Background-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. Methods and Results-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 36Ϯ2.7 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 (PaO 2 Ͻ25 mm Hg) and metabolic acidosis (pH Ͻ7.15) 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. Conclusions-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. Key Words: heart defects, congenital Ⅲ transposition of great vessels Ⅲ echocardiography P renatal detection of transposition of the great arteries (TGA) has been well established. [1][2][3][4] Of those neonates admitted with TGA, mortality is estimated around 4% and is mostly due to inadequate interatrial mixing despite prostaglandin E1 infusion. 5 We have previously reported that prenatal diagnosis of TGA reduced neonatal mortality and morbidity. 3 However, early demise of neonates with TGA has been reported even after a prenatal diagnosis, suggesting that there was no site available for mixing immediately after birth. 3,[5][6][7][8] Indeed, antenatal restriction of the foramen ovale and/or the ductus arteriosus were found predictive of significant neonatal morbidity and mortality. 9 Because the surgical mortality for the arterial switch operation is as low as 2% in many institutions, 10 -13 the preoperative mortality is a major issue in the management and outcome of infants with TGA. Here, we reviewed the prenatal features of the foramen ovale and of the ductus arteriosus in all our cases of prenatally diagnosed TGA to address the relation between prenatal echo features and need for urgent intervention. Methods PopulationOne hundred thirty consecutive patients with a prenatal diagnosis of TGA were identified over a period of 5.5 years (November 1, 1997 to February 28, 2003. TGA was suspected during routine prenatal ultrasonogra...
f Nowadays, antiretroviral therapy is recommended during pregnancy to prevent mother-to-child transmission of HIV. However, for many antiretroviral drugs, including maraviroc, a CCR5 antagonist, very little data exist regarding placental transfer. Besides, various factors may modulate this transfer, including efflux transporters belonging to the ATP-binding cassette (ABC) transporter superfamily. We investigated maraviroc placental transfer and the influence of ABC transporter expression on this transfer using the human cotyledon perfusion model. Term placentas were perfused ex vivo for 90 min with maraviroc (600 ng/ ml) either in the maternal-to-fetal (n ؍ 10 placentas) or fetal-to-maternal (n ؍ 6 placentas) direction. Plasma concentrations were determined by ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Fetal transfer rates (FTR) and clearance indexes (CLI) were calculated as ratios of fetal to maternal concentrations at steady state (mean values between 30 and 90 min) and ratios of FTR of maraviroc to that of antipyrine, respectively. ABC transporter gene expression levels were determined by quantitative reverse transcription (RT)-PCR and ABCB1 protein expression by Western blotting. For the maternal-to-fetal direction, the mean FTR and CLI were 8.0% ؎ 3.0 and 0.26 ؎ 0.07, respectively, whereas the mean CLI was 0.52 ؎ 0.23 for the fetal-to-maternal direction. We showed a significant inverse correlation between maraviroc CLI and ABCC2, ABCC10, and ABCC11 placental gene expression levels (P < 0.05). To conclude, we report a low maraviroc placental transfer probably involving ABC efflux transporters and thus in all likelihood associated with a limited fetal exposition. Nevertheless, these results would need to be supported by in vivo data obtained from paired maternal and cord blood samples.
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