Society for Maternal-Fetal Medicine Statement: RhD immune globulin after spontaneous or induced abortion at less than 12 weeks of gestation.

Guidelines for the management of first-trimester spontaneous and induced abortion vary in terms of rhesus factor D (RhD) testing and RhD immune globulin (RhIg) administration. These existing guidelines are based on limited data that do not convincingly demonstrate the safety of withholding RhIg for first-trimester abortions or pregnancy losses. Given the adverse fetal and neonatal outcomes associated with RhD alloimmunization, prevention of maternal sensitization is essential in RhD-negative patients who may experience subsequent pregnancies. In care settings in which RhD testing and RhIg administration are logistically and financially feasible and do not hinder access to abortion care, we recommend offering both RhD testing and RhIg administration for spontaneous and induced abortion at <12 weeks of gestation in unsensitized, RhD-negative individuals. Guidelines for RhD testing and RhIg administration in the first trimester must balance the prevention of alloimmunization with the individual- and population-level harms of restricted access to abortion.

Live birth prevalence of hemolytic disease of the fetus and newborn in the United States from 1996 to 2010.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is mediated by maternal alloantibodies, a consequence of immune sensitization during pregnancy with maternal-fetal incompatibility with ABO, Rhesus factor (Rh), and/or other red blood cell antigens. RhD, Kell, and other non-ABO alloantibodies are the primary cause of moderate to severe HDFN, whereas ABO HDFN is typically mild. HDFN live birth prevalence owing to Rh alloimmunization among newborns in the United States was last estimated to be 106 per 100,000 births in 1986. HDFN live birth prevalence owing to all alloantibodies was estimated to be 817 to 840 per 100,000 in Europe. There is a need for updated prevalence estimates in the United States and a better understanding of disease demographics, severity, and treatments. OBJECTIVE: This study aimed to estimate the live birth prevalence of HDFN and the proportion of severe cases of HDFN in the United States, to describe the associated risk factors, and to compare the clinical outcomes and treatments among healthy newborns, newborns with HDFN, and newborns who are sick without HDFN using a nationally representative hospital discharge database. STUDY DESIGN: In this retrospective, observational cohort study, we used data from the 1996 to 2010 National Hospital Discharge Survey to identify live births, defined by inpatient visits with the newborn flag, with and without a diagnosis of HDFN across 200 to 500 sampled hospitals (≥6 beds) per year. Patient and hospital characteristics, alloimmunization status, disease severity, treatment, and clinical outcomes were evaluated. Frequencies and weighted percentages were calculated for all variables. Logistic regression was used to compare the characteristics between newborns with HDFN and other newborns using odds ratios. RESULTS: Of 480,245 live births identified, 9810 HDFN cases were recorded. When weighted to the United States population, this corresponded to a live birth prevalence of 1695 per 100,000 live births. Compared with other newborns, newborns with HDFN were more likely to be female, Black, living in the South (vs the Midwest or West), and treated at larger (>100 beds) and government-owned hospitals. ABO and Rh alloimmunization accounted for 78.1% and 4.3% of newborns with HDFN, respectively, whereas HDFN caused by other antigens, such as Kell and Duffy, accounted for 17.6% of the cases. Among newborns with HDFN, 22% received phototherapy, 1% received simple transfusions, and 0.5% received exchange transfusions or intravenous immunoglobulin. Newborns affected by HDFN caused by Rh alloimmunization were more likely to require medical interventions, including simple or exchange transfusions, and more likely to be delivered by cesarean delivery. Overall, HDFN was associated with a longer hospital length of stay in the neonatal intensive care unit when compared with healthy and other sick newborns, a higher rate of cesarean delivery, and a higher rate of nonroutine discharge than healthy newborns. CONCLUSION: Overall, the live birth prevalence of HDFN was higher than those previously reported, whereas Rh-induced HDFN live birth prevalence was similar to those previously reported. HDFN live birth prevalence owing to Rh alloimmunization decreased over time, likely because of continued Rh immune globulin prophylaxis. Treatment patterns for newborns with HDFN and the comparative clinical outcomes when compared with healthy newborns confirm the continued clinical needs of this population.

"Provoked" feto-maternal hemorrhage may represent insensible cell exchange in pregnancies from 6 to 22 weeks gestational age.

OBJECTIVE: To quantify spontaneous and provoked fetal to maternal cell exchange in the first half of pregnancy. Transfer of fetal red blood cells (FRBCs) into the maternal circulation during the first half of pregnancy is poorly characterized but of clinical relevance for miscarriage management and invasive procedures. STUDY DESIGN: Prospective, descriptive cohort study of women presenting for surgical termination of pregnancy with sonographically confirmed gestational age (GA). Pre-procedural and post-procedural blood samples were collected to characterize both spontaneous (pre) and provoked (post) cell exchange with analysis via flow cytometry to quantify FRBC count. RESULTS: A total of 100 patients at 6-22 weeks GA contributed 200 matched pre- and post-procedural samples. FRBCs were identified in 69 patients including 4 who exhibited FRBCs pre-procedure only and 9 post-procedure only, for a total of 65 patients having post-procedural FRBCs. Of patients with FRBCs following their procedure, the majority (n=56, 86%) also exhibited evidence of cells before the procedure with just 9 patients (14%) exhibiting FRBCs only after. No dose-response relationship was appreciable between GA and FRBC count. CONCLUSION: After experiencing disruption of the placenta with instrumentation, roughly two thirds of patients had detectable FRBCs in maternal circulation following their procedure but-among those that did-the majority also exhibited cell presence prior to the procedure. This leads to further questions regarding the relationship between risk events and alloimmunization potential in previable pregnancies as the rate of spontaneous transplacental cell exchange may be underappreciated and the magnitude of provoked transfer may be overestimated. IMPLICATIONS: The relationship between feto-maternal hemorrhage risk events and alloimmunization potential in previable pregnancies has previously been poorly characterized but these data reveal spontaneous transplacental cell exchange may be underappreciated and the magnitude of provoked transfer may be overestimated.

Elimination of ABO Blood Group Incompatible Fetal Red Blood Cells in the Maternal Circulation: Relevance to the Diagnosis of Fetal-Maternal Hemorrhage.

BACKGROUND: Fetal-maternal hemorrhage (FMH) occurs when fetal red blood cells (RBC) pass into the maternal circulation as a result of obstetric- or trauma-related complications to pregnancy. Their detection in the maternal blood is commonly used as a diagnostic test. There is, however, a serious and general limitation to this test that is sometimes ignored. Fetal RBC carrying the father's antigens (most crucially, the ABO blood antigens) may be incompatible with the mother's plasma. They are expected to be eliminated by the maternal natural antibodies, thus, negative results may be false. OBJECTIVES: By simulating fetal-maternal ABO incompatibility, we studied the fate of fetal RBC in vitro. METHODS: Adult blood samples (n = 6) of O-blood group (type) were mixed with 1-5% cord blood or neonatal blood of A- or O-type, representing incompatible and compatible fetal RBC, respectively. The survival of fetal RBC was quantified after an overnight incubation. The supernatant was assayed for fetal hemoglobin (HbF) using the spectrophotometric alkaline-resistance benzidine assay, while the pellet was assayed for HbF/carbonic anhydrase (CA) expression in RBC by flow cytometry. The HbFhigh/CAlow phenotype characterizes fetal RBC. RESULTS: Both assays demonstrated disappearance of the fetal RBC due to lysis upon incubation in incompatible blood. CONCLUSIONS: A similar situation may also occur in vivo. Thus, under these conditions, negative results in the FMH test may be false, and lead to misdiagnosis.

Pathological Findings in Feto-maternal Hemorrhage.

Feto-maternal hemorrhage (FMH) is the cause of late fetal death in 1.6%-11% of cases. In spite of this high frequency, its pathological features have received little attention. The definitive diagnosis of lethal FMH requires confirmation of sufficient fetal blood volume loss. This is determined by tests such as the Kleihauer-Betke test, which may not have been obtained or not have been available before the autopsy. The pathologist may offer a tentative diagnosis of FMH from the autopsy findings. The objective of this study was to better characterize the placental and fetal autopsy findings in lethal FMH. This was a retrospective study of 17 cases of FMH proven by a positive Kleihauer-Betke test. The cases were selected from the autopsy files of the Department of Pathology, Centre Hospitalier Universitaire de Bordeaux. The pathological reports as well as the placental and fetal photographs and the microscopic slides of each case were systematically reviewed. The fetal autopsy findings in FMH are characterized by a eutrophic pale macerated fetus, low liver weight, absent intrathoracic petechiae, increased extramedullary hematopoiesis in the liver and kidney, and increased circulating nucleated red blood cells. The placenta shows an increased frequency of intervillous thrombi. Although nonpathognomonic, some of the pathological features are strongly suggestive of FMH. When the latter is present, a Kleihauer-Betke test should be performed, even some days after the delivery.

The use of middle cerebral artery Doppler ultrasonography to guide delivery of a viable pregnancy complicated by metastatic gestational chroriocarinoma.

Background: Choriocarcinoma is a rare, aggressive subtype of gestational trophoblastic neoplasia. The diagnosis of metastatic choriocarcinoma in the setting of a viable intrauterine pregnancy is exceedingly rare and often associated with feto-maternal hemorrhage. Case: An otherwise healthy Gravida 1 Para 0 at 34 weeks gestational age presented with metastatic choriocarcinoma and a viable fetus. Measured Doppler peak systolic velocity of the middle cerebral artery was used to detect fetal anemia, thus optimising the timing of delivery. Conclusion: This is the first case report to our knowledge using Doppler ultrasonography to detect fetal anemia in an effort to guide delivery in a case of choriocarcinoma diagnosed during pregnancy. If choriocarcinoma is diagnosed during pregnancy, middle cerebral artery Doppler ultrasonography may serve as a critical tool to help detect anemia, allowing pregnancy prolongation to promote fetal maturity while screening for the development of feto-maternal hemorrhage.

Two Cases of Severe Neonatal Anemia associated with Massive Feto-Maternal Hemorrhage / 대한주산의학회잡지

Feto-maternal hemorrhage, the presence of fetal red blood cells in the maternal circulation, occurs in up to 75% of pregnancies. But its volume is usually very small. Feto-maternal hemorrhage of more than 30 ml of whole blood is relatively rare. The key features that lead to early diagnosis are the maternal history, fetal monitoring, the clinical and laboratory findings of anemia and a negative Coombs' test. Diagnosis is confirmed by Kleihauer-Betke test. Perinatal problems include fetal distress, neonatal anemia, hypovolemic shock, and death. The fetal outcome depends on the amount and rate of bleeding. The initial hemoglobin level was a better predictor than the volume of bleeding. We present two cases of severe neonatal anemia associated with massive feto-maternal hemorrhage, which was confirmed by Kleihauer-Betke test.

A Case of Matemal Hemorrhage

Fetomaternal hemorrhage is very common and the commonest cause of anernia in the newborn. But, few blood cells enter the maternal circulation in most pregnancies. Occasionally large intrauterine bleeding results in severe fetal and neonatal anemia, shock, and rarely death. To identify the fetal blood in the maternal circu1ation, acid elution technique of Kleihauer-Betke test is usually used. And imrnedate neonatal blood transfusion should be done for good prognosis. We report a case of massive feto-maternal hemorrhage (>100 ml) in a preterm neonate with severe anemia at birth, which was diagnosed by Kleihauer-Betke test and was treated with blood transfusion.