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.

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.