The Early External Cephalic Version (ECV) 2 Trial: an international multicentre randomised controlled trial of timing of ECV for breech pregnancies.

OBJECTIVE: To investigate whether initiating external cephalic version (ECV) earlier in pregnancy might increase the rate of successful ECV procedures, and be more effective in decreasing the rate of non-cephalic presentation at birth and of caesarean section. DESIGN: An unblinded multicentred randomised controlled trial. SETTING: A total of 1543 women were randomised from 68 centres in 21 countries. POPULATION: Women with a singleton breech fetus at a gestational age of 33(0/7) weeks (231 days) to 35(6/7) weeks (251 days) of gestation were included. METHODS: Participants were randomly assigned to having a first ECV procedure between the gestational ages of 34(0/7) (238 days) and 35(6/7) weeks of gestation (early ECV group) or at or after 37(0/7) (259 days) weeks of gestation (delayed ECV group). MAIN OUTCOME MEASURES: The primary outcome was the rate of caesarean section; the secondary outcome was the rate of preterm birth. RESULTS: Fewer fetuses were in a non-cephalic presentation at birth in the early ECV group (314/765 [41.1%] versus 377/768 [49.1%] in the delayed ECV group; relative risk [RR] 0.84, 95% CI 0.75, 0.94, P=0.002). There were no differences in rates of caesarean section (398/765 [52.0%] versus 430/768 [56.0%]; RR 0.93, 95% CI 0.85, 1.02, P=0.12) or in risk of preterm birth (50/765 [6.5%] versus 34/768 [4.4%]; RR 1.48, 95% CI 0.97, 2.26, P=0.07) between groups. CONCLUSION: External cephalic version at 34-35 weeks versus 37 or more weeks of gestation increases the likelihood of cephalic presentation at birth but does not reduce the rate of caesarean section and may increase the rate of preterm birth.

Experimenting with feasibility of telemedicine in Alaska: successes and lessons learned.

Alaska may be ideally suited as a test site for telemedicine. It is by far the nation's largest state, with a population of only 550,000 clustered around a few cities and towns or widely spread across an area almost two and a half times as large as Texas. Its ratio of doctors to patients is the second lowest in the nation, and the cost of medical care exceeds that in the lower 48 states by 90%. Almost half of its residents are affiliated with the federal government in some way. Active duty and retired members of the military and their families (including children) represent 70,000 of the state's residents, and another 160,000 are affiliated with the Coast Guard, the Indian Health Service, and the Department of Veteran Affairs. In 1995, a telemedicine initiative was launched under the auspices of the 3rd Medical Center at Elmendorf Air Force Base. Its mission was to integrate video conferencing and store-and-forward technology into patient care. Brief but well-documented efforts yielded many valuable lessons on how relatively simple, low-bandwidth technology can be effectively used and its limitations. In addition, unexpected changes were observed in the way health care was delivered. This experience should provide valuable lessons for those embarking on this path to health care delivery.

Masking of fetal supraventricular tachycardia by electronic monitoring artefact.

In a fetus of 42 weeks' gestation electronic monitoring demonstrated a heart rate of 120 beats/min that lacked the normal variability. Auscultation with a fetoscope revealed the true rate to be 240 beats/min. When used in the external Doppler mode the fetal monitor had a 250-ms refractory period after the recognition of a fetal cardiac event. This precluded recognition of the next beat and produced the artefactual halving of the heart rate. With the increasing reliance upon electronic fetal monitoring, those practising obstetrics should be aware of the possibility of artefacts and ensure that they can recognize truly representative information about the fetus.

Comparative cervical microflora shifts after cefoxitin or cefazolin prophylaxis against infection following cesarean section.

The aerobic and anaerobic cervical microflora was determined before operation and on day 4 after operation in groups of women undergoing a clinical trial of prophylaxis with three doses of cefoxitin, cefazolin, or placebo for infectious complications of nonelective cesarean section. Floral shifts occurred post partum, with return of Escherichia coli and Bacteroides fragilis and a decrease in Candida colonization. No significant differences in flora existed preoperatively among patients receiving cefoxitin, cefazolin, or placebo, but by day 4, both antibiotic groups had greater enterococcal colonization. This difference was more marked with cefoxitin than with cefazolin. No difference in E. coli or B. fragilis colonization was noted by day 4 in placebo and antibiotic groups. Resistance developing in isolates in the antibiotic groups was mainly a result of enterococcal colonization. Results of this study indicate that a three-dose cephalosporin prophylactic regimen resulted in a significant selection of resistant enterococcal colonization but there was no increase in nosocomial infection in the antibiotic groups compared to the placebo group. There did not appear to be significant differences in either species selection or antibiotic resistance of aerobic or anerobic microflora between the cefoxitin and cefazolin groups.

Multicenter comparison of cefoxitin versus cefazolin for prevention of infectious morbidity after nonelective cesarean section.

A randomized double-blind placebo-controlled comparison of prophylactic cefoxitin, an antibiotic with good activity against anaerobic bacteria, with cefazolin, an agent effective predominantly against aerobes, was undertaken in 354 women who underwent nonelective cesarean section (124 receiving cefoxitin, 119 cefazolin, and 111 placebo). Among the placebo group, 24.3% developed genital tract-related infection, in comparison to 5.6% of the cefoxitin patients and 6.7% of the cefazolin patients (P less than 0.001). Standard febrile morbidity, fever index, and duration of postoperative hospital stay were also significantly less in the antibiotic prophylactic groups. For patients with febrile morbidity, the mean fever index was less in the cefoxitin group (24.8 degree-hours) than that in the cefazolin group (42.7 degree-hours), and this difference approached statistical significance (P less than 0.1, greater than 0.05). Postoperative hospital stay longer than 1 week for infectious morbidity occurred in 26% of cefoxitin patients, a significantly lower incidence compared to the 66% rate for patients who received cefazolin, and the 57% incidence for patients in the placebo group (P less than 0.05).

Changes in plasma cortisol and progesterone after administration of enkephalins to newborn lambs.

Methionine-enkephalin and leucine-enkephalin were injected into the brachiocephalic artery of lambs at 8-18 days of age. There was a significant increase in the concentration of cortisol in plasma 15-30 min after leucine-enkephalin (10-, 100-, and 500-micrograms bolus). After the 100-micrograms bolus, there was a biphasic response and a second significant rise in cortisol was seen at 90 min. Plasma progesterone was elevated significantly at 15-30 min and at 90 min after the 100- and 500-microgram injections of leucine-enkephalin. Methionine-enkephalin (100 micrograms) produced a transient rise in plasma cortisol at 15-30 min, although the mean concentrations were not statistically different from the control period. We conclude that in newborn lambs, enkephalins may influence adrenal function. It is likely that such an action is secondary to effects on brain or pituitary hormone release.

The fetal membranes as a possible source of progesterone in the amniotic and allantoic fluids of pregnant sheep.

To assess the possible source of progesterone in the fetal fluids of pregnant sheep, we measured the changes in progesterone concentrations in amniotic fluid (AF) and allantoic fluid (ALF) during pregnancy and compared these values with those in the maternal and fetal circulations. In acute experiments, the concentration of progesterone in ALF was greater than that in AF, and in both compartments, progesterone rose progressively between day 50 of pregnancy and term (day 145). In contrast, in maternal peripheral and uterine venous blood as well as in umbilical cord blood the mean concentration of progesterone increased until day 130, but fell at term. Similar results were obtained in chronically catheterized sheep during late pregnancy. The pattern of progesterone change in the AF and ALF suggested that the steroid might originate from a different source than progesterone in the vascular compartments. By means of in vitro incubation studies, we showed that the chorioallantoic membrane and amnion from sheep at term pregnancy had the capacity to convert [3H]pregnenolone to [3H]progesterone. These results raise the possibility that there may be local changes in steroid hormone concentrations within the tissues and fluids of the pregnant uterus. These changes could be of importance in altering the intrauterine endocrine milieu at the time of birth.

Maternal steroid changes after fetal death until delivery of the dead sheep fetus.

Progesterone, estrone, and estradiol have been determined during late pregnancy and at parturition in the maternal plasma of sheep bearing live and dead fetuses. Mean concentrations of the steroids at days 125--130 after mating were lower after fetal death, although the differences were not significant. The mean interval between fetal death and delivery was 11.8 +/- 5.8 (0.01 +/- 0.01 ng/mL) on the day of delivery. There was no preparturient rise in maternal estrogen levels in animals with dead fetuses. The ratios of progesterone:estradiol and progesterone:estrone fell from 130 and 140 to 2.9 and 1.2, respectively, during the 5 days prior to delivery due entirely to the fall in progesterone. In normal animals the ratios of progesterone:estradiol and progesterone:estrone decreased from 186.1 and 81.7 at 5 days before parturition to 9.4 and 2.0 on the day of birth. This was attributable partly to a fall in progesterone but largely to the preparturient rise in estrone and estradiol. We conclude that some placental steroid output continues after fetal death in the sheep but that deliveries of both dead and live fetuses are associated with an abrupt change in the ratio of progesterone:estrogens in maternal blood.

Adrenal responses to prostaglandin E2 in newborn lambs.

Prostaglandin E2 (PGE2) is present in fetal sheep and stimulates adrenal steroidogenesis in the fetal and newborn sheep. We have examined the site of this prostaglandin effect and the changes in adrenal responsiveness to exogenous PGE2 and adrenocorticotropic hormone (ACTH) in in vivo studies with newborn lambs. A bolus injection of PGE2 (50 micrograms) into the brachiocephalic trunk or descending aorta raised plasma cortisol (F) 25.3 +/- 4.5 (SE) ng/ml to 75.5 +/- 5.4 ng/ml at 15 to 30 minutes and 23.2 +/- 3.0 to 60.5 +/- 7.1 ng/ml at 15 to 30 minutes, respectively (both P less than 0.001). Intra-aortic infusion of PGE2 (1.25 micrograms/ml) produced a similar significant rise in F. Basal plasma F decreased from 34.3 +/- 7.4 ng/ml at 9 to 11 days to 14.1 +/- 4.0 ng/ml at 12 to 13 days and 18.2 +/- 5.7 ng/ml at 17 to 18 days. Peak F during a 60-minute PGE2 infusion was significantly greater at 9 to 11 days (127.3 +/- 14.6 ng/ml) than at the two later times (57.2 +/- 7.07 and 55.7 +/- 14.6 ng/ml, respectively, both P less than 0.01). The response to ACTH was greater 24 hours after birth than at 7 or 28 days of age. Injection of ACTH or alpha-melanocyte-stimulating hormone during an intra-aortic PGE2 infusion did not further elevate plasma F over the rise seen with PGE2 alone. The results suggest both direct and indirect stimulatory effects of PGE2 on adrenal function in newborn sheep, and are consistent with a role of endogenous PGE2 as an intermediate factor in ACTH action.

The availability of cortisol in amniotic fluid to the fetus and chorionic and amniotic membranes.

This study examined whether cortisol, present in amniotic fluid (AF), could reach the fetal blood, and might be available to various fetal organs and to the fetal membranes and placenta. [3H]Cortisol ([3H]F) was injected into the AF of five sheep at 130--143 days gestation. Samples of AF and fetal blood were collected for 120 min, at which time the fetuses were delivered and fetal organs and fluid were collected for measurement of the [3H]F content. [3H]F disappeared from AF with an initial half-life of about 40 min and was detected in fetal blood by 30 min after intraamniotic injection. At 120 min after injection, [3H]F was widely distributed within the pregnant uterus, and the highest concentrations of radioactivity were found in allantoic fluid, fetal membranes, and placental tissue. The concentration of [3H]F in the umbilical vein was higher than in umbilical arterial blood in four of five sheep. [3H]F and [3H]cortisone were found in several fetal tissues, including adrenal, kidney, pancreas, lung, and liver. [3H]F in tracheal and stomach fluid was generally less than in fetal blood. We conclude that 1) cortisol can reach the fetus from AF, 2) a major route of entry may be via the vasculature of the fetal membranes, 3) a considerable proportion of [3H]F is retained by the fetal membranes, and 4) interconversion of [3H]F and [3H]cortisone may occur in some fetal tissues.

Conversion of PGE2 to PGF2alpha by fetal sheep blood.

In an attempt to explain the differences in the concentration of primary prostaglandins in the circulation of adult and fetal sheep, we have examined the ability of whole blood from adult and fetal sheep to reduce PGE2 to PGF2alpha in vitro. PGF2alpha was the principal radioactive product formed from 3H PGE2 by both adult and fetal blood. The enzyme initial reaction velocity was significantly higher (P = 0.02) per ml of fetal than adult blood. The optimum enzyme pH (7.0 - 7.5) was similar for both adult and fetal blood. The Km of the enzyme in fetal and adult blood were 3.59 x 10(-7) M and 5.02 x 10(-7) M respectively (P greater than 0.05). There was no detectable metabolism of PGF2alpha by either adult or fetal sheep blood. The results indicate that prostaglandin 9-ketoreductase is present in both adult and fetal sheep blood. Differences in the activity of this enzyme are unlikely to explain the higher concentrations of PGE reported in the plasma of fetal lambs.