Effect of taurocholic acid on fetoplacental arterial pressures in a dual perfusion placental cotyledon model: a novel approach to intrahepatic cholestasis of pregnancy.

OBJECTIVE: To determine if continuous infusion of taurocholic acid into the fetoplacental and intervillous circulation of a placental cotyledon affects the fetal arterial pressure response after injection of the thromboxane mimetic U44619. Taurine conjugated bile acid is one bile acid putatively mediating intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN: We selected 5 placentas from normal, unlabored patients. Two cotyledons from each placenta were isolated and dually perfused. Taurocholic acid was continuously infused into the fetoplacental and intervillous circulation of the test cotyledon. After 30 minutes U44619 was injected into both the test and control cotyledon vascular circuits. Pressure excursions were measured and compared to baseline pressures using a paired Student's t test. RESULTS: There was significant attenuation of the pressure excursion in the cotyledons perfused with taurocholic acid as compared to controls after injection of U44619. The difference from baseline in the taurocholic cotyledon compared with controls was 44.2 mmHg vs. 71.8 mmHg (p = 0.009). CONCLUSION: The perfusion of taurocholic acid attenuated the pressure response to thromboxane mimetic U44619 in the fetoplacental arterial circulation of a placental cotyledon as compared to control. This finding in our ex-vivo model may represent changes that occur in the placental vasculature with intrahepatic cholestasis of pregnancy. These placentas may have dysregulated vascular tone, which could contribute to the adverse fetal effects observed in ICP.

Continuous infusion of 17-hydroxyprogesterone caproate into either the fetoplacental or intervillous circulation of a placental cotyledon attenuates vasoconstriction of the fetoplacental arteries by thromboxane mimetic U46619.

OBJECTIVE: The objective of the study was to determine whether pretreatment of fetal or maternal placental vasculature with 17-hydroxyprogesterone caproate (17-P) attenuates the vasoactive effect of the thromboxane mimetic U46619. STUDY DESIGN: Two cotyledons were obtained from each placenta studied. For the first 5 placentas, the fetal artery of 1 cotyledon from each pair was infused with 17-P. After 30 minutes, a bolus dose of U46619 was administered to both cotyledons. An identical procedure was carried out on the next 5 placentas except that 17-P was infused into the intervillous space. RESULTS: The pressure excursion caused by bolus administration of U46619 was less in the cotyledons infused with 17-P, both in the 5 cases in which the fetal vasculature was infused with 17-P (P = .0035) and in the 5 cases in which the maternal vasculature was infused with 17-P (P = .038). CONCLUSION: Pretreatment of either the fetal or maternal circuits of the placenta with 17-P attenuates U46619-mediated fetoplacental vasoconstriction.

The effect of membrane sweeping on prelabor rupture of membranes: a randomized controlled trial.

OBJECTIVE: To estimate if membrane sweeping increases the rate of prelabor rupture of membranes. METHODS: This randomized trial of term, uncomplicated pregnancies included 300 patients. Patients were randomly assigned into sweep or no-sweep groups, with patients and delivering providers blinded to group allocation. Only the examining provider in the clinic was unblinded to group allocation. Membranes were then swept or not swept at each weekly visit from 38 weeks of gestation onward, depending on the randomization. Data collected included parity, cervix examination at each visit, estimated gestational age at delivery, rupture of membranes, and maternal or fetal complications. RESULTS: A total of 162 patients were randomly assigned to the membrane sweep group and 138 to the no-sweep group. There was no difference in baseline characteristics or obstetric and neonatal outcomes between the groups. The average gestational age at delivery and induction rate were not different. The overall prelabor rupture of membranes rate was not significantly higher in the membrane sweep group (12% compared with 7%) (P=.19); however, patients with a cervix more than 1 cm dilated at time of membrane sweeping were more likely to have prelabor rupture of membranes if they were in the membrane sweep group (9.1% compared with 0%; relative risk 1.10, 95% confidence interval 1.03-1.18). CONCLUSION: No benefit in gestational age at delivery or reduction of postmaturity occurred from membrane sweeping. Although the overall prelabor rupture of membranes rates were similar, patients with membrane sweeping occurring at more than 1 cm cervical dilation may be at increased risk of prelabor rupture of membranes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00294242. LEVEL OF EVIDENCE: I.

17-Hydroxyprogesterone caproate reverses induced vasoconstriction of the fetoplacental arteries by the thromboxane mimetic U46619.

OBJECTIVE: This study was undertaken to determine whether 17-hydroxyprogesterone caproate (17P) has a vasoactive effect on fetoplacental vasculature. STUDY DESIGN: Two cotyledons were obtained from each of 5 placentas. Baseline perfusion was established with Hanks-based solution. One cotyledon from each pair was then infused with perfusate to which U46619 a thromboxane sympathomimetic had been added. After 30 minutes, a dose of 17P was then administered to each cotyledon. Finally, a vasoconstricting dose of angiotensin II was administered to each cotyledon. Perfusion pressures were recorded throughout. Statistical analysis of pressure change for a single cotyledon was performed by using a paired t test. Statistical analysis of mean perfusion pressure difference between U46619 exposed and nonexposed cotyledons was analyzed by using a students t test. RESULTS: 17P did not significantly alter the perfusion pressure of the control cotyledon. (30.6 +/- 8.3 mm Hg vs 30.1 +/- 7.8 mm Hg P = .48). 17P administration significantly lowered the perfusion pressure of the U46619 preconstricted vessels in comparison with preadministration. (60.1 +/- 13 mm Hg vs 27.3 +/- 7.1 mm Hg P = .03). Both groups of cotyledons responded with vasoconstriction to angiotension II with no difference in response between groups (38.3 +/- 12 mm Hg vs 45.8 +/- 8.2 mm Hg P = .63). CONCLUSION: 17P reverses induced vasoconstriction by U46619 in fetoplacental arteries.

Progesterone modulation of inflammatory cytokine production in a fetoplacental artery explant model.

OBJECTIVE: The purpose of this study was to determine if progesterone has an effect on fetoplacental artery production of inflammatory cytokines. STUDY DESIGN: Chorionic plate arteries were dissected from 5 placentas obtained from normal pregnancies after delivery at term. Arteries were incubated in Dulbecco's modified Eagle's medium (DMEM) alone, DMEM and lipopolysaccharide (LPS), DMEM with progesterone (P4), and DMEM with P4 and LPS. Samples of the tissue culture media were collected and evaluated for interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-10 (IL-10) by immunoassay. RESULTS: There was a significant decrease in the production of IL-6 in P4-exposed fetoplacental arteries after LPS stimulation (P < .001). IL-10 and TNF-alpha levels were similar in control and treatment groups after LPS exposure. CONCLUSION: Pretreating fetoplacental arteries with P4 significantly decreased the production of IL-6 after LPS stimulation without altering the production of TNF-alpha or IL-10.

The effects of a cyclo-oxygenase II inhibitor on placental artery production of thromboxane and prostacyclin.

OBJECTIVE: The study was undertaken to determine the effects of a cyclo-oxygenase II inhibitor on fetoplacental artery production of prostacyclin and thromboxane A(2). STUDY DESIGN: Eight placentas were obtained from normal parturients at delivery and four chorionic plate arteries were dissected from each placenta. Arteries were incubated in media alone, media plus angiotensin II (1x10(-10) mol), media plus rofecoxib (300 ng/mL), or media plus angiotensin II and rofecoxib. Serial samples were assayed for metabolites of thromboxane B(2) and prostacyclin by enzyme-linked immunosorbent assay. Results were compared by analysis of variance, and P<.05 was considered significant. RESULTS: At 24 hours, 6-keto-prostaglandin F(1alpha) levels in the rofecoxib group (1.74+/-1.39 ng/mg tissue, P<.01) and the rofecoxib plus angiotensin II group (2.15+/-1.85 ng/mg tissue, P<.01) were significantly lower than levels in the control group (4.25+/-2.03 ng/mg tissue). Thromboxane B(2) levels were lower in the angiotensin II group (0.65+/-0.33 ng/mg tissue) than the control group (1.22+/-0.70 ng/mg tissue, P<.05). CONCLUSION: Cyclo-oxygenase II inhibition decreases the production of prostacyclin in fetoplacental arteries and alters the normal ratio of thromboxane A(2) to prostacyclin.

Fetoplacental vascular tone is modified by magnesium sulfate in the preeclamptic ex vivo human placental cotyledon.

OBJECTIVE: The purpose of this study was to evaluate fetoplacental vascular tone and response to a vasoconstrictor in placentas of preeclamptic and normotensive pregnancies with and without the presence of magnesium sulfate. STUDY DESIGN: Two cotyledons from each placenta were selected from preeclamptic (n=8) and normotensive (n=7) pregnancies. In one cotyledon from each pair, the maternal circuit was perfused with magnesium sulfate. The fetal arteries were injected sequentially with angiotensin II (10(-10)mol and 10(-11.5) mol). Perfusion pressures and response to angiotensin II were compared, with regard to preeclampsia and exposure to magnesium sulfate. RESULTS: Perfusion pressure was higher in preeclamptic placentas, compared with normotensive placentas (30.4 mm Hg vs 24.4 mm Hg, P=.02). There was a decrease in perfusion pressure with exposure to magnesium sulfate in preeclamptic placentas (22.5 mm Hg, P<.01), but not in normotensive placentas. Fetoplacental vascular response to angiotensin II was not affected by preeclampsia or magnesium sulfate. CONCLUSION: In placentas from preeclamptic pregnancies there is increased fetoplacental perfusion pressure, which decreases with exposure to sulfate.

Perinatal hospice. Comprehensive care for the family of the fetus with a lethal condition.

OBJECTIVE: To describe our experience in providing a program of structured interdisciplinary care for the families of fetuses prenatally diagnosed with a lethal congenital anomaly. STUDY DESIGN: We developed a comprehensive "perinatal hospice" program for the supportive care of families with fetuses known to have a lethal condition. Upon prenatal diagnosis of a lethal fetal condition, parents were presented with the option of elective pregnancy termination versus a multi-disciplinary program of ongoing supportive care until the time of spontaneous labor or until delivery was required for obstetric indications. We evaluated patient use of this new service and the natural history of pregnancies managed in this fashion. RESULTS: The population consisted of 33 patients carrying a fetus with a clearly delineated lethal anomaly. Twenty-eight (85%) chose to participate in the perinatal hospice program. Of these, 11/28 (39%) had an intrauterine fetal death and 17/28 (61%) delivered a live-born infant. Among the live-born infants were 12 vaginal deliveries, 4 preterm and 8 at term. Obstetric indications or maternal request resulted in cesarean delivery for 5/28 (18%), 4 preterm and 1 at term, all live born. All live-born infants died within 20 minutes to 2 months. There were no maternal complications. CONCLUSION: The availability of a structured program providing ongoing, comprehensive, multidisciplinary, supportive perinatal care offers a tangible and safe alternative to early elective pregnancy termination for patients carrying a fetus with a lethal congenital condition.