Effect of type 2 diabetes mellitus on the pharmacokinetics and transplacental transfer of nifedipine in hypertensive pregnant women.

AIMS: Diabetes mellitus can inhibit cytochrome P450 3A4, an enzyme responsible for the metabolism of nifedipine, used for the treatment of hypertension in pregnant women. We aimed to assess the effect of type 2 diabetes mellitus (T2DM) on the pharmacokinetics, placental transfer and distribution of nifedipine in amniotic fluid in hypertensive pregnant women. METHODS: The study was conducted in 12 hypertensive pregnant women [control group (CG)] and 10 hypertensive pregnant women with T2DM taking slow-release nifedipine (20 mg, 12/12 h). On the 34th week of gestation, serial blood samples were collected (0-12 h) after administration of the medication. At delivery, samples of maternal and fetal blood and amniotic fluid were collected for determination of nifedipine distribution in these compartments. RESULTS: The median pharmacokinetic parameters of CG were: peak plasma concentration (Cmax ) 26.41 ng ml-1 , time to reach Cmax (tmax ) 1.79 h, area under the plasma concentration vs. time curve from 0-12 h (AUC0-12 ) 235.99 ng.h ml-1 , half-life (t½) 4.34 h, volume of distribution divided by bioavailability (Vd/F) 560.96 l, and ClT /F 84.77 l h-1 . The parameters for T2DM group were: Cmax 23.52 ng ml-1 , tmax 1.48 h, AUC0-12 202.23 ng.h ml-1 , t½ 5.00 h, Vd/F 609.40 l, and apparent total clearance (ClT /F) 98.94 l h-1 . The ratios of plasma concentrations of nifedipine in the umbilical vein, intervillous space and amniotic fluid to those in the maternal vein for CG and T2DM were 0.53 and 0.44, 0.78 and 0.87, respectively, with an amniotic fluid/maternal plasma ratio of 0.05 for both groups. The ratios of plasma concentrations in the umbilical artery to those in the umbilical vein were 0.82 for CG and 0.88 for T2DM. CONCLUSIONS: There was no influence of T2DM on the pharmacokinetics or placental transfer of nifedipine in hypertensive women with controlled diabetes.

Changes in amniotic fluid index after maternal oral hydration in pregnancies with fetal gastroschisis: initial observations.

OBJECTIVE: To evaluate the effect of maternal oral hydration on amniotic fluid index (AFI) in pregnancies with fetal gastroschisis. METHODS: AFI was evaluated at 24-hour intervals, during 4 consecutive days, under a continuous maternal oral water hydration regimen, in singleton pregnancies with isolated fetal gastroschisis. RESULTS: Nine pregnancies were examined at a mean gestational age of 31.6 weeks (+/-1.4) and mean maternal daily oral water intake was 3,437 (+/-810) ml. Mean AFI on days 0-3 were 13.2 (+/-2.9), 14.8 (+/-3.3), 14.5 (+/-3.1) and 14.8 (+/-2.6), respectively. AFI on day 0 was significantly lower compared to all the other 3 days (p = 0.01 and 0.02). Significant correlation was found in relative difference in AFI between day 0 and day 1 and gestational age (r = -0.67, p = 0.05) and the amount of water intake in the previous 24 h (r = 0.76, p = 0.02). CONCLUSION: Maternal oral water hydration significantly increases AFI in pregnancies with isolated fetal gastroschisis.

Fetal learning about ethanol and later ethanol responsiveness: evidence against "safe" amounts of prenatal exposure.

Near-term fetuses of different mammalian species, including humans, exhibit functional sensory and learning capabilities. The neurobiological literature indicates that the unborn organism processes sensory stimuli present in the amniotic fluid, retains this information for considerable amounts of time, and is also capable of associating such stimuli with biologically relevant events. This research has stimulated studies aimed at the analysis of fetal and neonatal learning about ethanol, a topic that constitutes the core of the present review. Ethanol has characteristic sensory (olfactory, taste, and trigeminal) attributes and can exert pharmacologic reinforcing effects. The studies under examination support the hypothesis that low to moderate levels of maternal ethanol intoxication during late pregnancy set the opportunity for fetal learning about ethanol. These levels of prenatal ethanol exposure do not generate evident morphologic or neurobehavioral alterations in the offspring, but they exert a significant impact upon later ethanol-seeking and intake behaviors. Supported by preclinical and clinical findings, this review contributes to strengthening the case for the ability of prenatal ethanol exposure to have effects on the postnatal organism.

Polihidramnios: informe de un caso y manejo actual / Polyhydramnios: report of a case and present handling

El polihidramnio es una patología relativamente frecuente en obstetricia que puede complicar el embarazo según el grado de severidad. La mayoría de los casos no tienen una causa demostrable auque ahora con las nuevas técnicas de diagnóstico un porcentaje de ellos tienen afecciones genéticas. El tratamiento actual consta de fármacos junto a la amniocentesis con control ultrasonográfico. En el presente informe se describe un caso de polihidramnios severo en el cual no se demostró etiología y se manejó con indometacina y amniocentesis

[The induction of fetal lung maturity in pre-eclampsia]. / Inducción de madurez pulmonar fetal en preeclampsia.

The consensus of the world literature shows that the prematurity is the first cause of perinatal morbidity and mortality. In this period several are the complications to short and long term that they can be presented, but seems be that it is the respiratory distress syndrome (RDS) the principal cause of this problems. This syndrome is frequent in the neonate of mothers with severe preeclampsia of early appearance in which exists the need of interruption the pregnancy. There are some articles, that show that preeclampsia by itself or the steroids given antenatally to the mother may accelerated the fetal lung maturity. The objective of the present study was analyze the behavior of the phospholipids responsible for the fetal lung maturity in amniotic fluid, with the administration of steroids to mothers with preeclampsia, and its correlation with the presentation of the RDS in the RDS in the newborn. 31 patients were included in the study, all of them with severe preeclampsia without complications, between 28 and 33 weeks of pregnancy. Twenty one patients received 12 mg of betametasone i.m. in 2 doses one each day (Group 1) and 10 patients who did not receive the steroid (Group 2). All the births were by cesarean section, amniocentesis was done during this procedure. The relation L/E > or = were observed in 81% of the patients of group 1. In the group 2 the relation L/E < or = 2 were observed in 80% of the cases. The RDS was present in 47% of the neonates in Group 1 and in 100% of the group that did not receive betametasone (p 0.004). The perinatal mortality (20%) was present only in the that did not receive betametasone. The findings of the present paper shows that the administration of betametasone in patients with severe preeclampsia accelerated the fetal lung maturity more the disease in consequence the frequency and severity of the RDS were less.

Interactions between perinatal and neonatal associative learning defined by contiguous olfactory and tactile stimulation.

Tactile stimulation of the neonate, as performed by the mother during and after delivery, has been described as an effective unconditioned stimulus during early ontogeny (Leon, 1987; Ronca & Alberts, 1994). The present experiments examined the interaction between perinatal and neonatal learning determined by the explicit association between alcohol odor and vigorous body stimulation of the perinatal organism. In Experiment 1, rat fetuses were exposed to either alcohol or saline 10 min prior to cesarean delivery. The alcohol administration procedure here employed was sufficient to provide sensory contamination of the amniotic fluid but avoid fetal alcohol intoxication. Pups in the two prenatal treatments later experienced the smell of alcohol, tactile stimulation, or both stimuli explicitly paired or unpaired. Other postnatal groups were composed of pups that had no explicit experience with either experimental stimulus. Pups subjected to alcohol odor in utero displayed more overall motor activity in response to that odor than saline controls. The increased motor responses were further potentiated in pups that experienced additional postnatal alcohol odor paired with tactile stimulation. In Experiment 2, pups were exposed to alcohol in the amniotic fluid 10 or 30 min prior to birth. As previously demonstrated the memory acquired in utero appears highly dependent upon contingency between exposure to this particular scent and delivery procedures. Pups in both prenatal treatment groups were then exposed to alcohol odor paired or unpaired with tactile stimulation. Some control animals received no further experience with either stimuli. Those pups exposed to alcohol odor paired with tactile stimulation both pre- and postnatally later showed maximum motor activity elicited by the odor of alcohol. The results support the notion of fetal associative learning comprising alcohol's chemosensory cues and behaviorally activating stimuli. Furthermore, the conditioned response under analysis is potentiated whenever neonates are reexposed to contingent presentations of the elements that defined the original associative memory.

Modulation of 72-kilodalton type IV collagenase (Matrix metalloproteinase-2) by ascorbic acid in cultured human amnion-derived cells.

Extensive research has been done to investigate the effects of nutrients on placental and fetal development. It is now evident that environmental factors such as diet may exert a profound effect on gene expression during pregnancy. A low intake of vitamin C during pregnancy has been linked to a higher risk of premature rupture of the membranes (PROM) because of its well-known role in collagen biosynthesis. Here we report a new effect of ascorbic acid acting as a modulator of the 72-kDa type IV collagenase (matrix metalloproteinase-2; MMP-2). MMP-2 expression/activity is down-regulated by vitamin C in human amnion cultured cells. The regulatory effect is exerted at the transcriptional level and is specific for MMP-2. Matrix metalloproteinases are implicated in tissue remodeling, and our results allow us to suggest a molecular mechanism that relates poor availability of vitamin C during pregnancy and the development of PROM.