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ABSTRACT: We previously reported decreases in fetal heart rate (FHR) variability and body and breathing movements after maternal betamethasone administration. We now test the hypothesis that fetal responsiveness to betamethasone depends on the gestational age at which glucocorticoid therapy is started.
1-h recordings of FHR (n=350) and fetal movements (n=310) made during a 5-day period (days 0-4) were available for analysis. The recordings had been obtained from 63 pregnant women at high risk for preterm delivery who received betamethasone (two doses of 12 mg 24 h apart) between 26 and 34 weeks' gestational age (wGA). The response to betamethasone, i.e. the direction and magnitude of change in FHR and movement parameters compared with baseline (day 0), was studied in relation to gestational age at drug administration.
Fetuses exposed to betamethasone at 29-34 wGA showed a decrease in FHR on day 1 (indicative of baroreceptor reflex), and reduced breathing activity and prolonged episodes of quiescence with a concomitant decrease in body movements on days 1 and 2. However, these changes were not observed if betamethasone administration occurred at 26-28 wGA. Betamethasone-induced reductions in FHR variability were similar in young and older fetuses.
Age-related differential responsiveness to betamethasone was found for all studied fetal processes (body and breathing movements, FHR, and quiescence), except FHR variability. Our results suggest ontogenic changes in the mechanisms presumed to underlie these processes (glucocorticoid receptor (GR) maturation, cardiovascular and neuro-endocrine development).
Early Human Development 02/2004; 76(1):65-77. · 2.05 Impact Factor
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ABSTRACT: To determine whether the diurnal blood pressure profiles in pregnant women with pre-eclampsia and/or intrauterine growth restriction (IUGR) differ from those in normal pregnant controls, and, if so, to establish whether such a difference is accompanied by altered diurnal rhythms of fetal heart rate (FHR) and its variation.
Twenty-two women in the third trimester of pregnancy with pre-eclampsia, IUGR, or both, entered the study. Eleven healthy pregnant women served as controls. Maternal systolic and diastolic blood pressures and heart rate (MHR) were determined automatically at 30-min intervals during a period of 26 h starting at 09.00. During the study period, nine 1-h recordings of FHR were made at predetermined timepoints. FHR was analyzed numerically.
Systolic and diastolic blood pressures and MHR showed diurnal patterns, with the highest values during the day and a trough during the night in all women. Daytime and night-time blood pressures were higher in pre-eclamptic women (p < 0.001), and the day-night difference was smaller than in controls (p < 0.001). Diurnal patterns of FHR and its variation did not differ qualitatively between the three study groups. However, FHR was affected by the maternal blood pressure profile, and all FHR parameters and their diurnal ranges were quantitatively different in IUGR fetuses (p < 0.05).
In pre-eclamptic women, there was blunting of the diurnal blood pressure profile. This altered maternal hemodynamics was associated with a similar reduction in FHR amplitude during the 26-h period but not with FHR variation. Although diurnal rhythms of FHR and its variation persisted qualitatively in the IUGR fetuses, they seemed to have been reset quantitatively, leading to a flattened diurnal pattern.
Journal of Maternal-Fetal and Neonatal Medicine 05/2002; 11(5):313-20. · 1.50 Impact Factor
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ABSTRACT: We sought to determine the effects of the intramuscular maternal administration of betamethasone to the pregnant baboon at 0.7 of gestation on fetal blood pressure and heart rate.
We treated pregnant baboons at 0.7 of gestation with intramuscular betamethasone (n = 4), at a weight-adjusted dose equivalent to the daily dose administered to women in preterm labor or with saline solution (n = 5). Four injections were given at 12-hour intervals. Fetal and maternal blood pressure and heart rate were recorded continuously. Within-group differences and between-group differences were analyzed with repeated measures analysis of variance.
Fetal blood pressure increased significantly after betamethasone treatment. Fetal heart rate, maternal blood pressure, and heart rate did not change.
Exposure of the developing primate fetus to exogenous glucocorticoid at 0.7 of gestation elevates fetal blood pressure. These findings confirm and extend the observations in the fetal sheep. Further studies are needed to evaluate the mechanisms that are involved and possible long-term consequences of these cardiovascular effects of antenatal glucocorticoid exposure in the fetal primate.
American Journal of Obstetrics and Gynecology 05/2002; 186(4):812-7. · 3.47 Impact Factor
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ABSTRACT: The aim of this study was to determine the effect of corticosteroids, gestational age, and birth on the expression of genes encoding prostanoid receptors in the lamb and baboon ductus arteriosus. The ductus arteriosus was obtained from 34 lambs and eight baboons, including chronically instrumented fetuses of both species exposed to either corticosteroid or vehicle. Expression of prostanoid receptor genes was quantified using Northern blot analysis relative to each of two housekeeping genes. Expression of both the EP3 and EP4 receptor genes was detected in lamb ductus and the level of expression of both genes was unaffected by corticosteroids. Expression of the EP4 receptor gene was lower in the ductus obtained from term lambs compared with preterm lambs and was lower still in neonatal animals, whereas no variation was observed in EP3 receptor gene expression. Expression of the EP4 receptor gene was also confirmed in fetal baboon ductus arteriosus, and maternal administration of corticosteroid did not reduce EP4 receptor gene expression in the baboon. We conclude that advancing gestational age and birth may inhibit prostaglandin E2-mediated relaxation of the ductus through a corticosteroid-independent reduction in EP4 receptor gene expression.
Journal of Cardiovascular Pharmacology 07/2001; 37(6):697-704. · 2.29 Impact Factor
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ABSTRACT: At 110-111 days gestation, instrumented fetal sheep were administered saline or dexamethasone (2.2 microgram. kg(-1). h(-1) iv) for 48 h. Measurement of fetal blood pressure showed a greater increase in dexamethasone-treated (n = 6) compared with control (n = 5) fetuses (7.3 +/- 2.3 vs. 0.6 +/- 2.3 mmHg, P < 0.05). Fetuses were delivered by cesarean section, and the femoral muscle and brain were obtained under halothane anesthesia. Femoral and middle cerebral arteries (approximately 320-micrometer internal diameter) were evaluated using wire myography. Sensitivity to KCl (2.5-125 mM) and the magnitude of the maximal vasoconstriction to 125 mM K(+) were similar in femoral and middle cerebral arteries from dexamethasone-treated vs. control fetuses. Acetylcholine-induced vasorelaxation was similar in femoral arteries from control and dexamethasone-treated fetuses. Middle cerebral arteries did not relax to acetylcholine. Sensitivity to endothelin-1 (ET-1; 0.1 pM-0.1 microM) and magnitude of the ET-1-induced vasoconstriction were greater in femoral arteries from dexamethasone-treated vs. control fetuses (P < 0.05). Autoradiographical studies with receptor-specific ligands demonstrated increased ET(A)-receptor binding, the principal receptor subtype, in femoral muscle vessels (P < 0.001) but decreased ET(A)-receptor binding in middle cerebral arteries (P < 0.01) from dexamethasone-treated compared with control fetuses. Relatively little ET(B)-receptor binding was evident in all tissues examined. We conclude that hyperreactivity to ET-1, due to increased ET(A)-receptor binding, may be involved in the dexamethasone-induced increase in peripheral vascular resistance in fetal sheep in vivo.
AJP Regulatory Integrative and Comparative Physiology 07/2001; 281(1):R261-8. · 3.34 Impact Factor
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ABSTRACT: We sought to identify regional differences in prostaglandin H synthase 2 messenger ribonucleic acid expressions in various intrauterine tissues in the pregnant baboon as an indicator of prostaglandin production capability to explain the various interactive roles of different intrauterine tissues in the processes that precede, promote, and complete labor.
Prostaglandin H synthase 2 messenger ribonucleic acid expression was measured by reverse transcriptase-polymerase chain reaction or Northern blot analysis in the uterine fundus, lower uterine segment, cervix, amnion, chorion, and placenta during late pregnancy and spontaneous term labor in the pregnant baboon. Myometrial electromyography enabled clear relation of the findings to uterine contractile activity.
There were dramatic increases of prostaglandin H synthase 2 messenger ribonucleic acid expressions during late gestation and during labor in the lower uterine segment, cervix, and decidua. The amniotic prostaglandin H synthase 2 messenger ribonucleic acid expression increased during labor. In contrast, the prostaglandin H synthase 2 messenger ribonucleic acid expressions in the uterine fundus, chorion, and placenta did not change during late gestation and labor.
Demonstrated increased lower uterine segment and cervical prostaglandin H synthase 2 abundances would promote lower uterine segment elongation and cervical effacement. Engagement of the fetal presenting part would stimulate local prostaglandin H synthase 2 expression and obstruct diffusion of high forebag prostaglandin to the rest of the uterus, as reported previously in human pregnancy. These data support a new conceptual mechanistic framework for preparatory changes in the lower uterine segment and cervix preceding labor as precisely related to myometrial contractility changes.
American Journal of Obstetrics and Gynecology 12/2000; 183(5):1287-95. · 3.47 Impact Factor
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ABSTRACT: The present study was designed to characterize prostaglandin dehydrogenase (PGDH) mRNA expression in critical intrauterine tissues of pregnant baboons in late gestation and at spontaneous labor. In addition, we determined regulatory effects of betamethasone in vivo on chorionic and placental PGDH mRNA expression. PGDH mRNA was present in chorion, decidua, lower uterine segment, fundal myometrium, and cervix in late gestation but undetectable in amnion. PGDH mRNA significantly decreased in decidua and cervix during late gestation and in chorion and fundus during spontaneous labor. PGDH mRNA in lower uterine segment, decidua, cervix, and placenta was unchanged during spontaneous labor from late gestation levels. Betamethasone had no effect on chorionic and placental PGDH mRNA expression. In summary, our data suggest that PGDH mRNA expression is tightly controlled in gestation- and tissue-specific manners. Decreased chorionic and fundal PGDH abundance during labor and decreased decidua and cervical PGDH mRNA in late gestation allow local uterine prostaglandin accumulation and assist prostaglandin transfer to myometrium. Local differences in PGDH function may regulate tissue- and region-specific requirements for prostaglandins to promote and complete labor.
AJP Regulatory Integrative and Comparative Physiology 10/2000; 279(3):R1082-90. · 3.34 Impact Factor
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S.V. Koenen
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