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.

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.

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.

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.