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The objective of our study was to evaluate serum CX3CL1/Fractalkine, a monocyte/macrophage chemoattractant expressed in cytotrophoblasts and decidual cells, as a predictive biomarker for the occurrence of preterm premature rupture of membranes (PPROM). A case-control study of 438 pregnancies including 82 PPROM cases and 64 preterm labor with intact membranes cases with blood samples collected at first trimester, second trimester and delivery was conducted. The predictive ability of CX3CL1 and maternal risk factors for the occurrence of PPROM was assessed by receiver operating characteristic curve analysis. A second, independent cohort was prospectively constituted to confirm the case-control study results. First trimester CX3CL1 was significantly increased in PPROM cases when compared to matched controls. Multivariate regression analysis highlighted a significant difference for CX3CL1 measured during the first trimester (p<0.001). Alone, CX3CL1 predicts PPROM with a 90 % sensitivity and a specificity around 40 %. The area under the receiver operating characteristic curve for PPROM prediction were 0.64 (95% confidence interval: 0.57–0.71) for first trimester CX3CL1, and 0.61 (95% confidence interval: 0.54–0.68) for maternal risk factors (body mass index<18.5 kg/m2, nulliparity, tobacco use and the absence of high school diploma). The combination of CX3CL1 and maternal risk factors significantly improved the area under the curve: 0.72 (95% confidence interval: 0.66–0.79) (p<0.001). The results were confirmed on a second independent cohort. CX3CL1 is a promising blood biomarker in the early (first trimester) prediction of PPROM. [ABSTRACT FROM AUTHOR]

Background: Blood tryptase and fecal calprotectin levels may serve as biomarkers of necrotizing enterocolitis. However, their interpretation may be hindered by the little-known effects of perinatal factors. The aim of this study was to compare the tryptase and calprotectin levels in newborns according to their term, trophicity, and sex. Method: One hundred and fifty-seven premature newborns and 157 full-term newborns were included. Blood tryptase and fecal calprotectin were assayed. Results: Blood tryptase levels were higher in premature than in full-term newborns (6.4 vs. 5.2 µg/L; p < 0.001). In situations of antenatal use of corticosteroids (p = 0.007) and non-exclusive use of human milk (p = 0.02), these levels were also higher. However, in multiple linear regression analyses, only prematurity significantly influenced tryptase levels. Fecal calprotectin levels were extremely wide-ranging and were much higher in female than in male newborns (300.5 vs. 110.5 µg/g; p < 0.001). Conclusions: The differences in tryptase levels according to term could be linked to early aggression of the still-immature digestive wall in premature newborns, in particular, by enteral feeding started early. The unexpected influence of sex on fecal calprotectin levels remains unexplained. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury management is a tricky issue in children and pregnant women (due to adverse effects of computer tomography). To facilitate management, we report the main analytical performances and reference ranges for blood tests for the well-established S100B biomarker in under-16 children on a DiaSorin® Liaison XL analyzer and in pregnant women on DiaSorin® Liaison XL and Roche Diagnostics® Cobas e411 analyzers. Methods: Serum S100B concentrations were determined by chemiluminescent immunoassay on a DiaSorin® analyzer in a population of 409 healthy children aged 0-16 years and on DiaSorin®/Roche Diagnostics® instruments in a population of 50 pregnant women (one blood sample for each trimester). The analytical performances of both instruments and the influence of blood cells and skin pigmentation on the assay were also studied. Results: For children, four age-groups emerged, i.e. 0-3 months (mean: 0.97 μg/L; standard deviation (SD): 0.36; 95th percentile: 1.55), 4-9 months (mean: 0.58 μg/L; SD: 0.30; 95th: 1.18), 10-24 months (mean: 0.31 μg/L; SD: 0.12; 95th: 0.54) and 2-16 years (mean: 0.20 μg/L; SD: 0.07; 95th: 0.32). For pregnant women, serum S100B concentrations were similar to defined ranges for adults and not significantly different between trimesters on DiaSorin® (p=0.652)/Roche Diagnostics® (p=0.877) analyzers. We also found S100B expression (protein, total mRNA) in lymphocytes, an influence of skin pigmentation, and good analytical performances for both instruments. Conclusions: Data provided here is useful for interpreting serum S100B test results, in terms of preanalytical conditions, analytical performances, pediatric and pregnancy' environment. [ABSTRACT FROM AUTHOR]

Background: Although it is well known that France has a cultural history of alcohol use, no recent French data on alcohol consumption during pregnancy in a large sample are available. Methods: To determine the alcohol consumption patterns among pregnant women in France, we analyzed data from a 1-year multicenter self-survey. Sociodemographic profile, obstetrical history, neonatal data, and a self-report for assessing drinking patterns during pregnancy including AUDIT were recorded from women who delivered recently. Cases of fetal alcohol syndrome (FAS) were also reported. Results: A total of 837 pregnant women have described all parameters. The mean age at delivery of our sample was 29.7 years (SD = 4.8 years). A total of 52.2% of women indicated that they had consumed alcohol at least once during their pregnancy, and among abstainers 54.5% had a positive AUDIT score. Of the pregnant women who consumed alcohol, 13.7% reported at least one binge drinking episode (5 or more drinks on 1 occasion) during pregnancy. Binge drinking is significantly more frequent than regular alcohol consumption (at least 1 drink more than 1 time per week) during pregnancy. A prevalence rate of FAS of 1.8 per 1,000 live births was observed. Conclusions: There is a large population of women who still drink alcohol during pregnancy, particularly in binge drinking episodes. This underlines the need to clearly inform women of childbearing age about the dangers of alcohol during pregnancy as related to all types of consumption. Moreover, acting to prevent alcohol consumption prior to pregnancy may also greatly influence prenatal drinking. [ABSTRACT FROM AUTHOR]

The placenta is a transitory structure indispensable for the proper development of the embryo and fetus during mammalian gestation. Like other members of the nuclear receptor family, the peroxisome proliferator-activated receptors (PPARs) are known to be involved in the physiological and pathological events occurring during the placentation. This placental involvement has been recently reviewed focusing on the early stages of placental development (implantation and invasion, etc.), mouse PPARs knockout phenotypes, and cytotrophoblast physiology. In this review, we describe the placental involvement of PPARs (e.g., fat transport and metabolism, etc.) during the late stages of gestation and in the amniotic membranes, highlighting their roles in the inflammation process (e.g., chorioamnionitis), metabolic disorders (e.g., diabetes), and parturition. [ABSTRACT FROM AUTHOR]

Background: As a first step to explore the possible relationships existing between the effects of low oxygen pressure in the first trimester placenta and placental pathologies developing from mid-gestation, two subtracted libraries totaling 2304 cDNA clones were constructed. For achieving this, two reciprocal suppressive/subtractive hybridization procedures (SSH) were applied to early (11 weeks) human placental villi after incubation either in normoxic or in hypoxic conditions. The clones from both libraries (1440 hypoxia-specific and 864 normoxia-specific) were spotted on nylon macroarrays. Complex cDNAs probes prepared from placental villi (either from early pregnancy, after hypoxic or normoxic culture conditions, or near term for controls or pathological placentas) were hybridized to the membranes. Results: Three hundred and fifty nine clones presenting a hybridization signal above the background were sequenced and shown to correspond to 276 different genes. Nine of these genes are mitochondrial, while 267 are nuclear. Specific expression profiles characteristic of preeclampsia (PE) could be identified, as well as profiles specific of intra-uterine growth retardation (IUGR). Focusing on the chromosomal distribution of the fraction of genes that responded in at least one hybridization experiment, we could observe a highly significant chromosomal clustering of 54 genes into 8 chromosomal regions, four of which containing imprinted genes. Comparative mapping data indicate that these imprinted clusters are maintained in synteny in mice, and apparently in cattle and pigs, suggesting that the maintenance of such syntenies is requested for achieving a normal placental physiology in eutherian mammals. Conclusion: We could demonstrate that genes induced in PE were also genes highly expressed under hypoxic conditions (P = 5.10-5), which was not the case for isolated IUGR. Highly expressed placental genes may be in syntenies conserved interspecifically, suggesting that the maintenance of such clusters is requested for achieving a normal placental physiology in eutherian mammals. [ABSTRACT FROM AUTHOR]

Assesses retinol status and transport modalities of retinol in well-nourished women with normal pregnancies. Measurement of the maternal and cord blood concentrations of retinol; Serum circulatory amounts of retinol, vitamin E and binding proteins in pregnant women; Modification of homeostasis and transport during normal human pregnancy.

Background: After maternal alcohol consumption during pregnancy, many neonates affected by less apparent forms of fetal alcohol syndrome disorder (FASD) do not receive proper diagnosis or treatment. There is thus a need for laboratory markers for early detection of alcohol-exposed neonates. The aim of our study was to assess the efficiency of the usual alcohol biomarkers measured in cord blood to identify alcohol-exposed neonates immediately after birth. Methods: A 1-year study was conducted in the labor wards of the maternity units of the Auvergne, Central France at the time of term delivery. The patients answered an anonymous self-completion survey concerning alcohol use (Alcohol Use Disorder Identification Test; AUDIT) during their pregnancy. Aspartate aminotransferase, alanine aminotransferase, and γ-glutamyltransferase concentrations and the percentage of carbohydrate-deficient transferrin were measured in maternal and cord blood. Results: We collected 870 maternal-fetal sample pairs. Two cases (0.2%) of typical FASD were detected. We report a non-significant correlation between maternal and cord blood biomarkers. None of the cord blood biomarkers differed significantly between newborns of alcohol-exposed and unexposed mothers. Conclusions: We demonstrate that the usual alcohol biomarkers are not effective in cord blood for identifying alcohol-exposed neonates. Clin Chem Lab Med 2007;45:546–8. [ABSTRACT FROM AUTHOR]

: ObjectiveTo summarize the recent knowledge on the implications of placenta and cytokines in normal and preeclamptic pregnancies.: Data sourcesA literature search was conducted of applicable articles related to interactions between trophoblast and cytokines in generating preeclampsia.: ConclusionsThe initiating event in preeclampsia has been postulated to be the reduced uteroplacental perfusion as a result of abnormal extravillous cytotrophoblast invasion and remodeling of the uterine spiral arteries. Focal ischemia and hypoxia, deportation of hypoxemic trophoblast cells and abnormal expression of various placental biologic molecules, particularly the cytokines, are thought to lead to widespread dysfunction of the maternal vascular endothelium resulting in overproduction of endothelin and thromboxane, enhanced vascular sensitivity to angiotensin II, and reduced secretion of vasodilators such as nitric oxide and prostacyclin. These alterations, in turn, cause hypertension, proteinuria and edema, and pathologies in many organ systems (kidney, lung, liver, brain). [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the detection rate of prenatal diagnosis and its impact on outcome in congenital diaphragmatic hernia (CDH). Study design: We retrospectively studied 51 cases of CDH registered in the Auvergne area from January 1992 to December 2003 (Birth Defect Registry of Auvergne, Institut Européen des Génomutations). Our main outcome measurements were the detection rate of prenatal diagnosis, the incidence and types of associated anomalies and outcome (termination of pregnancy, in utero fetal demise, neonatal death, survival at the time of registration). Results: Twenty-nine cases of isolated CDH were identified of which 13 were detected prenatally (45%) at a mean gestational age of 26.1 weeks and 22 cases of CDH with associated anomalies with prenatal diagnosis of CDH or any associated anomaly in 16 (73%; p =0.03) at a mean gestational age of 23.9 weeks. In the prenatally detected group (29 cases), there was 1 (3%) in utero fetal death (IUFD), 17 (59%) terminations of pregnancy (TOP) and 11 (38%) live births with early neonatal death in 7 (24%) cases despite delivery in a tertiary care centre in 10/11 cases (four survivors=14%). Most of the undetected cases were isolated CDH (16/22=73%) of which 1 (5%) was a stillborn and 21 (95%) live births with 17 survivors (77%) although 15/21 (71%) were not born at the tertiary care centre (p =0.001). The overall survival rate was 41% with a large variability depending on associated anomalies and prenatal diagnosis (p <0.0001) (prenatally detected cases: 3/13 (23%) isolated CDH and 1/16 (6%) CDH with associated anomalies; undetected cases: 13/16 (81%) isolated CDH and 4/6 (67%) CDH with associated anomalies). Conclusion: Prenatal diagnosis of CDH leads to the delivery of affected babies in tertiary care centres but it remains a challenge in particular for isolated CDH cases and it is associated with a lower survival rate. Associated anomalies contribute to prenatal detection, are related to a higher TOP rate but do not facilitate the detection of diaphragmatic defect per se. [Copyright &y& Elsevier]

Abstract: The presence and integrity of amniotic fluid is fundamental for the normal development of the human fetus during pregnancy. Its production rate changes throughout pregnancy and is mainly related to the functions of the different fetal, placental and amniotic compartments. Premature rupture of the membranes (PROM) occurs in about 5% of deliveries, with complications such as infection and preterm birth. The management of patients with PROM, regardless of gestational age, remains controversial, and it is therefore important to develop new biological tests in order to achieve accurate diagnoses by identifying the presence of specific amniotic fluid markers in vaginal environment. We recently showed the usefulness of amniotic fluid proteomics in identifying a series of peptides that were absent from the corresponding maternal plasma. Several peptides corresponded to fragments of plasma proteins. Two peptides, absent from plasma samples of pregnant women, were identified in amniotic fluid. They corresponded to the COOH-terminal parts of perlecan (SwissProt: P98160) and of agrin (SwissProt: O00468) protein cores, two major heparan sulfate proteoglycans of basement membranes. In this review we will discuss modern proteomic strategies that may improve the laboratory assessment of PROM, and will focus on some of the biochemical characteristics of agrin and perlecan fragments identified in amniotic fluid. [Copyright &y& Elsevier]

During mammalian development, the placenta is a transitory but indispensable structure for a harmonious gestation involving several biological processes, such as adhesion, differentiation, apoptosis or cellular guidance. Nevertheless, the molecular pathways implicated during the placentation are still not totally understood. We previously described, the subcommissural organ (SCO)-spondin, a member of the ‘thrombospondin’ super-family, which is strongly expressed during mammalian central nervous system development. This extra-cellular matrix glycoprotein shows a unique arrangement of several conserved domains, including thrombospondin type 1 repeats, low-density lipoprotein receptor type A domains, two epidermal growth factor-like domains, and N- and C-terminal von Willebrand factor cysteine-rich domains. The presence of these domains strongly suggests the SCO-spondin involvement in cellular events occurring during placental development and physiology. In order to define this new role of SCO-spondin during development, we demonstrated its expression at relevant steps of gestation in human and mouse placenta, using RT-PCR, immunohistochemistry and Western-blot experiments. These data initiate further insights into the molecular and genetic functions of the neuronal gene SCO-spondin during trophoblastic and more globally during placental physiology and development. [Copyright &y& Elsevier]