and foetal survival rates were increased. Further studies on the use of different IUT techniques will extend our findings.

Severe neonatal hyperbilirubinemia in the southeast region of Turkey

Background/aim: Severe neonatal hyperbilirubinemia is an important cause of morbidity and mortality in developing countries. The aim was to assess etiologic reasons for development of severe hyperbilirubinemia and define risk factors for exchange transfusion and acute bilirubin encephalopathy (ABE) in Sanliurfa located in the southeast region of Turkey. Materials and methods: An observational cohort study included 115 infants with ≥35 weeks of gestation admitted with diagnosis of severe hyperbilirubinemia in a period of 18 months. Potential risk factors associated with exchange transfusion and development of ABE were analyzed. Results: Among 115 infants, 67 (58.3%) received exchange transfusion and 45 (39.1%) developed ABE. Rh isoimmunization (OR: 24.6, 95% CI = 2.2­271, P = 0.009), glucose-6-phosphate dehydrogenase deficiency (G6PD) (OR: 21.1, 95% CI = 1.8­238.4, P = 0.01), early discharge (OR: 14.4, 95% CI = 4.2­48.9, P ≤ 0.001), and male sex (OR: 4.3, 95% CI = 1.3­14.1, P = 0.02) were independently associated with an increased risk for exchange transfusion. Being a refugee (OR: 6.8, 95% CI = 1.8­25.8, P = 0.005) and G6PD deficiency (OR: 9.9, 95% CI = 1.3­71.9, P = 0.02) were associated with development of ABE. Conclusion: Early discharge, Rh isoimmunization, and G6PD deficiency are significant risk factors for severe hyperbilirubinemia and exchange transfusion. Prevention of early hospital discharges, family education to increase awareness for hazardous effects of hyperbilirubinemia, and early follow-up visits after discharge would reduce the disease burden.

Intraperitoneal transfusion for severe, early-onset rhesus disease requiring treatment before 20 weeks of gestation: A consecutive case series.

OBJECTIVE: To describe the management and perinatal outcomes of pregnancies affected by severe, early onset Rhesus isoimmunization treated with fetal intraperitoneal transfusions (IPTs). STUDY DESIGN: A ten-year consecutive case series of fetuses undergoing IPTs before 20 weeks gestation at Wessex Fetal Medicine Unit, Southampton, UK. Women with fetuses at risk of early onset fetal anaemia (before 20 weeks gestation) were identified from their obstetric history and maternal antibody levels at the time of booking. They were referred to our tertiary referral center. The decision to initiate transfusion was aided by middle cerebral artery peak systolic velocity as an indicator of fetal anaemia. No fetus was hydropic at the first transfusion. IPTs were commenced from as early as 15 weeks gestation in fetuses with difficult vascular access and performed regularly using this method until the cord could be successfully entered for intravascular transfusions. The main outcome measures were procedure and non procedure-related perinatal losses. RESULTS: 11 fetuses underwent 45 IPTs. 10/11 (91%) were delivered after 33 weeks gestation. There was one perinatal loss 1/11 (9%: 95% C.I 1.6-38%) from a cord accident during intravascular transfusion at 26 weeks gestation. There were no procedure related fetal losses or complications at the time of early IPTs. CONCLUSIONS: Previous studies report a perinatal loss rate with early intrauterine transfusion of 24% in gestations below 20 weeks using the intravascular route. This series suggests that intraperitoneal transfusion can be a safe and effective treatment for severe fetal anaemia at early gestations where vascular access is difficult.

Hyporegenerative anemia and other complications of rhesus hemolytic disease: to treat or not to treat is the question.

Rhesus hemolytic disease of the newborn is rarely found after the implementation of anti-D immunoglobulin prophylaxis. However, it may lead to cholestasis, elevated liver transaminases, iron overload and late hyporegenerative anemia when it occurs. Etiology of this type of anemia is not defined yet and treatment is controversial. It is typically recognized after two weeks of life which is characterized by low hemoglobin and reticulocyte count. We have reported a case of a neonate with Rh hemolytic disease with late hyporegenerative anemia that was noted at day 18 of life. We treated this anemia by erythropoietin (EPO) 250 U/kg three times per week. Two weeks after initiation of erythropoietin treatment, a stable hemoglobin was noted along with an increased reticulocyte count. The patient required one further blood transfusion in the third week of therapy. Other associated findings were self-limited. A year of follow-up showed an appropriate development for age.

Hyperferritinaemia following intrauterine transfusions for Rh isoimmunisation.

Intrauterine transfusion is one of the mainstays of treatment in isoimmunised pregnancies guided by the changes in middle cerebral artery Doppler of the fetus. The common postnatal complications associated with Rh isoimmunisation are high unconjugated bilirubin requiring blood exchange transfusions, cholestasis due to bile inspissation, thrombocytopenia and anaemia. Hyperferritinaemia is an uncommon adverse effect observed in Rh isoimmunised pregnancies. In this case report, we describe the clinical course of a Rh isoimmunised neonate with hyperferritinaemia and transfusion acquired cytomegalovirus disease which resolved. Iron chelation therapy was not necessary.

Neonatal hyperbilirubinemia secondary to combined anti e and anti C isoimmunisation: a literature review.

A term male infant was admitted at 48 h of postnatal life to the neonatal unit for jaundice. The investigation showed total serum bilirubin (TSB) of 17.1 mg/dl, haemoglobin of 11 g/dl, reticulocyte count of 9.5% and peripheral smear was suggestive of macrocytic, normochromic red blood cell (RBC) with target cells and multiple spherocytes with occasional nucleated RBC. The infant's blood group was B positive. Direct antiglobulin test was strongly positive by gel method (3+). Mother's blood group was B positive and indirect antiglobulin test was positive when tested postnatally. Extended minor blood grouping and cross matching showed this as a case of combined anti e and anti C antibodies isoimmunisation. Infant was treated with phototherapy for 72 h and was shifted to mother side. Infant was serially monitored with TSB level every sixth hourly and American Academy of Pediatrics (AAP) phototherapy charts were followed to see for rebound hyperbilirubinemia. The neonate was discharged and there was no readmission for hyperbilirubinemia. It is very rare and we report the third case of its type till date.

Chelation therapy for secondary neonatal iron over load: Lessons learned from rhesus hemolytic disease.

Khdair-Ahmad F, Aladily T, Khdair-Ahmad O, Badran EF. Chelation therapy for secondary neonatal iron overload: Lessons learned from rhesus hemolytic disease. Turk J Pediatr 2018; 60: 335-339. Secondary neonatal iron overload occurs with intrauterine and post-natal blood transfusions. Treatment with intravenous Deferoxamine was reported only in four cases in the literature. Herein we report a case of a patient born at 36 weeks of gestation, who had rhesus hemolytic disease. He developed secondary iron overload, causing liver injury, after a total of six blood transfusions: four intrauterine and 2 post-natal transfusion therapies. Intravenous Deferoxamine treatment was started at the age of 45 days due to a ferritin level of 40,000 mg/L, progressive rise of liver enzymes, and worsening cholestasis. Treatment resulted in marked reduction in ferritin level (down to 829 mg/L at the age of 6 months), significant improvement in the liver enzymes, and resolution of cholestasis.

Anti-D in a mother, hemizygous for the variant RHD*DNB gene, associated with hemolytic disease of the fetus and newborn.

BACKGROUND: Individuals with the partial D phenotype when exposed to D+ red blood cells (RBCs) carrying the epitopes they lack may develop anti-D specific for the missing epitopes. DNB is the most common partial D in Caucasians and the clinical significance for anti-D in these individuals is unknown. STUDY DESIGN AND METHODS: This article describes the serologic genotyping results and clinical manifestations in two group D+ babies of a mother presenting as group O, D+ with alloanti-D. RESULTS: The mother was hemizygous for RHD*DNB gene and sequencing confirmed a single-nucleotide change at c.1063G>A. One baby (group A, D+) displayed bilirubinemia at birth with a normal hemoglobin level. Anti-A and anti-D were eluted from the RBCs. For the next ongoing pregnancy, the anti-D titer increased from 32 to 256. On delivery the baby typed group O and anti-D was eluted from the RBCs. This baby at birth exhibited anemia, reticulocytosis, and hyperbilirubinemia requiring intensive phototherapy treatment from Day 0 to Day 9 after birth and was discharged on Day 13. Intravenous immunoglobulin was also administered. Both babies were heterozygous for RHD and RHD*DNB. CONCLUSION: The anti-D produced by this woman with partial D DNB resulted in a case of hemolytic disease of the fetus and newborn (HDFN) requiring intensive treatment in the perinatal period. Anti-D formed by women with the partial D DNB phenotype has the potential to cause HDFN where the fetus is D+. Women carrying RHD*DNB should be offered appropriate prophylactic anti-D and be transfused with D- RBCs if not already alloimmunized.

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

OBJECTIVE: Prophylactic intravenous immunoglobulin (IVIg) does neither reduce the need for exchange transfusion nor the rates of other adverse neonatal outcomes in neonates with rhesus hemolytic disease of the fetus and newborn (rhesus HDFN) according to our randomized controlled trial analysis. Our objective was to assess the long-term neurodevelopmental outcome in the children included in the trial and treated with either IVIg or placebo. METHODS: All families of the children included in the trial were asked to participate in this follow-up study. The long-term neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests. The primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe cognitive and/or motor developmental delay (with a test score of less than -2 SD), bilateral deafness or blindness. RESULTS: Sixty-six of the 80 children (82.5%) who had been recruited to the initial randomized controlled trial participated in the follow-up study. The children were assessed at a median age of 4 years (range 2-7). The median cognitive score was 96 (range 68-118) in the IVIg group and 97 (range 66-118) in the placebo group (p = 0.79). There was no difference in the rate of neurodevelopmental impairment between the IVIg and the placebo group [3% (1/34) vs. 3% (1/32); p = 1.00]. CONCLUSIONS: The long-term neurodevelopmental outcome in children treated with IVIg was not different from that in children treated with placebo. Standardized long-term follow-up studies with large enough case series and sufficient power are needed to replicate these findings.

Fetal cerebellar damage in fetuses with severe anemia undergoing intrauterine transfusions.

OBJECTIVE: To evaluate radiologic findings and outcomes of cerebellar injuries in fetuses with severe anemia due to RhD alloimmunization undergoing intrauterine transfusions. METHODS: Imaging of multiplanar neurosonography and magnetic resonance imaging (MRI) were reviewed. Pregnancy outcomes were recorded. RESULTS: Cerebellar injuries were identified after the first intravascular transfusion in four fetuses. Two of these cases were previously reported. The median hemoglobin concentration was 2.1 g/dL. Prenatal neurosonography identified an echogenic collection involving the cerebellum suggestive for hemorrhage in three cases. A progressive hypoplasia of a hemisphere was demonstrated at follow-up examination in one of these cases. Hypoplasia of a cerebellar hemisphere was seen in the fourth fetus. Ultrasound diagnosis was confirmed by prenatal MRI in two cases. In the third case, the postnatal MRI showed as additional finding vermian involvement. One pregnancy was terminated and autopsy confirmed the presence of infratentorial hemorrhage. The remaining infants were delivered alive. At time of writing, a truncal ataxia was diagnosed in the child with vermian hypoplasia, while the other children have met all age-appropriate milestones. CONCLUSIONS: A severe anemia seems to put the fetus at risk of cerebellar damage, despite successful intravascular transfusion.

[THE FETAL MIDDLE CEREBRAL ARTERY PEAK SYSTOLIC VELOCITY AS A PEDICTOR OF FETAL ANEMIA IN RH-ALLOIMMUNIZED PREGNANCY].

UNLABELLED: Rh-isoimmunization is a pathological condition in which the fetal red blood cells of a Rh (+) fetus are destroyed by the isoantibodies of a Rh (-) woman sensitized in a previous event. Despite of the wide spread implementation of anti D-gammaglobolin prophylaxis this is still the most common cause for fetal anemia. Recently, sonographic measurement of the fetal middle cerebral artery peak systolic velocity (MCA-PSV) has been shown to be an accurate non-invasive test to predict low fetal hemoglobin levels. We present a case report of Rh-alloimmunized pregnancy with moderate fetal anemia, followed-up by weekly MCA-PSV measurements. CASE REPORT: A 37-year-old Rh (-) negative gravida 3, para 1, without anti-D gammaglobolin prophylaxis in her previous pregnancies, presented at 27+0 weeks of gestation (w.g.) for a routine third trimester scan. Subsequent ultrasound measurements of MCA-PSV confirmed a progressive increase of the peak systolic velocities from 40 to 80 cm/sec, as well as a gradual rise in the anti-D titers. The evidence of developing fetal anemia necessitated elective Caesarean section performed at 35 wg. The neonate was admitted in the intensive care unit and required resuscitation, one exchange blood transfusion and several courses of phototherapy. The patient was discharged two weeks post partum. CONCLUSIONS: There is a strong correlation between the high peak systolic velocities in the middle cerebral artery (MCA-PSV) and the low levels of fetal hemoglobin. The high sensitivity and positive predictive value concerning the development of fetal anemia, as well as its good repeatability, makes this non-invasive test a valuable asset in the management of all pregnancies complicated by severe Rh-alloimmunization.