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.

Peripartum myocardial ischemia: a review of Canadian deliveries from 1970 to 1998.

OBJECTIVE: The purpose of this study was to evaluate the incidence of peripartum myocardial ischemia in Canada. STUDY DESIGN: We identified the cohort of women who were admitted to Canadian hospitals for delivery between 1970 and 1998 to calculate the incidence rate and to evaluate potential risk factors. RESULTS: One hundred fourteen of 10,032,375 women delivered in Canadian hospitals between 1970 and 1998 had peripartum myocardial ischemia recorded as a discharge diagnosis. The overall crude incidence rate was 1.1 (95% confidence interval 0.93, 1.37) women with peripartum myocardial ischemia per 100,000 women delivering per year as noted in the Canadian Hospital Morbidity database. Rates did not increase over time but increased with maternal age. Identified risk factors were diabetes mellitus, hyperlipidemia, and chronic heart disease. The case fatality rate among women with the disease was 1.8%. CONCLUSION: The incidence of peripartum myocardial ischemia did not increase between 1970 and 1998 in Canada, despite an aging cohort with more prevalent medical comorbidities. Maternal mortality from this event is lower than previously described.

Renin stimulates decidual prostaglandin production via a novel mechanism that is independent of angiotensin II formation.

Renin is a proteolytic enzyme that has been considered to have only one function which is to cleave angiotensinogen between the 10th and 11th amino acids to form angiotensin-1. This is then converted to angiotensin-II, a potent vasoconstrictor, antinatriuretic and antidiuretic by angiotensin-converting enzyme. We have investigated the action of renin to stimulate prostaglandin production by decidual cells and in so doing have generated data that challenge the prevailing dogma. Renin stimulates decidual prostaglandin production in a concentration-related fashion that is unaffected by saralasin treatment. This stimulatory action of renin is enhanced rather than reduced by arachidonic acid treatment but abolished by treatment with cycloheximide or actinomycin D. Renin caused a more rapid recovery of decidual prostaglandin biosynthesis from acetylsalicylic acid treatment than did control media. Moreover, renin treatment of both decidual and amnion cells induced increased levels of PGHS-2 within 2 h. Collectively, these results indicate that renin can act directly, separately from the generation of angiotensin-I and II. In this case renin can induce PGHS expression.

Outcome of children born to women treated during pregnancy for the antiphospholipid syndrome.

OBJECTIVE: To determine the rate of neonatal and childhood medical complications in the offspring of women with the antiphospholipid syndrome who are treated during pregnancy. METHODS: We compared 29 infants born to 23 mothers with antiphospholipid syndrome with a group of control children matched for year and gestational age at birth and route of delivery. During pregnancy, mothers with antiphospholipid syndrome were treated with accepted therapeutic regimens, including prednisone and low-dose aspirin, heparin and low-dose aspirin, and others. RESULTS: Neonatal complications in the study infants included hyperbilirubinemia (14), respiratory distress syndrome (three), bronchopulmonary dysplasia (two), necrotizing enterocolitis (two), intraventricular hemorrhage (two), neonatal sepsis (one), coarctation of the aorta (one), hypothyroidism (one), hypoglycemia (one), and death (one). Two children had feeding problems, four had delayed psychomotor development, and eight were small for their age. However, the overall rate of neonatal or childhood complications did not differ from that in the control children. CONCLUSIONS: Our data indicate that prematurity and neonatal problems are common, but the childhood course for these offspring is similar to that of other premature infants.

Hysterotomy to effect vaginal delivery with mentum anterior head entrapment.

BACKGROUND: Entrapment of the aftercoming head after mentum anterior rotation is a life-threatening complication of vaginal breech delivery. Few options exist when rotation and flexion from this position cannot be performed successfully either transabdominally or with vaginal maneuvers. CASE: A term primigravida presented with a singleton breech in advanced labor. The fetal torso and arms delivered vaginally, but the aftercoming head became extended and was entrapped in a mentum anterior position. The fetal head could not be rotated and flexed, either vaginally or transabdominally with suprapubic pressure. Laparotomy and hysterotomy were performed, and vaginal delivery of a live fetus was accomplished after rotation and flexion of the fetal head through this incision. CONCLUSION: Hysterotomy is a safe and effective maneuver for delivery of the entrapped fetal head with mentum anterior rotation after standard procedures have failed.

Mechanism of cytokine stimulation of prostaglandin biosynthesis in human decidua.

OBJECTIVE: The purpose of this study was to determine the mechanism of action of the cytokines tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) on the stimulation of prostaglandin (PG) production in human decidua. METHODS: Decidual cells from term placentas were grown in culture until confluent. Incubations were performed with TNF alpha or IL-1 beta, and with cycloheximide, actinomycin D, arachidonic acid, or acetylsalicylic acid (ASA). Prostaglandin E2 was measured by radioimmunoassay and cellular protein determined. RESULTS: The concentration-related stimulation of decidual PGE2 production by IL-1 beta and TNF alpha was completely abrogated by cycloheximide and actinomycin D treatment. Although arachidonic acid alone stimulated decidual PGE2 biosynthesis, the addition of IL-1 beta or TNF alpha consistently augmented this effect. Both cytokines induced recovery of PGE2 biosynthesis from ASA pretreatment more rapidly than controls. CONCLUSIONS: Interleukin-1 beta and TNF alpha both act on decidual PG biosynthesis in a manner requiring new protein synthesis. In combination with our other results, this suggests that IL-1 beta and TNF alpha act to induce PG endoperoxide synthase activity.

Cesarean deliveries at a university hospital: analysis of rates and indications.

The objective of this paper is to evaluate the influence of patient risk status on the incidence of and indications for cesarean delivery. All live births > or = 23 weeks at the University of Vermont in 1995 (n = 2395) were retrospectively analyzed for delivery route, indication for cesarean, gestational age, parity, and practice group (to reflect risk status). The total cesarean rate was 14.4% (344 of 2395), and the primary rate was 11.4% (244 of 2144). Abnormal presentation was the most common indication (25.6%, 88 of 344). The "corrected" cesarean rate (maternal-fetal medicine and transported patients excluded) was 12.4% (273 of 2194), and the "corrected" primary rate was 9.6% (190 of 1975). Furthermore, when all deliveries were analyzed, regardless of risk status but limited to gestational age > or = 36 weeks, the rates did not change (12.6%, 280 of 2214; primary 9.2%, 183 of 1994). Arrest of dilation was the most common indication in both "corrected" subgroups (23.4 and 24.6%, respectively). Cesarean rates at tertiary care hospitals should be compared with rates at community hospitals only after correcting for dissimilar patient groups or gestational age.

Intrauterine infection and the effects of inflammatory mediators on prostaglandin production by myometrial cells from pregnant women.

OBJECTIVE: Our purpose was to evaluate the effects of known stimulants of prostaglandin production on cultured myometrial cells from women in labor with and without intrauterine infection. STUDY DESIGN: Myometrial segments were obtained from 16 patients between 33 and 40 weeks' gestation who had been in labor for > or = 8 hours at cesarean delivery; 8 patients had clinical chorioamnionitis and 8 did not. Myometrial cells were isolated and grown in culture. Incubations were conducted with interleukin-1 beta, tumor necrosis factor-alpha, or epidermal growth factor. Prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha (the stable metabolite of prostacyclin) were measured by radioimmunoassay, and cellular protein was determined. RESULTS: Cultured human myometrial cells from patients with and without prior intrauterine infection produced prostaglandins in response to interleukin-1 beta, tumor necrosis factor-alpha, and epidermal growth factor at a significantly increased rate (p<0.05 vs controls at and above 10 ng/ml of interleukin-1 beta, tumor necrosis factor-alpha, and epidermal growth factor). The major prostaglandin produced in response to each stimulant was 6-keto-prostaglandin F1 alpha; however, this response was attenuated in cells from patients with intrauterine infection. CONCLUSIONS: Cultured human myometrial cells from patients with and without prior intrauterine infection respond to known stimulants of prostaglandin production. Prior intrauterine infection has no effect on baseline prostaglandin production, but the amount of prostacyclin produced as a response to cellular stimulants is decreased with prior intrauterine infection. This effect may have a role in regulating myometrial function in intrauterine infection.

Effects of gestational age on prostaglandin production and its regulation in human myometrial cells.

The objective of this study was to evaluate the effects of known stimulants of prostaglandin production on cultured myometrial cells from women who are at various gestational ages. To evaluate this, myometrial segments were obtained from 12 patients at 27-40 weeks gestation at cesarean delivery. Myometrial cells were then isolated and grown to confluence in culture. Incubations were conducted in quadruplicate for 16 hours with interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA), or ionomycin. Prostaglandins E2, F2 alpha, and 6-keto F1 alpha (the stable metabolite of prostacyclin) were measured by radioimmunoassay and cellular protein determined. The results revealed that cultured myometrial cells produced prostaglandins in response to IL-1 beta, TNF-alpha, EGF, PMA, and ionomycin at all gestational ages tested at a significantly increased rate (P < 0.05 vs controls at and above 10 ng/ml of IL-1 beta, TNF alpha, and EGF; 1 microM for PMA, and 5 microM for ionomycin). The major prostaglandin produced in response to each stimulant was 6-keto-PGF1 alpha. Cultured human myometrial cells respond to known stimulants of prostaglandin production throughout the third trimester of pregnancy in the absence of labor. The myometrium may therefore be a source of prostaglandins that influences uterine activity.

Tumor necrosis factor alpha stimulates amnion prostaglandin biosynthesis primarily via an action on fatty acid cyclooxygenase.

The purpose of this study was to determine how tumor necrosis factor alpha (TNF alpha) stimulates prostaglandin E2 production in human amnion. Amnion cells were isolated from term placentae and grown to confluence in culture. Incubations were conducted in quadruplicate wells for 16 hours with TNF alpha and protein synthesis inhibitors cycloheximide and actinomycin D, or arachidonic acid, acetylsalicylic acid (ASA), or staurosporine or H7 which inhibit protein kinase C activity. Prostaglandin E2 (PGE2) was measured by radioimmunoassay and cellular protein determined. The stimulatory action of TNF alpha on amnion PGE2 production was blocked by protein synthesis inhibitors, and the addition of arachidonic acid always enhanced the stimulatory properties of TNF alpha. TNF alpha consistently induced more rapid recovery from ASA treatment, and protein kinase C inhibition attenuated the stimulatory effects of TNF alpha. These results suggest that the stimulatory action of TNF alpha on amnion PGE2 production is likely at the level of induction of fatty acid cyclooxygenase activity and is partially dependent upon activation of protein kinase C.

Uterine rupture during induced trial of labor among women with previous cesarean delivery.

OBJECTIVE: This study was undertaken to compare the rates of uterine rupture during induced trials of labor after previous cesarean delivery with the rates during a spontaneous trial of labor. STUDY DESIGN: All deliveries between 1992 and 1998 among women with previous cesarean delivery were evaluated. Rates of uterine rupture were determined for spontaneous labor and different methods of induction. RESULTS: Of 2119 trials of labor, 575 (27%) were induced. The overall rate of uterine rupture was 0.71% (15/2119). The uterine rupture rate with induced trial of labor (8/575; 1.4%) was significantly higher than with a spontaneous trial of labor (7/1544; 0.45%; P =.0004). Uterine rupture rates associated with different methods of induction were compared with the rate seen with spontaneous labor and were as follows: prostaglandin E(2) gel, 2.9% (5/172; P =.004); intracervical Foley catheter, 0.76% (1/129; P =.47); and labor induction not requiring cervical ripening, 0.74% (2/274; P =.63). The uterine rupture rate associated with inductions other than with prostaglandin E(2) was 0.74% (3/474; P =.38). The relative risk of uterine rupture with prostaglandin E(2) use versus spontaneous trial of labor was 6.41 (95% confidence interval, 2. 06-19.98). CONCLUSION: Induction of labor was associated with an increased risk of uterine rupture among women with a previous cesarean delivery, and this association was highest when prostaglandin E(2) gel was used.

Evidence for a common mechanism of action of interleukin-1 beta, tumor necrosis factor-alpha, and epidermal growth factor on prostaglandin production in human chorion cells.

PROBLEM: Although chorion produces prostaglandins in response to interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and epidermal growth factor (EGF), little attention has been given to the mechanisms of action of prostaglandin biosynthesis in this tissue. METHODS: IL-1 beta, TNF alpha, and EGF induced a concentration-related stimulation of prostaglandin E2 (PGE2) biosynthesis in human chorion cells, and this stimulation was enhanced by the addition of exogenous arachidonic acid. RESULTS: Protein synthesis inhibition with cycloheximide or actinomycin D resulted in complete abrogation of the stimulation of PGE2 production by IL-1 beta, TNF alpha, and EGF. Finally, all three stimulants induced a more rapid recovery of PGE2 production in chorion cells after acetylsalicylic acid pretreatment than controls. CONCLUSIONS: It is suggested that IL-1 beta, TNF alpha, and EGF all act to stimulate human chorion PGE2 production primarily via induction of prostaglandin endoperoxide synthase activity.

Incidence of uterine rupture among women with müllerian duct anomalies who attempt vaginal birth after cesarean delivery.

OBJECTIVE: The purpose of this study was to determine and compare the incidences of uterine rupture among women with and without müllerian duct anomalies who were attempting vaginal birth after cesarean delivery. STUDY DESIGN: There were 1813 attempts at vaginal birth after cesarean delivery between 1992 and 1997 at the Foothills Hospital in Calgary, Alberta, Canada. Of the patients 25 had known müllerian duct anomalies and 1788 did not. The records of these 1813 women were reviewed with respect to uterine rupture, other complications, mode of delivery, and characteristics of the trial of labor. Comparisons were made with the Fisher exact test. RESULTS: The rates of uterine rupture were 8% (2/25) in the group with müllerian duct anomalies and 0.61% (11/1788) in the group without müllerian duct anomalies (P =.013). The cesarean delivery rates were 20% (5/25) and 25.1% (448/1788), respectively. All cesarean deliveries among women with müllerian duct anomalies were performed urgently in response to severe fetal heart rate abnormalities. The rates of fetal heart rate abnormalities necessitating immediate delivery (60% vs 14.1%, P =.013), operative vaginal delivery (40% vs 19.6%, P =.02), and cord prolapse (8% vs 0.45%, P =.0076) were significantly greater in the group with müllerian duct anomalies. CONCLUSIONS: Vaginal delivery is common among women with müllerian duct anomalies who attempt vaginal birth after cesarean delivery, but the rates of uterine rupture and other complications are high.

Wireless and Web-based medical monitoring in the home.

A remote medical monitoring system is described, which continuously monitors patients' state of health. The system uses the services provided by intranets and the Internet to allow remote supervision of patients, who may be domiciled in their own home. A hardware/software prototype system has been constructed to demonstrate the use of non-invasive and minimally intrusive sensors attached to patients. Continuous real-time data is acquired, stored and processed. A wireless system or wires connect these monitor devices to the World Wide Web and, on request, information is delivered to authorized medical staff via a web browser or Wireless Application Protocol-enabled mobile telephones. Medical staff may examine real-time data or graphical information and make comparisons with historical data. Parameters may be set to select and control the data acquisition devices. The potential exists for augmentation of patient health by development of novel sensors and low-power electronic circuitry, and this research continues.

Signal averaging in Wolff-Parkinson-White syndrome: evidence that fractionated activation is not necessary for body surface high-frequency potentials.

It is commonly assumed that the presence of high frequency components in body surface potentials implies that fractionated activation fronts, caused by heterogeneously viable tissue, are present in the heart. However, it is possible that non-fractionated activation fronts can also give rise to high frequency surface potentials and that the relative amount of high frequency power is related to the complexity of the activation sequence. In a test of this idea, averaged body surface potentials were recorded during the entire QRS complex of nine Wolff-Parkinson-White (WPW) patients in situations in which fractionated activation fronts should not have been present, but which represent increasing degrees of complexity of ventricular activation: (1) postoperative ectopic pacing from subepicardial wires placed during surgery, when a single coherent activation front was present throughout most of the QRS; (2) Preoperative preexcited rhythm, when a single coherent activation front was present for one portion of the QRS (the delta wave); and (3) postoperative normal rhythm, when two or more activation fronts were present in the ventricles throughout most of the QRS. For comparison, averaged body surface potentials were also analyzed during the last 40 ms of the QRS complex and the ST segment of 14 postinfarction patients with chronic ventricular tachycardia. In the patients with WPW syndrome, relatively high frequency content increased (attenuation -36.7 vs -27.2 vs -18.3 dB) and QRS width decreased (160.7 vs 125.9 vs 94.1 ms) significantly from paced to preoperative to postoperative beats. Significant high frequency content was present in all cases, showing that coherent activation fronts can give rise to high frequencies. Interestingly, the postoperative QRS of WPW patients contained a larger proportion of high frequency power than did the late potentials of the patients with ventricular tachycardia. Thus, while the presence of late fractionated body surface potentials may be a marker for ventricular tachycardia, these potentials by themselves do not necessarily signify that the underlying cardiac activation giving rise to these signals is fractionated.

Maternal haemolysis, elevated liver enzymes and low platelets syndrome: perinatal and neurodevelopmental neonatal outcomes for infants weighing less than 1250 g.

OBJECTIVES: To study mortality and short-term morbidity of infants born to women with HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome and to compare the long-term neurodevelopmental morbidity of a subgroup with birth weight (BWT) less than 1250 g (study group) with weight matched controls. METHODS: Retrospective chart review and prospective neurodevelopmental follow-up through a Perinatal Follow-up clinic. Analysis of perinatal and neonatal data for women diagnosed with HELLP from 1993 to 1996. Neurodevelopmental outcome for the study group was compared to a group of weight matched controls. RESULTS: A total of 109 infants (mean gestational age 32.6 weeks, mean BWT 1766 g) were born to 104 women with HELLP syndrome. There was a significant decrease in mortality (P = 0.002) and morbidity (P < 0.05) with increasing gestational age and birthweight. No significant differences in neonatal mortality and morbidity were present between the infants weighing less than 1250 g study and weight matched control group. However, at 3 years, the study group had fewer children with cerebral palsy (P = 0.024) and mental disability (P trend = 0.07). Mean cognitive index was 99 versus 91 in the controls (P = 0.101). CONCLUSION: Improved health outcomes occur with increased gestational age. Infants with BWT less than 1250 g born to women with HELLP syndrome were not at risk of increased neurodevelopmental disability compared to controls.