Clinical Chorioamnionitis and Neurodevelopment at 5 Years of Age in Children Born Preterm: The EPIPAGE-2 Cohort Study.

OBJECTIVE: To assess the association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born preterm. STUDY DESIGN: EPIPAGE 2 is a national, population-based cohort study of children born before 35 weeks of gestation in France in 2011. We included infants born alive between 240/7 and 346/7 weeks after preterm labor or preterm premature rupture of membranes. Clinical chorioamnionitis was defined as maternal fever before labor (>37.8°C) with ≥2 of the following criteria: maternal tachycardia, hyperleukocytosis, uterine contractions, purulent amniotic fluid, or fetal tachycardia. The primary outcome was a composite, including cerebral palsy, coordination disorders, cognitive disorders, sensory disorders, or behavioral disorders. We also analyzed each of these disorders separately as secondary outcomes. We performed a multivariable analysis using logistic regression models. We accounted for the nonindependence of twins and missing data by generalized estimating equation models and multiple imputations, respectively. RESULTS: Among 2927 children alive at 5 years of age, 124 (3%) were born in a context of clinical chorioamnionitis. Overall, 8.2% and 9.6% of children exposed and unexposed, respectively, to clinical chorioamnionitis had moderate-to-severe neurodevelopmental disorders. After multiple imputations and multivariable analysis, clinical chorioamnionitis was not associated with the occurrence of moderate-to-severe neurodevelopmental disorders (aOR, 0.9; 95% CI, 0.5-1.8). CONCLUSIONS: We did not find any association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born at <35 weeks of gestation after preterm labor or preterm premature rupture of membrane.

Intravenous immunoglobulin for the treatment of severe maternal alloimmunization: individual patient data meta-analysis.

OBJECTIVE: This study aimed to investigate the outcomes associated with the administration of maternal intravenous immunoglobulin in high-risk red blood cell-alloimmunized pregnancies. DATA SOURCES: Medline, Embase, and Cochrane Library were systematically searched until June 2023. STUDY ELIGIBILITY CRITERIA: This review included studies reporting on pregnancies with severe red blood cell alloimmunization, defined as either a previous fetal or neonatal death or the need for intrauterine transfusion before 24 weeks of gestation in the previous pregnancy as a result of hemolytic disease of the fetus and newborn. METHODS: Cases were pregnancies that received intravenous immunoglobulin, whereas controls did not. Individual patient data meta-analysis was performed using the Bayesian framework. RESULTS: Individual patient data analysis included 8 studies consisting of 97 cases and 97 controls. Intravenous immunoglobulin was associated with prolonged delta gestational age at the first intrauterine transfusion (gestational age of current pregnancy - gestational age at previous pregnancy) (mean difference, 3.19 weeks; 95% credible interval, 1.28-5.05), prolonged gestational age at the first intrauterine transfusion (mean difference, 1.32 weeks; 95% credible interval, 0.08-2.50), reduced risk of fetal hydrops at the time of first intrauterine transfusion (incidence rate ratio, 0.19; 95% credible interval, 0.07-0.45), reduced risk of fetal demise (incidence rate ratio, 0.23; 95% credible interval, 0.10-0.47), higher chances of live birth at ≥28 weeks (incidence rate ratio, 1.88; 95% credible interval, 1.31-2.69;), higher chances of live birth at ≥32 weeks (incidence rate ratio, 1.93; 95% credible interval, 1.32-2.83), and higher chances of survival at birth (incidence rate ratio, 1.82; 95% credible interval, 1.30-2.61). There was no substantial difference in the number of intrauterine transfusions, hemoglobin level at birth, bilirubin level at birth, or survival at hospital discharge for live births. CONCLUSION: Intravenous immunoglobulin treatment in pregnancies at risk of severe early hemolytic disease of the fetus and newborn seems to have a clinically relevant beneficial effect on the course and severity of the disease.

Fetal Anemia: Determinants and Perinatal Outcomes according to the Method of Intrauterine Blood Transfusion.

INTRODUCTION: Fetal anemia from hemolytic disease treated by intrauterine transfusion (IUT) can be performed by intraperitoneal, intracardiac, and intravascular transfusion (IVT). Objective of our study was to compare different transfusion techniques. METHODS: Retrospective review of IUT secondary to red cell alloimmunization was conducted at eight international centers from 2012 to 2020. Severe anemia suspected if middle cerebral artery peaks systolic velocity ≥1.5 multiples of the median. Demographic, delivery, and postnatal variables were analyzed. RESULTS: Total of 344 procedures, 325 IVT and 19 other techniques (non-IVT) included. No difference in demographics, history of stillbirth (20.5 vs. 15.8%, p = 0.7), prior pregnancy IUT (25.6 vs. 31.6%, p = 0.5) or neonatal transfusion (36.1 vs. 43.8%, p = 0.5). At first IUT, non-IVT had higher hydrops (42.1% vs. 20.4%, p = 0.03), lower starting hematocrit (13.3% [±6] vs. 17.7% [±8.2], p = 0.04), and trend toward lower gestational age (24.6 [20.1-27] vs. 26.4 [23.2-29.6] weeks, p = 0.08). No difference in birthweight, neonatal phototherapy, exchange, or simple transfusion was observed. CONCLUSION: This is one of the largest studies comparing techniques to treat fetal anemia. IVT was most performed, other techniques were more likely performed in hydrops, and lower starting hematocrit was seen. Neither technique affected outcomes. This study may suggest that physician's experience may be the strongest contributor of outcomes.

Prenatal management of fetal anemia due to pyruvate kinase deficiency: A case report.

BACKGROUND: Pyruvate Kinase (PK) deficiency is the most common enzyme defect of glycolysis, leading to congenital hemolytic anemia, which can occur during the neonatal period. STUDY DESIGN AND METHODS: We report the prenatal management of fetal anemia related to PK deficiency in a family with a severe proband. RESULTS: The couple had a first child born with hydrops, whose PK deficiency was diagnosed at 18 months of life. He was treated with allogeneic bone marrow transplantation. The second child was free from disease. For the third pregnancy, the amniocentesis revealed a PK deficiency. Weekly ultrasound monitoring of the middle cerebral artery velocity allowed the detection of severe fetal anemia. Two intrauterine red blood cell transfusions (IUTs) were performed, raising the fetal hemoglobin from 6.6 to 14.5 g/dl at 28 weeks' gestation and from 8.9 to 15.3 g/dl at 31 weeks. A hematopoietic stem cell allograft was discussed prenatally but not chosen, as it would not have significantly changed the perinatal prognosis. The patient delivered a 2730 g girl at 37 weeks, with hemoglobin of 13.6 g/dl. The child presented with neonatal jaundice treated with phototherapy and received postnatal transfusions. DISCUSSION: When a proband is identified in a family, fetal investigation is warranted, to set up third-trimester ultrasound surveillance and perinatal management. In case of fetal severe anemia of unknown etiology, the workup on fetal blood sampling before IUT should comprise the search for erythrocytes enzymopathies, such as PK deficiency. IUTs allow safer full-term delivery in cases with PK deficiency.

COVID-19-related medicine utilization study in pregnancy: The COVI-PREG cohort.

AIM: The objective of this study was to describe the use of COVID-19-related medicines during pregnancy and their evolution between the early/late periods of the pandemic. METHODS: Pregnant women who tested positive for SARS-CoV-2 from March 2020 to July 2021 were included using the COVI-PREG registry. Exposure to the following COVID-19-related medicines was recorded: antibiotics, antivirals, hydroxychloroquine, corticosteroids, anti-interleukin-6 and immunoglobulins. We described the prevalence of medicines used, by trimester of pregnancy, maternal COVID-19 severity level and early/late period of the pandemic (before and after 1 July 2020). FINDINGS: We included 1964 pregnant patients who tested positive for SARS-CoV-2. Overall, 10.4% (205/1964) received at least one COVID-19-related medicine including antibiotics (8.6%; 169/1694), corticosteroids (3.2%; 62/1964), antivirals (2.0%; 39/1964), hydroxychloroquine (1.4%; 27/1964) and anti-interleukin-6 (0.3%; 5/1964). The use of at least one COVID-19-related medicine was 3.1% (12/381) in asymptomatic individuals, 4.2% (52/1233) in outpatients, 19.7% (46/233) in inpatients without oxygen, 72.1% (44/61) in those requiring standard oxygen, 95.7% (22/23) in those requiring high flow oxygen, 96.2% (25/26) in patients who required intubation and 57.1% (4/7) among patients who died. The proportion who received medicines to treat COVID-19 was higher before than after July 2020 (16.7% vs. 7.7%). Antibiotics, antivirals and hydroxychloroquine had lower rates of use during the late period. CONCLUSION: Medicine use in pregnancy increased with disease severity. The trend towards increased use of corticosteroids seems to be aligned with changing guidelines. Evidence is still needed regarding the effectiveness and safety of COVID-19-related medicines in pregnancy.

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.

Cause of preterm birth and late-onset sepsis in very preterm infants: the EPIPAGE-2 cohort study.

BACKGROUND: The pathogenesis of late-onset sepsis (LOS) in preterm infants is poorly understood and knowledge about risk factors, especially prenatal risk factors, is limited. This study aimed to assess the association between the cause of preterm birth and LOS in very preterm infants. METHODS: 2052 very preterm singletons from a national population-based cohort study alive at 72 h of life were included. Survival without LOS was compared by cause of preterm birth using survival analysis and Cox regression models. RESULTS: 437 (20.1%) had at least one episode of LOS. The frequency of LOS varied by cause of preterm birth: 17.1% for infants born after preterm labor, 17.9% after preterm premature rupture of membranes, 20.3% after a placental abruption, 20.3% after isolated hypertensive disorders, 27.5% after hypertensive disorders with fetal growth restriction (FGR), and 29.4% after isolated FGR. In multivariate analysis, when compared to infants born after preterm labor, the risk remained higher for infants born after hypertensive disorders (hazard ratio HR = 1.7, 95% CI = 1.2-2.5), hypertensive disorders with FGR (HR = 2.6, 95% CI = 1.9-3.6) and isolated FGR (HR = 2.9, 95% CI = 1.9-4.4). CONCLUSION: Very preterm infants born after hypertensive disorders or born after FGR had an increased risk of LOS compared to those born after preterm labor. IMPACT: Late-onset sepsis risk differs according to the cause of preterm birth. Compared with those born after preterm labor, infants born very preterm because of hypertensive disorders of pregnancy and/or fetal growth restriction display an increased risk for late-onset sepsis. Antenatal factors, in particular the full spectrum of causes leading to preterm birth, should be taken into consideration to better prevent and manage neonatal infectious morbidity and inform the parents.

The Myelic Limited Dorsal Malformation: Prenatal Ultrasonographic Characteristics of an Intermediate Form of Dysraphism.

OBJECTIVES: The aim of the study was to report a subtype of dysraphism designated as myelic limited dorsal malformation (MyeLDM) and to describe its characteristics at prenatal ultrasound (US). METHODS: It was a retrospective study from 2014 to 2020 based on second-line US evaluation of patients referred to our institution for myelomeningocele (MMC). Magnetic resonance imaging and acetylcholine esterase evaluation in the amniotic fluid were also offered. Major and minor criteria for open and closed dysraphism were defined and recorded for each patient. Patients were included as MyeLDM when both criteria of closed and open dysraphism were observed in the same fetus. Correlations were obtained with the postpartum data. RESULTS: Twenty patients fulfilled the inclusion criteria, some of them being very close to MMC, others very close to limited dorsal myeloschisis (LDM), and others lying in between. There were 13 live-born neonates and 7 terminations of pregnancy. Correlations between prenatal and postpartum data were overall very good. CONCLUSION: Our series describe the ultrasonographic characteristics of an intermediate type of dysraphism and suggest that there is a continuum between MMC and LDM with numerous possibilities of hybrid forms (MyeLDM) sharing characteristics of both open and closed dysraphisms.

[Vitamin D and pregnancy]. / Vitamine D et grossesse.

Vitamin D deficiency affects more than half of the general population. During pregnancy vitamin D insufficiency is associated with a higher risk of complications such as an increased incidence of miscarriages. Preterm delivery, preeclampsia, gestational diabetes, growth retardation and low birth weight as well as postpartum hemorrhage are all pathologies whose incidence seems to be increased with hypovitaminosis D. This could be linked to the pregnancy changes of the immune system, on which vitamin D plays a well-known modulating role. Substitution, even if its benefit is not clearly established, should be considered as there are no side effects. Although lack of evidence regarding the timing of the introduction of treatment, substitution may be proposed before conception.

Un déficit en vitamine D concerne plus de la moitié de la population générale. Une carence en vitamine D en cours de grossesse est associée à une augmentation du risque de complications comme les fausses couches. Les accouchements prématurés, la prééclampsie, le diabète gestationnel, le retard de croissance et le petit poids de naissance ainsi que les hémorragies du post-partum sont toutes des pathologies dont l'incidence semble augmentée lors d'hypovitaminose D. Cela pourrait être en lien avec la modification du système immunitaire lors de la grossesse, sur lequel la vitamine D joue un rôle modulateur. Ainsi, même si son effet bénéfique n'est pas clairement établi et que les évidences concernant le moment de son introduction manquent, une substitution en vitamine D devrait être proposée en préconceptionnel.

Association of Chorioamnionitis with Cerebral Palsy at Two Years after Spontaneous Very Preterm Birth: The EPIPAGE-2 Cohort Study.

OBJECTIVE: To assess whether chorioamnionitis is associated with cerebral palsy (CP) or death at 2 years' corrected age in infants born before 32 weeks of gestation after spontaneous birth. STUDY DESIGN: EPIPAGE-2 is a national, prospective, population-based cohort study of children born preterm in France in 2011; recruitment periods varied by gestational age. This analysis includes infants born alive after preterm labor or preterm premature rupture of membranes from 240/7 to 316/7 weeks of gestation. We compared the outcomes of CP, death at 2 years' corrected age, and "CP or death at age 2" according to the presence of either clinical chorioamnionitis or histologic chorioamnionitis. All percentages were weighted by the duration of the recruitment period. RESULTS: Among 2252 infants born alive spontaneously before 32 weeks of gestation, 116 (5.2%) were exposed to clinical chorioamnionitis. Among 1470 with placental examination data available, 639 (43.5%) had histologic chorioamnionitis. In total, 346 infants died before 2 years and 1586 (83.2% of the survivors) were evaluated for CP at age 2 years. CP rates were 11.1% with and 5.0% without clinical chorioamnionitis (P = .03) and 6.1% with and 5.3% without histologic chorioamnionitis (P = .49). After adjustment for confounding factors, CP risk rose with clinical chorioamnionitis (aOR 2.13, 95% CI 1.12-4.05) but not histologic chorioamnionitis (aOR 1.21, 95% 0.75-1.93). Neither form was associated with the composite outcome "CP or death at age 2." CONCLUSIONS: Among infants very preterm born spontaneously, the risk of CP at a corrected age of 2 years was associated with exposure to clinical chorioamnionitis but not histologic chorioamnionitis.

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.

The Pubic Diastasis Measurement, a Key Element for the Diagnosis, Management, and Prognosis of the Bladder Exstrophy.

OBJECTIVE: To demonstrate the feasibility of measuring the fetal pubic diastasis (PD) distance on antenatal ultrasound in normal fetuses and to compare it to fetuses with bladder exstrophy. METHODS: Firstly, a prospective multicentric study was conducted to determine the feasibility of the PD ultrasound measurement during the second half of pregnancy. Secondly, data from a single center were used to develop a nomogram for PD values in normal fetuses. Thirdly, retrospective PD measurements were collected from fetuses with bladder exstrophy, diagnosed in seven French Multidisciplinary Centers for Prenatal Diagnosis (MCPDs). RESULTS: Operators from several MCPDs examined 868 fetuses and found that overall PD ultrasound measurement was feasible in 71% of cases and that the ossification of pubic points increased to be always visible from 27 weeks of gestation onward. Performed in a single center by a referring operator on 1,539 fetuses, the feasibility reached 94.74%. Both set of measurements were concordant (mean PD distance value of 5.42 ± 1.8 mm). Interestingly, all 23 fetuses with bladder exstrophy showed a significantly larger PD distance (mean 15.74 ± 3.9 mm). CONCLUSION: PD measurement in the fetus is feasible and reliable in the second half of gestation and can be used to support the antenatal diagnosis of bladder exstrophy with PD values exceeding 10 mm.

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.

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.