Bruno Carbonne

Detection of hepatitis C virus RNA (HCV RNA) in amniotic fluid: a prospective study

BACKGROUND/AIMS Mother-to-infant transmission of hepatitis C virus (HCV) has been reported, but the transmission route is unknown. The aim of our study was to detect HCV RNA in amniotic fluid of pregnant women seropositive for HCV. METHODS Twenty-two HCV seropositive women were included in the study (median age: 39 years). An amniocentesis was performed in all patients during the 4th month of pregnancy. Sixteen women also tested positive for HCV RNA in serum. The range of HCV RNA titers was 0.3 to 15.1x10(6) Eq/ml (Quantiplex HCV RNA 2.0 Assay, Chiron Diagnostics). Of these 16 viremic patients, four had an anterior placenta, ten had a posterior placenta and the position of the placenta was not determined in two cases. PCR (Amplicor HCV, Roche Diagnostics) was used to detect HCV RNA in the amniotic fluid. We also studied 11 HCV seronegative women as a control group. RESULTS In the viremic group (n = 16), HCV RNA was detected once in amniotic fluid. The positive specimen was collected from a patient with an HCV RNA serum value equal to 1.1x10(6) Eq/ml. The placenta was in an anterior position. A PCR inhibitor was detected in one case. No HCV RNA was detected in the amniotic fluid of six seropositive non-viremic patients, nor in the control group. Serum HCV RNA was negative in the ten children tested. The woman whose amniotic fluid contained HCV RNA was the mother of one of them. CONCLUSIONS HCV RNA detection in amniotic fluid is rarely positive. The anterior position of the placenta in the only positive detection cannot rule out contamination of the amniotic fluid during the transplacental amniocentesis.

Multicenter study on the clinical value of fetal pulse oximetry

OBJECTIVE Our purpose was to compare the predictive value of intrapartum fetal pulse oximetry with that of fetal blood analysis for an abnormal neonatal outcome in case of an abnormal fetal heart rate. STUDY DESIGN A prospective multicenter observational study was conducted from June 1994 to November 1995. Fetal oxygen saturation was continuously recorded with a Nellcor N-400 fetal pulse oximeter in case of an abnormal fetal heart rate during labor. Simultaneous readings of fetal oxygen saturation and fetal blood analysis obtained before birth (i.e., either at full dilatation or before cesarean section when indicated) were compared with the neonatal status. The criteria for an abnormal neonatal outcome were (1) an umbilical arterial blood pH < or = 7.15 and (2) a combined variable including 5-minute Apgar score < or = 7, umbilical arterial pH < or = 7.15, secondary respiratory distress, transfer in a neonatal care unit, or neonatal death. RESULTS At a 7.20 threshold for fetal scalp pH and 30% for fetal oxygen saturation (i.e., the 10th percentile in the study population), the predictive value of fetal pulse oximetry was similar to that of fetal blood analysis for an arterial umbilical pH < or = 7.15 and for an abnormal neonatal outcome (positive predictive value 56% vs 55%, negative predictive value 81% vs 82%, sensitivity 29% vs 35%, and specificity 93% vs 91%, respectively). The receiver-operator characteristic curve showed similar performance of either technique for cutoff values < or = 7.20 for fetal blood pH and < or = 30% for fetal oxygen saturation, whereas fetal pulse oximetry became superior at higher thresholds. CONCLUSION The predictive value of intrapartum fetal pulse oximetry can be favorably compared with that of fetal blood analysis. Randomized controlled management trials can now be performed to assess potential clinical benefits of this new tool.

Nicardipine versus salbutamol in the treatment of premature labor. A prospective randomized study

OBJECTIVE To compare the tocolytic action and the side effects of nicardipine to those of salbutamol in patients presenting premature labor in order to propose nicardipine as a promising alternative to salbutamol in the treatment of premature labor. STUDY DESIGN Ninety patients admitted to the Saint-Antoine Hospital (Paris, France) for premature labor were included in this prospective randomized open study comparing nicardipine and salbutamol. Each study group included 45 patients. RESULTS The mean term of delivery in the nicardipine group was 38.4 +/- 1.7 and 37.6 +/- 2.1 weeks in the salbutamol group (P < 0.05). The percentage of deliveries after 37 gestational weeks was higher with nicardipine (P < 0.05). The birthweight of infants was 3131 +/- 488 g with patients treated with nicardipine and 3019 +/- 494 g with the salbutamol group (NS). The Apgar scores were identical in the two groups at 1 and 5 min. There was no statistically significant difference in the number of neonates admitted into intensive care nor the premature infant center between the two groups. Nicardipine reduced the systolic and diastolic blood pressure whereas there was no change in the salbutamol group. Maternal pulse rate was significantly increased in the salbutamol group (P < 0.01) and was unchanged in the nicardipine group. The most common side-effects with nicardipine were headaches, and with salbutamol, tremors and palpitations. CONCLUSIONS Nicardipine is a tocolytic agent as effective as salbutamol in the treatment of premature labor. The use of nicardipine is an interesting alternative to salbutamol, especially in cases of hypertension, diabetes or maternal cardiopathy.

Multicenter study on the clinical value of fetal pulse oximetry: I. Methodologic evaluation☆☆☆★

OBJECTIVE Our purpose was to evaluate the feasibility of intrapartum fetal pulse oximetry, the distribution of fetal oxygen saturation values, and the relationship with the neonatal outcome in a population with an abnormal fetal heart rate. STUDY DESIGN A prospective multicenter observational study was performed from June 1994 to November 1995. Fetal oxygen saturation was continuously recorded with use of a Nellcor N-400 fetal pulse oximeter in case of an abnormal fetal heart rate during labor. Simultaneous readings of fetal oxygen saturation and fetal blood analysis were obtained at inclusion and before birth. Feasibility, adverse effects, distribution of fetal oxygen saturation values, and relationship with neonatal outcome were assessed. RESULTS One hundred seventy-four patients were included. From 172 attempted sensor placements, the procedure was impossible in three cases and fetal oxygen saturation values were obtained in 164 cases (95.3%). Physicians considered sensor placement an easier task than an attempt at fetal blood analysis (easy in 87.5% vs 78.9% for fetal blood analysis, p = 0.03). The mean reliable signal time (+/- SD) was 64.7% +/- 32% during the first stage. There were no serious adverse effects in the study population. The mean fetal oxygen saturation during the first stage of labor was 42.2% +/- 8.0% (10th to 90th percentile range 30% to 53%). Fetal oxygen saturation was significantly correlated with scalp pH (r = 0.29, p = 0.01) but not with neonatal umbilical artery pH or gas values. There was a significant association between low fetal oxygen saturation (< 30%) and poor neonatal condition. CONCLUSION The feasibility of fetal pulse oximetry is satisfactory in clinical practice. It is easy to use and provides a fair rate of recorded values, even in a population with suspicion of fetal distress. A low fetal oxygen saturation is significantly associated with an abnormal neonatal outcome.

Hypoxia-activated genes from early placenta are elevated in Preeclampsia, but not in Intra-Uterine Growth Retardation

BackgroundAs 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.ResultsThree 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.ConclusionWe 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.

Catastrophic antiphospholipid syndrome and pregnancy: an experience of 13 cases

OBJECTIVE Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening disease caused by the onset of rapidly progressive and widespread small-vessel thromboses in the presence of aPLs. The aim of this study was to examine pregnancy-related CAPS. METHODS Retrospective series of 13 patients with pregnancy-related CAPS with special focus on the follow-up. RESULTS; Eleven patients had known APS and had been treated with low-molecular-weight heparin (n = 10), aspirin (n = 8), oral anticoagulants (n = 1), HCQ (n = 3) and/or steroids (n = 1) during pregnancy. The most frequent manifestations of CAPS were cutaneous (n = 11), hepatic (n = 11), renal (n = 10), cardiac (n = 8) and neurological (n = 5). CAPS usually followed haemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome (n = 12), which was associated with pre-eclampsia (n = 6) or with eclampsia (n = 3). No maternal death was observed. The perinatal mortality of 54% was related to prematurity with a mean gestational age of 26.6 weeks at onset of CAPS or HELLP syndrome. During a mean follow-up of 4.8 years (range 2-8 years), seven new pregnancies occurred in five patients and led to one miscarriage, four successful pregnancies and two HELLP syndrome with pre-eclampsia or eclampsia that occurred at 28 weeks gestation in both cases despite optimal treatment. No relapse of CAPS was observed. Two mothers suddenly died 2.5 and 6 years after CAPS. CONCLUSION The occurrence of HELLP syndrome in a patient with APS should raise the suspicion of CAPS in the following days, and anticoagulation should be maintained post-partum or post-abortum. Subsequent pregnancies are at very high risk.

Obstetrical APS : Is there a place for hydroxychloroquine to improve the pregnancy outcome?

The use of the conventional APS treatment (the combination of low-dose aspirin and LMWH) dramatically improved the obstetrical prognosis in primary obstetrical APS (OAPS). The persistence of adverse pregnancy outcome raises the need to find other drugs to improve obstetrical outcome. Hydroxychloroquine is widely used in patients with various autoimmune diseases, particularly SLE. Antimalarials have many anti-inflammatory, anti-aggregant and immune-regulatory properties: they inhibit phospholipase activity, stabilize lysosomal membranes, block the production of several pro-inflammatory cytokines and, in addition, impair complement-dependent antigen-antibody reactions. There is ample evidence of protective effects of hydroxychloroquine in OAPS similar to the situation in SLE arising from in vitro studies of pathophysiological working mechanism of hydroxychloroquine. However, the clinical data on the use of hydroxychloroquine in primary APS are lacking and prospective studies are necessary.

Fetal oxygen saturation measured by pulse oximetry during labour with clear or meconium-stained amniotic fluid.

OBJECTIVE To compare fetal oxygen saturation, scalp pH and arterial cord blood gases in cases of clear or meconium-stained amniotic fluid with and without meconium aspiration (MAS). STUDY DESIGN Thirty-eight women in labour at term with abnormal fetal heart rate were included. Fetal oxygen saturation was continuously monitored using a Nellcor N-400 fetal pulse oximeter and FS-14 sensor. Fetal scalp blood samples were taken systematically at full dilatation or immediately before cesarean section. Arterial cord blood gases were analysed at birth. Fetal oxygen saturation, scalp pH and neonatal blood gases were compared between fetuses with clear amniotic fluid, meconium-stained amniotic fluid without MAS and meconium stained amniotic fluid with MAS. RESULTS Moderate or thick meconium was observed in 13 cases during labour. Three newborns had a meconium aspiration defined as meconium below the vocal cords. No differences were observed in scalp pH, scalp base excess, umbilical arterial blood pH or base excess between groups. On the other hand, fetal oxygen saturation (fSpO2) obtained before birth was significantly lower in cases of MAS when compared to the other groups. This difference appears to be large compared to that which might be attributed to meconium and its direct effect on fetal pulse oximetry readings. Fetal oxygen saturation dropped dramatically in cases with meconium aspiration between the first stage of labour (44.7 +/- 8.0%) and the last measurement before birth (27.0 +/- 8.5%). CONCLUSION Meconium aspiration is more likely to be associated with fetal hypoxemia than with fetal acidosis.

Non-random, individual-specific methylation profiles are present at the sixth CTCF binding site in the human H19/IGF2 imprinting control region

Expression of imprinted genes is classically associated with differential methylation of specific CpG-rich DNA regions (DMRs). The H19/IGF2 locus is considered a paradigm for epigenetic regulation. In mice, as in humans, the essential H19 DMR—target of the CTCF insulator—is located between the two genes. Here, we performed a pyrosequencing-based quantitative analysis of its CpG methylation in normal human tissues. The quantitative analysis of the methylation level in the H19 DMR revealed three unexpected discrete, individual-specific methylation states. This epigenetic polymorphism was confined to the sixth CTCF binding site while a unique median-methylated profile was found at the third CTCF binding site as well as in the H19 promoter. Monoallelic expression of H19 and IGF2 was maintained independently of the methylation status at the sixth CTCF binding site and the IGF2 DMR2 displayed a median-methylated profile in all individuals and tissues analyzed. Interestingly, the methylation profile was genetically transmitted. Transgenerational inheritance of the H19 methylation profile was compatible with a simple model involving one gene with three alleles. The existence of three individual-specific epigenotypes in the H19 DMR in a non-pathological situation means it is important to reconsider the diagnostic value and functional importance of the sixth CTCF binding site.

Static and dynamic MRI features of the levator ani and correlation with severity of genital prolapse

Background. To describe the static and dynamic MRI features of the levator ani, and evaluate whether they are associated with the MRI evaluation of the severity of genital prolapse. Methods. Static and dynamic MRI of 40 patients, referred for evaluation prior to genital prolapse surgery, were reviewed retrospectively. Prolapse severity was evaluated on MRI at maximal straining by descent of the bladder neck under the pubococcygeal line for the anterior compartment, by descent of the uterine cervix under the pubococcygeal line for the middle compartment, and by anterior bulging of the rectum for the posterior compartment. For evaluation of the levator ani, the following parameters were recorded: (1) at rest: thinning or defects in both puborectalis and iliococcygeus muscles, (2) at rest and at straining: urogenital hiatus length and width, M line, iliococcygeal and levator plate angles. The levator ani features were tested for potential associations with the MRI evaluation of prolapse severity. Results. Bladder neck descent at straining was correlated with the levator plate angle at rest (p = 0.001), and with the hiatus length at rest (p = 0.02), and at straining (p = 0.008). Uterine cervix descent at straining was correlated with the hiatus length (p = 0.0005), and width (p = 0.014) at straining, M line (p = 0.002) and levator plate angle (p = 0.007) at straining, whereas anterior rectal bulging at straining was paradoxically inversely correlated with the hiatus width at rest (p = 0.04). Conclusion. In a population of women with genital prolapse, MRI evaluation of the levator ani was associated with MRI evaluation of the severity of genital prolapse.