[Which supervision and treatment to use in case of exposure to Parvovirus B19 during pregnancy?]. / Quelles surveillance et thérapeutique appliquer en cas de contage avec le Parvovirus B19 en cours de grossesse?

Fifty percent of young women are not immunized against Parvovirus B19 and may be infected during their pregnancy. Because of the scarcity of the foetal complications, the behaviour to be held in case of Parvovirus B19 exposure is badly known. In this view, we realized a review of the literature to answer the questions put by Parvovirus B19 during pregnancy, in particular in case of maternal exposure. About 33% of Parvovirus B19 infections of the pregnant women are complicated by foetal contamination. This foetal infection does not always result in foetal complications. The foetal complications are more frequent before 20 weeks of gestation (11 to 15% of spontaneous abortion and foetal death, 3% of foetal hydrops). After 20 weeks of gestation, it remains 1% of foetal hydrops. Without treatment, they may sometimes lead to foetal death. In the case of Parvovirus B19 exposure, it is advisable to control the maternal serology to know its initial status. According to the result, a weekly ultrasonographic supervision will be proposed to detect foetal anaemia (ascites, pericardial effusion). In the case of foetal hydrops, an in utero transfusion reduce the risk of foetal loss. The long-term outcome of infected foetuses is mostly good. Authors describe a survival without after-effect in 90% of the cases. More ample studies are necessary to evaluate long-term neurodevelopmental outcome of hydropic foetuses.

[Practical questions in case of maternal death]. / Questions pratiques en cas de survenue d'un décès maternel.

Every year, in France, about 70 women die during their pregnancy or the delivery. Any maternal death during labour is a traumatic event for the medical team and the family. The medical team has to face many "new" problems. We try to identify all the problems which the medical team has to face in front of a maternal death and try to solve them by a medical literature and French laws review. The medical team often feels powerless when a maternal death occurs. This work was made to be a guideline.

[Liver hernia. Prognosis and report of 11 cases]. / Les hépatocèles exclusives. Evaluation du pronostic. A propos de 11 observations.

OBJECTIVES: Exclusive hepatocele is defined as a hernia containing in majority the liver with possibly some intestinal loops. This study was undertaken to evaluate neonatal morbidity and mortality in this series of exclusive hepatoceles. MATERIALS AND METHODS: We reviewed 11 cases of exclusive hepatoceles with delivery at the hospital Jeanne-de-Flandre in the CHRU of Lille, in France. RESULTS: The mean gestational age of diagnosis was 14.5+/-3.4 weeks of gestation. Karyotype determination was performed in 100% of cases: it was abnormal in one case of 11. One termination of pregnancy was performed because of trisomy 13. The mean gestational age at delivery was 38+/-1.8 weeks of gestation. Cesarean deliveries were performed in nine cases. Morbidity was important with: one case of fetal growth retardation on total hepatocele, three cases of severe respiratory distress, two cases of severe digestive complications. The mean length of stay was 42.8 days. The mean length of parenteral feeding was 14.4 days. Postnatal mortality concerned one child, which died because of a severe respiratory distress due to pulmonary hypoplasia. CONCLUSION: In this series, morbidity is thus important, making of exclusive hepatoceles a full entity among the omphaloceles. The multidisciplinary take care is more complex but conceivable.

[Is a non-invasive management allowed for maternofetal alloimmune thrombocytopenia? Experience over a 10-year period]. / Peut-on prendre en charge l'allo-immunisation plaquettaire foetomaternelle de manière non invasive? Expérience sur dix ans.

OBJECTIVES: Our purpose was to study a non-invasive management of fetomaternal alloimmune thrombocytopenia (FMAIT). PATIENTS AND METHODS: Between 1996 and 2005, 18 women were treated. The population was divided into 2 groups: patients with a history of intracranial haemorrhage (ICH) in the older sibling received weekly intravenous immunoglobulin (IVIG) therapy to the mother (1 g/kg per week) without initial cordocentesis whereas patients with a history of neonatal thrombocytopenia did not undergo any treatment. RESULTS: All pregnancies with a previous FMAIT were monitored with serial ultrasound scans without cordecentesis. 15 patients had HPA-1, 2 HPA-3 and 1 HPA-5 immunizations. Weekly intravenous immunoglobulin therapy was administered in 5 patients with a history of ICH in the older sibling. Two of these delivered thrombocytopenic children; one had a platelet count < 50 x 10(9)/l. For the 13 women (one twin) who had a sibling with neonatal thrombocytopenia, 11/14 newborns had a platelet count < 50 x 10(9)/l. Predelivery fetal blood sampling were performed in 8/18 pregnancies. The neonatal periods of the 19 children were uncomplicated and no ICHs were observed. DISCUSSION AND CONCLUSION: Our results suggest that a non-invasive strategy avoiding serial cordocentesis may be an effective therapy in patients who are at risk of fetal and neonatal alloimmune thrombocytopenia.

[The HELLP syndrome: diagnosis and therapeutic burden]. / Le HELLP syndrome: diagnostic et prise en charge thérapeutique.

Management of HELLP syndrome is still controversial. In order to improve maternal and foetal prognosis, 2 approaches are usually considered: immediate termination of pregnancy (risk of foetal complications related to prematurity) or conservative treatment (maternal risk of complications related to hematologic disorders). Choice of treatment needs to be taken after evaluation of the maternal and fetal risk/benefit ratio.

[Post-partum broad ligament hematoma embolization: a case report]. / Embolisation d'un hématome du ligament large du post-partum: à propos d'un cas.

We relate the embolization of a hematoma of the broad ligament which developed suddenly in the post-partum period. The radiological intervention could be considered as an alternative treatment. The decision for embolization must be a multidisciplinary decision involving all the specialists concerned (interventional radiologist, intensive care specialist, and obstetrician).

[Evaluation of conventional hemi nested PCR analysis for fetal RHD determination in maternal plasma]. / Evaluation de la détermination du statut Rhésus-D foetal sur plasma maternel par la technique d'hemi-nested PCR.

AIMS: The aim of our study was to evaluate the possibility of identifying the fetal RhD status in maternal plasma using conventional hemi nested PCR analysis. SUBJECTS AND METHODS: After informed written consent, 20 mL of peripheral blood were collected in 99 D-negative pregnant women either at an amniocentesis for prenatal diagnosis or at a prenatal checkup. Fetal DNA extracted from 400 microL of maternal plasma was analyzed by two different operators with a hemi-nested PCR extending an area of the RhD gene exon 10. The results were compared to the fetal RhD status obtained by PCR amniotic fluid analysis or blood analysis of newborns after delivery. The influence of mother's and baby's phenotype were also studied. RESULTS: Among the 99 D-negative pregnant women, all Caucasian, 47 were in their second trimester and 52 in their third trimester (mean: 27.20 weeks of gestation +/-8.25). Sixty-nine fetuses were D-positive and thirty D-negative. The sensitivity and specificity of our technique were respectively 100% and 86.7% and 15% of discordant results were observed between the two operators. Four false positives were observed. According to maternal phenotype, a fetal unexpressed RHD gene was suspected in only one case because of a particular fetal phenotype (ddCcEe). CONCLUSION: A conventional hemi nested PCR analysis of maternal plasma could be used for accurate fetal RhD status. However this procedure is difficult to apply for routine analysis because of the importance of anti-contamination measures required to obtain good results. Real time quantitative PCR analysis on fetal DNA is more suitable. Whatever the operating procedure used, polymorphism of RhD gene may follow in either false negative from presence of rearranged gene or false positive from occasional presence of a non functional RHD gene.

[Spontaneous intrauterine depression skull: myth or reality?]. / Traumatismes crâniens obstétricaux spontanés: mythe ou réalité?

In spite of the fact that there are many articles considering that intrauterine depressed skull fractures are caused essentially by instrumental extraction, literature is scarce about spontaneous foetal head injuries. Here, we report the case of two depressed skull fractures and one of linear fracture not associated with any known trauma during the pregnancy or delivery. The etiological process leading to the idiopathic character of such lesions, the aetiology, the treatment and the prognostic will be discussed. The forensic problem raised by such cases is very important.

[What public health measures could reduce antenatal exposure to tobacco and improve the quality of perinatal care: the gynecologist-obstetrician's point of view]. / Quelles sont les mesures de santé publique susceptibles de réduire l'exposition anténatale au tabac et d'améliorer les indicateurs de qualité des soins périnatals? Le point de vue du gynécologue-obstétricien.

The progression of addiction to smoking among young women is particularly alarming. The fatal effects of the nicotine-poisoning on the pregnancy and on the child constitute a serious public health issue. For young women, the period of maternity plays an essential educational role. Contact with medical care during pregnancy offers a special opportunity to establish a sound basis for health. Clinicians must strive to help women become fully aware of the fatal effects of smoking, providing methods and support for abstinence through a global, structured strategy of health care. The "Maternity without tobacco" network was developed to achieve these objectives. Expired CO analysis can be an interesting tool to search for active or passive addiction to smoking, and more generally carbon monoxide poisoning.

[Epidemiology of maternal mortality by infectious cause in France, 2007-2009, using data from confidential maternal mortality report]. / Épidémiologie de la mortalité maternelle de cause infectieuse en France, période 2007-2009, à partir des données du rapport confidentiel de mortalité maternelle.

Although deaths caused by infection during pregnancy and the postpartum period are rare in France, mortality rates have increased in several countries of the European community. In France, the rate of maternal mortality by infectious cause has decreased over the last 12 years. Infectious causes are currently in fifth place of maternal deaths. Over the period 2007-2009, 18 deaths occurred, eight by direct infectious causes and 10 by indirect infectious causes. Among the 18 deaths, 17 were examined by the National Expert Committee on Maternal Mortality (CNEMM) with the objectives to determine the direct or indirect link with pregnancy, the adequacy of care and the preventability of death. Among 8 deaths from direct infectious causes, four deaths were deemed "preventable" or "possibly preventable" because of inadequate care. Among nine deaths from indirect infectious causes, preventability could not be established in two deaths, five were non-preventable and two were preventable due to non-optimal care. These cases of puerperal septicemia show that when sepsis is clinically manifest, infection is already well established and widespread deterioration is therefore often irreversible. Maternal mortality is preventable in most cases if several points are observed: early diagnosis, probabilistic antibiotics targeting most frequently involved bacteria including Escherichia coli and Streptococcus A, early transfer to ICU, control septic portal entry, simple preventive measures, influenza vaccination. A "microbiological clinical diagnosis" approach must be initiated at the first clinical signs.

Thymocyte and thymic microenvironment alterations during a systemic HIV infection in a severe combined immunodeficient mouse model.

OBJECTIVE: A new model for systemic and multifocal HIV-1 infection was developed in severe combined immunodeficient (SCID) mice to study the alterations of thymocytes and of the thymic microenvironment that occur during a disseminated HIV infection. DESIGN AND METHODS: We grafted SCID mice with the classical human fetal thymus/liver co-implants together with fragments of autologous lungs (SCID-huLLT). These organs achieved normal differentiation and were productively infected after an intraperitoneal inoculation of two HIV-1 primary isolates. At time of sacrifice, thymic biopsies and thymic cell suspensions were analysed by immunohistochemistry, flow cytometry and lymphocyte function assays. RESULTS: At weeks 2-4 post-inoculation we observed the following thymocyte abnormalities: a minor to severe depletion of the immature CD1+CD4+CD8+ T cells (range, 0-73% thymocytes), compared with the persistence of mature CD4+ cells (11-50%) and amplification of CD8+ T cells (6-92%). The immature subset depletion was inversely related to the thymic HIV-1 viral load, suggesting the preferential infection of this subset. The residual mature thymocytes were functional as assessed by their sustained proliferative responses to CD3-triggering which contrasted with the lack of HIV-specific cytotoxic activity. A quantitative analysis of immunostained thymic sections revealed a disorganization and a densification of the thymic epithelial cells (TEC) network which occurred in all HIV-infected SCID-hu mice independently of the thymic CD1+CD4+CD8+ T-cell depletion. CONCLUSION: These results suggest that a systemic HIV infection induces in human thymuses from SCID-huLLT mice a preferential depletion of the immature thymocytes in the absence of mature CD4+ T-cell depletion, HIV-specific cytotoxic T-lymphocyte activity or thymic epithelial cell death, but is associated with dysplasia of the thymic microenvironment, and is therefore opening new perspectives for studying immune cell reconstitution strategies in HIV infection.

Synthesis and biological evaluation of isomeric dinucleoside monophosphates and monomethylphosphonates of 9-beta-D-arabinofuranosyladenine and related analogues.

The 3'----5',3'----3' and 5'----5' dinucleoside monophosphates and methylphosphonates of 9-beta-D-arabinofuranosyladenine, as well as its 5'-(hydrogen phosphonate) and 5'-(methyl methylphosphonate) derivatives have been the subject of a systematic synthesis and examination of their biological, i.e. antiviral and cytostatic, properties. First the properly protected monomeric building blocks were prepared and then condensed to give fully protected intermediates. These latter were then deblocked to afford the unprotected compounds, which were fully characterized. Only the 3'----5' phosphodiester isomers 13 and 16 and, to a lesser extent, the 5'-(hydrogen phosphonate) derivative 21 showed marked biological activity.

Consecutive successful pregnancies in a combined liver and kidney transplant recipient with type 1 primary hyperoxaluria.

Pregnancy is now a common, but high-risk event, in young women who have received transplants. Consequences to the fetus are known, but pregnancy may also interfere with graft function. We report the outcome of two successive and successful pregnancies in a 29-year-old woman with type 1 hyperoxaluria, who received a combined liver and kidney transplant. Two healthy children were born at 35 and 37 weeks of gestation, with low birth weight. Liver function remained normal before, during, and after pregnancies up to 52 months after transplantation. Renal function was impaired before the first conception, worsened during both pregnancies, and returned to the previous level in both immediate postpartum periods. However, renal function has declined 17 months after the last delivery. This report shows the feasibility of successive pregnancies in multiple organ transplant recipients, but raises the question of long-term maternal kidney graft survival.

Brachmann-de Lange syndrome: pre- and postnatal findings.

Brachmann-de Lange syndrome (BDLS) is a well-delineated and relatively common syndrome. However, prenatal diagnosis has never been reported, even if in some cases ultrasonography demonstrated one or more manifestations of the syndrome. We report on 3 cases: in the first 2 cases, prenatal ultrasonography demonstrated some signs of the condition. The third represents, to our knowledge, the first prenatal diagnosis of BDLS. We also present a review of the literature concerning pre- and postnatal findings in this syndrome.

Intracellular delivery of nucleoside monophosphates through a reductase-mediated activation process.

On the basis of three different models (namely: ddU, AZT and PMEA), mononucleotide phosphotriester derivatives were designed to be able to liberate the corresponding monophosphate (or phosphonate) inside the cell through a reductase-mediated activation process. It was demonstrated that the use of bis[S-(2-hydroxyethylsulfidyl)-2-thioethyl] esters of ddUMP (11), AZTMP (12) and PMEA (17) resulted in intracellular delivery of the parent monophosphate (or phosphonate). This point was corroborated by observation of an anti-HIV effect of, 11 in various cell lines, for 12 in CEM TK- cells and by the enhanced activity observed for 17. Furthermore, the reported decomposition data in cell extracts fully confirm the validity of this approach and show unambiguously the potential for intracellular reductase-mediated activation of the starting drug.

Inhibition of HIV-1 replication in cultured cells with phosphorylated dideoxyuridine derivatives encapsulated in immunoliposomes.

Among the 2',3'-dideoxynucleoside 5'-triphosphates containing a physiological base, 2',3'-dideoxyuridine 5'-triphosphate (ddUTP) has been reported to be among the most powerful inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT) in cell-free systems. However, in contrast to other dideoxynucleosides, 2',3'-dideoxyuridine (ddU) is inactive in treatment of HIV-infected cells in culture, since it is a poor substrate for cellular nucleoside kinases. This problem cannot be overcome by the use of phosphorylated ddU because such compounds are unable to cross cell membranes. To promote entry and thus bypass the limiting steps of intracellular phosphorylation, we have encapsulated mono- and tri-phosphorylated ddU in liposomes coupled to monoclonal antibodies (immunoliposomes). We investigated antiviral effects in two human T cell lines (MT-4, CEM). We observed that ddU nucleotides remain phosphorylated for several weeks after encapsulation in immunoliposomes, and potent antiviral activity is obtained when these drugs are delivered into infected cells by cell-specific antibodies (ED50 < or = 1 microM on CEM). In contrast, no inhibition was observed with non-targeted liposomes containing phosphorylated ddU, or with empty liposomes, whether targeted or not.

Synthesis and biological evaluation of dinucleoside methylphosphonates of 3'-azido-3'-deoxythymidine and 2', 3'-dideoxycytidine.

The 5'----5' dinucleoside methylphosphonates of 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (DDC) were prepared and evaluated for their inhibitory properties against different viruses, including human immunodeficiency virus (HIV). The synthesis of the compounds was achieved by reaction of AZT or N4-(4-monomethoxytrityl)-2',3'-dideoxycytidine with in situ prepared methylphosphonic bis (triazolide), followed in the latter case by an acidic treatment. The two title compounds showed in vitro anti-HIV activity, that was 200- to 450-fold less pronounced that that shown by the corresponding monomeric nucleosides AZT and DDC. The decreased antiviral activity may be ascribed to nuclease resistance of the methylphosphonate linkage.

Successful treatment of extremely severe fetal anemia due to Kell alloimmunization.

BACKGROUND: Repeated plasmapheresis was used to prevent fetal death from severe anti-Kell alloimmunization until intrauterine transfusions were feasible. CASE: Repeated maternal plasma exchanges (N = 40) beginning at 7 weeks' gestation were used to treat severe anti-Kell alloimmunization. Ultrasound examination at 19 weeks' gestation revealed diffuse hydrops in this fetus (umbilical venous hemoglobin, 1.2 g/dL), which then required nine intrauterine transfusions through 34 weeks. A healthy 3840-g girl was delivered by cesarean delivery at 36 weeks. Despite aplastic anemia during the first 3 months of life, she is healthy and has no observable abnormalities at age 8. CONCLUSION: A highly aggressive course of plasmapheresis and intrauterine transfusions can successfully treat fetal anemia caused by anti-Kell alloimmunization even when fetal hemoglobin is extremely low.

Direct analysis of the lectin reactivity of alpha-fetoprotein in maternal serum by crossed affinity radio-immunoelectrophoresis.

Affinity experiments with the lentil (Lens culinaris) lectin have revealed the existence of two distinct molecular populations of alpha-fetoprotein: lectin reactive and lectin non-reactive. Using a combination of crossed lectin immunoelectrophoresis and radio-immunoelectrophoresis, it has been possible to obtain directly the lentil lectin affinity patterns of alpha-fetoprotein present in maternal sera. The lentil lectin reactivity of maternal alpha-fetoprotein decreases almost linearly with the gestational age from week 15 to 35.

[Exact determination of the lecithin/sphingomyelin ratio in amniotic fluid. Suggestion of a reference methods (author's transl)]. / Determination precise du rapport lecithine/sphingomyeline dans le liquide amniotique: Proposition d'une methode de reference.

Pulmonary maturity of the fetus can be evaluated by the lecithin/sphingomyelin (L/S) ratio in amniotic fluid. To existing methods of lipid extraction, precipitation with acetone and chromatography, we add a simple and accurate estimation of sphingomyelins (S) and precipitated lecithins (Lp) without acid digestion. The method is reproducible (C.V. less than 9%) for the measurement of Lp/S ratio and gives with accuracy the concentrations of Lp, avoiding possible errors in interpretation of Lp/S. Our results show that at 35 weeks of normal gestation, Lp/S ratio is about 2 and Lp concentration, 10 mg/1.