Clinical interventions to reduce stillbirths in sub-Saharan Africa: a mathematical model to estimate the potential reduction of stillbirths associated with specific obstetric conditions.

OBJECTIVE: Stillbirths are among the most common adverse pregnancy outcomes, with 98% occurring in low-income countries. More than one-third occur in sub-Saharan Africa (SSA). However, the medical conditions causing stillbirths and interventions to reduce stillbirths from these conditions are not well documented. We estimated the reductions in stillbirths possible with combinations of interventions. DESIGN: We developed a computerised model to estimate the impact of various interventions on stillbirths caused by the most common conditions. The model considered the location of obstetric care (home, clinic or hospital) and each intervention's efficacy, penetration and utilisation. Maternal transfers were also considered. SETTING AND POPULATION: Pregnancies in SSA in 2012. METHODS: For each condition, we created a series of scenarios involving different combinations of interventions and modelled their impact on stillbirth rates. MAIN OUTCOME MEASURES: Stillbirths associated with various maternal and fetal conditions and the percentage reduction with various interventions. RESULTS: Eight to ten maternal and fetal conditions were responsible for most stillbirths, but none for more than 15%. The most common conditions causing stillbirths in SSA include obstructed labour and uterine rupture, fetal distress and umbilical cord complications, fetal growth restriction, pre-eclampsia/eclampsia, and placental abruption/placenta praevia. Syphilis and malaria contribute smaller numbers. Reducing stillbirths requires appropriate diagnosis and management of each condition, usually including hospital care for monitoring and delivery, often by caesarean section. Maternal syphilis and malaria were the only conditions for which outpatient management alone reduced stillbirth. CONCLUSIONS: Most stillbirths in low-income countries occur at term and during labour and therefore are preventable by appropriate obstetric care. Management focused on the maternal and fetal conditions that cause stillbirths is necessary to achieve stillbirth rates approaching those found in high-income countries. TWEETABLE ABSTRACT: Reducing stillbirth incidence requires appropriate management of each causative condition and often caesarean delivery.

Cervical funneling or intra-amniotic debris and preterm birth in nulliparous women with midtrimester cervical length less than 30 mm.

OBJECTIVE: To evaluate whether the presence of cervical funneling or intra-amniotic debris identified in the second trimester is associated with a higher rate of preterm birth (PTB) in asymptomatic nulliparous pregnant women with a midtrimester cervical length (CL) less than 30 mm (i.e. below the 10th percentile). METHODS: This was a secondary cohort analysis of data from a multicenter trial in nulliparous women between 16 and 22 weeks' gestation with a singleton gestation and CL less than 30 mm on transvaginal ultrasound, randomized to treatment with either 17-alpha-hydroxyprogesterone caproate or placebo. Sonographers were centrally certified in CL measurement, as well as in identification of intra-amniotic debris and cervical funneling. Univariable and multivariable analysis was performed to assess the associations of cervical funneling and intra-amniotic debris with PTB. RESULTS: Of the 657 women randomized, 112 (17%) had cervical funneling only, 33 (5%) had intra-amniotic debris only and 45 (7%) had both on second-trimester ultrasound. Women with either of these findings had a shorter median CL than those without (21.0 mm vs 26.4 mm; P < 0.001). PTB prior to 37 weeks was more likely in women with cervical funneling (37% vs 21%; odds ratio (OR), 2.2 (95% CI, 1.5-3.3)) or intra-amniotic debris (35% vs 23%; OR, 1.7 (95% CI, 1.1-2.9)). Results were similar for PTB before 34 and before 32 weeks' gestation. After multivariable adjustment that included CL, PTB < 34 and < 32 weeks continued to be associated with the presence of intra-amniotic debris (adjusted OR (aOR), 1.85 (95% CI, 1.00-3.44) and aOR, 2.78 (95% CI, 1.42-5.45), respectively), but not cervical funneling (aOR, 1.17 (95% CI, 0.63-2.17) and aOR, 1.45 (95% CI, 0.71-2.96), respectively). CONCLUSIONS: Among asymptomatic nulliparous women with midtrimester CL less than 30 mm, the presence of intra-amniotic debris, but not cervical funneling, is associated with an increased risk for PTB before 34 and 32 weeks' gestation, independently of CL. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth: a case-control study.

OBJECTIVE: To determine whether ß2 -adrenoceptor (ß2 AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester. DESIGN: A case-control ancillary study to a multicentre randomised controlled trial. SETTING: Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. POPULATION: Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length. METHODS: Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. ß2 AR genotype was determined at positions encoding for amino acid residues 16 and 27. MAIN OUTCOME MEASURES: Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks. RESULTS: Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited. CONCLUSIONS: ß2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with ß2 AR genotype do not appear to involve a short cervix pathway.

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis.

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles. SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75). AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids.

OBJECTIVE: The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. STUDY DESIGN: This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. RESULTS: CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. CONCLUSION: Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.

Vitamin D status and recurrent preterm birth: a nested case-control study in high-risk women.

OBJECTIVE: To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption. DESIGN: A nested case-control study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. SETTING: Fourteen academic health centres in the USA. POPULATION: Women with prior spontaneous preterm birth. METHODS: In 131 cases (preterm delivery at <35 weeks of gestation) and 134 term controls, we measured serum 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) from samples collected at baseline (16-22 weeks of gestation). Logistic regression models controlled for study centre, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment. MAIN OUTCOME MEASURES: Recurrent preterm birth at <37 and <32 weeks of gestation. RESULTS: The median mid-gestation serum 25(OH)D concentration was 67 nmol/l, and 27% had concentrations of <50 nmol/l. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR 1.33; 95% CI 0.48-3.70 for lowest versus highest quartiles). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/l, or higher, with those with <50 nmol/l generated an odds ratio of 0.80 (95% CI 0.38-1.69). Contrary to our expectation, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (-0.18, P < 0.01). CONCLUSIONS: In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth.

Chlorhexidine vaginal and neonatal wipes in home births in Pakistan: a randomized controlled trial.

OBJECTIVE: To assess tolerance and safety of 0.6% chlorhexidine vaginal and neonatal wipes to improve perinatal outcomes in home deliveries in Pakistan and the ability of traditional birth attendants and project staff to perform a randomized trial of this intervention. METHODS: Focus groups of pregnant and nonpregnant women and in-depth interviews of traditional birth attendants explored barriers to the use of chlorhexidine wipes. Then, a study was performed of women delivering at home attended by traditional birth attendants. Consenting women were randomly assigned to receive either 0.6% chlorhexidine or saline vaginal and neonatal wipes. Women and their infants were followed up on postpartum days 7, 14, and 28. Acceptability and tolerance of vaginal and neonatal wipes, as well as maternal and neonatal outcomes, were assessed. RESULTS: The focus groups and interviews indicated that the chlorhexidine intervention would be acceptable to women and their providers. Of the 213 eligible pregnant women approached, 203 (95%) gave informed consent and were enrolled and allocated to groups. Traditional birth attendants had no difficulty administering chlorhexidine vaginal and neonatal wipes in a home setting. Of the 203 births, 103 (51%) of whom received 0.6% chlorhexidine, there were no allergic reactions, vaginal itching, burning, or requests for study termination. Follow-up at 28 days postpartum was more than 95%. Although this study was not powered to show significant differences in neonatal outcomes between treatment groups, the lower rates of some neonatal adverse clinical outcomes in the chlorhexidine group were encouraging. CONCLUSION: Use of 0.6% chlorhexidine vaginal and neonatal wipes for the prevention of neonatal infection is well-tolerated and seems safe. A trial of this intervention by traditional birth attendants in a home-delivery setting is feasible. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00121394 LEVEL OF EVIDENCE: I.

Short-term studies of taurocholate uptake by ileal brush border membrane vesicles: anion effects.

Experiments allowing Na+-dependent short-term uptake measurements by ileal brush border vesicles were described. Glucose uptake was compared with taurocholate uptake in the presence of NaCl, NaSCN and Na2SO4. In contrast to the observation made with glucose, taurocholate transport was the same for the three electrolytes, indicating electroneutral taurocholate transport.

Rapid testing and zidovudine treatment to prevent vertical transmission of human immunodeficiency virus in unregistered parturients: a cost-effectiveness analysis.

OBJECTIVE: To assess the potential effectiveness and costs of a program to prevent vertical transmission of human immunodeficiency virus (HIV) in parturients without prenatal care. METHODS: A decision-analysis model was constructed to compare three management strategies for unregistered women presenting in labor: 1) the current standard of treating no one; 2) HIV testing with a rapid antibody assay, followed by zidovudine treatment according to AIDS Clinical Trial Group Protocol 076 if seropositive; and 3) treating all women without rapid testing. Cost and probability data were obtained from a literature review and local estimates. Sensitivity analyses were performed for pertinent uncertainties. RESULTS: Under baseline assumptions (5% HIV prevalence, treatment efficacy of an 18% reduction in transmission rate, and lifetime cost of pediatric HIV $103,708), giving no treatment resulted in 1275 infected infants per 100,000 mother-infant pairs. The rapid-test strategy prevented 183 cases of infant HIV infection and resulted in a net savings to the medical system of $57,997 per case averted. The treat-all strategy prevented an additional 46 cases per 100,000 mother-infant pairs, but at a cost of $342,068 per additional case averted. With other estimates at baseline, rapid testing was cost-saving when the HIV prevalence exceeded 0.97%, the treatment efficacy exceeded a 5.8% reduction in the transmission rate, and the lifetime cost of pediatric HIV infection exceeded $33,625. CONCLUSION: Rapid HIV testing of unregistered parturients followed by zidovudine treatment if seropositive would be cost saving to the medical system.

Criteria for failed labor induction: prospective evaluation of a standardized protocol.

OBJECTIVE: To assess the safety and efficacy of a protocol that mandated at least 12 hours of oxytocin administration after membrane rupture before cesarean delivery for failed labor induction in the latent phase. METHODS: Gravidas at or beyond 36 weeks' gestation undergoing indicated induction with cervical dilatation up to 2 cm were studied prospectively. Prior cesarean was an exclusion criterion. If the fetal heart rate pattern was reassuring, cesarean was not permitted before the active phase of labor (4-cm dilatation and at least 90% effacement or 5-cm dilatation regardless of effacement) unless the membranes had been ruptured and oxytocin administered for at least 12 hours. RESULTS: Five hundred nine women were treated according to protocol; 360 (71%) were nulliparas and 149 (29%) were parous. Twenty-five percent of nulliparas and 9% of parous women were delivered by cesarean. After 6 hours of ruptured membranes and oxytocin, 14% of nulliparas were still in the latent phase; 39% of whom delivered vaginally, compared with 7% still in the latent phase after 9 hours (vaginal delivery rate 28%), and 4% after 12 hours (vaginal delivery rate 13%). In contrast, after 6 hours of ruptured membranes and oxytocin, only five (3%) parous women were still in the latent phase. Among those, none remained in the latent phase for 12 hours and all were delivered vaginally. No women had serious complications. Severe neonatal morbidities were infrequent and not related to duration of the latent phase. CONCLUSION: By requiring a minimum of 12 hours of oxytocin after membrane rupture before failed labor induction could be diagnosed, many nulliparas who remained in the latent phase at 6 and 9 hours had safe vaginal deliveries, and failed labor induction was eliminated as an indication for cesarean in parous women.

Active-phase labor arrest: oxytocin augmentation for at least 4 hours.

OBJECTIVE: To assess a labor-management protocol that mandated at least 4 hours of oxytocin augmentation before cesarean delivery for active-phase labor arrest. METHODS: We prospectively evaluated term gravidas in spontaneous labor with active-phase labor arrest (cervix at least 4 cm dilated and 1 cm or less of cervical progress in 2 hours). Exclusion criteria included nonvertex presentation, previous cesarean, multiple gestation, and a nonreassuring fetal heart rate tracing or chorioamnionitis at the time of labor arrest. After the diagnosis of active-phase arrest, oxytocin was initiated with an intent to achieve a sustained uterine contraction pattern of greater than 200 Montevideo units. Cesarean delivery was not performed for labor arrest until at least 4 hours of a sustained uterine contraction pattern of greater than 200 Montevideo units, or a minimum of 6 hours of oxytocin augmentation if this contraction pattern could not be achieved. RESULTS: Five hundred forty-two women were managed by the protocol, and 92% delivered vaginally. The subsequent vaginal delivery rate for parous women who had not progressed (1 cm of cervical dilation or less) despite 2 hours of oxytocin augmentation was 91%, and it was 74% for nulliparas. With no labor progress after 4 hours of oxytocin augmentation, the subsequent vaginal delivery rates were 88% for parous women and 56% for nulliparas. There were no severe maternal complications. One neonate had persistent fetal circulation and one had a positive blood culture, but both did well. CONCLUSION: Extending the minimum period of oxytocin augmentation for active-phase labor arrest from 2 to at least 4 hours was effective and safe.

Intraoperative hypothermia and post-cesarean wound infection.

OBJECTIVE: To determine whether intraoperative hypothermia during cesarean delivery is a risk factor for wound infection. METHODS: Eighteen cases with wound infection and 18 controls matched for age, weight, presence of gestational hypertension, and surgery length were selected from a cohort of 900 women who underwent cesarean delivery and who were assessed for wound infection according to strict criteria. Because immediate postoperative temperatures reflect intraoperative temperature nadir accurately and were available universally, we compared the mean immediate postoperative temperatures between cases and controls. RESULTS: In addition to the intentionally matched factors, the groups were well-matched for race, parity, presence of labor, presence of meconium, and duration of membrane rupture. The mean initial postoperative temperatures were similar between the two groups (36.3+/-0.9C versus 36.6+/-1.0C, respectively; P=.8). This study had a power of 90% to detect an intergroup difference of 1C. CONCLUSION: In this case-control study of cesarean delivery, intraoperative hypothermia was not a risk factor for wound infection.

Screening and treatment of asymptomatic bacteriuria of pregnancy to prevent pyelonephritis: a cost-effectiveness and cost-benefit analysis.

OBJECTIVE: To compare the effectiveness, benefits, and costs of two asymptomatic bacteriuria screening and treatment strategies to prevent pyelonephritis in pregnancy. METHODS: A decision analytic model was created to compare strategies based on either 1) a leukocyte esterase-nitrite dipstick, or 2) on urine culture, with a policy of no screening or treatment. A literature search was conducted to generate probability estimates. Cost estimates were based on a local pharmacy and laboratory survey and supplemented by recent literature estimates. Sensitivity analyses were performed over wide ranges of probability and cost estimates. RESULTS: Under baseline assumptions, no screening resulted in 23.2 cases of pyelonephritis per 1000 pregnancies, versus 16.2 cases with the dipstick strategy and 11.2 with the culture strategy. The cost of screening and treatment of asymptomatic bacteriuria per 1000 pregnancies was $1968 with dipstick and $19,264 with culture. The cost of treating pyelonephritis with no screening was $57,562, versus $40,257 with dipstick and $27,832 with culture. Therefore, both the dipstick strategy and the culture strategy were cost-beneficial (based on a pyelonephritis cost of $2485) when compared with no screening. However, because it cost $3492 to prevent each additional case of pyelonephritis with culture that was not prevented by dipstick, the culture strategy was not cost-beneficial compared with the dipstick strategy. These results were sensitive to varying estimates for the prevalence of asymptomatic bacteriuria, the rate of progression of asymptomatic bacteriuria to pyelonephritis, the sensitivity of the dipstick, culture costs, and the cost of a case of pyelonephritis. CONCLUSION: When compared with a policy of no screening, screening for and treatment of asymptomatic bacteriuria to prevent pyelonephritis in pregnancy is cost-beneficial whether based on the leukocyte esterase-nitrite dipstick or on urine culture. However, the culture strategy is not cost-beneficial when compared with the dipstick strategy.

Fundal height as a predictor of preterm twin delivery.

OBJECTIVE: To determine whether fundal height might predict early delivery in twin pregnancies; that is, whether larger fundal heights predispose to earlier delivery. METHODS: From the charts of 336 well-dated twin pregnancies, we generated a series of fundal height curves. RESULTS: Within our population of twin pregnancies, the mean fundal height at any given gestational age did not differ between pregnancies delivered before 34 weeks and those delivered at or after 34 weeks. A single fundal height measurement above the 90th percentile before 34 weeks yielded a sensitivity of 23% and a specificity of 79% for delivery before 34 weeks, with a positive predictive value of 38% and a negative predictive value of 64%. CONCLUSION: Factors other than uterine overdistention (as measured by fundal height) must be implicated in preterm twin delivery.

Antenatal screening for factor V Leiden mutation: a critical appraisal.

Thromboembolic disease is a leading cause of maternal mortality in the United States. Recently, inherited resistance to activated protein C has been recognized as a major risk factor for thrombosis and has been demonstrated in 20-60% of patients with clinically evident thrombosis. The factor V Leiden mutation, which is readily detectable by molecular DNA techniques, is responsible for 90-95% of cases of activated protein C resistance. Because 5% of whites and 1% of blacks in the United States are heterozygous for the Leiden mutation, at least one group has suggested that screening of asymptomatic gravidas for the mutation should be considered. Therefore, we conducted a combined MEDLINE and bibliographic literature search for relevant data and evaluated screening for the factor V Leiden mutation in the context of well-elucidated desirable characteristics for a successful screening program. Based on this evaluation, we conclude that routine antenatal screening for the factor V Leiden mutation cannot be recommended at the present time.

Management of the presumed susceptible varicella (chickenpox)-exposed gravida: a cost-effectiveness/cost-benefit analysis.

OBJECTIVE: To compare the cost-effectiveness and cost-benefit of different strategies for managing the presumed susceptible varicella (chickenpox)-exposed gravida. METHODS: Three strategies were evaluated: 1) a do-nothing or observation strategy; 2) a testing strategy, in which immune status was assessed and varicella-zoster immune globulin was administered to those who tested nonimmune; and 3) a universal-administration strategy, in which varicella-zoster immune globulin was given to all exposed, presumed susceptible gravidas. Because precise data are unavailable about varicella mortality and hospitalization rates in pregnancy, a range of potential rates was evaluated, from one to greater than 20 times healthy nonpregnant adult rates. The potential efficacy of varicella-zoster immune globulin varied from 1 to 99%. A strategy was defined as cost-effective if it cost less than $50,000 per life-year gained. RESULTS: If the mortality rate from varicella infection in pregnancy was increased fivefold over the nonpregnant healthy adult rate (ie, from 31/100,000 to 155/100,000 cases), efficacy would have to be at least 49% for the immune-testing strategy to be cost-effective. If pregnancy only doubled the varicella mortality rate, then even with perfect efficacy, the immune-testing strategy would not be cost-effective. Under most assumptions, the universal-administration strategy was cost-ineffective when compared with the immune-testing strategy. Similar results were obtained in the parallel cost-benefit analysis, which considered hospitalization costs and rates. The analysis was sensitive to the varicella transmission rate and the discount rate. CONCLUSION: From a cost-effectiveness/cost-benefit standpoint, management based on immune testing is preferable to universal varicella-zoster immune globulin administration when caring for the varicella-exposed gravida with a negative or indeterminate infection history.

Treatment of the small unruptured ectopic pregnancy: a cost analysis of methotrexate versus laparoscopy.

OBJECTIVE: To compare the economic costs between two strategies for management of the small unruptured ectopic pregnancy: initial treatment with methotrexate versus initial treatment with laparoscopic salpingostomy. METHODS: We assumed that both treatment strategies would result in identical clinical outcomes: resolution of the ectopic pregnancy without maternal mortality or long-term morbidity. Based on a literature review, estimates were derived for the likely clinical outcomes of a single injection of methotrexate (50 mg/m2) and for the likely clinical outcomes of the laparoscopy strategy. A range of values was evaluated for the initial success rate of each strategy and varying assumptions made about the type of treatment modality used for initial treatment failures. Direct medical costs of each strategy were estimated based on actual reimbursement rates of a third-party payer for the components of each strategy. The treatment strategies were compared in best-case/worst-case scenarios to determine the potential range of differences in costs between the two strategies. RESULTS: The cost of the methotrexate strategy ranged from $438 to $1390, and the cost of laparoscopic salpingostomy ranged from $2506 to $2974; therefore, the methotrexate strategy was less costly than laparoscopy, with a cost difference ranging from $1124 (best-case laparoscopy-worst-case methotrexate scenario) to $2536 (worst-case laparoscopy-best-case methotrexate scenario). Sensitivity analyses demonstrated that initial therapy with methotrexate was less costly over a wide range of probability and cost estimates. CONCLUSION: Initial methotrexate is a cost-effective alternative to laparoscopic salpingostomy in the treatment of the small unruptured ectopic pregnancy.

Active phase labor arrest: revisiting the 2-hour minimum.

OBJECTIVE: To generate contemporary uterine activity and labor progress data for oxytocin-augmented labor, and assess whether 2 hours of active phase labor arrest with at least 200 Montevideo units justifies cesarean delivery. METHODS: Five hundred and one consecutive spontaneously laboring term women with abnormally progressive labor were managed by a standardized protocol: oxytocin and intrauterine pressure catheter with an intent to sustain at least 200 Montevideo units for 4 hours or more before cesarean for labor arrest. Uterine activity was measured, and maternal and neonatal outcomes were evaluated. With a sample of this size, the upper 95% confidence interval limit for an event with an observed rate of 1% is below 3%. RESULTS: During oxytocin augmentation, nulliparas who were delivered vaginally dilated at a median rate of 1.4 cm/hour versus 1.8 cm/hour for parous women. In both groups, the 5th percentile of cervical dilation rate was 0.5 cm/hour. Thirty-eight women experienced labor arrest for over 2 hours despite at least 200 sustained Montevideo units; 23 (61%) achieved a vaginal delivery. Rates of chorioamnionitis and endometritis for the 38 women were 26%. None of their infants sustained a serious complication, including brachial plexus injury, even though three of the 23 vaginal deliveries (13%) were complicated by shoulder dystocia. CONCLUSION: These data demonstrate that oxytocin-augmented labor proceeds at substantially slower rates than spontaneous labor, and support our previous contention that the criteria of labor arrest for 2 hours, despite at least 200 sustained Montevideo units, are insufficiently rigorous for the performance of cesarean.