Obstetric & Gynaecology

Obstetrics
    

• S. Guaschino, F. D. Seta, A. Sartore, G. Ricci, D. D. Santo, M. Piccoli, and S. Alberico (Trieste, Italy) 
  Efficacy of Maintenance Therapy with Topical Boric Acid in Comparison with Oral Itraconazole in the Treatment of Recurrent Vulvovaginal Candidiasis 
  Am J Obstet Gynecol March. 2001; 184: 598-602
        
  Objective : The purpose was to examine the efficacy of a topical long-term treatment with boric acid versus an oral long-term treatment (itraconazole) in the cure and prevention of recurrent vulvovaginal candidiasis.
        
  Results : During the treatment, the positive culture results (15.1% vs 12.1%) and the signs and symptoms (33.3% vs 24.2%) were similar within the 2 groups, with no significant statistical difference. With the withdrawal, after 6 months relapses were common in the 2 groups (54.5%).
       
  Conclusion : Boric acid seems to be a valid and promising therapy both in the cure of the vaginal infection and in the prevention of relapses of recurrent vulvovaginal candidiasis, but its efficacy ends with the suspension of the therapy. 
        
  Comments : 300 mg of boric acid was used daily for 2 weeks. An alternative drug such as boric acid could be as safe and effective as an oral antimycotic drug (itraconazole).
        
  The rate of compliance with boric acid therapy, the resolution of symptoms, and the cure rate, in comparison with itraconazole therapy, indicate that the use of boric acid is a valid alternative to oral maintenance therapy. 
       
  Van Slyke et al, for example, reported cure rates of 92% at 7 to 10 days after treatment and of 72% at 30 days, whereas the authors’ results show a cure rate of 82% at 15 days after treatment. 
       
  For patients with <12 episodes a year empiric self-treatment at the onset of symptoms with an over-the-counter agent is less expensive than and is preferable to monthly prophylaxis.
       

• B. P. Yawn, P. Wollan, K. McKeon, and C. S. Field (Rochester, Minnesota) 
  Temporal Changes in Rates and Reasons for Medical Induction of Term Labor, 1980-1996
  Am J Obstet Gynecol March. 2001; 184: 611-9
         
  Objective : This study was undertaken to assess temporal changes in rates and reasons for medical induction of term labor. 
         
  Study Design : A retrospective medical record review was conducted on a population-based cohort of 1293 women with term deliveries.
        
  Results : The rate of medical labor induction increased from 12.9% in 1980 to 25.8% in 1995. Stated indications also changed, with a 2-fold increase in induction for postdate gestation, a 23-fold increase in induction for macrosomia, a 15-fold increase in elective induction, and a 22-fold decline in induction for premature rupture of membranes. The average gestational age at delivery of postdate pregnancies declined from 41.9 weeks in 1980 to 41.0 weeks in 1995. By 1995, the average maternal length of stay and the percentage of cesarean deliveries were higher among women with induced labor at term than among those with spontaneous labor at term.
        
  Conclusion : Induction of term labor has almost doubled in prevalence during the past 15 years. The most common indications are elective induction and postdate pregnancy, often applied to gestations of 40 to 41 weeks’ duration. 
          
  Comments : The American College of Obstetricians and Gynecologists considers postterm pregnancy as an indication for induction of labor beginning at 42 weeks’ gestation. Research data suggest that induction of labor in pregnancies between 41 and 42 weeks’ gestation may decrease the rate of stillbirth and lower the costs associated with prenatal monitoring.
       
  Anecdotal reports suggest that both the physician and the mother value the elective induction of term labor, and therefore elective induction is appropriate whenever desired.
       
  The rates of cesarean delivery after elective induction of labor were higher than rates among women with spontaneous term labor. Since 1986, among primiparous women in whom labor was induced at term, 1 in every 4 has been delivered abdominally.
         
  Labor inductions associated with premature rupture of membranes, the only nonemergency indication with clear evidence for improved fetal and maternal outcomes, have decreased.
          

• Deborah Josefson 
  Scientists Fertilise Mouse Eggs Without Sperm
  BMJ Vol. 7305, 21 July 2001; Pg. 127
        
  Dr. Orly Lacham-Kaplan devised a procedure, which is an alternative to sperm donation for infertile men.
       
  Dolly was created by transferring a full set of chromosomes from an adult somatic cell into an oocyte that had been stripped of its own genetic material.
       
  By contrast, in the method used by the researchers at Monash, the oocyte retains its chromosomes but the somatic cell is persuaded, via chemical means, to jettison one set of its own chromosomes after fertilisation. }
     

• G.F. Jacobson, A M Autry, et al (Milwaukee, Wisconsin)
  A Randomized Controlled Trial Comparing Amoxicillin And Azithromycin for the Treatment of Chlamydia trachomatis in Pregnancy.
  Am J Obset Gynecol June 2001; 184: 1352-6
         
  Objective : To compare the efficacy of azithromycin with that of amoxicillin for the treatment of Chlamydia trachomatis infection during pregnancy.
         
  Study Design : A randomized controlled trial of pregnant women with cervical C trachomatis infection receiving care at two inner-city, university-based prenatal clinics. Pregnant women were randomly assigned to receive either oral amoxicillin, 500mg, three times daily for 7 days, or oral azithromycin, 1 g, in a single dose. Partners were referred for treatment. Tests of cure were scheduled 4 weeks after initiation of treatment. Statistical analysis was performed by using the Student t test and ?2 analysis.
        
  Results : One hundred twenty-nine pregnant women were enrolled, and 110 (85%) completed the protocol. There was similar treatment efficacy between amoxicillin and azithromycin (58% vs 64%, respectively, P = .56). In the amoxicillin group 3 women (5.5%) were intolerant, compared with 6 (10.9%) in the azithromycin group (P= .31).
         
  Conclusion : Amoxicillin and azithromycin are equally efficacious in the treatment of cervical C trachomatis during pregnancy.
        

• Judith U Hibbard, M A Ismail, Y Wang et al (Chicago, Illinois)
  Failed Vaginal Birth After A Cesarean Section: How Risky Is It? 
  Am J Obstet Gynecol, 2001; 184: 1365-73
         
  Objective : To determine the maternal risks associated with failed attempt at vaginal birth after cesarean compared with elective repeat cesarean delivery or successful vaginal birth after cesarean.
          
  Study Design : From 1989 to 1998 all patients attempting vaginal birth after cesarean and all patients undergoing repeat cesarean deliveries were reviewed. Data were extracted from a computerized obstetric database and from medical charts. The following three groups were defined: women who had successful vaginal birth after cesarean, women who had failed vaginal birth after cesarean, and women who underwent elective repeat cesarean. Criteria for the elective repeat cesarean group included no more than two previous low transverse or vertical incisions, fetus in cephalic or breech presentation, no previous uterine surgery, no active herpes, and adequate pelvis. 
         
  Predictor variables included age, parity, type and number of previous incisions, reasons for repeat cesarean delivery, gestational age, and infant weight. Outcome variables included uterine rupture or dehiscence, hemorrhage >1000 mL, hemorrhage >2000 mL, need for transfusion, chorioamnionitis, endometritis, and length of hospital stay. The Student t test and the c2 test were used to compare categoric variables and means; maternal complications and factors associated with successful vaginal birth after cesarean were analyzed with multivariate logistic regression, allowing odds ratios, adjusted odds ratios, 95% confidence intervals, and P values to be calculated.
         
  Results : The overall rate of uterine disruption was 1.1% of all women attempting labor; the rate of true rupture was 0.8%; and the rate of hysterectomy was 0.5%. Blood loss was lower and chorioamnionitis was higher in women who attempted vaginal births after cesarean.
         
  Conclusion : Patients who experience failed vaginal birth after cesarean have higher risks of uterine disruption and infectious morbidity compared with patients who have successful vaginal birth after cesarean or elective repeat cesarean delivery. Because actual numbers of morbid events are small, caution should be exercised in interpreting results and counseling patients. More accurate prediction for safe, successful vaginal birth after cesarean delivery is needed.
    

• R Bukowski, L MacKay, et al (Galveston, Texas)
  Inhibition of Cervical Ripening by Local Application of Cyclooxygenase 2 Inhibitor
  Am J Obstet Gynecol, June 2001; 184: 1374-79
         
  Objective : To test the hypothesis that the previously demonstrated progesterone- independent prolongation of pregnancy in rats treated with cervical application of the cyclooxygenase 2 inhibitor nimesulide is the result of inhibition of cervical ripening.
         
  Results : Animals treated with cervical application of nimesulide had significantly higher resistance to stretch than controls (slope: 0.2564 ± 0.1213 vs 0.1387 ± 0.0652; P = .019). The cervical content of cross-linked collagen was not significantly different between nimesulide-treated animals and controls (light-induced fluorescence ratios: 3.2134 ± 0.7390 vs 2.7892 ± 0.8518; P = .227).
          
  Conclusions : Treatment with cervical application of the cyclooxygenase 2 inhibitor nimesulide prevents the physiologic process of cervical ripening in late pregnancy. The inhibition is not the result of changes in cross-linked collagen content. Inhibition of cervical ripening with locally administered cyclooxygenase 2 inhibitor may be a potentially valuable treatment for patients at risk for preterm delivery.
         
  Comment : The cervix is central to most tests used to predict preterm delivery, such as cervical length measurement or cervicovaginal fetal fibronectin, and risk factors associated with preterm delivery, such as bacterial vaginosis. However, the clinical usefulness of these tests or risk factors is limited by the lack of available effective interventions. By addressing the pathophysiologic mechanism directly and more timely than interventions that are based on inhibition of uterine contractility, local cervical application of a COX-2 inhibitor may prove to be of benefit in women at risk for preterm delivery.
        

• S J Fortunato and R. Menon (Nashville, Tennessee)
  Distinct Molecular Events Suggest Different Pathways for Preterm Labor and Premature Rupture of Membranes
  Am J Obstet Gynecol June 2001; 184: 1399-1406
          
  Objective : On a clinical level, the etiologies associated with premature rupture of the membranes and preterm labor are virtually identical, though these conditions end in distinctly different events. This study was designed to determine differences between preterm labor and preterm premature rupture of membranes by using molecular markers of extracellular matrix degradation and apoptosis.
          
  Conclusions : Authors delineated 2 divergent molecular pathways for premature rupture of membranes and preterm labor. Most likely, this is the beginning of the identification of differences that will become evident with the use of molecular biology.
          
  Comment : Preterm birth complicates 10% to 15% of all pregnancies, and it accounts for high fraction of the perinatal morbidity and mortality rate. Spontaneous preterm birth, caused by preterm labor (PTL) (contractions before 36 weeks’ gestation) or preterm premature rupture of the membranes (PROM) (membrane rupture before the onset of labor) or both account for ~80% of preterm deliveries. PROM is associated with 50% of the PTL cases. The frequency of premature birth has actually increased over the past 3 decades, which in part can be attributed to the fact that the exact cause of these conditions is still unknown.
            
  The etiology of PTL and PROM is multifactorial, and most of the causes are still unknown. Microbial invasion of the intra-amniotic cavity and infection of the intraamniotic cavity are associated with a majority of these cases. Infection induces a maternal and fetal inflammatory response (histologic chorioamnionitis), increases production and release of the inflammatory cytokines (interleukin [IL]-1, IL-6, IL-8, and tumor necrosis factor-a [TNF-a]), which induce prostaglandin production leading to cervical ripening and prostaglandin mediated contractility. Elevations of these biologic messengers (cytokines and prostaglandins) are considered markers of PTL and PROM. These factors are common to both PTL and PROM and are elevated in the amniotic fluid even in the absence of microbial invasion of the intra-amniotic cavity and infection of the intra-amniotic cavity when compared with term labor.
        

• Mark A. Klebanoff, J. Christopher Carey, et al 
  Failure of Metronidazole to Prevent Preterm Delivery Among Pregnant Women with Asymptomatic Trichomonas vaginalis Infection 
  The New England Journal of Medicine Vol.345 (7), August 16, 2001, Pg. 487-493
         
  Summary : Infection with Trichomonas vaginalis during pregnancy has been associated with preterm delivery. In this study 617 women with asymptomatic trichomoniasis who were 16-23 weeks pregnant received 2 doses of 2 g metronidazole (320 women) or placebo (297 women) 48 hours apart. 
          
  The same 2 dose regimen was repeated at 24 to 29 weeks of gestation. The primary outcome was delivery before 37 weeks of gestation.
         
  The conclusion of the study was that treatment of pregnant women with asymptomatic trichomoniasis did not prevent preterm delivery. Routine screening and treatment of asymptomatic pregnant women for this condition cannot be recommended.
         

• E. F. Hamilton, E. Bujold, et al (Montreal, Quebec, Canada)
  Dystocia Among Women with Symptomatic Uterine Rupture 
  Am J Obstet Gynecol March 2001; 184: 620-4 
        
  Objective : The purpose of this study was to analyze cervical dilatation patterns among women with uterine rupture by means of a mathematic model and to use the results to determine optimal intervention criteria.
         
  Study Design : This was a case-control review that compared a case patient group of 19 women with uterine rupture during labor with control groups with either no previous cesarean deliveries, vaginal birth after cesarean delivery, or failure of attempted vaginal birth after cesarean delivery. The mathematic model quantified dilatation and adjusted for conditions specific to each patient. Case patients were compared with matched control subjects by means of paired t tests, analysis of variance, odds ratios, and conditional logistic regression.
         
  Results : Dystocia was present in 31.6% to 47.4% of patients with uterine rupture, versus 2.6% to 13.2% of the control group with no previous cesarean deliveries (P £ .001). The incidence of an arrest disorder among patients with uterine rupture was similar to that seen in the control group with failure of attempted vaginal birth after cesarean delivery. However, the interval from diagnosis to rupture or cesarean delivery was 5.5 ± 3.3 hours among case patients with uterine rupture and 1.5 ± 1.3 hours in the control group with failure of attempted vaginal birth after cesarean delivery.
           
  Conclusion : When cervical dilatation was lower than the 10th percentile and was arrested for ³ 2 hours, cesarean delivery would have prevented 42.1% of the cases of uterine rupture and resulted in excess 2.6% and 7.9% cesarean delivery rates among women with no previous cesarean deliveries and women with vaginal birth after cesarean delivery, respectively.
        

• L. M. Glynn, P. D. Wadhwa, et al (Irvine and Los Angeles, California, and Lexington, Kentucky)
  When Stress Happens Matters: Effects of Earthquake Timing on Stress Responsivity in Pregnancy 
  Am J Obstet Gynecol March 2001; 184: 637-42
        
  Objective : The purpose of the study was to assess the effects of the timing of stress during pregnancy on emotional responses and birth outcome. It was hypothesized that as pregnancy advanced women would become increasingly resistant to the adverse effects of stress, and so early stress would have more profound effects than later stress.
        
  Study Design : Forty pregnant women who had experienced an earthquake during pregnancy or shortly afterward were identified. Using regression analyses it was determined whether the timing of the earthquake was related to an affective response to this event and to length of gestation.
       
  Results : The earthquake was rated as more stressful when it occurred early in pregnancy compared with late in pregnancy, and postpartum ratings were similar to first-trimester ratings (r_quad= .39; P< .05). Stress experienced early in pregnancy was associated with shorter gestational length (r= .35; P < .05).
         
  Conclusions : As pregnancy advances, women become decreasingly sensitive to the effects of stress. This decrease in vulnerability may reflect increasing protection of the mother and fetus from adverse influences during pregnancy.
          

• J. D. Iams, R. L. Goldenberg, et al for the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network 
  The Preterm Prediction Study: Can Low-Risk Women Destined For Spontaneous Preterm Birth Be Identified? 
  Am J Obstet Gynecol March 2001; 184: 652-5
         
  Objective : Half of all preterm births occur in women without clinical risk factors. The goal was to assess fetal fibronectin assay, Bishop score, and cervical ultrasonography as screening tests to predict which low-risk pregnancies will end in preterm birth.
          
  Study Design : A secondary analysis was performed on data collected at 22 to 24 weeks’ gestation from low-risk subjects enrolled in the Preterm Prediction Study, an observational study of risk factors for preterm birth conducted by the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Analysis was limited to primigravid women and to women who did not have a history of preterm birth or spontaneous pregnancy loss at <20 weeks’ gestation. Bishop score (³4), fetal fibronectin level (³50 ng/mL), and cervical length (£ 25 mm) at 24 weeks’ gestation were evaluated alone and in sequence as tests to predict spontaneous delivery before 35 weeks’ gestation.
          
  Results : Of the 2929 subjects enrolled in the original study, 2197 (1207 primigravid women and 900 low-risk multiparous women) met criteria for this analysis. There were 64 spontaneous births before 35 weeks’ gestation (3.04%). All three tests were significantly related to birth before 35 weeks’ gestation (high Bishop score; relative risk, 3.6; 95% confidence interval, 2.1-6.3; fetal fibronectin detection: relative risk, 8.2; 95% confidence interval, 4.8-13.9; short cervical length: relative risk, 6.9; 95% confidence interval, 4.3-11.1). However, the sensitivities of the tests alone were low (23.4% for high Bishop score, 23.4% for fetal fibronectin detection, and 39.1% for short cervix), as were the sensitivities for Bishop score followed by cervical ultrasonography (14.1%) and fetal fibronectin assay followed by cervical scan (15.6%).
             
  Conclusion : In the setting of low-risk pregnancy, fetal fibronectin assay and cervical ultrasonography have low sensitivity for preterm birth before 35 weeks’ gestation. Sequential screening with Bishop score or fetal fibronectin assay followed by cervical ultrasonography further decreased sensitivity to only 15% among low-risk women. 
              

• D. Chelmow, M. S. Ruehli, et al (Boston, Massachusetts) 
  Prophylactic Use of Antibiotics for Nonlaboring Patients Undergoing Cesarean Delivery with Intact Membranes: A Meta-analysis 
  Am J Obstet Gynecol March 2001; 184: 656-61
         
  Objective : A meta-analysis was performed to examine the role of antibiotic prophylaxis in preventing postoperative infections among nonlaboring women undergoing cesarean delivery with intact membranes.
        
  Study Design : A computerized literature search was performed with MEDLINE. Studies were included if they contained data on patients undergoing cesarean delivery in the absence of labor and ruptured membranes. Only randomized trials with a placebo control group were included.
         
  Results : Seven studies were found. Use of antibiotics decreased the risk of all infectious outcomes reported. When the results of 4 studies were pooled, prophylactic antibiotic use was associated with a significant reduction in postoperative fever (relative risk, 0.25; 95% confidence interval, 0.14-0.44). A similar reduction was noted for endometritis in 4 studies (relative risk, 0.05; 95% confidence interval, 0.01-0.38). Two studies reported on wound infection and showed a trend toward a protective effect (relative risk, 0.59; 95% confidence interval, 0.24-1.45)
         
  Conclusion : The prophylactic use of antibiotics reduces the risk of postoperative infectious complications after cesarean delivery even in the population at lowest risk.
         

• C. Breymann, E. Visca, et al (Zurich, Switzerland)
  Efficacy and Safety of Intravenously Administered Iron Sucrose With And Without Adjuvant Recombinant Human Erythropoietin for the Treatment of Resistant Iron-Deficiency Anemia During Pregnancy 
  Am J Obstet Gynecol March 2001; 184: 662-7
        
  Objective : This study was undertaken to determine the efficacy and safety of intravenously administered iron sucrose with versus without adjuvant recombinant human erythropoietin in the treatment of gestational iron-deficiency anemia resistant to therapy with orally administered iron alone.
         
  Study Design : Forty patients with gestational iron-deficiency anemia were randomly assigned to receive intravenously iron sucrose plus recombinant human erythropoietin or iron sucrose alone twice weekly. Target hemoglobin value was 11.0 g/dL. Efficacy measures were reticulocyte count, increase in hematocrit, and time to target hemoglobin level (treatment duration in weeks and need for continued therapy after 4 weeks).
         
  Conclusion : Adjuvant recombinant human erythropoietin safely enhanced the efficacy of iron sucrose in the treatment of gestational iron-deficiency anemia resistant to orally administered iron alone.
        

• J. F. Frfen, M. Arnestad, et al (Oslo, Norway)
  Risk Factors for Sudden Intrauterine Unexplained Death: Epidemiologic Characteristics of Singleton Cases in Oslo, Norway, 1986-1995 
  Am J Obstet Gynecol March 2001; 184: 694-702
         
  Objective : The epidemiologic characteristics of unexplained stillbirths are largely unknown or unreliable. The authors define sudden intrauterine unexplained death as a death that occurs antepartum and results in a stillbirth for which there is no explanation despite postmortem examinations, and they present the risk factors for this type of stillbirth in singleton gestations.
         
  Study Design : Singleton antepartum stillbirths (n=291) and live births (n=582) in Oslo were included and compared with national data (n=2025 and n=575,572, respectively). Explained stillbirths (n=165) and live births in Oslo served as controls for the cases of sudden intrauterine unexplained death (n=76) in multiple logistic regression analyses.
        
  Results : One fourth of stillbirths remain unexplained. The risk of sudden intrauterine unexplained death (1/1000) increased with gestational age, high maternal age, high cigarette use, low education, and overweight or obesity. Primiparity and previous stillbirths or spontaneous abortions were not associated with sudden intrauterine unexplained death.
        
  Conclusions : Risk factors for sudden intrauterine unexplained death are identifiable by basic antenatal care. Adding unexplored stillbirths to the unexplained ones conceals several risk factors and underlines the necessity of a definition that includes through postmortem examinations.
        

• C. I. Onyeije and M. Y. Divon (New York, New York)
  The Impact of Maternal Ketonuria on Fetal Test Results in the Setting of Postterm Pregnancy
  Am J Obstet Gynecol March 2001; 184: 713-8
        
  Objective : The aim of this study was to determine whether ketonuria, a commonly assessed urinary marker of maternal starvation and dehydration, is associated with abnormal fetal test results in the setting of postterm pregnancy.
          
  Study Design : During a 4-year period (January 1993-December 1996), a total of 3655 visits for antepartum maternal-fetal testing of postterm pregnancies (³ 41 weeks’ gestation) occurred at the authors’ institution. Maternal assessment included vital signs and urinalysis. The presence and degree of maternal ketonuria was correlated against abnormal results of fetal heart rate tests, nonstress tests, amniotic fluid index measurements, and biophysical profile scores performed on the same day.
        
  Results : There were 3601encounters suitable for inclusion in the study. Clinically detectable ketonuria occurred in 10.9% of the patients studied. Patients with clinically detectable ketonuria were at increased risk relative to patients without ketonuria for abnormal outcomes during postterm testing, including the presence of oligohydramnios (24% vs 9.3%; P < .0001), nonreactive nonstress tests (6.2% vs 2.15%; P < .0001), and fetal heart rate decelerations (14% vs 9.2%; P = .0039).
         
  Conclusion : Maternal ketonuria among patients with postterm pregnancy was associated with >2-fold increase in the occurrence of oligohydramnios, a 3-fold increase in nonreactive nonstress tests, and a significant increase in fetal heart rate decelerations. Further studies are required to evaluate the potential benefits of treating ketonuria before fetal testing. 
         

• T. Tongsong, C. Wanapirak, et al (Chiang Mai, Thailand)
  Fetal Loss Rate Associated with Cordocentesis At Midgestation 
  Am J Obstet Gynecol March 2001; 184: 719-23
         
  Objective : The aim of this study was to assess the risk of fetal loss attributable to cordocentesis at midgestation.
        
  Study Design : A cohort study was conducted during the period 1989-1999. Women undergoing cordocentesis between 16 and 24 weeks’ gestation with singleton pregnancies without obvious fetal anomaly were recruited into the study group. The control subjects were selected prospectively on a one-to-one basis with strict matching for maternal age, parity, gestational age at recruitment, and socioeconomic status. Both groups were prospectively followed up until delivery.
        
  Results : A total of 1281 women with successful cordocentesis and their matched control subjects were recruited to the study. After exclusion of some pairs because of loss to follow-up or fetal malformations or severe disease necessitating termination of pregnancy, 1020 matched pairs were available to be compared with respect to fetal loss rate and pregnancy outcomes. The fetal loss rate was significantly higher among the study group (3.2% vs 1.8%; P < .05, McNemar test). However, there were no significant differences in other obstetric complications between the study and control groups.
         
  Conclusion : The incremental fetal loss rate associated with cordocentesis at midgestation was about 1.4%.
         

• J. A. Low, H. Pickersgill et al (Kingston, Ontario, Canada)
  The Prediction and Prevention of Intrapartum Fetal Asphyxia in Term Pregnancies 
  Am J Obstet Gynecol March 2001; 184: 724-30
        
  Objective : This study was undertaken to examine the roles of clinical risk scoring, electronic fetal heart rate monitoring, and fetal blood gas and acid-base assessment in the prediction and prevention of intrapartum fetal asphyxia in term pregnancies.
          
  Study Design : The outcomes of 166 term pregnancies with biochemically confirmed fetal asphyxia (umbilical artery base deficit at delivery, >12 mmol/L) were examined. This population included 83 pregnancies delivered abdominally matched with 83 pregnancies delivered vaginally. Antepartum and intrapartum clinical risk factors and neonatal complications were documented. Fetal assessments included fetal heart rate patterns in the fetal heart rate record and fetal capillary blood gas and acid-base assessments. Fetal asphyxia was classified as mild, moderate, or severe on the basis of umbilical artery base deficit (cutoff > 12 mmol/L) and neonatal encephalopathy and other organ system complications.
        
  Conclusion : Although fetal heart rate patterns will not discriminate all asphyxial exposures, continuous fetal heart rate monitoring supplemented by fetal blood gas and acid-base assessment can be a useful fetal assessment paradigm for intrapartum fetal asphyxia. Such an assessment paradigm will not prevent all cases of moderate or severe fetal asphyxia. However, prediction and diagnosis with intervention and delivery during the first and second stage of labor could prevent the progression of mild asphyxia to moderate or severe asphyxia in some cases.
        

• W. Holzgreve, J. C. Li, et al (Basel, Switzerland, et al)
  Elevation in Erythroblast Count in Maternal Blood Before the Onset of Preeclampsia 
  Am J Obstet Gynecol January 2001; 184: 165-8
        
  Objective : It was recently shown that both maternal and fetal erythroblast counts are elevated in the peripheral blood of pregnant women with preeclampsia. The purpose of this study was to examine whether this elevation actually occurs before the clinical onset of the disorder.
        
  Study Design : Erythroblasts were enriched and enumerated in 97 maternal blood samples obtained in the second trimester, and results were subsequently correlated with pregnancy outcomes.
        
  Results : Significantly higher quantities of erythroblasts (mean, 6041.7 vs 928.9; P = .008) were detected in blood samples obtained from women who later acquired preeclampsia (n=15) than in blood samples from the control cohort (n=72). Intrauterine growth restriction (n=10) was not accompanied by a similar rise in erythroblast count.
        
  Conclusion : Because a large proportion of the erythroblasts in maternal blood are fetal, the data suggests that fetal-maternal cell traffic is affected early in pregnancies that are later complicated by preeclampsia but not in those affected only by intrauterine growth restriction.
       

• J. A. Thorp, A. M. H. Jones (Kansas City, Missouri, et al)
  The Effect of Multidose Antenatal Betamethasone on Maternal and Infant Outcomes 
  Am J Obstet Gynecol January 2001; 184: 196-202
        
  Objective : This study was undertaken to determine whether prolonged betamethasone therapy is, as has been suggested, associated with adverse maternal or neonatal outcomes.
           
  Study Design : A secondary multivariate analysis of a randomized controlled trial was performed to determine whether duration of betamethasone therapy was associated with adverse maternal or neonatal outcomes.
        
  Results : There were 414 fetuses whose mothers were randomly assigned to trial groups. Final models included only valid cases without missing or averaged data (N=367 to N=412, depending on the model). Three or more sets of weekly betamethasone injections were given in 21.3% of cases and ³4 sets were given in 12.3% of cases. Prolonged antenatal betamethasone therapy was not associated with increases in incidences of antenatal fever, chorioamnionitis, reduced birth weight, suppressed neonatal adrenal function, neonatal sepsis, or neonatal death. It was associated with larger birth weights (P < .05).
         
  Conclusion : Prolonged antenatal betamethasone therapy was not associated with higher risks of antenatal maternal fever, chorioamnionitis, reduced birth weight, neonatal adrenal suppression, neonatal sepsis, and neonatal death.
         
  Comment : According to Dr. Ingle recently there have been many publications emphasizing that I.U.G.R. results from multidose antenatal metamethazone therapy.
        

• J. Burlingame, A. McGaraghan, et al (San Francisco, California)
  Maternal and Fetal Outcomes in Pregnancies Affected By Von Willebrand Disease Type 2
  Am J Obstet Gynecol January 2001; 184: 229-30
         
  The authors’ report a case series that lends support for both the maternal and neonatal safety of vaginal delivery in pregnancies complicated by heritable von Willebrand disease types 2A and 2B. With proper hematologic support, a cesarean delivery may be indicated only for obstetric reasons.
        

• G. A. Macones, S. J. Marder, et al (Philadelphia, Pennsylvania)
  The Controversy Surrounding Indomethacin for Tocolysis
  Am J Obstet Gynecol February 2001; 184: 264-72
        
  Indomethacin is a prostaglandin synthetase inhibitor sometimes used for tocolysis. Several placebo-controlled trials comparing indomethacin to other potential first-line tocolytic agents support its efficacy for delaying delivery for >48 hours. 
       
  Recent observational studies, however, have raised concerns about the safety of indomethacin, implicating it with increased rates of intraventricular hemorrhage and necrotizing enterocolitis. Careful analysis of these observational studies suggests that these results should be viewed with caution, because of uncontrolled confounding by indication. A recent decision analysis supports the risk /benefit analysis of indomethacin in this setting. Still, the future of indomethacin in preterm labor should be guided by well-designed prospective clinical trials. Such studies are underway.
        

• A. C. Sciscione, J. S. Manley, et al (Newark, Delaware)
  Intracervical Fibrin Sealants: A Potential Treatment for Early Preterm Premature Rupture of the Membranes
  Am J Obstet Gynecol February 2001; 184: 368-73
        
  Study Design : This is an observational study of a referred patient population, with preterm premature rupture of membranes at < 24 weeks’ gestation.
       
  Results : Twelve women consented to the protocol. The mean gestational age at preterm premature rupture of membranes was 19 weeks 4 days (range, 13-23 weeks); the mean gestational age at treatment was 20 weeks 5 days (range, 17-23 weeks). All women had a diminution in the amount of amniotic fluid leakage with an increase in amniotic fluid index. Among the 12 pregnancies (13 fetuses), there were 7 surviving neonates. Two women had apparent “resealing” of the membranes.
        
  Conclusion : Fibrin sealants in midtrimester rupture of the membranes may lead to improved outcomes and now warrant formal evaluation.
        

• S. A. Treloar, D. W. Cooper, et al (Brisbane, Queensland, et al)
  An Australian Twin Study of the Genetic Basis of Preeclampsia and Eclampsia 
  Am J Obstet Gynecol February 2001; 184: 374-81
        
  Objective : The authors’ investigated maternal versus fetal genetic causes of preeclampsia and eclampsia by assessing concordance between monozygotic and dizygotic female co-twins, between female partners of males monozygotic and dizygotic twin pairs, and between female twins and partners of their male co-twins in dizygotic opposite-sex pairs.
       
  Study Design : Two large birth cohorts of volunteer Australian female twin pairs (N=1504 pairs and N=858 pairs) were screened and interviewed, and available medical and hospital records were obtained and reviewed where indicated, with diagnoses assigned according to predetermined criteria.
        
  Results : With strict diagnostic criteria used for preeclampsia and eclampsia, no concordant female twin pairs were found. Collapsing diagnoses of definite, probable, or possible preeclampsia or eclampsia resulted in very low genetic recurrence risk estimates.
       
  Conclusion : Results from these two cohorts of female twin pairs do not support clear, solely maternal genetic influences on preeclampsia and eclampsia. Numbers of parous female partners of male twins were too low for conclusions to be drawn regarding paternal transmission. 
        

• R. B. Newman, R. L. Goldenberg, et al for the National Institute of Child Health and Human Development Maternal-Fetal Medicien Units Network
  Occupational Fatigue and Preterm Premature Rupture of Membranes 
  Am J Obstet Gynecol February 2001; 184: 438-46
         
  Objective : The aim of this study was to prospectively determine the relationship between occupational fatigue and spontaneous preterm delivery segregated into the etiologically distinct categories of spontaneous preterm labor, preterm premature rupture of membranes, and indicated preterm delivery.
        
  Conclusion : The occupational fatigue index of Mamelle et al discriminated a group of nulliparous women at increased risk for preterm premature rupture of membranes. The relationship between preterm premature rupture of membranes and occupational fatigue or hours worked may provide guidelines according to which nulliparous women and their employers can be advised.
        

• W.W. Hurd, S. S. Chee, et al (Indianapolis, Indiana, et al)
  Location of the Ureters in Relation to the Uterine Cervix by Computed Tomography
  Am J Obstet Gynecol February 2001; 184: 336-9
        
  Objective : The aim was to determine the distance of the ureter from the cervix and the influence of age and weight on this distance.
        
  Study Design : The distance of the ureter from the uterine cervix was determined by evaluating the computed pelvic tomograms from 52 women. Age and body mass index were compared to this distance by means of regression analysis.
          
  Results : At the most dorsal reflection of the ureter, the average distance from the ureter to cervical margin was 2.3 ± 0.8 cm (range, 0.1-5.3 cm). There was no relationship to age, but there was a linear relationship between this distance and body mass index (R² = 0.075; P = .049); thus the ureter was slightly more proximal to the cervical margin in heavier women.
         
  Conclusions : In women with apparently normal pelvic anatomy, the average distance between the ureter and cervix is > 2cm. The finding that this distance is < 0.5 cm in 12% of the women studied may explain the relatively common occurrence of ureteral injury during hysterectomy. The relationship between body mass index and location is clinically insignificant.
           

• Rebecca S Hartley, Irvin Emanuel and Jane Hitti (Seattle, Washington)
  Perinatal mortality and neonatal morbidity rates among twin pairs at different gestational ages: Optimal delivery timing at 37 to 38 weeks’ gestation.
  Am J Obstet Gynecol, Feb.2001, p.451-8
       
  Objective : The aim of this study was to determine the gestational age at delivery associated with the lowest rates of perinatal mortality, respiratory distress syndrome, and long hospital stays among twins, with pair rates used to account for both infants in each twin pregnancy.
        
  Study Design : The authors conducted a population-based retrospective study that analyzed linked birth certificates, fetal and infant death certificates, and hospital discharge data for 8150 twin pairs born in Washington State during 1987 through 1997. The c2 or Fisher exact test was used to assess the statistical significance.
        
  Results : The nadirs of perinatal mortality rate, respiratory distress syndrome incidence, and long hospital stay rate were seen at delivery dates of 39, 40 and 38 weeks’ gestation, respectively. Restriction to pairs delivered vaginally without the induction of labor revealed that the perinatal mortality rate was lowest for delivery at 37 weeks’ gestation, the gestational age at which the highest numbers of such spontaneously timed pairs were born.
        
  Conclusion : Induction of labor should be routinely considered for twins at 37 to 38 weeks’ gestation.
        

• Peter A.M.Weiss, H S Scholz, J Haas, and K F Tamussino (Graz, Austria)
  Effect of fetal hyperinsulinism on oral glucose tolerance test results in patients with gestational diabetes mellitus.
  Am J. Obstet Gynecol, Feb.2001, 184: 470-5
        
  Objective : This study was undertaken to evaluate the impact of the fetoplacental glucose steal phenomenon on the results of oral glucose tolerance testing in pregnancies complicated by gestational diabetes mellitus with fetal hyperinsulinism.
        
  Study Design : This was an analysis of the cases of 34 patients with two consecutive abnormal oral glucose tolerance test results and amniotic fluid insulin measurement before institution of insulin therapy. Patients were divided into groups on the basis of normal versus elevated amniotic fluid insulin concentrations.
         
  Results : Oral glucose tolerance tests were done at a mean (±SD) of 24.9 ± 5.7 and 30.7 ± 3.2 weeks’ gestation, and amniotic fluid insulin measurements were done at 31.1 ± 3.2 weeks’ gestation. In 13 women with gestational diabetes mellitus with normal amniotic fluid insulin concentration, maternal postload blood the glucose levels at 1 hour increased by 12mg/dL (168 vs 180mg/dL; 9.3 vs 10.0mmol/L; P =.0006) during the course of 6 weeks. In contrast, in 21 women with gestational diabetes mellitus with elevated amniotic fluid insulin levels (>7 mI/mL; >42 mmol/L), 1-hour postload blood glucose levels decreased by 22 mg/dL (201 vs 179 mg/dL; 11.2 vs 9.9 mmol/L; P=.0020 during the same period. The higher the amniotic fluid insulin level, the larger the decrease (R=0.504; P=.02). Although low amniotic fluid insulin levels were correlated significantly with 1-hour glucose levels of the first and second oral glucose tolerance tests, high insulin levels were no longer correlated with the second oral glucose tolerance test.
         
  Conclusion : Exaggerated fetal glucose siphoning may provide misleading oral glucose tolerance test results in pregnancies complicated by fetal hyperinsulinism by blunting maternal postload glucose peaks. Consequently, oral glucose tolerance test results in a pregnancy complicated by gestational diabetes mellitus with a fetus that already has hyperinsulinemia may erroneously be considered normal.
          

• Katharine D Wenstrom, Gary L Johanning, Kelley E Johnston and Mary Dubard (Birmingham, Alabama)
  Association of the C677T methylenetetrahydrofolate reductase mutation and elevated homocysteine levels with congenital cardiac malformations.
  Am J Obstet Gynecol April 2001; 184: 806-17
    
  Data indicate that the same pathogenetic mechanism that causes neural tube defects, involving the C677T MTHFR mutation and elevated amniotic fluid homocysteine levels, is at least partially responsible for certain cardiac defects as well. Although disruption of the metabolic pathway appears to account for a substantial portion of defects, other mechanisms must also be operational, because folic acid supplementation does not prevent 28% of neural tube defect recurrences, and only 50% of women whose fetuses had cardiac defects in our study had any evidence of abnormal homocysteine metabolism.
    

• D Ware Branch, T Flint Porter et al (Salt Lake City, Utah, Pittsburgh, Pennsylvania,etc)
  Antiphospholipid antibodies in women at risk for preeclampsia
  Am J Obstet Gynecol, 2001; 184: 825-34
    
  Objective: The aim of this study was to determine whether positive results of tests for any of 5 antiphospholipid antibodies are associated with recurrent preeclampsia among women with a history of preeclampsia in a previous pregnancy.
   
  Study Design: Second-trimester serum samples were obtained from 317 women with preeclampsia in a previous pregnancy who were being followed up in a prospective treatment trial. The serum samples were measured by enzyme-linked immunoassay for immunoglobulin G and immunoglobulin M antibodies against 5 phospholipids. Positive results were analyzed with regard to preeclampsia, severe preeclampsia, intrauterine growth restriction, and preterm delivery.
   
  Conclusion: Positive results of testing for antiphospholipid antibodies in the second trimester were not associated with recurrent preeclampsia among women at risk because of a history of preeclampsia. Positive results for immunoglobulin G antiphosphatidylserine antibody were associated with severe preeclampsia, and positive results for immunoglobulin G anticardiolipin, antiphosphatidylinositol, and antiphosphatidylglycerol antibodies were associated with intrauterine growth restriction. However, the positive predictive values for all these associations were modest. Testing for antiphospholipid antibodies during pregnancy is of little prognostic value in the assessment of the risk for recurrent preeclampsia among women with a history of preeclampsia.
      

• Amanda M Cotter, Anne M Molloy, John M Scott, and Sean F Daly (Dublin, Ireland)
  Elevated plasma homocysteine in early pregnancy: A risk factor for the development of severe preeclampsia.
  Am J Obst.Gyneccol October 2001; 185: 781-5
     
  Objective: The aim of our study was to determine if an elevated plasma homocysteine level in early pregnancy is associated with the development of severe preeclampsia.
    
  Study Design: Blood samples were obtained from patients attending their first antenatal visit. Cases were asymptomatic women who subsequently developed severe preeclampsia. Controls were matched for gestational age and date of sample collection. Plasma homocysteine level was measured by using fluorescence polarization immunoassay.
    
  Results: There were 56 patients with severe preeclampsia from whom blood samples were obtained at a mean (± SD) gestation of 15.3 weeks (± 4.04 weeks) and 112 controls at 14.9 weeks (±3.41 weeks). The preeclampsia cases had a mean (±SD) homocysteine level of 9.8 mmol/L (±3.3 mmol/L), whereas controls had a mean homocysteine level of 8.4mmol/L (±1.9 mmol/L), P£ .001
    
  Conclusion: Women who develop severe preeclampsia have higher plasma homocysteine levels in early pregnancy than women who remain normotensive throughout pregnancy. An elevated plasma homocysteine level in early pregnancy can increase the risk of developing severe preeclampsia by almost threefold.
     

• E.N. Gofton, V Capewell, R Natal and R J Gratton
  Obstetrical intervention rates and maternal and neonatal outcomes of women with gestational hypertension
  Am J Obstet Gynecol, Oct.2001, Vol.185 (4), pg.798-803
    
  Objective: The purpose of this study was to determine the obstetrical intervention rates and maternal and neonatal outcomes of women with gestational hypertension.
    
  Study Design: Induction and operative delivery rates and indices of maternal and neonatal morbidity were determined in women (37-41 completed weeks) with gestational hypertension (n=979), preeclampsia (n=165), chronic hypertension (n=187), and control subjects (n=11,434) in a retrospective review of St. Joseph’s Health Care Perinatal Database from November 1, 1995, to October 31, 1999. Data were analyzed by chi-square test, analysis of variance, Dunnett’s t-test, and pair wise chi-square tests with Bonferroni correction.
    
  Results: The induction and cesarean delivery rates in gestational hypertension were similar to preeclampsia and chronic hypertension groups and almost double of control subjects. The length of labor and postpartum stays and the incidence of operative vaginal delivery, postpartum hemorrhage, and neonatal intensive care involvement were greater in the gestational hypertension group than in the control subjects.
     
  Conclusion: Women with gestational hypertension have obstetrical intervention rates much higher than control subjects and similar to those with preeclampsia and chronic hypertension.
       

• Cynthia V Maxwell, Ellice Lieberman, Mary Norton, Amy Cohen et al (Boston, Mass and San Francisco, Calif)
  Relationship of twin zygosity and risk of preeclampsia
  Am J Obstet Gynecol, Oct.2001,185: 819-21.
     
  Objective: Twin gestations are known to be at higher risk for preeclampsia. One theory suggests that maternal recognition of fetal and trophoblastic tissues as foreign may be a factor. If that hypothesis is true, mothers carrying monozygous (MZ) gestations (i.e. a single fetal graft) might be predicted to have a lower rate of preeclampsia than those carrying dizygous (DZ) gestations. To evaluate this hypothesis the rate of preeclampsia in mothers with MZ and DZ twin gestations was compared.
    
  Study Design: Seven hundred sixty-eight twin deliveries from 1994 to 1999 were reviewed. Placental pathology reports were reviewed to determine the chorionic state of each placenta. Monochorionic placentas were assumed to be MZ. Dichorionic placentas were categorized as DZ if the neonates were of different sexes of different blood types. Maternal and fetal data were abstracted from the medical records. Preeclampsia was defined by standard criteria of the National Institutes of Health Working Group on High Blood Pressure. Our analysis was limited to women with pregnancies reaching at least 30 weeks of gestation where zygosity could be determined.
    
  Conclusions: These results do not support the hypothesis that zygosity affects the rate of preeclampsia in twin gestations, though the number of subjects was too small to allow definitive conclusions. Larger studies are needed to evaluate this finding.
      

• George C Lu, Dwight J Rouse, et al (Birmingham, Ala)
  The effect of the increasing prevalence of maternal obesity on perinatal morbidity
  Am J Obstet Gynecol, Oct. 2001, 185: 845-9
     
  Objective: In this study, authors assessed the temporal trends and relative and attributable perinatal risks of maternal obesity over a 20-year period.
    
  Study Design: The authors conducted a retrospective cohort study between 1980 and 1999 by using a computerized perinatal database of all women who received prenatal case and delivered their infants within a regional health care system. The main outcome measures were as follows: (1) annual mean body weight and the percentage of women classified as obese at the first prenatal visit and (2) relative and attributable risks of obesity for selected maternal and perinatal morbidities in successive 5-year periods.
    
  Results: From 1980 to 1999, the mean maternal weight of women at the first prenatal visit increased 20% (144-172 lb), as did the percentage of women ³200 lb (1.9-10.7), the percentage ³300 lb (0.5-4.9), and the percentage with a body mass index > 29 kg/m2 (16.3-36.4), P<.01 for all. Controlling for maternal age, race and smoking status, obese women were at increased risk at each period for cesarean delivery (range of adjusted relative risk, 1.5-1.8), gestational diabetes (range, 1.8-2.9), and large (>90th percentile) for gestational age infants (range, 1.8-2.2). From the earliest 5-year period (1980-1984) to the most recent (1995-1999), the percentage of obesity-attributable cesarean deliveries more than tripled from 3.9 – 11.6. Similar percentage increases were observed for the obesity-attributable risks for gestational diabetes (12.8-29.6) and large for gestational age infants (6.5-19.1). Trends for secondary obesity definitions were similar, although the magnitude of the increased attributable risks was similar.
    
  Conclusions: Efforts to reduce the frequency of certain perinatal morbidities will be constrained unless effective measures to prevent, or limit the risks of, maternal obesity are developed and implemented.
       

• Jeffrey R. Johnson, David F Colombo, et al (Columbia, Ohio)
  Optimal dosing of penicillin G in the third trimester of pregnancy for prophylaxis against group B Streptococcus.
  Am J Obstet Gynecol, Oct.2001, 185: pg.850-3
     
  Objective: To determine the optimal dose of intravenous penicillin (PCN) in the third trimester of pregnancy for the prophylaxis of group B Streptococcus.
    
  Study Design: Healthy women in the third trimester with a singleton pregnancy were recruited. Eligibility included no previous penicillin or cephalosporin allergy and no history of renal disease. A baseline 24-hour urine collection for total protein concentration and creatinine clearance was obtained. Two intravenous catheters were placed, and 1 million units of penicillin G (PCN G) sodium was infused through one catheter. Serial blood samples were obtained through the second catheter at 1,5,15,30,60,90, 120, 150, 180, 210 and 240 minutes. Serum was stored at -80°C until assays were performed. Reverse-phase high performance liquid chromatography was used to determine serum concentrations.
    
  Conclusions: The Cmax was 67 mg/mL (670 x minimum inhibitory concentration). One million units of intravenous PCN G exceed MIC in the treatment of GBS. The dosing interval should be 4 hours to ensure anti GBS activity in all patients. More frequent dosing does not increase activity. Current recommendations for GBS prophylaxis, which use PCN G, should be modified pending future studies of neonatal PCN concentrations.
    
  Comment: The use of antibiotics in obstetrics has increased dramatically over the past decade because of increased awareness of early-onset GBS disease in the newborn. This pathogen remains an important cause of newborn sepsis within 7 days of delivery.
      

• James A Thorp, Philip G Jones et al (Kansas City and Lee’s Summit)
  Perinatal factors associated with severe intracranial haemorrhage
  Am J Obstet Gynecol, Oct.2001, 185: 859-62
      
  Objective: The purpose of this study was to assess the incidence of perinatal factors that are associated with severe intracranial hemorrhage in a large and recent multicenter experience.
     
  Study Design: Retrospective analyses of nonanomalous newborns who were admitted to 100 neonatal intensive care units from 23 to 34 6/7 weeks’ gestation were analyzed by multiple gestations.
     
  Results: There were 12,578 premature newborns with a mean (±SD) gestational age of 31.3 ±2.9 weeks and a birth weight of 1685 ± 571g, respectively. The overall incidence of severe intracranial hemorrhage was 2.9%; in 4575 newborns who weighed £1500g the incidences of intracranial hemorrhage was 7.1%. Factors with positive and negative associations with severe intracranial hemorrhage are listed in order of decreasing statistical significance: gestational age (negative), surfactant (positive), antenatal indomethacin (positive), neonatal transport (positive), cesarean birth (negative), poor prenatal care (positive), 5- minute Apgar score of < 7 (positive), chorioamnionitis (positive), antenatal terbutaline (negative), preterm premature rupture of fetal membranes (negative), and abruption (positive).
     
  Conclusion: The incidence of severe intracranial hemorrhage has dramatically declined over the past 2 decades. Antenatal steroids were not associated with reductions in severe intracranial hemorrhage.
      

• Lisa J Farkouh, James A Thorp, et al (Denver, Colo, Kansas City, Mo and Sunrise)
  Antenatal magnesium exposure and neonatal demise
  Am J Obstet Gynecol, Oct.2001, 185: 869-72
    
  Objective: To assess the effect of antenatal magnesium sulfate exposure on neonatal demise.
     
  Study Design: A retrospective analysis of prospectively capture data from 100 tertiary centers between May 1997 and January 2000 was performed. Included were nonanomalous newborns who were admitted to the neonatal intensive care unit between 23 and 34 completed weeks’ gestation. Predictors of neonatal demise were determined from a pool of 24 candidate variables in a univariate analysis. A multivariate predictive model for mortality was constructed by using the variables that had significant interactions with the rate of demise (P £. 1)
    
  Results: A total of 12,876 cases were available for analysis. When these cases were stratified according to gestational age, magnesium was associated with a significant reduction in neonatal demise. The effect remained when controlling for both gestational age and indication for therapy. The effect was similar in direction and magnitude in the final model after controlling for additional antenatal factors.
    
  Conclusion: Antenatal magnesium exposure is not associated with neonatal death, regardless of indication for therapy.
     

• Kenneth W Jackson, John R Allbert, et al (Charlotte, North Carolina)
  A randomized controlled trial comparing oxytocin administration before and after placental delivery in the prevention of postpartum hemorrhage
  Am J Obstet Gynecol, Oct.2001, 185: 873-7
      
  Objective: To determine if the timing of the administration of prophylactic oxytocin influences the incidence of postpartum hemorrhage caused by uterine atony, retained placenta, and third-stage duration.
     
  Study Design: Parturients who presented for vaginal delivery were randomized in a double-blinded fashion to receive oxytocin, 20 units in a 500 mL crystalloid intravenous bolus, beginning upon delivery of either the fetal anterior shoulder or placenta. For all patients, the third stage of labor was managed with controlled cord traction until placental expulsion, followed by at least 15 seconds of fundal massage. Patients were excluded if they had a previous cesarean section, multiple gestation, antepartum hemorrhage, or bleeding disorder.
     
  Results: A total of 1486 patients were enrolled: 745 in the before-placenta group and 741 in the after placenta group. The groups were similar with respect to gestational age, fetal weight, labour duration, maternal age, parity, and ethnicity. The incidence of postpartum hemorrhage did not differ significantly between the two groups (5.4% vs 5.85; crude OR, 0.92; 95% CI, 0.59 to 1.43). There were no significant differences between the two groups with respect to incidence of retained placenta (2.4% vs 1.6%; OR 1.49; 95% Cl, 0.72 to 3.08), or third-stage duration (7.7 minutes vs 8.1 minutes; P=.23).
    
  Conclusions: The administration of prophylactic oxytocin before placental delivery does not reduce the incidence of postpartum hemorrhage or third-stage duration, when compared with giving oxytocin after placental delivery. Early administration, however, does not increase the incidence of retained placenta.
    

• Tammy S Gerstenfeld, and Deborah A Wing
  Rectal misoprostol versus intravenous oxytocin for the prevention of postpartum hemorrhage after vaginal delivery.
  Am J Obstet Gynecol, Oct.2001, 185: 878-82
     
  Objective: To compare rectally administered misoprostol to intravenously administered oxytocin for the management of third-stage labour.
      
  Study Design: Subjects were randomized to receive two, 200 µg misoprostol tablets rectally plus 2mL saline in Ringer’s lactate intravenously or two lactose tablets rectally plus 20 units oxytocin in Ringer’s lactate intravenously (control medication). Blood loss was determined by estimation, measurement, and change in hematocrit values from admission to postpartum day 1. Subjects were excluded if cesarean delivery was required.
    
  Results: A total of 325 women underwent analysis. By estimation, 21% of subjects and 15% of controls had postpartum hemorrhage (P=.17). By using measured blood loss, it was determined that 70 of 154 (46%) study subjects and 61 of 161 (38%) control subjects had postpartum hemorrhage (P=.17). For 36 (23%) misoprostol subjects and 18(11%) oxytocin subjects at lest one additional agent was required to control bleeding (P=.004).
    
  Conclusion: Rectal misoprostol (400 mg) was no more effective than intravenous oxytocin in preventing postpartum hemorrhage.
     

• Carolyn Gardella, Melanie Taylor, et al 
  The effect of sequential use of vacuum and forceps for assisted vaginal delivery on neonatal and maternal outcomes
  Am J Obstet Gyneco, Oct.2001, 185, 896-902.
     
  Objective: To determine the risk of neonatal and maternal disease associated with the sequential use of vacuum and forceps compared with spontaneous vaginal delivery.
     
  Study Design: Using Washington state birth certificate data linked to hospital discharge records, authors compared 3741 vaginal deliveries by both vacuum and forceps, 3741 vacuum deliveries, and 3741 forceps deliveries to 11,223 spontaneous vaginal deliveries.
     
  Results: Compared with spontaneous vaginal deliveries, deliveries by sequential use of vacuum and forceps had significantly higher rates of intracranial hemorrhage (relative risk (RR), 3.9; 95% confidence interval (CI), 1.5 to 10.1), brachial plexus (RR, 3.2; 95% CI, 1.6 to 6.4), facial nerve injury (RR), 13.3; 95% CI, 4.7 to 37.7), seizure (RR, 13.7; 95% CI, 2.1 to 88.0), depressed 5-minute Agar score (RR, 3.0; 95% CI, 2.2 to 4.0), assisted ventilation (RR, 4.8; 95% CI, 2.1 TO 11.0) fourth degree (RR, 11.4; 95% CI, 6.4 to 20.1 among multifarious women) and other lacerations, hematoma (RR, 6.2;95% CI, 2.1 to 18.1 among multifarious women) and postpartum hemorrhage (RR, 1.6; 95% CI, 1.3 to 2.0). The relative risk of sequential vacuum and forceps use was greater than the sum of the individual relative risks of each instrument for intracranial hemorrhage, facial nerve injury, seizure, hematoma, and perinea and vaginal lacerations.
    
  Conclusion: Sequential use of vacuum and forceps is associated with increased risk of both neonatal and maternal injury.
      

• Carolyn M Slop, Thomas D Shipp, et al (New York, Boston, Mass and Omaha)
  Outcomes of trial of labor following previous cesarean delivery among women with fetuses weighing >4000g
  Am J Obstet Gynecol, Oct. 2001; 185: 903-5.
    
  Objective: To compare outcomes at term of a trial of labor in women with previous cesarean delivery who delivered neonates weighing >4000g versus women with those weighing £4000g.
     
  Study Design: Authors reviewed medical records for all women undergoing a trial of labor after prior cesarean delivery during a 12-year period. The current analysis was limited to women at term with one prior cesarean and no other deliveries. The rates of cesarean delivery and symptomatic uterine rupture for women with infants weighing > 4000g were compared to the rates for women with infants weighing £4000g. Logistic regression was used to control for the potential confounding by use of epidural, maternal age, labor induction, labor augmentation, indication for previous cesarean, type of uterine hysterotomy, year of delivery, receiving public assistance, and maternal race. Adjusted odds ratios and 95% confidence intervals were calculated.
    
  Results: Of 2749 women, 13% (365) had infants with birth weights >4000 g. Cesarean delivery rate associated with birth weights £4000g was 29% versus 40% for those with birth weights >4000g (P=.001). With use of logistic regression, authors found that birth weight £4000g was associated with a 1.7-fold increase in risk of cesarean delivery (95% CI, 1.3- 2.2). The rate of uterine rupture for women with infants weighing £4000 g was 1.0% versus a 1.6% rate for those with infants weighing >4000g (P=.24). Although the logistic regression analysis revealed a somewhat higher rate of uterine rupture associated with birth weights of >4000g (adjusted OR, 1.6; 95% CI, 0.7-4.1), this difference was not statistically significant. The rate of uterine rupture was 2.4% for women with infants weighing >4250g, but this rate did not differ significantly from the rate of uterine rupture associated with birth weights £4250 g (P=.1).
     
  Conclusion: A trial of labor after previous cesarean delivery may be a reasonable clinical option for pregnant women with suspected birth weights of >4000 g, given that the rate of uterine rupture associated with these weights does not appear to be substantially increased when compared to lower birth weights. However, some caution may apply when considering a trial of labor in women with infants weighing >4250g. In these women with infants weighing >4000 g, the likelihood of successful vaginal delivery, although lower than for neonates weighing £4000g, is still 60%.
      

• Stephanie A Fisher, V Paul Mackenzie and Gregory A.L. Davies
  Oral versus vaginal misoprostol for induction of labor: A double-blind randomized controlled trial
  Am J Obstet Gynecol, Oct.2001; 185: 906-10
     
  Objective: To determine the efficacy of oral misoprostol (50 µg) administered every 3 hours compared to vaginal misoprostol (50 µg) administered every 6 hours for induction of labor.
    
  Study Methods: In this double-blind randomized trial, 126 women received misoprostol (50 µg) either orally every 3 hours or vaginally every 6 hours for induction of labor. Outcomes included time from induction to delivery, oxytocin augmentation, incidence of hyperstimulation and tachysystole, mode of delivery and neonatal outcomes.
    
  Results: Median time to delivery was shorter in those women who were receiving vaginal misoprostol (vaginal 14.3 hours vs oral 23.1 hours; P=.0004) and more women in the oral group required oxytocin augmentation of labor (73% vs 42%) (RR, 1.98; 95% CI, 1.29 to 3.06). The incidence of hyperstimulation was similar between the groups, but there was an increased incidence of tachysystole in the vaginal group (26.5% vs 9.7%) (RR, 2.74; 95% CI, 1.16 to 6.51). There was no difference between the groups with respect to mode of delivery or neonatal outcome.
      
  Conclusion: Vaginal misoprostol administered every 6 hours is more effective for induction of labor than oral misoprostol administered every 3 hours. The higher rates of tachysystole with use of vaginal misoprostol in the current study warrant further investigation.
     

• Helen Y How, Lori Leaseburge, et al (Cincinnati, Ohio)
  A comparison of various routes and dosages of misoprostol for cervical ripening and the induction of labor
  Am J Obstet & Gynecol, Oct. 2001, 185: 911-5.
      
  Objective: The purpose of this study was to compare the efficacy of different routes of misoprostol administration for cervical ripening and the induction of labor.
    
  Study Design: Three hundred thirty women at ³32 weeks gestation with a Bishop score £6 and an indication were randomized to 1 of 3 double-blinded groups : (1) 25µg orally administered misoprostol plus 25µg vaginally administered misoprostol, (2) orally administered placebo plus 25µg vaginally administered misoprostol, or (3) 25µg orally administered misoprostol plus vaginally administered placebo. Doses were repeated every 4 hours until onset of labor or a maximum of 12 doses were given. The primary outcome of the trial was vaginal delivery within 24 hours of the initiation of induction. Secondary outcomes were the time from induction to delivery, need for oxytocin augmentation, mode of delivery, frequency of side effects, and neonatal and maternal outcome. Analysis of variance, chi-square test, and logistic regression were used for analysis.
    
  Results: There were no significant differences in maternal characteristics or indications for induction. The percentage of women who achieved vaginal delivery within 24 hours was highest in the vaginally administered misoprostol group: 67% compared with 53% in the oral-plus-vaginal group (P <.05) and 36% in the oral group (P <.05). The median time to vaginal delivery was shorter in the vaginal and oral-plus-vaginal misoprostol groups, 13.5 hours and 14.3 hours, respectively, when compared with 23.9 hours in the oral group (P<.05). The rate of cesarean delivery was lowest in the vaginal misoprostol group (17% compared with 30% in the oral-plus-vaginal group and 32% in the oral group; P,.05). Uterine tachysystole occurred lest frequently in the oral misoprostol group (10% compared with 32% in the vaginal group and 34% in the oral-plus -vaginal group; P<.05). Uterine hyperstimulation also occurred least frequently in the oral misoprostol group (4% compared with 15% in the vaginal group and 22% in the oral-plus-vaginal group; P<.05).
    
  Conclusion: At the doses studied, induction of labor with vaginally administered misoprostol is more efficacious than either oral-plus-vaginal or oral-only route of administration.
      

• Michael J Lucas, Shiv K Sharma, et al (Dallas, Texas)
  A randomized trial of labor analgesia in women with pregnancy-induced hypertension.
  Am J Obstet Gynecol, Oct. 2001; 185: 970-5
    
  Objective: The purpose of this study was to compare the peripartum and perinatal effects of epidural with intravenous labor analgesia in women with pregnancy-induced hypertension.
    
  Study Design: Women with pregnancy-induced hypertension who had consented to participate were randomized to receive either epidural or intravenous analgesia for labor pain. Both methods were given according to standardized protocols. All women received magnesium sulfate seizure prophylaxis. Obstetric and neonatal outcomes were compared according to intent-to-treat allocation.
    
  Results: Seven hundred thirty-eight women were randomized: 372 women were given epidural analgesia, and 366 women were given intravenous analgesia. Maternal characteristics were similar, including the severity of hypertension. Epidural analgesia was associated with a significantly prolonged second-stage labor, an increase in forceps deliveries, and an increase in chorioamnionitis. Cesarean delivery rates and neonatal outcomes were similar. Pain relief was superior with the epidural method. Hypotension required treatment in 11% of women in the epidural group.
    
  Conclusion: Epidural labor analgesia provides superior pain relief but no additional therapeutic benefit to women with pregnancy-induced hypertension.
      

• Alessandro Ghidini, and Catherine Y Spong
  Severe meconium aspiration syndrome is not caused by aspiration of meconium
  Am J Obstet Gynecol, Oct. 2001: 185: 931-8
    
  Meconium aspiration syndrome can present clinically with different degrees of severity, ranging from a mild form of respiratory compromise to severe forms that may result in perinatal death despite mechanical ventilation or extracorporeal membrane oxygenation. However, advances in our knowledge concerning meconium aspiration syndrome have revealed that most cases of severe meconium aspiration syndrome are not in fact causally related to the aspiration of meconium but rather are caused by other pathologic processes occurring in utero, primarily chronic asphyxia and infection. Proper understanding of the causative processes underlying fetal or neonatal compromise in these cases is essential to direct future research into preventive or therapeutic treatments and for counseling of the parents of an affected child.
     

• Karen L Koscica, Joseph C Canterino, et al (Neptune and New Brunswick, NJ)
  Assessing genetic risk: Comparison between the referring obstetrician and genetic counselor
  Am J Obstet Gynecol, Nov.2001, vol.185:1032-4
    
  Objective: To compare the genetic risk assessment of the referring obstetrician to the risk assessment of the genetic counselor.
    
  Study Design: All patients evaluated between January 1, 1999, and March 31, 1999, and who required genetic counseling were retrospectively reviewed. The genetic risk assessment of the referring obstetrician was compared to the genetic risk assessment following counseling by a genetic counselor who used a questionnaire and a three-generation pedigree. The number of patients with additional genetic risk factors identified by the genetic counselor were recorded and compared by using the McNemar chi-square test. Group demographics and characteristics were evaluated.
     
  Results: Among the 145 patients evaluated, 38% (n=55) had additional genetic risk factors detected by the genetic counselor (P=.01). The maternal demographics and characteristics did not differ between the two groups.
    
  Conclusion: The practice of referring high-risk obstetric patients for genetic counseling improves the detection of identifiable genetic risk factors.
     

• Michal A Elovitz, Joseph Baron and Mark Phillippe (Chicago, Ill)
  The role of thrombin in preterm parturition
  Am J Obstet Gynecol, Nov.2001; 185: 1059-63.
     
  Objective: Previous reports from the laboratory have shown that thrombin is a potent uterotonic agonist; those studies have suggested a role for thrombin during parturition, especially with regard to intrauterine bleeding. Thrombin activation can be quantified in peripheral blood by measurement of thrombin-antithrombin III (TAT) complex levels. This study sought to determine whether thrombin activation, as measured by thrombin-antithrombin III levels, is associated with premature labor.
    
  Study Design: Thrombin-antithrombin III levels were measured in patients and control subjects with preterm labor. Quantitative TAT levels were determined by use of an enzyme-linked immunoassay with a working range from 0 to 60 ng/mL. All patients were monitored for pregnancy outcome. Receiver operating curve analysis was performed to determine the optimal TAT cutoff values. Further statistical analyses with one-way ANOVA, the c2 test, or the Fisher exact test were performed to determine statistical significance (P<.05).
    
  Conclusions: This study showed that TAT levels are elevated in patients with preterm labor who are destined to deliver before term. These results suggest that preterm labor resulting in premature delivery is associated with the activation of thrombin. Future studies will further elucidate the role of thrombin in preterm parturition and confirm whether tests for thrombin activation can accurately identify those patients destined for preterm delivery.
        

• R D T Farmer, T J Williams, et al
  Effect of 1995 pill scare on rates of venous thromboembolism among women taking combined oral contraceptives: analysis of General Practice Research Database.
  BMJ, Vol.321, 19-26 August 2000; pg.477-9
         
  To compare the incidence of venous thromboembolism among women taking combined oral contraceptives before and after the October 1995 pill scare.
         
  This is an analysis of General Practice Research Database. The subjects were women aged 15-49 taking combined oral contraceptives and the main outcome measure was the incidence of venous thromboembolism.
        
  The findings are not compatible with the assertion that third generation oral contraceptives are associated with a twofold increase in risk of venous thromboembolism compared with older progestogens.                                     
                                                                                              

• Miles J Novy, Amita Gupta et al.                                                         
  Cervical cerclage in the second trimester of pregnancy: A historical cohort study                     
  Am J Obstet Gynecol, vol.184, June 2001, 1447-56                                                  
                                                                                                                    
  Objective: The purpose of this study was to compare second-trimester transvaginal cervical cerclage with conservative management on duration of pregnancy and perinatal outcome in patients with early or advanced cervical changes.   
                                                                                                                                    
  Study Design: A historical cohort analysis was performed. Maternal and neonatal records between 1995 and 1999 were retrospectively reviewed for women presenting between 18 and 27 weeks of gestation with early cervical changes (length <3cm, dilatation <2cm, funneling of fetal membranes shown by transvaginal ultrasonography) (group 1, n=31) and for women with advanced cervical effacement and dilatation (cervical dilatation ³ 2cm, but £ 5 cm, fetal membranes visible) (group 2, n=39). In each group, patients who underwent Shirodkar or McDonald cerclage were compared with patients treated conservatively with bed rest. Both groups also received multifactorial treatment with tocolytic agents, broad-spectrum antibiotics, and indomethacin. Outcome variables were analyzed for statistical significance by parametric and nonparametric methods.    
                                                                                                                                                                                   
  Conclusions : Diagnosis of premature cervical changes by ultransonogrpahy was correlated with treatment earlier in gestation and with a favourable impact on perinatal outcome in both patients treated with cerclage and those treated conservatively. Cervical cerclage was associated with an improved perinatal outcome (in comparison with conservative therapy) in women with early cervical changes detected by ultrasonography and in patients with advanced cervical dilatation and visible membranes. However, the apparent therapeutic effect of cerclage in patients with mild cervical incompetence may be due in part to an increased use of antibiotics and indomethacin in conjunction with cerclage.                                     
                                                 

• Howard Blanchette, Martha Blanchette, et al                                                        
  Is vaginal birth after cesarean safe? Experience at a community hospital                                  
  Am J Obstet Gynecol, June 2001; 184: 1478-87.                                        
                                                                                                     
  Objective: To evaluate the effectiveness and safety of promoting a trial of labor after prior cesarean birth in a community hospital.                                                     
                                                        
  Study Design: A 4-year prospective cohort study was conducted of all patients who had prior cesarean births (N=1481). A comparison of outcomes was performed between those who elected repeat cesarean delivery (n=727) and those who attempted a trial of labor after previous cesarean(s) (n=754).                                                 
                                                                                                         
  Results: The vaginal birth after cesarean attempt rate was 50.9% and declined significantly during the last 2 years of the study. The elective repeat cesarean rate was 49.1% and increased significantly during the last 2 years of the study. In addition, neonatal outcomes were similar, with the exception of 2 neonatal deaths caused by uterine rupture. Twelve uterine ruptures occurred (1.6%) and 11 of the 12 ruptures involved either induction or augmentation of labor, or both.                
                                                                                                                      
  Conclusions: A trial of vaginal birth after cesarean is safe provided that induction of labor is not used. The uterine rupture rate of 1.6% is higher than reported in the literature; this may reflect underreporting by community hospitals.         
                                         

• Craig V Towers, Tamerou Asrat, and Pamela Rumney                        
  The presence of hepatitis B surface antigen and deoxyribonucleic acid in amniotic fluid and cord blood.                                     
  Am J Obstet Gynecol, vol.184, June 2001, pg.1514-20                        
                                                                                                    
  Objective: It is uncertain whether neonatal infection with hepatitis B, despite treatment after delivery with immunoglobulin and vaccine, is the result of prior in utero transmission of the virus or treatment failure. Furthermore, the potential risk of hepatitis B transmission from the mother to the fetus at the time a genetic amniocentesis is performed is also a concern. In an attempt to better elucidate these controversies, amniotic fluid and cord blood specimens obtained from pregnant women positive for hepatitis B surface antigen were analyzed for the presence of hepatitis B surface antigen and hepatitis B deoxyribonucleic acid.
                                                                                                                 
  Study Design: This study was a prospective longitudinal analysis that identified hepatitis B surface antigen-positive patients who presented for amniocentesis. Cord blood was obtained from these patients at the time of delivery. Cord blood was also obtained from a group of hepatitis B surface antigen-positive patients for whom no amniocentesis was performed. All samples were analyzed for the presence of hepatitis B surface antigen and hepatitis B deoxyribonucleic acid.     
                                                                                               
  Conclusions: This study found that hepatitis B viral deoxyribonucleic acid is rarely present in cord blood and was not identified in amniotic fluid obtained by amniocentesis. This finding suggests that in utero transmission of the virus is rare prior to the onset of labor. These data further confirm the reports in the current literature that the risk of hepatitis B transmission to the fetus during amniocentesis is low. Because hepatitis B surface antigen can exist as an isolated entity devoid of nuclear material, in some cases this protein may be able to traverse the placental and amniotic membrane barrier in a manner similar to other proteins, such as a-fetoprotein. Recommendations for genetic amniocentesis in women positive for hepatitis B surface antigen are discussed.        
          

• Alisa B Goldberg, Mara B Greenberg, Philip D Darney
  Misoprostol and Pregnancy
  The NEJM, Vol.344(1), Jan.4, 2001, pg.38-46
  
  Misoprostol is useful for elective medical abortion, cervical ripening before surgical abortion, evacuation of the uterus in cases of embryonic or fetal death, and induction of labor. The drug may also be used to treat and even prevent postpartum haemorrhage.
  
  The most common adverse effects of misoprostol are nausea, vomiting, diarrhoea, abdominal pain, chills, shivering, and fever, all of which are dose-dependent . Although other prostaglandins (prostaglanding E2 and prostaglandin F2a) can cause myocardial infarction and bronchospasm, misoprostol does not. Toxic doses of misoprostol have not been determined; however, cumulative doses of up to 2200mg administered over a period of 12 hours have been tolerated by pregnant women, with no serious adverse effects.
  
  The effects of misoprostol on the reproductive tract are increased, and gastrointestinal adverse effects are decreased, if the oral preparation of misoprostol is administered vaginally.
  
  Among women who were 9 to 11 weeks pregnant and given misoprostol before a surgical abortion, intrauterine pressure began to increase an average of 8 minutes after oral administration and 21 minutes after vaginal administration and was maximal 25 minutes after oral administration and 46 minutes after vaginal administration. Uterine contractility initially increased and then plateaued one hour after oral administration, whereas uterine contractility increased continuously for four hours after vaginal administration. Maximal uterine contractility was significantly higher after vaginal administration.
  
  Möbius syndrome (congenital facial paralysis) and limb defects have occurred in the infants of women who have taken misoprostol during the first trimester in an unsuccessful attempt to induce abortion.
  
  In a recent study of 4673 malformed infants and 4980 control infants, the Latin Amercian Collaborative Study of Congenital Malformations noted an increased frequency of transverse limb defects, ring-shaped constrictions of the extremites, arthrogryposis, hydrocephalus, holoprosencephaly, and exstrophy of the bladder, but not Möbius syndrome, in infants exposed to misoprostol in utero.
  
  In particular, methotrexate has been associated with craniofacial and digital anomalies. Mifepristone may also be teratogenic; however, the risk of malformations appears to be lower with mifepristone than with methotrexate or misoprostol.
  
  MISOPROSTOL IN THE FIRST TRIMESTER OF PREGNANCY.
  
  For 91 to 97 percent of women who were no more than 49 days pregnant, 600 mg of oral mifepristone, followed 48 hours later by 400 mg of oral misoprostol, resulted in complete abortion. For women who were no more than 56 days pregnant, the success rate was 83 to 95 percent. Lowering the dose of mifepristone to 200 mg does not reduce efficacy. Administration of 200mg of oral mifepristone followed by 600 mg of oral misoprostol resulted in complete-abortion rates of 96 to 97 percent among women no more than 49 days pregnant and 89 to 93 percent among women 50 to 63 days pregnant.
  
  Among women with complete abortion, 93 percent had the abortion within four hours and 97 percent within five days after taking misoprostol. In studies of women who were no more than 56 days pregnant or no more than 63 days pregnant, the rate of complete abortion was also high (97 to 98 percent) after the administration of 200mg of oral mifepristone followed 48 hours later by 800 mg of vaginal misoprostol.
  
  A combined regimen of mifepristone and misoprostol resulted in complete abortion in 94 to 95 percent of women 9 to 13 weeks pregnant; however, the incidence of heavy vaginal bleeding may be higher than in women with less advanced pregnancies.
  
  Misoprostol has also been used alone for medical abortions, with variable efficacy. Up to three 800 ug doses of vaginal misoprostol given every 48 hours resulted in complete abortions in up to 96 percent of women who were no more than63 days pregnant. 
  
  The variation in rates of complete abortion among women given misoprostol alone may be due to differences in study design, since rates are often lowest in randomized trials, or to efforts to increase vaginal absorption of misoprostol in some studies. For example, in one study in which the success rate was high, the vagina was cleansed with either sterile water or saline, the misoprostol tablets were moistened with two or three drops of water or saline and then placed in the posterior fornix of the vagina, and the women were required to remain supine for three hours after placement of the tablets.
  
  There was no significant difference in the rate of complete abortion (95 percent with moistened tablets and 92 percent with dry tablets, P=0.40)
  
  Failed pregnancy or Fetal death
  After mifepristone or methotrexate “destabilizes” an ongoing pregnancy, misoprostol helps expel the products of conception. If spontaneous expulsion is delayed, drug therapy may be indicated to evacuate the uterus, in order to avoid surgery or a prolonged wait for expulsion.
  
  The rate of complete expulsion within 48 hours after the first dose of misoprostol was 25 percent in the oral-misoprostol group and 88 percent in the vaginal-misoprostol group. Thus 800 ug of misoprostol given vaginally once or twice (with the second dose given 24 hours after the first) is effective in evacuating the uterus in the case of an early failed pregnancy or embryonic death.
  
  The mean haemoglobin concentration fell significantly in women in the misoprostol group, but not in women in the surgical group. On the basis of these findings, misoprostol is currently not recommended for the treatment of inevitable or incomplete abortion.
  
  Misoprostol is less expensive than gemeprost, is more easily stored, has fewer side effects, and is equally successful in dilating the cervix before abortion. For cervical dilatation, 400 µg of vaginal misoprostol is equivalent to one medium laminaria used for four hours preoperatively, but laminaria placement is more painful than misoprostol placement. Vaginal misoprostol causes greater dilatation than the same dose of oral misoprostol.
  
  These findings suggest that the best regimen for cervical ripening in the first trimester is 400 mg of vaginal misoprostol given three to four hours before suction curettage.
  
  MISOPROSTOL IN THE SECOND TRIMESTER OF PREGNANCY
  
  It is likely that the duration of the pregnancy after fetal death influences both the rate of successful induction of labor and the time from induction to delivery.
  
  In some studies, all fetuses with cardiac activity, received intracardiac potassium chloride before induction of labor.
  
  In the third trimester, doses in the range of 25 to 50 mg induce labor. The optimal dose of vaginal misoprostol for induction of labor in the second trimester probably lies somewhere between 50 and 800 mg. Within this range higher doses may be needed to cause abortions early in the second trimester, whereas lower doses may be sufficient later in the second trimester.
  
  The usual regimen for induction of labor in the second trimester is 200 mg of misoprostol given vaginally every 12 hours. The highest doses were associated with higher rates of adverse effects, including a temperature above 38 C (0 percent, 2 percent and 28 percent respectively).
  
  Uterine rupture was reported in two women undergoing abortion with the use of misoprostol in the second trimester. One woman had undergone two cesarean deliveries and the other woman, who had two prior vaginal deliveries and one spontaneous abortion had no history of uterine surgery or curettage. The risk of uterine rupture associated with induction of labor with misoprostol in the second trimester is unknown, and nearly all trials of misoprostol for induction of labor in the second trimester have excluded women with uterine scars.
  
  It appears that 200 to 600 mg of misoprostol given vaginally every 12 hours or 400 mg given vaginally every 3 hours successfully induces labor in the second trimester.
  
  As with medical abortion in the first trimester, induction of labor in the second trimester with misoprostol is more successful if mifepristone is given 36 to 48 hours before misoprostol.
   
  MISOPROSTOL IN THE THIRD TRIMESTER OF PREGNANCY
  Induction of labor with a viable fetus.
  
  These studies included most indications for which labour is induced, including premature rupture of membranes.
  
  The time from induction of labor to delivery was 4.6 hours shorter and the rate of cesarean delivery was lower in the misoprostol group.
  
  The Cochrane Pregnancy and Childbirth Group reviewed 26 randomized trials comparing misoprostol with placebo, oxytocin or prostaglandin E2 for cervical ripening or induction of labor with a viable fetus in the third trimester.
  
  Vaginal misoprostol (25 to 100 mg) was more effective than oxytocin or prostaglandin E2 for inducing vaginal delivery within 24 hours. However, uterine hyperstimulation with associated changes in the fetal heart rate was more common in women who received misoprostol than in women who received oxytocin or prostaglandin E2.
  
  The frequency of meconium-stained amniotic fluid was higher in the misoprostol group than in the prostaglandin E2 group, although it was not higher than that in the oxytocin group. Whether this difference was due to increased fetal distress in the misoprostol group or to a direct effect of misoprostol on the fetal gastrointestinal tract is unknown.
  
  The available data suggest that the best dose of misoprostol for induction of labor is 25 mg given vaginally every four to six hours.
  
  Induction of labor after Fetal Death
  A dose of 100 mg of vaginal misoprostol given every 12 hours results in success rates that approach 100 percent. For fetal death at term a dose as low as 50 mg given every 12 hours may be adequate for induction of labor.
  
  Induction of labor in Women with Previous Cesarean Delivery
  Until it has been proved safe, misoprostol should not be used to induce labor in women with uterine scars.
  
  Conclusion: Misoprostol may also prevent postpartum haemorrhage when parenteral medications are not available.
  

• J.E.Manson and K.A. Martin
  Postmenopausal hormone-replacement therapy.
  New Eng. J Med. Vol.345, July 5, 2001, pg.39
  

  Short-term HRT Use (<5 years)

  Long-Term HRT use (³ 5 years)

                Symptoms of
                menopause?

  

  
  

• Piotr Milkiewicz, Catherine Williamson et al 
  Obstetric Cholestasis
  BMJ, 19 Jan. 2002, pg.123
      
  Obstetric cholestasis is associated with cholesterol gallstones.
     
  It may lead to premature births in upto 60%, fetal distress in upto 33% and intrauterine death in up to 2% of patients. 
     
  Historically obstetric cholestasis has been associated with the cholestatic effect of oestradiol metabolites, in particular 17-b oestradiol glucuronide. Progesterone metabolites, however, play an even more important part in its pathogenesis.
     
  Excess of these metabolites in the urine in obstetric cholestasis may be related to malfunction of biliary canalicular transporters normally responsible for their secretion from hepatocytes into bile.
     
  Obstetric cholestasis classically manifests itself in the second or third trimester of pregnancy with generalised pruritus, most pronounced in palms and soles. Jaundice is relatively uncommon.
      
  Ursodeoxycholic acid is effective in reducing pruritus and abnormalities in liver function tests.
     

• Irving L. Weissman
  Stem Cells – Scientific, Medical, and Political Issues
  New Engl Jr Med. Vol.346, May 16, 2002, pg.1576-79
     
  Stem cells have the unique capacity not only to give rise to more stem cells (self-renewal) but also to generate differentiated progeny. They are present at all stages of development and probably exist in all multicellular organisms. In the blastocyst stage of the embryo before implantation, the inner cell mass contains cells that will become the fetus. Some of these cells are pluripotent stem cells that give rise to all types of somatic and germ-line cells. When these pluripotent cells are grown in vitro, they become embryonic stem cell lines.
    
  The developmental stages between pluripotent embryonic cells and multipotent tissue-specific stem cells, such as hematopoietic stem cells, are still unclear. Pluripotent stem cells generate germ-line stem cells plus tissue-specific stem cells.
    
  Multipotent tissue-specific stem cells can be found from the fetal stage onward. In adults, they can participate in the renewal and regeneration of tissue, and during fetal life they may be units of tissue generation.
    
  Critical properties of stem cells – self-renewal and differentiation – should be the gold standard for all such studies.
    
  The author believes that using the currently available embryonic stem-cell lines to delineate developmental lineages of human cells will be extremely valuable. Knowledge gained from such studies should spawn a search for molecules or factors that cause particular cells to follow particular pathways and inhibit them from following others.
    
  How could such stem-cell lines be generated? One way is by transferring somatic-cell nuclei into enucleated eggs (nuclear transplantation). When stimulated to divide, the cell can form blastocysts of predefined nuclear genotype (with the mitochondrial DNA coming from the egg). Cells from the inner cell mass of these blastocysts can be isolated, cultured, and used to generate embryonic stem-cell lines of predefined genotype.
    
  It is possible that religious and ethical considerations will lead to a ban on such research, because of the fear that nuclear transplantation into enucleated eggs might be used to clone a human being.
    
  For some segments of society, blastocysts produced by nuclear transplantation are embryos to be accorded full human rights, and their destruction or biopsy to produce embryonic stem-cell lines constitutes the taking of lives.
    
  The author believes that such research will be as valuable to medicine as recombinant DNA research has proved to be.
    

• H W Jones, and J A Schnorr
  Multiple pregnancies: a call for action
  Fert.&Ster. Vol.75(1), Jan.2001, pg. 11
    
  The significant increase in multiple births appears to coincide with two overlapping and related trends. The first is the older age at childbearing, because within spontaneous conceptions, older women are more likely to have a multiple birth. Second, there is an increase in the availability and use of fertility-enhancing therapies, which typically result in a high percentage of multiple pregnancies. It has been estimated that approximately one third of the increase in multiple births since the early 1980s has been attributed to a shift in maternal age distribution; the remaining two thirds is likely the result of ovulation induction, gamete intrafallopian transfer (GIFT) , and in vitro fertilization (IVF), the principal fertility-enhancing therapies. If these estimates are reliable, the fertility-enhancing therapies translate into more than 225,000 multiple births over the study period of 1980-1997.
    
  IVF allows more control over the multiple-pregnancy rates by allowing the patient and physician to determine the optimum number of embryos to transfer.
    

• C.J. Glueck, H. Phillips et al
  Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study
  Fert.& Ster. Vol.75(1), Jan.2001, pg.46-52
   
  Objective: To determine whether metformin would safely reduce the rate of first-trimester spontaneous abortion without teratogenicity in 19 women with polycystic ovary syndrome (PCOS).
     
  Design: Prospective pilot study.
   
  Setting: Outpatient.
   
  Patient(s): Twenty-two previously oligoamenorrheic, nondiabetic women with PCOS; 125 women with PCOS who were not currently pregnant and who had ³1 previous pregnancy while they were not receiving metformin.
   
  Interventions: Metformin, 1.5-2.55 g/day, throughout pregnancy.
     
  Main Outcome Measures: Rates of first-trimester spontaenous abortion and teratogenicity.
    
  Results: Before metformin, 10 women had 22 previous pregnancies with 16 first-trimester spontaneous abortions (73%). While receiving metformin, these 10 women had 6 normal live births (60%), 1 spontaenous abortion (10%), and 3 normal ongoing pregnancies (305) (all ³ 13 weeks; median gestation, 23 weeks). Among women receiving metformin, including those with live births and normal pregnancy for at least the first trimester, 1 of 10 (10%) had first-trimester spontaneous abortion compared with 73% in 22 previous pregnancies without metformin (P<.002). To date, the 19 women receiving metformin have had no adverse maternal side effects, and no birth defects have occurred; 9(475) had normal term live births, 2 (11%) had normal and appropriate for gestational age births (one at 33 an done at 35 weeks), 6 (32%) have ongoing normal pregnancies lasting longer than the first trimester, and 2 (10.5%) had first-trimester spontaneous abortions. Sonography showed normal fetal development without congenital defects in the 6 ongoing pregnancies (median gestation, 23 weeks). Among women who received metformin before conception, reductions in insulin and plasminogen activator inhibitor activity were correlated (r=0.65, P=.04).
     
  Conclusions: Metformin therapy throughout pregnancy in women with PCOS reduces the otherwise high rate of first-trimester spontaneous abortion seen among women not receiving metformin and does not appear to be teratogenic.
     

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