Chronic prenatal exposure to phenobarbital and long-term behavior effects on mice offspring.

OBJECTIVE: To assess the impact of chronic prenatal exposure to phenobarbital on long-term behavior in mice offspring. METHODS: Twenty-eight C3H/He mice were randomized to receive diet chow containing either a daily therapeutic dose of phenobarbital (2.5 mg in 10-g chow) or a placebo for 1 week before mating and throughout gestation. Offspring from eight litters of each treatment group were evaluated using motor function, arousal/motivation, anxiety-provoking and cognition tasks. RESULTS: No significant differences between groups were found in duration of gestation, litter size and birth weights. Fewer counts in a locomotor chamber were observed in phenobarbital-exposed offspring (524 +/- 31 vs. 688 +/- 54 for 60 min, p < 0.02; 4174 +/- 229 vs. 5230 +/- 406 for 22 h, p < 0.05). Initial reactions to a startle were more apparent among phenobarbital-exposed offspring (p < 0.03). Impaired co-ordination of hindlimbs was observed in the phenobarbital-exposed offspring during the wire maneuver (p < 0.001). Fewer entries into the mirrored chamber were observed after phenobarbital exposure (2.1 vs. 4.5; p < 0.05). Exposure to phenobarbital was not found to affect responses to learning and memory tasks (homing, tube runway, water runway, Morris maze). CONCLUSION: Although cognition was unaffected by prenatal exposure to phenobarbital, subtle effects on locomotor activity, hindlimb co-ordination and responses to anxiety-provoking conditions require human correlation.

Multiple courses of antenatal betamethasone and cognitive development of mice offspring.

OBJECTIVE: To measure the effect of multiple courses of antenatal betamethasone, used for lung maturation, on long-term cognition of mice offspring. METHODS: Forty gravid CD-1 mice were randomly assigned to receive one of four treatments (n = 10 per group): 0.1 mg betamethasone or saline placebo, given subcutaneously either once daily on gestational days 13-16 or twice daily on days 14 and 15. This dose of betamethasone given on gestational day 14 causes fetal lung maturation in mice. Three offspring per gender in each litter underwent standard cognitive tasks as juveniles and as adults. Analysis of variance or Kruskal-Wallis testing was used to compare data. RESULTS: Learning acquisition and memory were indistinguishable between the betamethasone-exposed and the corresponding placebo-exposed offspring when performing the following tasks: juvenile runway with adult memory, adult water runway and Morris spatial maze. This lack of difference in task performance between treatment groups persisted after controlling for gender and for each multiple-course regimen. CONCLUSION: Multiple courses of antenatal corticosteroids did not impact the mouse offsprings' long-term learning and memory.

Placebo-controlled, blinded comparison of antenatal betamethasone on mouse liver development.

The objective of this investigation was to evaluate, in a placebo-controlled manner, the developing mouse liver after antenatal exposure either to a single dose or to a multidose of betamethasone. Ninety gravid CD-1 mice were randomly divided into three groups (n = 30/group) to receive either saline (0.25 mL s.c.) or betamethasone (0.10 mg s.c.) as a single dose on gestational day (GD) 14 of a 19-day gestation or as a 0.10 mg dose given twice daily on GD 14 and on GD 15 (4 doses). GD 0 is defined by the presence of a copulatory plug. These exposures of betamethasone cause fetal mouse lung maturation as would be observed in premature humans at 24-34 weeks of gestation. The livers were removed either from the fetuses on GD 16.5 or from the offspring on postnatal day 1, 3, 5, and 120. Special stains were used to evaluate hepatocyte architecture, glycoprotein and glycogen content, extramedullary hematopoiesis and iron storage. Hepatocyte intranuclear DNA content, cell size, and cell shape were measured by image analysis (CAS 200). At GD 16.5, betamethasone produced a significant decrease in the liver/body weight ratio that, when compared with the placebo group, was greater with the multidose (p < 0.01) than with the single dose (p < 0.05). 16.5 GD single dose hepatocytes were smaller in size as compared to placebo without impact on intranuclear DNA (p < 0.01). Single dose PND 1 hepatocytes demonstrated an increase in intranuclear DNA as compared to placebo but without change in cell size (p < 0.001). The prenatal reduced liver weight recovered in the newborn period. No difference in microscopic architecture of the hepatocytes or histologic differences between either of the three treatment groups was found in glycogen deposition, extramedullary hematopoiesis or iron metabolism at GD 16.5 and postnatally. It was concluded antenatal betamethasone can cause a decrease in the liver/body weight ratio in the fetal mouse that recovers eventually without any functional impact as assessed histologically.

Effect of prenatally administered hypericum (St John's wort) on growth and physical maturation of mouse offspring.

OBJECTIVE: Our purpose was to determine whether prenatal exposure to the herb hypericum (St John's wort) affects long-term growth and physical maturation of mouse offspring. STUDY DESIGN: Forty CD-1 mice were randomly assigned to receive daily doses of either 180 mg/kg per day hypericum (n = 20) or a placebo (n = 20) for 2 weeks before conception and throughout gestation. Perinatal outcomes, growth, and physical milestones of the offspring were compared in a blinded manner. Variables were compared by analysis of variance or by chi2 testing. RESULTS: The gestational ages at delivery and litter sizes did not differ between the hypericum-exposed and the placebo-exposed offspring. The body weight, body length, and head circumference measurements from postnatal day 3 through adulthood increased in a manner that was indistinguishable between the two groups of offspring, regardless of gender. No differences in reaching physical milestones (teeth eruptions, eye opening, external genitalia) were noted between the 2 groups. The reproductive capability, perinatal outcomes, and growth and development of the second-generation offspring were unaffected by hypericum exposure. CONCLUSION: Maternal administration of hypericum before and throughout gestation did not affect long-term growth and physical maturation of exposed mouse offspring.

Impact of hypericum (St.-John's-wort) given prenatally on cognition of mice offspring.

This study investigated the cognitive impact of prenatal exposure to the herbal antidepressant hypericum in CD-1 mice. Hypericum (182 mg/kg/day) or a placebo was consumed in food bars for 2 weeks before mating and throughout gestation. The hypericin content in our hypericum formulation was in the middle range of standardized hypericum products. One offspring per gender from each litter (hypericum 13, placebo 12) was tested on each of the following tasks: juvenile runway with adult memory, adult Morris maze, adult passive avoidance, or adult straight water runway followed by a dry Cincinnati maze. Learning occurred in both genders in all tasks (P<.003) with no significant differences between treatments at the final trial. Female offspring exposed to hypericum, rather than to a placebo, required more time to learn the Morris maze task (P<.05). Postlearning sessions did not show any significant differences. In conclusion, prenatal exposure to a therapeutic dose of hypericum did not have a major impact on certain cognitive tasks in mice offspring.

Chronic prenatal exposure to paroxetine (Paxil) and cognitive development of mice offspring.

This study investigated the impact on cognitive development in CD-1 mice from chronic prenatal exposure to the antidepressant paroxetine. CD-1 mice were given either paroxetine as 30 mg/kg/day or a placebo in food bars for 2 weeks before mating and throughout gestation. One offspring per gender from each litter was tested on each of the following tasks: tube runway, spatial maze, passive avoidance chamber, and water straight runway followed by an unforced decision maze. Learning occurred in both genders in all tasks (p<0.001) with no significant differences between treatment groups at the final learning session. Juvenile runway was the only task in which the paroxetine-exposed males demonstrated a learning rate that was slower than the placebo-exposed offspring (p=0.06). Post learning sessions did not show any significant treatment differences during the juvenile and adult periods during the water straight runway, mazes, and avoidance chamber tasks. In conclusion, chronic prenatal exposure in mice of paroxetine did not impact cognition on select tasks.

Effect of antenatal exposure to Saint John's wort (Hypericum) on neurobehavior of developing mice.

OBJECTIVE: We conducted, in a randomized, placebo-controlled manner, behavioral testing on mice offspring exposed antenatally to the herbal antidepressant Saint John's wort (Hypericum ). STUDY DESIGN: A daily dose of Saint John's wort (0.75 mg/g of food consumed), equivalent to that in human beings according to body surface, was chosen because it has been shown to cause an antidepressant effect in adult mice. CD-1 mice were randomly assigned to consume either Saint John's wort (n = 45) or a placebo (n = 45) for 2 weeks before conception and throughout gestation. Behavioral testing consisted of early developmental tasks of geotaxis, separation vocalization, and homing, followed by motor, anxiety, and depression assessments into adulthood. RESULTS: Birth weights of male offspring were less in the Saint John's wort group than in the placebo group (1.68 vs. 1.75 g; P<.01). Offspring in both treatment groups showed no long-term statistical differences in early developmental tasks, locomotor activity, and exploratory behavior throughout development. Performances on a depression task (forced swim) and on anxiety tasks (elevated plus maze as juveniles and adults) revealed no differences between treatment groups. CONCLUSION: Antenatal exposure to a therapeutic dose of Saint John's wort showed no long-term deficits on selected behavioral tasks by developing mice offspring.

Impact of antenatal exposure of mice to fenfluramine on cardiac development and long-term growth of the offspring.

The objective of this investigation was to determine, in a placebo-controlled manner, whether antenatal exposure to formulations of fenfluramine and dexfenfluramine impacted cardiac development and long-term growth of exposed mice offspring. One hundred forty-four CD-1 mice were randomized to six treatment groups (n=23 or 25) to obtain, per group, 5 gravids for killing on gestational day (GD) 15 and < or =10 deliveries for assessing growth of the offspring. Either fenfluramine preparation was administered in feed bars in two doses: 1 and 3.2 times the equivalent human daily dosage according to body surface area. The drugs were given from 2 weeks before mating until GD 15. The mice ingested each drug at target values, averaging 10.5+/-0.3 and 31.8+/-1.9 mg/kg/d for fenfluramine and 5.0+/-0.2 and 16.2+/-0.4 mg/kg/d for dexfenfluramine. The drug concentration was about 36% in the fetal brain compared with the adult brain. The maternal and the offspring hearts, including mitral and aortic valves, of fenfluramine-exposed mice were indistinguishable from the placebo-exposed mice. The duration of gestation and the litter size were the same between the treatment groups. The mean body weights, body lengths, and head circumferences and early functional testing did not differ significantly between the fenfluramine or dexfenfluramine-exposed offspring and the placebo-exposed offspring. There were no significant treatment differences in growth measured as body weights to PND 120. Neither fenfluramine formulation, given before conception and during gestation, impacted cardiac development and long-term growth of the mice offspring.

Effect of antenatal exposure to paroxetine (paxil) on growth and physical maturation of mice offspring.

OBJECTIVE: Our purpose was to determine, in a placebo-controlled manner, whether antenatal exposure to paroxetine affected long-term growth and physical maturation of mice offspring. METHODS: Forty-one CD-1 mice consumed paroxetine (n = 21) or a placebo (n = 20) for 2 weeks before conception and throughout gestation. The daily dose of paroxetine (Paxil; 30 mg/kg/d) was known to achieve concentrations in the serum equivalent to the upper therapeutic level in humans and in the fetal brain equivalent to that of the adult mouse. Growth and physical maturation of the offspring were compared by paired t-test, Welch's corrected test, and Fisher's exact test. RESULTS: The maternal weight gain, litter sizes, number of fetal resorptions, and gestational age at delivery were not different between the paroxetine and the placebo-exposed offspring. Newborn pups exposed to paroxetine were more likely to have low birthweights (1.65 gm vs. 1.70 gm; P < 0.05) and narrower heads (7.7 mm vs. 8.1 mm; P < 0.05). Body weight, body length, and head circumference measurements increased in a manner that was indistinguishable between the two groups of offspring, regardless of gender. No differences in achievement of physical milestones (lower incisor eruption, eye opening, and development of external genitalia) were noted between the two groups. The reproductive capability and the perinatal outcomes of the second-generation offspring were unaffected by paroxetine exposure. CONCLUSION: A clinically relevant dose of paroxetine, when given throughout gestation, did not affect long-term growth and physical maturation of mice offspring.

Behavioral changes in developing mice after prenatal exposure to paroxetine (Paxil)

OBJECTIVE: The aim of this study was to conduct in a randomized, placebo-controlled manner behavioral testing on mice offspring exposed prenatally to the selective serotonin reuptake inhibitor paroxetine. STUDY DESIGN: Forty-one CD-1 mice consumed paroxetine (Paxil, n = 21) or a placebo (n = 20) for 2 weeks before conception and throughout gestation. The daily dose of paroxetine used, 30 mg x kg(-1) x d(-1), is known to achieve concentrations in the rat serum equivalent to the upper therapeutic level in human beings and to achieve concentrations in the fetal rat brain equivalent to those in the adult mouse. Behavioral testing consisted of multiple tasks during early development, followed by motor, anxiety, reproduction, and depression tasks in the juvenile and adult periods. RESULTS: Offspring in the 2 treatment groups showed no statistical differences in many early development tasks (geotaxis, homing, social play) or in locomotor and exploratory activities throughout development. Performances during a depression task (forced swim), anxiety tasks (elevated plus maze as juveniles and adults), and reproduction revealed no treatment differences. Offspring exposed prenatally to paroxetine had a 15% to 25% increase in separation vocalization (P <.04) and a significant increase in male aggression during cage changing (P <.03). CONCLUSION: Prenatal exposure to a clinically relevant dose of paroxetine in mice produced no major behavioral alterations but did heighten performance on select anxiety testing in infant offspring and on aggressive behavior in adult males.

Low backache during pregnancy. Acute hemodynamic effects of a lumbar support.

OBJECTIVE: To determine whether a commercially available elastic/Velcro lumbar and abdominal support (Mother-To-Be, CMO, Inc., Barberton, Ohio) affects the hemodynamics of the fetus and pregnant woman. STUDY DESIGN: Healthy volunteers with low backache at 24-36 weeks' gestation were sought from our obstetric clinic population. The fetal heart rate (FHR), maternal blood pressure and maternal cardiac output were monitored for 20-minute intervals before, during and after placement of the support while standing and sitting. A sufficient number of subjects was used to detect a difference of 10% in cardiac output. RESULTS: Twenty-five women were enrolled between 24 and 36 weeks' gestation. No significant changes were encountered in the FHR baseline or beat-to-beat variability during placement of the support. The few FHR decelerations were isolated and not attributable to the support. The maternal systolic, diastolic and mean arterial blood pressures were unaffected by the support. The right-sided and left-sided cardiac outputs were unchanged during the monitoring periods. Each woman, when questioned two weeks later, reported improvement in back discomfort while sitting and standing. CONCLUSION: This elastic/Velcro lumbar and abdominal support, available to relieve low backache, did not acutely affect the hemodynamics of the fetus and mother.

Placebo-controlled comparison between a single dose and a multidose of betamethasone in accelerating lung maturation of mice offspring.

OBJECTIVE: Our purpose was to determine, in a placebo-controlled manner with a mouse model, whether a multidose of betamethasone is more beneficial than a single dose in accelerating fetal lung maturation. STUDY DESIGN: Ninety gravid CD-1 mice were randomly assigned to 1 of 3 groups (n = 30) to receive either a placebo (0.25 mL subcutaneously) or betamethasone (0.1 mg subcutaneously) as a single dose on gestational day 14 or as a multidose twice daily on gestational day 14 and 15. Ten pregnancies in each group were terminated at gestational day 16.5 to observe the neonatal breathing pattern (scale 0 to 5; 5 is unlabored breathing) and the lung histologic findings (scale 0 to 5; 5 is alveolar budding). The lungs of the offspring belonging to the remaining 20 pregnancies in each group were removed and weighed at postnatal day 1, 3, 5, or 120. RESULTS: Fetuses exposed to a multidose of betamethasone displayed a higher breathing score at gestational day 16.5 than either to a single dose or to the placebo (mean score 4.6 vs 3.8 or 1.3; P <. 001). Alveolar development was greater after exposure to a multidose of betamethasone than after a single dose or after a placebo (mean score 4.4 vs 3.5 or 1.6; P <.001). The lung weights at gestational day 16.5 were less after a multidose of betamethasone than after a single dose of either betamethasone or a placebo (18.3 +/- 1.0 g vs 21.4 +/- 1.3 g or 23.3 +/- 1.3 g; P <.02). The lung/body weight ratio was similarly affected. This reduced weight of the lungs persisted postnatally into adulthood. CONCLUSIONS: With a CD-1 mouse model, a multidose of antenatal betamethasone accelerated fetal lung maturation more than after a single dose but was accompanied with a decrease in lung weight that persisted into adulthood.

Effect of in utero exposure to betamethasone on motivation/anxiety testing in mice offspring.

In utero exposure to a single dose of the long-acting corticosteroid betamethasone at GD 14 has been shown to induce specific differences in motivation/anxiety testing among offspring. Because multidosings are desired to enhance fetal lung maturation, our objective was to compare effects of multidosings of betamethasone with a placebo on postnatal tests of motivation and anxiety. Sixty gravid CD-1 mice were randomly assigned to receive one of six treatment regimens (n = 10) that consisted of a single or a double SC dosing of either betamethasone (Celestone soluspan 0.2 mg on GD 14; 0.1 mg on GD 13 to 16; 0.1 mg b.i.d. on GD 14 and 15; 0.1 mg b.i.d. on GD 13 to 16) or saline (0.25 ml on GD 13 to 16; 0.25 ml b.i.d. on GD 13 to 16). The percent of pups exhibiting separation vocalization was temporarily less at PND 5 after betamethasone exposure to four doses (p < 0.05) and to eight doses (p < 0.01). The percents of pups being successful in homing (PND 9) and in responding to startle stimulation (PND 12-15) were not different between the betamethasone-exposed and placebo-exposed groups. Exploratory performance in the radial arm maze revealed no delay in the activities of juvenile and adult offspring exposed to betamethasone. The percent of male offspring that fought as juveniles and as adults was not different between the betamethasone-exposed and the placebo-exposed groups. The previously reported altered responses using the elevated plus maze, among juvenile and adult offspring, after a single dose of betamethasone was not replicated in this multidose study. These data indicate that prenatal exposure to betamethasone did not affect the mouse offspring's long-term responses to motivation/anxiety testing.

Impact of multiple antenatal doses of betamethasone on growth and development of mice offspring.

OBJECTIVE: Our purpose was to determine in a randomized, placebo-controlled manner whether multiple antenatal doses of betamethasone affect long-term growth and development of exposed mouse offspring. STUDY DESIGN: Sixty pregnant CD-1 mice received either two, four, or eight antepartum doses of 0.1 mg betamethasone or placebo. Perinatal outcomes, growth, and development of the offspring were compared in a blinded manner. Variables were compared by analysis of variance or chi 2 testing. RESULTS: Betamethasone-exposed subjects gained less weight during pregnancy and were delivered of fewer live pups, with fewer male survivors and lower birth weights. These trends were dose related. Growth measurements were similar after the neonatal period. No differences in functional development and physical maturation in the offspring were noted. The reproductive capability, perinatal outcomes, and growth and development of the second-generation offspring were unaffected by betamethasone exposure. CONCLUSION: Multiple antenatal dosings of betamethasone, reaching toxic levels, did not have an impact on the long-term growth and development of the surviving mouse offspring.

A placebo-controlled, blinded comparison between betamethasone and dexamethasone to enhance lung maturation in the fetal mouse.

OBJECTIVE: To compare the effects of betamethasone and dexamethasone used to enhance lung maturity of the fetal mouse. METHODS: Adult CD-1 mice were administered a single dose of either a placebo or different strengths of betamethasone (0.01, 0.025, or 0.10 mg) or dexamethasone (0.025 or 0.10 mg) on day 14.0 (74%) of gestation. The eight gravid mice in each treatment cohort were killed on day 16.5 to assess fetal lung maturity (histologic changes and respiratory patterns) in a blinded manner. Another ten gravid mice in each treatment group were allowed to deliver spontaneously to assess perinatal outcomes. RESULTS: Compared with the effects from placebo exposure, the 0.10-mg doses of both betamethasone and dexamethasone demonstrated enhanced histologic maturational changes and improved neonatal respiratory efforts. Betamethasone was twofold to threefold more potent than dexamethasone. The fetal crown-rump lengths and the fetal body, lung, and heart weights were indistinguishable among the three treatment groups. Compared with the fetal liver weight in the placebo group (55.0 +/- 2.2 mg), the liver was less heavy after exposure to 0.10 mg of betamethasone (45.6 +/- 2.0 mg; P < .005), 0.025 mg of dexamethasone (47.6 +/- 1.7 mg; P < .02), or 0.10 mg of dexamethasone (43.8 +/- 1.5 mg; P < .001). No significant differences were observed between the 0.10-mg treatments of either corticosteroid and placebo for the duration of gestation, litter size, survival rate, birth weights, or weight gains to postnatal day 26. CONCLUSION: A single subcutaneous dose of 0.10 mg of betamethasone was twofold to threefold more potent than dexamethasone in accelerating fetal lung maturity without impairing fetal survival or weight gain. The unexpected finding of a reduced fetal liver weight with either corticosteroid warrants clinical correlation.

A placebo-controlled comparison between betamethasone and dexamethasone for fetal maturation: differences in neurobehavioral development of mice offspring.

OBJECTIVE: Our purpose was to determine whether antenatal betamethasone or dexamethasone is the preferred drug by use of neurobehavioral development assessment of exposed mice offspring. STUDY DESIGN: Thirty adult CD-1 mice were randomly assigned to one of three groups (n = 10) to be administered a single subcutaneous dose of either a placebo (0.9% sodium chloride), betamethasone (0.10 mg), or dexamethasone (0.10 mg) on day 14 (74%) of gestation. The offspring then performed a battery of sensory, motor, motivational-anxiety, cognitive, and social tasks. Data were compared with use of analysis of variance, Kruskal-Wallis, or chi2 testing where appropriate. RESULTS: The offspring from the three treatment groups were indistinguishable at birth. Dexamethasone exposure induced a brief developmental delay. Separation anxiety was increased in the dexamethasone-exposed group in the perinatal period, whereas exposure to both corticosteroids decreased anxiety in the juvenile period, continuing into adulthood among male betamethasone-exposed mice. Selective enhancement of a memory process occurred in betamethasone-exposed mice, whereas dexamethasone exposure resulted in a decrement. Socialization as to place preference while awake and asleep varied among the three treatment groups. Corticosteroid treatment did not induce significant changes in sensory, motor, motivation, and learning performances or in reproductive capability and progeny development. CONCLUSION: Subtle differences in offspring performances of neurobehavioral development tasks favored antenatal betamethasone rather than dexamethasone. This finding, along with the knowledge that dexamethasone is less potent in accelerating lung maturity in the fetal mouse, suggests that betamethasone may be the preferred corticosteroid to use when human preterm delivery is imminent.

Blood pressure monitoring during pregnancy. Accuracy of portable devices designed for obese patients.

OBJECTIVE: To compare the accuracy of three commercially available blood pressure monitoring devices having cuffs placed at different anatomic sites on obese pregnant women with large arms. STUDY DESIGN: Fifty-five obese pregnant women (body mass index > 27.3) were eligible for participation; each had an upper arm circumferences > 35 cm. The three different portable devices compared had cuffs that fit easily around either the index finger, wrist or large arm. Two recordings using each device were compared with those obtained simultaneously using a well calibrated monitor. RESULTS: Systolic, diastolic and mean arterial pressure recordings did not correlate between the monitor and devices with the cuff around the finger (r2 = .17, .17, .22), wrist (.30, .24, .33) or large arm (.44, .26, .40). The percentages of measurement differences within 5 mm Hg for the systolic, diastolic and mean arterial pressure were low for the device with the cuff around the finger (11.0%, 25.5%, 23.6%), wrist (33.0%, 46.4%, 35.5%) or large arm (38.5%, 29.4%, 46.7%). CONCLUSION: Despite their commercial appeal, none of these portable blood pressure monitoring devices was accurate for use by obese pregnant patients with large arms.

Effects of intracervical prostaglandin E2 on fetal heart rate and uterine activity patterns in the presence of oligohydramnios.

OBJECTIVE: Our purpose was to compare fetal heart rate patterns and uterine activity before and after preinduction prostaglandin E2 administration in the presence or absence of oligohydramnios. STUDY DESIGN: In a retrospective case-controlled review we examined cases in which prostaglandin E2 (Prepidil) was inserted intracervically for gravid women requiring an induction of labor in the presence of either oligohydramnios (amniotic fluid index < or = 5.0) or adequate fluid (amniotic fluid index 5.1 to 23.9). Uterine activity and fetal heart rate tracings that were begun 1 hour before and continued for 6 hours after dosing were interpreted without knowledge of amniotic fluid volume. RESULTS: Cases in the oligohydramnios (n = 51) and adequate fluid (n = 49) groups were the same for maternal age, race, parity, gestational age, and predose Bishop score. Patients with oligohydramnios had more high-amplitude contractions in the first hour after dosing (9.0 +/- 1.2 vs 6.1 +/- 0.9, p < 0.05), but there were no significant differences in the frequency or duration of contractions during the subsequent 5 hours. Uterine hyperstimulation was not seen, and there were no differences in the frequency of variable or late fetal heart rate decelerations. CONCLUSION: For pregnancies undergoing preinduction cervical ripening with intracervical prostaglandin E2, the presence of oligohydramnios was not associated with a greater risk of fetal heart rate decelerations, although contractions were more common during the first hour after dosing.

Double-blind comparison of intracervical and intravaginal prostaglandin E2 for cervical ripening and induction of labor.

OBJECTIVE: Our purpose was to compare the safety and effectiveness of prostaglandin E2 delivered sequentially as an intracervical (0.5 mg) or intravaginal (2.5 mg) gel. STUDY DESIGN: Hospitalized patients with an unfavorable cervix (Bishop score < or = 4) at > or = 35 weeks and requiring induction of labor were assigned to receive two 2.5 ml doses of gel intracervically and intravaginally in a double-blind, placebo-controlled manner. Second and third doses were given at 6-hour intervals until there were either regular uterine contractions or a Bishop score change > 3 points. RESULTS: The 100 evaluable cases received prostaglandin E2 either intracervically (n = 52) or intravaginally (n = 48). Difficulty with exact gel instillation was present with intracervical gel only, where spillage occurred in 85% of cases. Compared with intracervical therapy prostaglandin E2 given intravaginally was more likely to significantly change the Bishop score (60.4% vs 40.4%, p = 0.04) and stimulate regular contractions (72.9% vs 48.1%, p = 0.01). Uterine hyperstimulation was present in one case in each group. CONCLUSION: Although each was safe, instillation of prostaglandin E2 gel was better at a higher intravaginal dose than a lower intracervical dose because of its greater ease of administration and higher likelihood of cervical change.

Double-blind comparison of intravenous butorphanol (Stadol) and fentanyl (Sublimaze) for analgesia during labor.

OBJECTIVE: Our purpose was to compare the analgesic properties, effect on labor, and maternal-fetal side effects of intravenous butorphanol and fentanyl. STUDY DESIGN: One hundred patients with uncomplicated term pregnancies were enrolled during early active labor. Each patient received standard doses of either fentanyl (50 to 100 micrograms) or butorphanol (1 to 2 mg) hourly on request in a double-blind manner. Pain was scored independently by the nurse and patient with a 10-point visual analog scale. Categoric and measurement data were collected for comparison of the effects on uterine activity, maternal and fetal well-being, and neonatal outcomes. RESULTS: The fentanyl (n = 50) and butorphanol (n = 50) groups were identical with respect to maternal age, race, parity, and weight. Greater improvement in pain relief was found after the first dose of butorphanol than after fentanyl (p < 0.05). When fentanyl was given, either more doses were necessary (3.2 +/- 1.3 vs 2.1 +/- 1.1, p < 0.01) or epidural analgesia was requested more often (16%, 32% vs 9%, 18%, p < 0.05). Uterine contraction patterns for the first hour after dosing were unchanged, and the duration of the first and second stages of labor were not different between the two groups. No differences in maternal or newborn adverse effects were observed. CONCLUSIONS: Both drugs were equally safe and without effect on active labor. Butorphanol provided better initial analgesia than fentanyl with fewer patient requests for more medication or epidural analgesia.