Perinatal risk factors associated with severity of haemolytic disease of the foetus and newborn due to Rhc maternal-foetal incompatibility: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: Anti-c is the third red blood cell antibody responsible for haemolytic disease of the foetus and newborn (HDFN) requiring intrauterine transfusion. We aimed to identify risk factors associated with HDFN and severe HDFN due to Rhc maternal-foetal incompatibility. MATERIALS AND METHODS: A retrospective cohort study was conducted in Paris and the surrounding area (France), between 2013 and 2015. We included mothers and their children managed by the National Reference Centre in Perinatal Hemobiology for alloimmunization and maternal-foetal incompatibility for the Rhc antigen (N = 121). We conducted bivariate analyses to assess a relationship between perinatal factors (e.g., titre and concentration of anti-c antibodies, direct antiglobulin test) and HDFN, its severity and duration. RESULTS: The incidence of HDFN was 30% (n = 36), including 11% of severe HDFN (n = 13). Seven percent (n = 9) of neonates received at least one transfusion during the first week and 21% (n = 26) after this period until 3 weeks of life. During pregnancy, a concentration ≥7.5 IU/ml and a titre ≥4 and above were associated with HDFN and severe HDFN (p < 0.05). At birth, the high intensity of the quantitative direct antiglobulin test was associated with HDFN and severe HDFN (p < 0.05). A concentration ≥15 IU/ml is the best factor (area under curve [AUC] = 0.78) in predicting HDFN, followed by a titre ≥8 (AUC = 0.76). CONCLUSION: Anti-c alloimmunization causes neonatal anaemia, which is often belated. Paediatricians have to be aware of these risk factors and organize prolonged monitoring of neonates.

Discharge of newborns with risk factors of severe hyperbilirubinemia: description of a hospital at home-based care monitoring and phototherapy.

Neonatal jaundice is common and associated with delay in hospital discharge and risk of neurological sequelae if not treated. The objectives of the study were to report on our experience of the monitoring and treatment of neonatal jaundice in a home care setting and its feasibility and safety for neonates with high risk of severe hyperbilirubinemia. The 2-year study has been led in the greater Paris University Hospital At Home (Assistance Publique-Hôpitaux de Paris). The device of the intervention was the Bilicocoon® Bag, a light-emitting diode sleeping bag worn by the neonate when the total serum bilirubin value exceeds intensive phototherapy threshold, according to the guidelines from the American Academy of Pediatrics. One hundred and thirty-nine neonates had participated in the intervention and 39 (28%) were treated by phototherapy at home, as continuation of inpatient phototherapy or started at home. Seventy-five percent of the sample had more than two risk factors for development of severe hyperbilirubinemia. Twenty five percent of the cohort who received phototherapy at home had lower gestational age (p < 0.014) and had younger age at discharge from maternity (p < 0.09). Median length of stay in hospital at home was 5 days. Two patients needed readmission in conventional hospital (1%) for less than 24 h. In multivariate model, the length of stay decreased with the higher gestational age (p < 0.001) and increased significantly with the older age at discharge, the birth weight < 10th percentile, and a treatment by phototherapy at home.    Conclusion: Hospital at home, which is a whole strategy using an effective and convenient phototherapy device combined with a specialized medical follow-up, could be an alternative to conventional hospitalization for neonates at high risk of severe jaundice. The maternity discharge is facilitated, the mother-infant bonding can be promoted, and the risk of conventional rehospitalization is minimal, while guaranteeing the safety of this specific care. What is Known: • Managing neonatal jaundice is provided in conventional hospital with phototherapy. • Neonatal jaundice increases the risk of prolonged hospitalization or readmission. What is New: • Phototherapy is feasible in hospital at home for neonates with high risk of severe hyperbilirubinemia. • The care pathway of neonates from conventional hospital to hospital at home is described.

Multidisciplinary management of anti-PP1Pk or anti-P alloimmunization during pregnancy: A new case with anti-P and a literature review.

BACKGROUND: Red blood cell alloimmunization is the first cause of fetal and neonatal anemia. Alloimmunizations with anti-PP1Pk or anti-P can cause recurrent miscarriages and hemolytic disease of the fetus and newborn in the 2nd and 3rd trimesters of pregnancy. We report on a pregnant patient immunized with anti-P and a history of recurrent miscarriages. CASE REPORT: This P2k (GLOB:-1; P1PK:-1,3) patient had a first pregnancy marked by a caesarean at 38 weeks of gestation (WG) for non-reassuring fetal heart rate. Then, she had three early spontaneous miscarriages. The fifth pregnancy began with a high titer of anti-P at 128. Early initiation of treatment with Intravenous Immunoglobulins (IVIg) and plasma exchanges (PE) starting at 5 WG permitted us to reduce the titer of anti-P below 32. A healthy infant was delivered by caesarean at 38 WG without anemia at birth and no exchange transfusion was required. DISCUSSION AND REVIEW OF THE LITERATURE: The P and Pk antigens are expressed on placental, trophoblastic, and embryonic cells. This explains why P1k (GLOB:-1; P1PK:1,3), P2k (GLOB:-1; P1PK:-1,3), or Tj(a-)/p (GLOB:-1; P1PK:-1,-3) patients are prone to recurrent abortions in the first trimester of pregnancy. A literature review demonstrated 87% (68/78) of miscarriages in p patients. However, publication biases are possible with the most severe cases being reported. CONCLUSION: Immunizations to P and PP1Pk antigens differ from others in their physiopathology and precocity. The association of PE and IVIg seems to be an effective treatment in the management of anti-PP1Pk or anti-P fetomaternal incompatibilities.

Managing the Unusual Causes of Fetal Anemia.

BACKGROUND: Rare causes of fetal anemia requiring intrauterine transfusion (IUT) are challenging for fetal medicine specialists. OBJECTIVES: The aim of this study was to describe the perinatal patterns and prognosis in a consecutive series of fetuses transfused for fetal anemia of rare or unknown etiology, and to propose a protocol of investigation for fetal anemia of undetermined cause and for the management of subsequent pregnancies. METHOD: We conducted a retrospective descriptive study on fetuses transfused for severe anemia of rare or unknown etiology managed in our national referral center (Centre National de Référence d'Hémobiologie Périnatale) and born between 2010 and 2017. RESULTS: During the study period, 584 IUT were performed in 253 fetuses. Among those IUT, 23 (3.9%) were performed for a rare or unknown cause of anemia in 13 fetuses (5.1% of transfused fetuses). The median gestational age at diagnosis was 26 weeks of gestation (WG; range 21-33). Hemoglobin levels ranged from 1.6 to 9.1 g/dL (0.18-0.83 multiples of median) before the first IUT. The fetuses received between 1 and 6 IUT (39% received at least 2 IUT). The definitive etiologies for central anemia were: congenital syphilis, neonatal poikilocytosis, type II congenital dyserythropoietic anemia (CDA), and neonatal hemochromatosis. There was 1 case with suspected type I CDA and 1 with suspected Diamond-Blackfan anemia. There was 1 case of peripheral anemia, secondary to cerebral hemorrhages of different ages, related to a variant of the COL4A1 gene. In 6 fetuses corresponding to 4 mothers, no precise diagnosis was found despite a complete workup. In our series, there were 8 live births, 4 terminations of pregnancy, and 1 intrauterine fetal death. CONCLUSIONS: Fetal anemia of rare or unknown diagnosis represents 5% of all transfused fetuses in our cohort. Fetal and neonatal anemias can be recurrent in further pregnancies, with variable expressivity.

Fetal Brain Injury Associated with Parvovirus B19 Congenital Infection Requiring Intrauterine Transfusion.

BACKGROUND: Infection with parvovirus B19 (B19V) during pregnancy may cause severe fetal anemia, hydrops, and fe tal death. Furthermore, neurodevelopmental impairment among survivors may occur despite appropriate prenatal management, including intrauterine transfusion (IUT). OBJECTIVES: Our primary objective was to describe cerebral lesions on MRI in fetuses with severe anemia requiring IUT for B19V infection. Our secondary objective was to search for clinical and biological characteristics associated with the occurrence of such lesions. STUDY DESIGN: We performed a retrospective review of data on fetuses infected with B19V and requiring at least one IUT between 2005 and 2016. Fetuses with abnormal cerebral MRI results in the 3rd trimester were compared to those with normal MRI results. RESULTS: Of 34 transfused fetuses, 26 children were born at full term. Five intrauterine fetal deaths, 1 neonatal death, and 2 terminations of pregnancy occurred. Cerebral anomalies were observed in 7/27 fetuses on MRI, including cerebellar hemorrhage or a small cerebellum. Only viral load in fetal blood appeared to be associated with brain lesions (11.5 log10 copies/mL [10.5-12.5] in case of abnormal MRI results vs. 9.5 log10 copies/mL [7.8-10.0]; p = 0.05). CONCLUSIONS: Among the fetuses transfused for B19V infection, 26% presented with prenatal abnormal cerebral imaging results. In our study, viral load in fetal blood appeared to be the only factor associated with fetal brain lesions.

Clinical input of anti-D quantitation by continuous-flow analysis on autoanalyzer in the management of high-titer anti-D maternal alloimmunization.

BACKGROUND: In addition to titration by indirect antiglobulin test most widely used, anti-D quantitation by continuous-flow analysis (CFA) may be performed to assess severity of maternal immunization. Only five studies have reported its added value in the management of pregnancies complicated by anti-D immunization. STUDY DESIGN AND METHODS: A retrospective study of 74 severe anti-D-immunized pregnancies was conducted from January 1, 2013, to December 31, 2014, in the Trousseau Hospital in Paris (France). Concentration of maternal anti-D was measured by titration and by CFA two-stages method (2SM; total amount of anti-D) and one-stage method (1SM; high-affinity IgG1 anti-D). These biologic data were analyzed according to the severity of the hemolytic disease of the fetus and the newborn. RESULTS: The value of 5 IU anti-D/mL in maternal serum is validated as a threshold to trigger ultrasonographic and Doppler fetal close follow-up. A high 1SM/2SM ratio was associated with a higher risk of intrauterine transfusion (IUT). For pregnancies requiring IUT and without increasing titer, maternal 1SM anti-D concentration tends to correlate with the precocity of fetal anemia. In the "without-IUT" group 1SM and 2SM anti-D concentrations correlate significantly with cord bilirubin levels of the newborn at birth. CONCLUSION: Altogether our results underline the importance of anti-D quantitation by CFA to optimize the management of anti-D-alloimmunized pregnancies.

Effectiveness and costs of non-invasive foetal RHD genotyping in rhesus-D negative mothers: a French multicentric two-arm study of 850 women.

BACKGROUND: The determination of foetal Rhesus D (RHD) status allows appropriate use of IgRh prophylaxis by restricting its use to cases of RHD feto-maternal incompatibilities. There is a degree of uncertainty about the cost-effectiveness of foetal RHD determination, yet screening programs are being introduced into clinical practice in many countries. This paper evaluates the impact of non-invasive foetal Rhesus D (RHD) status determination on the costs of managing RHD-negative pregnant women and on the appropriate use of anti-D prophylaxis in a large sample of RHD-negative pregnant women using individual prospectively collected clinical and economic data. METHODS: A prospective two-armed trial of RHD negative pregnant women was performed in 11 French Obstetric Departments. Non-invasive foetal RHD genotyping was performed before 26 weeks' gestation in the experimental arm whereas the control arm participants received usual care. The costs associated with patient management in relation to their RHD negative status (biological tests, anti-D prophylaxis and visits) were calculated from inclusion to the end of the postpartum period. The costs of hospital admissions during pregnancy and delivery were also determined. RESULTS: A total of 949 patients were included by 11 centres between 2009 and 2012, and 850 completed follow-up, including medical and biological monitoring. Patients were separated into two groups: the genotyping group (n=515) and the control group (n=335). The cost of the genotyping was estimated at 140 euros per test. The total mean cost per patient was estimated at €3,259 (SD ± 1,120) and €3,004 (SD ± 1,004) in the genotyping and control groups respectively. The cost of delivery represented three quarters of the total cost in both groups. The performance of managing appropriately RHD negative anti-D prophylaxis was 88% in the genotyping group, versus 65% in the control group. Using the costs related to RHD status (biological tests, anti-D immunoglobulin injections and visits) the incremental cost-effectiveness ratio (ICER) was calculated to be €578 for each percentage gain in women receiving appropriate management. CONCLUSION: Early knowledge of the RHD status of the foetus using non-invasive foetal RHD genotyping significantly improved the management of RHD negative pregnancies with a small increase in cost. TRIAL REGISTRATION: Clinical trials registry- NCT00832962 -13 January 2009 - retrospectively registered.

[Immuno-hematological follow up of pregnant women]. / Suivi immuno-hématologique des femmes enceintes.

Immuno-hematological follow up of pregnant women. The goal of immuno-hematological follow-up during pregnancy is to organize maternal transfusion safety and optimal management of fetal and neonatal hemolytic disease, that may result from maternal immunization. This follow-up relies on scheduled antibodies detection following regulation. Since May 2017 the refund by social security of the fetal RHD genotyping analysis on maternal plasma, it is possible to limit prophylaxis of allo-immunization to RhD-negative women with a RhD positive fetus. If red blood cell antibody detection is positive, an identification and a quantification of the antibody must be performed. Furthermore, fetomaternal red blood cell incompatibility must be confirmed, in order to adapt the management of allo-immunized pregnancy, for detection of fetal anemia but also to anticipate possible transfusion requirements of the mother and the newborn long before delivery.

Suivi immuno-hématologique des femmes enceintes. L'objectif du suivi immuno-hématologique d'une femme enceinte est d'assurer sa sécurité transfusionnelle mais aussi la prise en charge optimale de la maladie hémolytique foetale et néonatale, pouvant compliquer une immunisation maternelle. Ce suivi repose sur le respect du calendrier de recherche des agglutinines irrégulières (RAI). Le remboursement depuis mai 2017 de l'analyse du génotypage RhD foetal sur sang maternel permet de cibler la prophylaxie anti-D aux seules femmes RhD-négatives avec un foetus RhD-positif. Lorsque la recherche d'agglutinines irrégulières s'avère positive, il est indispensable d'identifier l'anticorps, de le quantifier, de déterminer s'il existe une situation d'incompatibilité foeto-maternelle érythrocytaire. Cela afin d'adapter le suivi de la grossesse et la prise en charge néonatale. Enfin, la connaissance du phénotype de la patiente, allo-immunisée ou pas, est indispensable pour anticiper les éventuels besoins transfusionnels de la mère et du nouveau-né, bien en amont de l'accouchement.

Accuracy of Middle Cerebral Artery Doppler Assessment between 34 and 37 Weeks in Fetuses with Red Cell Alloimmunization.

BACKGROUND: The Doppler measurement of middle cerebral artery peak systolic velocity (MCA-PSV) is considered the gold standard for the noninvasive detection of moderate to severe anemia. However, the accuracy of this test has not been evaluated so far, specifically beyond 34 weeks. OBJECTIVES: To assess the accuracy of MCA-PSV to detect moderate to severe fetal anemia and to identify risk factors associated with false-positive and false-negative MCA-PSV values after 34 weeks. STUDY DESIGN: We studied a retrospective cohort of 150 pregnant women with severe alloimmunization who delivered between 2010 and 2014 and correlated MCA-PSV and fetal or neonatal hemoglobin levels. RESULTS: Sensitivity to predict severe anemia was 69%, with a false-negative rate of 3.6%. When MCA Doppler assessment was normal, the identification of serosal effusions increased the detection rate of severe fetal anemia to 94%, with a false-negative rate of 0.8%. False-positive MCA-PSV measurements were more frequent in fetuses with 1 previous intrauterine transfusion (p = 0.0002), but were not associated with MCA resistance index, intrauterine growth restriction and fetal heart rate. CONCLUSIONS: Between 34 and 37 weeks, sensitivity of MCA-PSV Doppler assessment alone is 69% and increases to 94% when also considering signs of hydrops. False-positive MCA-PSV measurements are more frequent in case of former fetal transfusion.

Clinical presentation and outcome of 20 fetuses with parvovirus B19 infection complicated by severe anemia and/or fetal hydrops.

AIM: The aim of this study was to assess the prognosis of parvovirus B19 infection with severely anemic and/or hydropic fetuses according to initial ultrasound and biological criteria. MATERIAL AND METHODS: Retrospective study of 20 cases of congenital parvovirus B19-proven infection (positive PCR) complicated by fetal anemia and/or hydrops was examined. Anemia was suspected on an elevated peak systolic velocity of the middle cerebral artery and was confirmed by fetal blood sampling. RESULTS: Survival rate was 70% (14/20) overall and 76% (13/17) for fetuses with one or more transfusions. When fetal effusion regressed after the transfusion, all 11 fetuses survived, and neonatal condition was favorable for all. Among the 14 live-born children, there was one neonatal death and one admission to the neonatal care unit with no major complications. CONCLUSION: Despite active management by transfusion in fetuses with parvovirus B19 infection, mortality remained substantial during the acute phase of anemia and fetal hydrops. Regression of effusion appears to be an important variable for prognosis. Non-anemic forms exist with isolated refractory ascites or pleural effusion. Maternal mirror syndrome appears to reflect the intensity and persistence of the fetal anemia.

Effect of intravenous immunoglobulins to postpone the gestational age of first intrauterine transfusion in very severe red blood cell alloimmunization: A case-control study.

BACKGROUND: Early intrauterine transfusion (IUT) is associated with a higher risk of fetal loss. Our objective was to evaluate the efficiciency of intravenous immunoglobulins (IVIG) to postpone the gestational age at first IUT beyond 20 weeks of gestation (WG) compared to the previous pregnancy in case of very severe red blood cell (RBC) alloimmunization. STUDY DESIGN AND METHODS: Very severe RBC alloimmunization was defined by a high titer of antibodies and a previous pregnancy complicated by a first IUT before 24 WG and/or perinatal death directly related to alloimmunization. We performed a single-center case-control study. Cases and controls were patients respectively treated with weekly IVIG infusions started before 13 WG, and without. RESULTS: Twenty cases and 21 controls were included. Gestational age (GA) at first IUT was postponed after 20 WG in 18/20 (90 %) of patients treated with IVIG and in 15/21 (71 %) in the control group (p = 0.24). Compared to the previous pregnancy, the GA at first IUT was postponed by a median of 22 [+11; +49] days in the IVIG group and occurred in average 2 days earlier [-17 ; +12] in the non-treated group (p = 0.02). There was no difference between number of IUT and need for exchange-transfusion. IVIG treatment was associated with a significant decrease of antibodies' quantitation. CONCLUSION: In our series, IVIG tends to differ first IUT beyond 20 WG and have a significant effect in postponing the gestational age of the first IUT in patients with very severe RBC alloimmunization.

[Analytical and clinical guidelines on neonatal bilirubinemia]. / Recommandations analytiques et cliniques pour l'utilisation de la bilirubinémie en néonatalogie.

The SFBC-CNBH-CNRHP "Neonatal bilirubin" working group performed a biological and clinical study on bilirubin use in neonates for reliable diagnosis and appropriate management of neonatal jaundice. A brief report of a national survey on analytical and biological practices in France is shown. The guidelines of the French Society of Neonatology (SFN) founded the decision of phototherapy set up upon an accurate lab measurement of total serum bilirubin. An abacus is proposed with defined thresholds, as a function of neonate lifetime in hours. However, several studies evidenced poor comparability of results obtained with the different available methods. This situation is partly due to the lack of reference materials, especially for high bilirubin concentrations. Clinical consequences might be observed. We present in this paper the results of a national harmonization study to progress on this issue. Beyond the analytical aspects, the clinical consequences of harmonization defects were investigated. Finally, guidelines for clinical laboratories are proposed, to be locally adapted.

Reduced fetal movement during pregnancy: Is the Kleihauer-Betke test really useful?

INTRODUCTION: Reduced fetal movement (rFM) is a frequent cause of consultation during the pregnancy and can reveal feto-maternal hemorrhage (FMH) that is sometimes responsible of severe fetal anemia. Our primary objective was to evaluate the contribution of the KBT in case of rFM. Our secondary objective was to compare it with ultrasound examination including peak systolic velocity of the middle cerebral artery (MCA-PSV) to predict neonatal anemia. MATERIALS AND METHODS: We conducted a retrospective study from January 2016 to December 2017 at Armand-Trousseau Hospital in Paris. We analyzed all patients consulting for rFM from 18 to 41 weeks of gestation. We compared the performance of KBT and MCA-PSV to predict neonatal anemia (Hemoglobin at birth under 13.5 g/dL) and severe neonatal anemia (Hb < 10 g/dL). RESULTS: Among the 338 patients, 327 KBT (96.7%) were performed. KBT was found positive in three cases (0.9%). Only one neonate (0.3%) presented with severe anemia requiring a postnatal transfusion. MCA-PSV was performed in 166 cases (49.1%). KBT and MCA-PSV were significantly correlated with neonatal hemoglobin at birth. KBT was better than MCA-PSV to predict neonatal anemia, while MCA-PSV was better than KBT to predict moderate to severe anemia. The KBT and MCA-PSV Doppler had excellent sensitivity and predictive negative values (100%), but they had poor predictive positive values for severe neonatal anemia. CONCLUSION: In case of decreased fetal movement, we suggest performing fetal cerebral Doppler. MCA-PSV could suffice in first approach. KBT may be performed if there is suspicion of fetal anemia in order to confirm FMH.

Prenatal diagnosis of anoxic cerebral lesions caused by profound fetal anemia secondary to maternal red blood cell alloimmunization.

BACKGROUND: The long-term neurological prognosis of severe fetal anemia is usually considered favorable, especially when fetal hydrops regresses after successful in utero transfusion. CASES: We report two cases of prenatally diagnosed fetal cerebral anoxic lesions associated with severe fetal anemia despite appropriate and successful treatment by in utero transfusion. The two pregnancies were terminated. CONCLUSION: Profound fetal anemia may cause anoxic lesions of the fetal brain that may be diagnosed prenatally. If new onset ventriculomegaly is observed on ultrasonography after in utero transfusion for severe fetal anemia, anoxic lesions could be suspected.

In utero treatment of severe fetal anemia resulting from fetomaternal red blood cell incompatibility: a comparison of simple transfusion and exchange transfusion.

OBJECTIVE: To compare in utero exchange transfusions (IUET) and in utero simple transfusions (IUST) for the treatment of fetal anemia resulting from red blood cell fetomaternal incompatibility. STUDY DESIGN: Retrospective comparative study from January 2006 through December 2011. The two techniques were compared for effectiveness, complications, and neonatal outcomes. RESULTS: 36 patients had 87 IUETs and 85 patients 241 IUSTs. Gestational age at the first transfusion was similar in both groups (IUET: 27±3.8 weeks; IUST: 27±4.7 weeks; NS) as was the initial fetal hemoglobin level (IUET: 6.4±2.8g/dL; IUST: 6.0±2.5g/dL; NS). No significant differences were noted for postprocedure complications or efficacy. The daily drop in hemoglobin level was similar in both groups (IUET: 0.41±0.23g/dL/day; IUST: 0.44±0.17g/dL/day; NS) as were the time intervals between two procedures. Gestational age at birth was earlier in the IUET group (34.4±1.3 weeks vs 35.5±1.8 weeks; p<0.001), but the postnatal transfusions or exchange transfusions rates and the duration of intensive phototherapy did not differ. No significant differences were noted for the overall survival rates (IUET: 100%; IUST: 96.4%; p>0.99). CONCLUSION: IUET does not appear to provide any benefits compared with IUST, neither to be associated with a higher complication rate. The choice of the technique depends on availability of packed blood cells with high hematocrit (70-80%).

Fetal anemia as a signal of congenital syphilis.

An upsurge in syphilis has been observed almost everywhere over the past decade. The mother's clinical presentation is often uninformative. The diagnosis of maternal syphilis infection is most often based on serologic tests that allow early Extencilline treatment. Syphilis ultrasound findings are non-specific, and delay before treatment can be decisive for prognosis. Fetal anemia is a physiological consequence of severe infection. We confirmed that syphilis can be suggested non-invasively by MCA-PSV measurements in a context of ascitis or atypical hydrops in the absence of usual causes. It is therefore important to perform maternal TPHA/VDRL serology if fetal anemia is suspected. In association with Extencilline treatment, intra uterine transfusion can limit consequences of infection. Reduced fetal movements and non-reactive fetal heart rate may prefigure acute perinatal complications or stillbirth.

Massive fetomaternal hemorrhage secondary to intrauterine intravascular transfusion.

BACKGROUND: Small-volume fetomaternal hemorrhage is frequently observed after intrauterine transfusion. The Kleihauer-Betke test, the reference method for identifying fetomaternal hemorrhage, cannot be used after intrauterine transfusion, because the adult red blood cells used for transfusion cannot be distinguished from maternal red blood cells. CASE: Massive fetomaternal hemorrhage secondary to intrauterine transfusion led to fetal hemorrhagic stroke. We used a method based on blood group identification in the maternal blood to confirm and to quantify fetomaternal hemorrhage. CONCLUSION: Fetal stroke may result from severe hypovolemia and low cerebral blood flow caused by fetomaternal hemorrhage, rather than from fetal anemia itself.

Management of very early fetal anemia resulting from red-cell alloimmunization before 20 weeks of gestation.

OBJECTIVE: To evaluate the results of management of very early fetal anemia (before 20 weeks of gestation) in cases of red-cell alloimmunization. METHODS: Retrospective study of the outcome of all in utero transfusions performed before 20 weeks of gestation and all pregnancies requiring an in utero transfusion before 20 weeks in our reference center from January 1990 through August 2011 in cases with severe alloimmunization. RESULTS: Twenty-five in utero transfusions were performed in 18 pregnancies in 16 patients during the study period. A vascular access was performed successfully in 22 of the 24 cases in which it was attempted. An intraperitoneal transfusion was necessary in two cases. Two in utero deaths attributable to the intravascular procedure occurred during attempts before 18 weeks of gestation and another, not associated with a transfusion, at 29 weeks. The overall survival rate was 83.3% (compared with 88.0% when the first in utero transfusion took place before 22 weeks). The risk of fetal loss for each transfusion was 8.0% before 20 weeks and 6.3% before 22 weeks. An intraperitoneal transfusion at 17 2/7 weeks allowed one fetus to survive until the first intravascular in utero transfusion could take place at 18 2/7 weeks. CONCLUSION: Fetal anemia before 20 weeks remains at high risk of lethal complications compared with later gestational ages. Technical difficulties in a vascular access are mainly encountered before 18 weeks of gestation. At an earlier gestational age, intraperitoneal transfusion may gain the days necessary to perform an intravascular transfusion more safely. LEVEL OF EVIDENCE: III.