Maternal hypercorticism from serial courses of betamethasone.
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Biomedical subjects
Publications and source records attributed to D Cabrol.
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OBJECTIVE: To investigate the usefulness of grade II uterine diastolic notch to predict maternal or perinatal outcome during conservative management of preeclampsia. STUDY DESIGN: We reviewed medical charts of 35 pregnant women admitted for hypertension and > or =1+ urine dipstick protein determination and who had a uterine Doppler examination at admission. Grade I notch was defined as a 'nadir' in early diastole higher than half of peak diastolic notch velocity. Grade II diastolic notch was defined as a 'nadir' in early diastole lower than half of peak diastolic notch velocity. RESULTS: Thirty-one preeclamptic women were admitted at 30.1+/-3 weeks. Of them, 23 had a grade I notch (group I) and eight a grade II notch (group II). Rates of abruptio placenta, eclampsia, thrombocytopenia, stillbirth, birth weight < or = 3rd centile, fetal distress before delivery and neonatal death were similar in the two groups. Rates of delivery before 32 weeks and newborn spending more than 48 h in neonatal intensive care unit were significantly higher in group II. Admission-to-delivery interval was significantly lower in group II (2.6+/-1.5 vs. 9.4+/-8.7 days, P<0.05). CONCLUSION: Grade II notch seems to identify in preeclamptic women those with a higher risk of early pregnancy termination.
OBJECTIVE: ACTH-producing non-pituitary tumours are often associated with altered precursor processing, particularly in the most aggressive ones. Since placental tissue is characterized by its ability to express the proopiomelanocortin (POMC) gene and rapid cellular proliferation, we examined whether intact POMC could be released physiologically during human gestation. SUBJECTS: One hundred and fifty six normal pregnant women, 12 with multiple pregnancies, and 23 non-pregnant controls. Twenty-eight women were studied in the immediate postpartum period. MEASUREMENTS: We measured plasma POMC levels with a specific immunoradiometric assay (IRMA) using a combination of antibodies directed against ACTH and beta endorphin. Results obtained with this first IRMA were confirmed in 22 subjects with a second assay using the same beta endorphin antibody and a more distal antibody directed against the N-terminal fragment of POMC. Reverse transcription-PCR detected full length, pituitary-like, POMC mRNA in human placenta. RESULTS: Plasma POMC was undetectable (< 60 U/ml) in 23 normal subjects. In normal monofetal pregnancies, POMC became detectable in most women by the third month and then increased steadily until midgestation: 168 +/- 108 (U/ml; mean +/- SD) between 12 and 15 weeks, 190 +/- 103 between 16 and 19 weeks, 324 +/- 180 between 20 and 23 weeks, 276 +/- 171 between 24 and 27 weeks, 292 +/- 177 between 28 and 31 weeks, 290 +/- 235 between 32 and 35 weeks and 308 +/- 210 between 36 weeks and parturition. Plasma POMC was significantly higher in multiple pregnancies with very high levels in three triplet-bearing mothers: 671, 941, and 1731 U/ml at 31, 33 and 32 weeks, respectively. POMC levels felt quickly in post partum, becoming undetectable in five of 13 women on day 1, seven of eight on day 2 and five of six on day 3. Plasma POMC displayed no diurnal variation, was not suppressed by glucocorticoid administration and did not correlate with plasma ACTH or cortisol. In contrast, plasma POMC positively correlated with plasma CRH. CONCLUSIONS: Pregnancy is the only condition in which POMC is produced and released physiologically, similar in some respects to the ectopic ACTH syndrome. POMC is derived solely from the placenta, with no interference from maternal pituitary secretion, and is thus a new and specific placental marker.
INTRODUCTION: A strong rise in the use of induced labor has been observed in France. The aim of this work was to analyze the different methods used for achieving induction of labor and their implications. METHODS: One out of four French obstetricians were randomly selected to answer a questionnaire on their practice for achieving induction of labor. Four hundred of the 997 obstetricians answered the questionnaire. Univariate and multivariate analysis was applied. RESULTS: A high rate of induced labor was correlated with some areas of the country and with private practice. Certain methods were used in spite of opposing advice by experts in the field: elective induction of labor with unfavorable cervix, use of prostaglandins in elective induction of labor, induction of labor in cases of scarred uterus or breech presentation, use of misoprostol. Some methods were still used in spite of their poor efficacy: intravenous oxytocin used with unfavorable cervix, use of intravensou PGE2. CONCLUSION: This study would show that theory and practice are often distinctly different. Induction of labor is currently used on a far wider scale than ever before. We obviously need studies for careful assessment of the circumstances in which induction of labor is used in order to improve methods and indications of such a clinical practice.
OBJECTIVE: Our purpose was to study the effects of the progestomimetic compound nomegestrol acetate on spontaneous and sulprostone-induced uterine contractility in pregnant cynomolgus monkeys. STUDY DESIGN: Intrauterine pressure was continuously monitored with use of an implanted intraamniotic catheter and a telemetric pressure transmitter from day 115 to 135 of gestation (term = 165 days). After surgery the animals received either nomegestrol acetate (5 mg per day orally, n = 3) or vehicle only (controls, n = 3). The intramuscular prostaglandin E2 analog sulprostone (25 micrograms) was administered as a single injection 10 days after amniotic catheter implantation. Spontaneous and sulprostone-induced uterine contractions were compared between nomegestrol acetate- and vehicle-treated animals. RESULTS: The frequency of spontaneous uterine contractions in control animals demonstrated a 24-hour pattern with a minimum at 12 hours and a maximum at 0 hours. The frequency of spontaneous contractions did not differ between nomegestrol acetate- and vehicle-treated animals. Sulprostone induced an increase in both the frequency and amplitude of contractions, reaching a maximum 12 hours after injection and fading out after 24 hours in vehicle-treated animals. In animals receiving nomegestrol acetate, the frequency of contractions increased moderately and transiently for a total duration of 6 hours only and returned to control levels thereafter. CONCLUSION: Nomegestrol acetate significantly decreases the contractile response of the pregnant uterus induced by the prostaglandin E2 analog sulprostone.
HELLP syndrome is associated with a high rate of maternal and perinatal morbidity and mortality, and often leads to immediate fetal extraction. However, this condition may occur very early in pregnancy and conservative approaches have been recently proposed. The limits of this approach are discussed with two cases of conservative management of HELLP syndrome complicated by abruptio placentae.
Uterine cervical modifications play a central role in preterm labor and are one of the main indicators for the clinical diagnosis of this syndrome. Modifications of the cervix are either isolated events "cervical incompetence" or associated with cervicovaginal infection, which is an important etiological factor. Furthermore, the extent of cervical modifications in preterm labor is probably related to the prognosis of preterm delivery. Certain developments in the treatment of preterm pregnancy have focused on the uterine cervix (e.g. cervical cerclage, treatment of cervicovaginal infections) and such strategies may facilitate the prevention of preterm delivery. The information currently available emphasizes an independent role for the uterine cervix in preterm labor. As a consequence, it should be realised that even though there is a direct association between cervical modifications and uterine contractions, management of preterm labour must not be directed exclusively at the control of uterine contractions and tocolysis.
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.
OBJECTIVE: The study of fetal lung circulation by means of pulmonary Doppler investigation. METHODS: Pulmonary Doppler ultrasound obtained with color pulsed-Doppler with a 3.5-5 Mhz probe. Measure of resistance index and pulsatility index. PATIENTS: Forty seven pregnant women with singleton, between 18 and 39.5 weeks gestation, were recruited to have a pulmonary Doppler ultrasound. 7 fetuses had intra uterine fetal growth retardation (IUGR). Overall, 50 Doppler velocity waveforms were measured. RESULTS: Resistance and pulsatility index were measured in all patients and at each examination. Resistance index (0.86 +/- 0.03) and pulsatility index (2.46 +/- 0.34) were found to be stable during pregnancy. Pulmonary pulsatility index in IUGR fetuses (2.71 +/- 0.33) were found to be higher than those in normotrophic infants (p = 0.006), whereas no difference was found in resistance index between the same subgroups. Moreover, no difference was found in pulsatility index measurements between preterm small-for-gestational age fetuses and normotrophic fetuses measured between 36 and 39.5 weeks gestation (2.68 +/- 0.31 vs 2.49 +/- 0.28). CONCLUSION: Pulmonary resistance index is not statistically different between nomotrophic and IUGR fetuses. In contrast pulmonary pulsatility index is significantly higher in IUGR fetuses when compared with normotrophic fetuses. Pulmonary Doppler ultrasound should be evaluated in a larger trial and correlation between Doppler measurements and fetal lung maturation should be studied.
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OBJECTIVE: To determine the effects of maternal left lateral, right lateral, and supine positions during labor on fetal oxygen saturation measured by pulse oximetry. METHODS: Fetal oxygen saturation measured by pulse oximetry was obtained in 15 laboring women randomly and successively adopting left lateral, supine, and right lateral positions for 10 minutes each. Repeated measures analysis of variance was used for statistical analysis. RESULTS: Changes in fetal oxygen saturation were observed in different maternal positions. The supine position was associated with a lower fetal oxygen saturation than the left lateral position. One supine hypotensive syndrome occurred and was associated with a drop in fetal oxygen saturation. CONCLUSION: Maternal supine position during labor is associated with a lower fetal oxygen saturation than the left lateral position.
OBJECTIVE: To study the effects of amniotic fluid obtained during early second trimester of normal human pregnancies on prostaglandin production in cultured myometrial and amniotic cells. STUDY DESIGN: Cultured human myometrial and amniotic cells were incubated with human amniotic fluid obtained by amniocentesis and fractionated by ultrafiltration. Prostaglandin E2 was measured in the incubation media. In one case, amniotic fluid was obtained during the days following intra-uterine fetal death (IUFD). RESULTS: PGE2 production in myometrial and amniotic cells was significantly decreased when incubated with the fraction of amniotic fluid containing molecules of molecular weight between 3 and 30 kD. This inhibition was still present after heating. After IUFD, the inhibitory activity of amniotic fluid was persistent for the first 3 days but had disappeared 6 days after IUFD. CONCLUSION: These data suggest that a factor contained in amniotic fluid, with a molecular weight within the 3- to 30-kD range, and possibly produced or controlled by the fetus, inhibits PG synthesis. Further work is necessary to characterize this factor and evaluate its physiological role in human parturition.
Polyhydramnios carries a poor fetal prognosis with an expected neonatal death rate of nearly 30%. Approximately one-fourth of this perinatal mortality is a result of the effects of prematurity. The poor outcome with usual management of polyhydramnios led us to introduce the therapeutic use of prostaglandin synthetase inhibitors so as to decrease amniotic fluid volume and to prevent premature labor. Twenty-two women (20 singleton and two twin pregnancies) were included in a retrospective study from 1983 to 1992. Indomethacin was given at a dose of 3 mg/kg/day. Treatment was started at 28.2 +/- 3.8 weeks of amenorrhea and discontinued after 35 weeks. We observed a significant effect of indomethacin on amniotic fluid volume and avoided severe preterm delivery in all patients. Mean gestational age at birth was 37.5 +/- 1.6 weeks of amenorrhea (range 35.5-39 weeks). We did not observe any maternal or neonatal side effects of indomethacin therapy. However, we reported three neonatal deaths out of 24 infants: two related to undiagnosed fetal anomalies (one Nager syndrome and one cerebral malformation) and one related to umbilical cord entanglement in a monoamniotic twin pregnancy. Since our first report, several open studies supporting our data have been published. However, although indomethacin appears to be effective in the treatment of polyhydramnios, our goal is to analyze efficacy and side effects, so as to define conditions of clinical use.
OBJECTIVE: To evaluate a possible effect of Mifepristone on amniotic fluid volume in near term pregnant macaque monkeys. STUDY DESIGN: Six pregnant near term monkeys (144 +/- 11 days of gestation) were either treated intramuscularly by Mifepristone (10 mg/kg, n = 3) or a placebo (n = 3). Amniotic fluid volumes were measured by a dilution technique using blue Evans, just prior to the injection of Mifepristone or placebo (t0h) and 24 h later (t24h). RESULTS: Amniotic fluid volume (AFV) measured at t0h was found to be statistically the same in placebo and Mifepristone-treated macaque monkeys (95 +/- 31 vs. 126 +/- 25 ml, respectively, P > 0.05). AFV was found to be lower at t24h when compared to AFV at t0h in placebo-treated (88 +/- 31 vs. 95 +/- 31 ml, respectively, P < 0.05) and in Mifepristone-treated macaque monkeys (72 +/- 7 vs. 126 +/- 25 ml, respectively, P < 0.05). Moreover, the ratio of AFV (t24h/t0h) was found to be significantly lower in Mifepristone-treated monkeys when compared to the placebo group (57.9 +/- 5.7% vs. 92.2 +/- 2.1%, P < 0.05) indicating a specific effect of the antiprogestin on AFV. CONCLUSION: In near term macaque monkeys, Mifepristone at 10 mg/kg induces a significant decrease of amniotic fluid volume within 24 h.
OBJECTIVE: To study the mechanism of action of prostaglandin E2 (PGE2) and its analogue sulprostone leading to production of glycosaminoglycans (GAGs) in the human uterine cervix. STUDY DESIGN: We analysed the effects of PGE2 and its analogue sulprostone upon production of adenosine 3',5'-monophosphate (cAMP), in human cultured fibroblasts. We also studied the effects of PGE2, sulprostone and a cAMP analogue (8-Bromo-cAMP), on the incorporation of [3H]glucosamine into GAGs in human cervical fibroblasts in culture. RESULTS: Following treatment with PGE2 (10(-4)-10(-6) M), we observed a significant increase in the production of cAMP from 96.3 +/- 8.4 pmol/10(6) cells without phosphodiesterase inhibitor 3-isobutyl-methylxanthine (IBMX) to 325 +/- 63 pmol/10(6) cells with 10(-4) M IBMX (Spearman correlation test; P < 0.05). Under the same conditions, the effects of sulprostone (10(-6) M) were limited (from 8.1 +/- 1.5 to 51.3 +/- 14.1 pmol/10(6) cells without and with IBMX, respectively; not significant). Both PGE2 and 8-bromo-cAMP (from 10(-12) to 10(-4) M) increased [3H]glucosamine uptake into GAGs (Spearman correlation test; P < 0.05). Sulprostone (10(-12)-10(-4) M) was unable to reproduce such an effect even after a 24 or 48 h treatment. CONCLUSION: Since firstly, PGE2 acts through EP1, EP2 and EP3 specific receptors, whereas the action of sulprostone is only mediated by EP1 and EP3, and secondly EP2 receptor is coupled with cAMP production, we conclude that cAMP is involved in mediating the action of PGE2 upon GAG synthesis by human cultured cervical fibroblasts.
AIM OF THE STUDY: To compare immediate labor induction by vaginal prostaglandins to immediate labor induction by oxytocin or to expectant management in case of prelabor rupture of the membranes at term. MATERIAL AND METHODS: A meta-analysis of all randomized trials indexed in Medline or in the Cochrane Database of Systematic Reviews comparing labor induction by vaginal prostaglandins to labor induction by oxytocin or to expectant management. The statistical analysis was performed according to Peto and Yussuf's modified Mantel Haenszel method. The results were expressed as odds-ratios. RESULTS: Ten published studies meeting the above criteria were found. These trials included 1004 patients. When comparing labor induction by prostaglandins to expectant management, we observed a reduction of the admission-to-delivery interval, a decreased maternal and neonatal infection rate, without difference in the cesarean section rate. When comparing labor induction by vaginal prostaglandins to labor induction by oxytocin, a decreased cesarean section rate was observed without difference in maternal or neonatal infection rates. CONCLUSION: Immediate labor induction by vaginal prostaglandins provides better maternal and neonatal outcomes than labor induction by oxytocin or expectant management in case of prelabor rupture of the membranes at term.
OBJECTIVE: To examine the existence of amniotic fluid inhalation in foetal rabbit near term. STUDY DESIGN: Rabbit red cells labelled with 51 radio-chromium (Cr51-S1: Injectable solution sodium chromate, volumic activity: 74 MBq/ml; Cis-BioInternational, France) were injected into the amniotic sac of 24 New Zealand White foetal rabbits (mean gestation: 31 days) at day 25 per-laparotomy. At day 26, just prior to caesarean section, human serum albumin labelled with 125 radio-active iode (125I-HSA) (SERALB-125: human serum albumin labelled with radioactive Iode 125, volumic activity: 185 kBq/ml, Cis-BioInternational, France) was injected into each amniotic sac. The lungs, digestive tracts, kidneys and liver were excised separately and radioactivity counted in each organ. RESULTS: On day 26 of gestation, the 51Cr-RC radioactivity rate per gram of tissue in lungs, digestive tract amniotic fluid, liver and kidneys were respectively 1.66 +/- 2.8%, 1.15 +/- 1.6%, 0.015 +/- 0.02% and 0.04 +/- 0.07% of the total amount of radioactivity injected into the amniotic sac at day 25. The lungs' radioactivity was significantly higher than liver (t = 2.94, P < 0.01) or kidneys radioactivity (t = 2.38, P < 0.05). The 125I-HSA injected just prior to caesarean section at day 26 was not found in any foetal organ. CONCLUSIONS: Lung radioactivity is not related to gasps induced by caesarean section, or to a vascular diffusion since lung radioactivity was significantly higher than liver or kidneys' radioactivity. The results of these series of experiments demonstrate that amniotic fluid inhalation does exist in foetal rabbit near term.
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