Publications (8)27.34 Total impact
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Article: Perinatal care and outcome of fetuses with trisomies 13 and 18 following a parental decision not to terminate the pregnancy.
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ABSTRACT: To describe pregnancy outcomes of fetuses affected by trisomies 13 and 18 following prenatal diagnosis and a decision to continue the pregnancy. A single-center, retrospective study of 34 cases with a diagnosis or strong suspicion of trisomy 13 or 18. Fourteen of 34 (41%) families chose to continue the pregnancy after a diagnosis of trisomy 13 or 18 was made. Nine fetuses subsequently died in utero (IUD). No prenatal signs were predictive of IUD. There were no intrapartum deaths. All 4 live-born babies were delivered vaginally; 2 died immediately after birth in the labor ward whilst 2 were transferred to the neonatal unit, dying at 10 and 11 days, respectively. Couples should be counseled that the precise outcome of trisomy 13 or 18 is unpredictable, and they should receive multidisciplinary support.Fetal Diagnosis and Therapy 02/2011; 29(3):233-7. · 1.05 Impact Factor -
Article: Modulation of endocrine and transport functions in human trophoblasts by saquinavir and nelfinavir.
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ABSTRACT: The distribution of drugs to the maternal-fetal interface is influenced by the expression of various efflux transporters. Among these transporters, P-glycoprotein (P-gp) is responsible for the efflux of a great number of drugs such as protease inhibitors of the human immunodeficiency virus, thus reducing the chemical exposure of the fetus. The effects of saquinavir and nelfinavir were evaluated on human trophoblast functions and integrity by investigating their effect on human chorionic gonadotropin (hCG) secretion and on P-gp expression and functionality. Nelfinavir significantly reduced hCG secretion by 30% after a 48-h treatment but it had no effect on syncytia formation. Saquinavir had no effect on hCG secretion but significantly increased both expression (to a 2-fold extent) and functionality (by 17.9%) of P-gp, whereas nelfinavir only increased functionality (by 23.1%) with a dissociation of P-gp from caveolin-1. These results suggest that the effects of saquinavir and nelfinavir differ on trophoblast functions.European journal of obstetrics, gynecology, and reproductive biology 09/2010; 152(1):55-9. · 1.97 Impact Factor -
Article: Contribution and limit of the model of perfused cotyledon to the study of placental transfer of drugs. Example of a protease inhibitor of HIV: nelfinavir.
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ABSTRACT: The perfused cotyledon model is a very useful method to study placental transfer of drugs. Here we studied placental transfer of the human immunodeficiency virus protease inhibitor nelfinavir using the non-recirculating dual human placental perfusion with a main goal to determining the clearance index of nelfinavir as related to maternal concentrations, and analyze the conditions under which ex vivo and in vivo data can be correlated. Thirteen human cotyledons, obtained after uneventful term pregnancies, were perfused in an open double circuit with nelfinavir (320-4436 microg/l) and a freely diffusing marker antipyrine 20 mg/l, in the presence of an albumin concentration of 2 g/l. Drug concentrations were determined by high-performance liquid chromatography. The mean clearance index of nelfinavir was very weak when maternal concentrations were under 500 microg/l (0.03+/-0.05). For maternal concentrations above 1200 microg/l, the mean fetal transfer rate was 14+/-3.4%, the mean clearance index was 0.39+/-0.10 and the fetal concentrations were between 133 and 671 microg/l. There was a good correlation between maternal and fetal concentrations (r=0.86; p<0.001). Our study with nelfinavir has achieved a good correlation between ex vivo and in vivo data. Our results also indicate that studies must be conducted under well defined conditions to obtain accurate and comparable data, underlining the fact that the ex vivo perfused cotyledon remains difficult to standardize as a model system.European journal of obstetrics, gynecology, and reproductive biology 09/2009; 147(2):157-60. · 1.97 Impact Factor -
Article: Functional role of p-glycoprotein and binding protein effect on the placental transfer of lopinavir/ritonavir in the ex vivo human perfusion model.
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ABSTRACT: Aims. To study the influence of P-glycoprotein (P-glycoprotein, ABCB1, MDR1) function on placental transfer of lopinavir with ritonavir at different albumin concentrations. Methods. Cotyledons were perfused with lopinavir, ritonavir, and the internal control antipyrin, at various albumin concentrations (10, 30, 40 g/L). After the control phase of each experiment, the P-glycoprotein inhibitor ciclosporin A was added at middle perfusion (45 minutes). Fetal Transfer Rate (FTR) and Clearance Index (CLI) were compared between the 2 phases. Results. In the control phase, the clearance index of lopinavir decreased from 0.401 +/- 0.058 to 0.007 +/- 0.027, as albumin concentrations increased from 10 g/L to higher concentrations (30, 40 g/L). When adding ciclosporin A at physiological albumin concentrations, the clearance index of lopinavir increased significantly 10.3 fold (95% of CI difference [-0.156, -0.002], P = .046) and became positive for ritonavir. Conclusions. Even at high albumin concentrations, inhibition of placental P-glycoprotein increased placental transfer of lopinavir, suggesting that this efflux pump actively reduces placental transfer of the drug. This mechanism may play a role in fetal exposure to maternal antiretroviral therapy.Obstetrics and Gynecology International 01/2009; 2009:726593. -
Article: Placental transfer of enfuvirtide in the ex vivo human placenta perfusion model.
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ABSTRACT: The objective of the study was to determine the placental transfer of the antiretroviral fusion inhibitor, enfuvirtide (Fuzeon). Human cotyledons were perfused for 90 minutes in an open dual circuit with enfuvirtide, and fetal venous samples were collected every 5 minutes. Three perfusion experiments were validated using antipyrine. Enfuvirtide was not detected in the fetal compartment in any of the 3 experiments. The mean concentration of the drug measured in the maternal compartment was 12,400 ng/mL (range, 6500-16,200 ng/mL), which is 2.5 times the maximum concentration recommended for patients treated with enfuvirtide. Even at maternal concentrations twice above therapeutic levels, no placental transfer of enfuvirtide was observed. The high molecular weight of the molecule (4492 kDa) and its ionized state may account for the lack of placental transfer. This result suggests that enfuvirtide could be used in HIV-infected pregnant women without causing fetal exposure.American journal of obstetrics and gynecology 05/2008; 198(4):433.e1-2. · 3.28 Impact Factor -
Article: Placental transfer of lopinavir/ritonavir in the ex vivo human cotyledon perfusion model.
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ABSTRACT: This study was done to determine the placental transfer of the human immunodeficiency virus protease inhibitor lopinavir with ritonavir. Twenty-five human cotyledons that were obtained after uneventful pregnancies and deliveries were perfused in an open double circuit with lopinavir (1099-10,606 microg/L) and ritonavir (254-1147 microg/L) at various albumin concentrations (2, 10, and 40 g/L). The fetal transfer rate of lopinavir, when combined with ritonavir, was 23.6% +/- 6.9% at an albumin concentration of 2 g/L. The fetal transfer rate decreased to 20.7% +/- 10% at an albumin concentration of 10 g/L and to 3.3% +/- 0.5% at an albumin concentration of 40 g/L. The placental transfer of lopinavir, a highly protein-bound molecule, was compatible with passive diffusion of the unbound fraction. Even at physiologic maternal albumin concentrations, the amount of drug transferred into the fetal compartment was well above the 50% inhibitory concentration.American journal of obstetrics and gynecology 08/2006; 195(1):296-301. · 3.28 Impact Factor -
Article: Sensitivity and specificity of prenatal features of physiological shunts to predict neonatal clinical status in transposition of the great arteries.
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ABSTRACT: Although prenatal diagnosis of transposition of the great arteries (TGA) reduces neonatal mortality, the preoperative course can be complicated in infants with a restrictive foramen ovale (FO) or a ductus arteriosus (DA) constriction. We sought to determine the specificity and sensitivity of prenatal features of physiological shunts in predicting postnatal clinical status in prenatally diagnosed TGA in babies delivered in a tertiary care center providing all facilities for neonatal urgent care. The outcomes of 130 fetuses with TGA were reviewed over a period of 5.5 years. Restriction of the FO and/or constriction of the DA could be analyzed in 119/130 fetuses at 36+/-2.7 weeks of gestation. Twenty-four out of 119 had at least 1 abnormal shunt (23 FO, 5 DA, and 4 both). Thirteen of 130 neonates had profound hypoxemia (PaO2<25 mm Hg) and metabolic acidosis (pH <7.15) in the first 30 minutes and required immediate balloon atrioseptostomy. Two who had abnormal FO and DA died despite aggressive resuscitation. The specificity and sensitivity of the fetal echo in predicting neonatal emergency were 84% and 54%, respectively. The specificity and sensitivity of a combination of restrictive FO and DA constriction were 100% and 31%, respectively. Restriction of the FO and/or of the DA has a high specificity to predict the need for emergency neonatal care in fetuses with TGA, but the sensitivity is too low to detect all high-risk fetuses. Exceptional procedures should be considered for fetuses that have a combination of restrictive FO and DA constriction.Circulation 09/2004; 110(13):1743-6. · 14.74 Impact Factor -
Article: Isolated fetal hyperechogenic bowel associated with intra-uterine parvovirus B19 infection.
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ABSTRACT: We report a case of fetal hyperechogenic bowel diagnosed at midgestation that was associated with fetal parvovirus B19 infection. Isolated hyperechogenic bowel was detected at 25 weeks. Cystic fibrosis, chromosomal abnormalities and cytomegalovirus infection were excluded, whereas polymerase chain reaction DNA for parvovirus B 19 was found positive on amniotic fluid. The hyperechogenic bowel decreased with complete resolution by 32 weeks of gestation. No other signs of fetal B19 infection were detected prenatally and the baby had normal postnatal outcome. This case provides additional arguments in favor of a possible intestinal tropism of parvovirus B19 during fetal life. Fetal B19 infection should be systematically incorporated in the prenatal evaluation of isolated fetal hyperechogenic bowel.Fetal Diagnosis and Therapy 20(6):498-500. · 1.05 Impact Factor
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Institutions
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2006–2011
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Assistance Publique – Hôpitaux de Paris
Paris, Ile-de-France, France
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2009
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Université Paris-Sud 11
Paris, Ile-de-France, France
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