Effectiveness of a rescue dose of antenatal betamethasone after an initial single course.

OBJECTIVE: To evaluate the effects of a single rescue dose of antenatal betamethasone after an initial single course on the frequency of neonatal respiratory distress syndrome and perinatal infectious morbidity in pregnancies complicated with preterm labor and delivery. STUDY DESIGN: We performed a cohort analysis of singleton pregnancies for which delivery occurred between 28 and 34 weeks' gestation after a single course of betamethasone administered before 28 weeks' gestation. Patients were then segregated into the following 2 groups on the basis of betamethasone exposure at the delivery admission: (1) a single 12-mg injection (rescue group) and (2) observation only (observation group). Patients who delivered infants within 24 hours of the rescue dose were excluded, as were those who had ruptured membranes for longer than 24 hours before delivery, those with diabetes that required insulin, and those with exposure to repeated doses of betamethasone before admission. Data were analyzed by use of the Student t test, chi2 test, and Fisher exact test. Multiple logistic regression was performed to examine the effect of each steroid dosing regimen on respiratory distress syndrome. Two-tailed P values <.05 were considered to be significant. RESULTS: A total of 152 patients were included, with 89 in the rescue group and 63 in the observation group. Both groups were similar with respect to maternal demographics, mean gestational age at the initial single course and at delivery, mode of delivery, and mean birth weights. Rescue administration was significantly associated with a reduction in the frequency of respiratory distress syndrome (odds ratio, 0.44; 95% confidence interval, 0.2 to 0.9) and mean ventilator days (odds ratio, 0.44; 95% confidence interval, 0.2 to 0.8) compared with observation alone. All other studied perinatal outcomes analyzed were similar between the groups. Multiple logistic regression confirmed an independent association between a single rescue dose and a reduction in the frequency of respiratory distress syndrome (odds ratio, 0.40; 95% confidence interval, 0.2 to 0.9). CONCLUSIONS: A single rescue dose of betamethasone is associated with a reduction in the frequency of respiratory distress syndrome without an apparent increase in perinatal infectious disease.

Prostaglandin inhibitors as tocolytic agents.

Indomethacin, a nonspecific prostaglandin synthetase inhibitor, gained popularity several decades ago as a potent tocolytic agent. This popularity, however, was tempered by concerns over fetal and neonatal complications associated with its use. However, with better recognition of the safety limitations, there has been a renewed interest in using indomethacin for acute tocolysis. More recently, the tocolytic potential of cyclooxygenase-2 (COX-2) specific inhibitors has gained much interest as well as the theoretical minimization of side effects associated with these agents. This article reviews the pharmacology and efficacy of indomethacin and some of the newer cyclooxygenase-2 inhibitors, and discusses the potential adverse fetal and neonatal effects associated with their use. Guidelines will be presented that will assist theclinician in using indomethacin as an effective tocolytic while avoiding untoward effects.

Scheduled cesarean delivery and the prevention of human immunodeficiency virus transmission: a survey of practicing obstetricians.

OBJECTIVE: To characterize practice patterns among obstetrician-gynecologists with respect to delivery for human immunodeficiency virus (HIV)-seropositive women, following publication of the 1999 American College of Obstetricians and Gynecologists (ACOG) Committee Opinion regarding scheduled cesarean delivery for HIV-infected patients. METHODS: A 25-question, multiple-choice survey was mailed to 2000 randomly selected obstetrician-gynecologists: 1000 maternal-fetal medicine specialists and 1000 general obstetrician-gynecologists. Mailing addresses were obtained from the 1999-2000 editions of the Society for Maternal-Fetal Medicine (SMFM) and ACOG membership directories. Information was requested about general perceptions of the 1999 ACOG Committee Opinion and about practice patterns with respect to management of HIV disease in pregnancy. Data were analyzed by using descriptive statistics and the chi-square test. Any P values <.05 were considered significant. RESULTS: After a single mailing we received 512 responses (25.6%), including 433 (43%) from SMFM members and 79 (8%) from ACOG members. Among the respondents, 47% disagreed with the current scientific validity of the 1999 ACOG Committee Opinion recommendation to offer cesarean delivery to all HIV-seropositive pregnant women. No statistically significant differences were detected in the demographic profiles, years of experience, or practice settings of participants who agreed with the scientific validity when compared to those who did not. Most respondents used viral load detection (87%) monitored on a trimester basis (67%) for clinical management decisions. Most practitioners (72%) do not recommend cesarean delivery for women who are compliant with antiretroviral therapy and who have undetectable viral loads regardless of CD4 counts. However, most practitioners (67%) do recommend cesarean delivery for those compliant women with detectable viral loads, irrespective of CD4 counts (67%). CONCLUSIONS: There is considerable disagreement among practicing obstetricians with respect to the 1999 ACOG Committee Opinion recommendation to offer cesarean delivery to all HIV-seropositive women. Most physicians use viral load detection to assist with the counseling in delivery options for HIV-infected pregnant women.

Antibiotic resistance patterns of group B streptococci in late third-trimester rectovaginal cultures.

OBJECTIVE: Our purpose was to determine the antibiotic sensitivity patterns of rectovaginal group B streptococcal isolates obtained from a heterogeneous obstetric population in the late third trimester. STUDY DESIGN: We performed a prospective observational study of rectovaginal group B streptococcal isolates obtained in the late third trimester during routine screening over a 12-month period. All cultures were prepared in a selective broth medium for 18 to 24 hours before plating onto sheep blood agar. Susceptibility testing of all isolates was performed for ampicillin, cefazolin, clindamycin, erythromycin, penicillin G, and vancomycin with the E-test method. RESULTS: A total of 2111 consecutive rectovaginal cultures were performed in which group B streptococci were isolated from 574 (27.2%) different patients. The "antibiogram" of the susceptible percentage is as follows: vancomycin, 100%; ampicillin, 98.2%; penicillin G, 98.2%; cefazolin, 98.1%; clindamycin, 92%; erythromycin, 81%. Ten isolates (1.8%) demonstrated intermediate susceptibility to both ampicillin and penicillin G. CONCLUSION: Routine susceptibility testing of group B streptococcal isolates collected during pregnancy should be considered because of the emergence of antibiotic resistance among group B streptococcal strains.

Is betamethasone effective longer than 7 days after treatment?

OBJECTIVE: To determine whether perinatal outcomes are influenced by the interval between antenatal betamethasone administration and delivery. METHODS: We did a retrospective cohort analysis of live-born singleton neonates born between 28 and 34 weeks' gestation after a single course of betamethasone, defined as two 12-mg doses over 24 hours. Subjects were grouped according to length of interval between initial betamethasone dose and delivery (1-2 days, 3-7 days, and 8-14 days). We excluded women who had membranes ruptured for longer than 24 hours before delivery, delivery before the second dose of betamethasone, or more than two doses of betamethasone. Data were analyzed by Student t test, chi(2) test, or Fisher exact test. Multiple logistic regression analyses were done using suspected risk factors for respiratory distress syndrome (RDS) and intraventricular hemorrhage (IVH). We calculated that a sample of 200 women would provide more than 80% power to detect a 50% reduction in incidence of RDS for a two-sided test of significance at a critical level of.05. RESULTS: Among 216 women, 97 delivered in 1-2 days, 78 in 3-7 days, and 41 in 8-14 days after a single course of betamethasone. Groups were similar in selected demographics, tocolytic exposure, gestational age at delivery, modes of delivery, and mean birth weights. There were no significant differences in frequencies of RDS (39.2%, 41.1%, and 36.6%, respectively) or grades 3-4 IVH (1.1%, 1.3%, and 0%, respectively) between groups. Frequencies of selected perinatal infectious outcomes also were similar between groups. Multiple logistic regression analyses found no association between RDS or IVH and delivery more than 7 days from betamethasone therapy. CONCLUSION: There were no differences in perinatal outcomes in pregnancies delivered 8-14 days after antenatal exposure to betamethasone compared with those delivered within 7 days of exposure.

Neonatal sepsis and death after multiple courses of antenatal betamethasone therapy.

OBJECTIVE: This study was undertaken to compare the effects of single versus multiple courses of betamethasone therapy on the frequencies of neonatal outcomes and perinatal infectious morbidity among singleton pregnancies complicated by preterm delivery. STUDY DESIGN: We performed a nonconcurrent prospective analysis of singleton pregnancies delivered between 24 and 34 weeks' gestation after antenatal betamethasone exposure. Patients were categorized into two groups according to betamethasone exposure: (1) two 12-mg doses in a 24-hour interval on admission (single-course group) and (2) repeated dosing after the initial single course (multiple-course group). All patients received prophylactic antibiotics for group B streptococci. Any patients with ruptured membranes for >24 hours before delivery were excluded. Data were analyzed with the Student t test, the chi(2) test, and the Fisher exact test. Multiple logistic regression analyses were performed to examine the effect of each steroid dosing regimen on early-onset neonatal sepsis and neonatal death. P <.05 was considered significant for all 2-tailed tests. RESULTS: A total of 453 patients were included, with 267 in the single-course group and 186 in the multiple-course group. The two groups were similar with respect to maternal demographic characteristics, gestational age at delivery, mode of delivery, birth weight, and maternal group B streptococcal colonization. Multiple courses were significantly associated with early-onset neonatal sepsis (odds ratio, 5.00; 95% confidence interval, 1.3-23. 2), chorioamnionitis (odds ratio, 9.96; 95% confidence interval, 2. 1-64.6), endometritis (odds ratio, 3.61; 95% confidence interval, 1. 7-8.1), and neonatal death (odds ratio, 2.92; 95% confidence interval, 1.3-6.9). The frequencies of the other neonatal outcomes analyzed, including respiratory distress syndrome and grade III or IV intraventricular hemorrhage, were similar between the 2 groups. Multiple logistic regression analyses confirmed that multiple courses of antenatal betamethasone were independently associated with early-onset neonatal sepsis (odds ratio, 1.25; 95% confidence interval, 1.1-1.9) and neonatal death (odds ratio, 1.70; 95% confidence interval, 1.1-1.9). CONCLUSIONS: Multiple courses of antenatal betamethasone are associated with increased risks of perinatal infectious morbidity and neonatal death.

Validation of bioimpedance estimates of cardiac output in preeclampsia.

OBJECTIVE: We sought to evaluate the capacity of a new thoracic electric bioimpedance system to estimate cardiac output in patients with preeclampsia. STUDY DESIGN: We performed a prospective comparison of thoracic electric bioimpedance and echocardiographic M-mode volumetric estimates of cardiac output (in liters per minute) in preeclampsia. Subjects with preeclampsia who were chosen by means of strict criteria (either a systolic blood pressure >/=140 mm Hg or a diastolic blood pressure 90 mm Hg, or both, and proteinuria >/=300 mg in 24 hours or >/=+1 on repeat dipstick measurement 6 hours apart) were asked to participate in an institutional review board-approved study. Thoracic electric bioimpedance and echocardiography were performed with the patients in the left lateral recumbent position. Thoracic electric bioimpedance estimates were recorded at bedside; investigators were blinded to 3 simultaneously obtained echocardiographic M-mode estimates of cardiac output. Means were entered as the estimate for each patient. To satisfy the assumption of independent samples, only 1 estimate from each technique was used for each patient. Data were analyzed by Bland-Altman comparison. Hemodynamic and demographic variables are presented as mean +/- SD. RESULTS: Fifteen patients were enrolled. Mean maternal age was 25.9 +/- 4.8 years, and mean gestational age was 34.0 +/- 3.5 weeks. Mean arterial pressure was 112 +/- 14 mm Hg. There was good agreement of thoracic electric bioimpedance-derived and M-mode-derived cardiac output estimates. CONCLUSIONS: In patients with preeclampsia, thoracic electric bioimpedance estimates of cardiac output compare well with echocardiographic M-mode estimates.

Effectiveness of antenatal corticosteroid administration after preterm premature rupture of the membranes.

OBJECTIVE: This study was undertaken to determine the effect of antenatal betamethasone administration on the incidences of respiratory distress syndrome, intraventricular hemorrhage, and perinatal infectious morbidity in the setting of preterm premature rupture of membranes. STUDY DESIGN: We performed a nonconcurrent prospective analysis of women with singleton pregnancies who were delivered between 24 and 32 weeks' gestation after preterm premature rupture of membranes. Patients were subdivided into 2 groups according to betamethasone exposure: (1) none (control group) and (2) two 12-mg doses in a 24-hour interval on admission (single-course group). Patients who received >2 doses of betamethasone were excluded. All patients received broad-spectrum prophylactic antibiotics. Data were analyzed with the Student t test, the chi(2) test, and the Fisher exact test. Multiple logistic regression analyses incorporated multiple variables considered risk factors for respiratory distress syndrome and intraventricular hemorrhage. P <.05 for all 2-tailed tests was considered significant. RESULTS: A total of 362 patients were included, with 203 in the control group and 159 in the single-course group. Patients in these groups were delivered at 31.0 +/- 3.0 and 30.2 +/- 2.7 (mean +/- SD) weeks' gestation, respectively. The groups were similar with respect to selected demographic characteristics, latency until delivery, mode of delivery, birth weight, and maternal group B streptococcal colonization status. Univariate analysis demonstrated significant decreases in the frequencies of both respiratory distress syndrome (odds ratio, 0.31; 95% confidence interval, 0.2-0.5) and grade III/IV intraventricular hemorrhage (odds ratio, 0.14; 95% confidence interval, 0.1-0.6) in the single-course group. The frequencies of early neonatal sepsis, chorioamnionitis, endometritis, and neonatal death were similar between groups. Multiple logistic regression analyses determined that a single course of betamethasone was independently associated with reductions in the frequencies of both respiratory distress syndrome (odds ratio, 0.16; 95% confidence interval, 0.1-0.4) and grade III/IV intraventricular hemorrhage (odds ratio, 0.18; 95% confidence interval, 0.1-0.4). CONCLUSIONS: A single course of betamethasone administered antenatally to patients with preterm premature rupture of membranes was associated with decreases in the frequencies of both respiratory distress syndrome and advanced grades of intraventricular hemorrhage without any increase in perinatal infectious morbidity.

Elevated circulating concentrations of platelet activating factor in preeclampsia.

OBJECTIVE: The aim of this study was to determine whether any association exists between preeclampsia and circulating platelet activating factor levels. STUDY DESIGN: We performed a cross-sectional observational study of circulating platelet activating factor concentrations in nonpregnant women, normotensive pregnant women in the third trimester, women with preeclampsia in the third trimester, and normotensive men. Platelet activating factor concentrations were measured with a commercially available platelet activating factor-specific radioimmunoassay (NEN Life Science Products, Inc, Boston, Mass). The primary outcome measure was the difference in mean platelet activating factor concentrations among the 4 study groups. Preeclampsia was determined according to the criteria of The American College of Obstetricians and Gynecologists. Data were analyzed with the Student t test, the chi(2) test, the Fisher exact test, analysis of variance, and the Tukey test for pairwise multiple comparisons, with significance established at P <.05. RESULTS: The mean (+/-SD) circulating concentration of platelet activating factor was significantly higher in the group with preeclampsia (338.1 +/- 26.9 ng/mL) than in either the normotensive pregnant group (217.9 +/- 25.9 ng/mL; P <.05) or the nonpregnant female group (237.9 +/- 20.9 ng/mL; P <.05). The 2 pregnant groups were similar with respect to selected demographic characteristics and gestational age at time of collection. There were no significant differences in the mean platelet activating factor concentrations between the group with preeclampsia and the normotensive male group or between the normotensive pregnant female group and the nonpregnant female group. CONCLUSION: Circulating platelet activating factor concentrations were increased in women with pregnancies complicated by preeclampsia with respect to those in normotensive pregnant women and normotensive nonpregnant women. Platelet activating factor may therefore serve as a marker for the risk of preeclampsia.

Amniotic fluid index values after preterm premature rupture of the membranes and subsequent perinatal infection.

OBJECTIVE: Our purpose was to determine whether an amniotic fluid index (AFI) <5 cm after preterm premature rupture of the membranes is associated with an increased risk of perinatal infection. STUDY DESIGN: We performed a nonconcurrent prospective analysis of 225 singleton pregnancies complicated by preterm premature rupture of the membranes, with delivery between 24 and 32 weeks' gestation. All included patients received 2 doses of betamethasone antenatally, in the first 24 hours after admission, and broad-spectrum antibiotic prophylaxis. Patients were categorized into 2 groups on the basis of a 4-quadrant AFI <5 cm (n = 131) or > or =5 cm (n = 94). Perinatal outcomes analyzed included latency until delivery, mode of delivery, and frequencies of clinical chorioamnionitis, postpartum endometritis, and culture-proved early neonatal sepsis. Continuous data were evaluated for normal distribution and tested for significance with the Student t test. Categoric data were tested with the chi(2) and Fisher exact tests. Multiple logistic regression analyses were performed with chorioamnionitis, endometritis, and early-onset neonatal sepsis each as the dependent variable in separate analyses. All 2-sided P values <.05 were considered significant. RESULTS: Both groups were similar with respect to selected demographics, gestational age at rupture of the membranes, birth weight, and maternal group B streptococcal colonization. Patients with an AFI <5 cm demonstrated a shorter mean latency until delivery (5.5 +/- 4.0 vs 14.1 +/- 5.2) (mean +/- SD) days (P =.02), greater frequency of amnioinfusion therapy (23.6% vs 5.3%) (P <.001), and cesarean delivery for nonreassuring fetal testing (18.3% vs 4. 3%) (P =.01). Multiple logistic regression analysis showed that an AFI <5 cm was the only significant risk factor independently associated with early-onset neonatal sepsis (P =.004) and chorioamnionitis (P =.024). CONCLUSIONS: An AFI <5 cm after preterm premature rupture of the membranes between 24 and 32 weeks' gestation is associated with an increased risk of perinatal infection and a shorter latency preceding delivery.

Late third-trimester treatment of rectovaginal group B streptococci with benzathine penicillin G.

OBJECTIVE: We sought to determine the efficacy of late third-trimester benzathine penicillin G administration in eradicating maternal group B streptococcal colonization at delivery. STUDY DESIGN: We performed a prospective trial of late third-trimester treatment with benzathine penicillin G versus observation in 78 obstetric patients colonized with group B streptococci. Patients were screened by use of rectovaginal swabs cultured in selective media between 34 and 37 completed weeks' gestation. Patients with positive cultures were offered antepartum treatment with 4.8 million units of intramuscular benzathine penicillin G or observation. Participants in both groups were recultured at their delivery admission before receiving standard intrapartum therapy. The primary outcome was the frequency of persistent maternal group B streptococcal colonization at the delivery admission. Other outcome variables included semiquantitative growth characteristics of all group B streptococcal cultures, the frequency of neonatal sepsis, and adverse maternal effects. Data were analyzed by the Student t test for continuous variables and the chi(2) or Fisher exact test for categoric variables, with significance established at P <.05. RESULTS: Both groups were similar with respect to selected demographics, gestational age at delivery, and frequency of heavy group B streptococcal growth in initial screening cultures. The mean interval from treatment until delivery was 19.4 +/- 7.5 days (mean +/- SD). There were no cases of neonatal sepsis in either group or any adverse maternal effects attributed to the treatment. Group B streptococcal culture characteristics at delivery admission were as follows. Positive results for group B streptococci were found in 7 (25%) treated patients and 41 (82%) patients under observation (relative risk, 0.30; 95% confidence interval, 0.16-0.59; P <.0001). Positive results for heavy growth of group B streptococci were found in 0 (0%) treated patients and 31 (62%) patients under observation (relative risk, 0.01; 95% confidence interval, 0.00-0.12; P <.0001). CONCLUSIONS: Treating group B streptococci carriers with benzathine penicillin G in the late third trimester eradicates or significantly reduces maternal group B streptococcal colonization at delivery. This may provide an adjuvant therapy to those mothers at risk for receiving inadequate intrapartum antibiotic prophylaxis against group B streptococci.

Wound infection after cesarean: effect of subcutaneous tissue thickness.

OBJECTIVE: To estimate the effect of the thickness of subcutaneous tissue at the surgery site on abdominal wound infection after cesarean delivery. METHODS: We measured the maximum vertical depths of subcutaneous incisions of women who had cesarean deliveries. The surgical technique for closure was standardized and drains were not used. Abdominal wound infection was defined by standard criteria and limited to the first 6 postoperative weeks. Additional demographic, intrapartum, and perioperative data previously associated with wound infection also were collected. Data were analyzed by Student t test, chi(2) test, and multiple logistic regression. RESULTS: Wound infection occurred in 11 of 140 women (7.8%) who delivered by cesarean. Risk factors identified as significantly associated with wound infection by univariate analysis were thickness of subcutaneous tissue, maternal weight, and body mass index. Multiple logistic regression analysis confirmed subcutaneous tissue thickness as the only significant risk factor for wound infection, with a relative risk of 2.8 (95% confidence interval 1.3, 5.9). There were no significant differences between women who developed wound infections and those without infections in terms of selected demographics, duration of ruptured membranes, number of vaginal examinations, chorioamnionitis, type of skin incision, or duration of surgery. CONCLUSION: Thickness of subcutaneous tissue appears to be the only significant risk factor associated with abdominal wound infection after cesarean delivery.

Adolescents and sexually transmissible diseases.

Sexually transmitted infections are alarmingly common among adolescents in the United States. Behavioral, biologic, and health care access factors place adolescent girls at high risk for many common infections. This population also experiences a disproportionate burden related to the sequelae of STDs. The costs are high for the individual adolescent and for society. Clinicians treating adolescent girls should address the general lack of knowledge about the risks and consequences of STDs. They should be prepared to offer confidential and comprehensive counseling, screening, and treatment according to established guidelines. Office policies that protect adolescent confidentiality are an important component in providing effective care. Adolescence is a period during which lifelong health behaviors are established. It provides a critical opportunity for promoting responsible behaviors and reducing risks through health promotion and prevention strategies.

Recent indomethacin tocolysis is not associated with neonatal complications in preterm infants.

OBJECTIVE: We sought to determine whether indomethacin tocolysis immediately before delivery is associated with any increased complications in neonates delivered between 24 and 32 weeks' gestation. STUDY DESIGN: We performed a case-control analysis of neonates delivered between 24 and 32 weeks' gestation after maternal indomethacin treatment for preterm labor. All infants were delivered within 48 hours of indomethacin exposure. Seventy-five patients were matched with 150 control subjects in a patient/control ratio of 1:2. Matching variables in order of priority included gestational age at delivery, fetal number, betamethasone exposure >24 hours before delivery, magnesium sulfate use, mode of delivery, infant sex, and race. Data were analyzed by using the Student t test, chi(2) analysis, and the Fisher exact test and Yates' correction. RESULTS: The gestational age at delivery (mean +/- SD) was 28.7 +/- 2.3 weeks in the indomethacin group and 28.3 +/- 2.1 weeks for the control subjects. Birth weights (mean +/- SD) were 1121 +/- 243 and 1141 +/- 287 g, respectively. All mothers received both magnesium sulfate and betamethasone before delivery. The median cumulative dose of indomethacin was 225 mg. The median interval from last dose of indomethacin until delivery was 12 hours. There were no significant differences between the groups in the incidence of necrotizing enterocolitis (odds ratio, 1.12; 95% confidence interval, 0.31-3.84), grade III/IV intraventricular hemorrhage (odds ratio, 0.37; 95% confidence interval, 0.10-1.19), patent ductus arteriosus (odds ratio, 0.85; 95% confidence interval, 0.44-1.64), bronchopulmonary dysplasia (odds ratio, 0.97; 95% confidence interval, 0.49-1.91), pulmonary hypertension (odds ratio, 0.49; 95% confidence interval, 0. 02-4.80), anuria (odds ration, 1.21; 95% confidence interval, 0.22-6. 01), thrombocytopenia (odds ratio, 1.14; 95% confidence interval, 0. 53-2.42), sepsis (odds ratio, 1.21; 95% confidence interval, 0.22-6. 01), or neonatal death (odds ratio, 1.34; 95% confidence interval, 0. 55-3.25). CONCLUSION: Maternal indomethacin exposure immediately before delivery was not associated with increased neonatal complications for infants delivered between 24 and 32 weeks' gestation.

A randomized, double-blind trial of oral nifedipine and intravenous labetalol in hypertensive emergencies of pregnancy.

OBJECTIVE: We sought to compare the efficacies of oral nifedipine and intravenous labetalol in the acute management of hypertensive emergencies of pregnancy. STUDY DESIGN: We performed a randomized double-blind trial of oral nifedipine (10 mg) and intravenous labetalol (20 mg) in 50 peripartum patients with sustained systolic blood pressure of >/=170 mm Hg or diastolic blood pressure of >/=105 mm Hg. Both agents were repeated at sequentially escalating dosages every 20 minutes until a therapeutic goal of systolic blood pressure of <160 mm Hg and diastolic blood pressure of <100 mm Hg was achieved. Crossover occurred if the treatment goal was not achieved after 5 doses. Primary outcome was time to achievement of the therapeutic goal. Secondary outcome variables were agent failure, urinary output, and adverse effects. Data were analyzed by unpaired t test, Mann-Whitney U test, and analysis of variance for repeated measures. RESULTS: The time to achieve the blood pressure goal was significantly shorter with nifedipine (mean +/- SD, 25 +/- 13.6 minutes) than with labetalol (43.6 +/- 25.4 minutes; P =.002). No patients required crossover therapy. Urine output was significantly increased (P <.001) at 1 hour after nifedipine dosing (99 +/- 99 mL) compared with labetalol (44.8 +/- 19.1 mL) and remained significantly increased at 2, 6, 12, 18, and 24 hours after initial administration. Adverse effects were infrequent. There were no differences in maternal age, gestational age, number of antepartum patients, or enrollment blood pressures between groups. CONCLUSIONS: Both oral nifedipine and intravenous labetalol are effective in the management of acute hypertensive emergencies of pregnancy; however, nifedipine controls hypertension more rapidly and is associated with a significant increase in urinary output.

A randomized, double-blind, hemodynamic evaluation of nifedipine and labetalol in preeclamptic hypertensive emergencies.

OBJECTIVE: Our purpose was to compare the hemodynamic effects of orally administered nifedipine and intravenously administered labetalol in preeclamptic hypertensive emergencies. STUDY DESIGN: Our study was a randomized, double-blind evaluation of nifedipine and labetalol in women with preeclampsia and a systolic blood pressure >170 mm Hg or a diastolic blood pressure >105 mm Hg. Nifedipine or labetalol and placebo were given, so patients received both tablet and intravenous solution. Hemodynamic parameters at dosing and at 15, 30, 60, and 120 minutes were recorded. Outcome measures were cardiac index, systemic vascular resistance index, mean arterial pressure, and heart rate. Data were analyzed by repeated-measures analysis of variance (Friedman test) with Dunn posttests, the Mann-Whitney U test, and the chi(2) test with the Yates correction. Significance was set at P <.05. RESULTS: At dosing, the nifedipine group (n = 6) had a cardiac index of 3.08 +/- 0.51 L/min per square meter. There was a 43% increase in the cardiac index after nifedipine administration (P =.0008). There was no significant effect in the labetalol group (P =.697). There was a significant decrease in the systemic vascular resistance index after nifedipine dosing (P =.002) but no significant effect on this index after labetalol use (P =.479). The mean arterial pressure was significantly affected in both groups as follows: nifedipine, P =. 001; labetalol, P =.004. The postanalysis showed significance at 60 minutes for both. An insignificant increase in heart rate with nifedipine (P =.147) and a significant decrease with labetalol (P =. 034) were noted. CONCLUSIONS: Nifedipine increases cardiac index, whereas labetalol may not do so.

Neonatal sepsis after betamethasone administration to patients with preterm premature rupture of membranes.

OBJECTIVE: We sought to determine the effect of antenatal betamethasone exposure on the incidence of early onset neonatal sepsis in patients with preterm premature rupture of membranes. STUDY DESIGN: We performed a nonconcurrent prospective analysis of infants delivered between 24 and 34 weeks' gestation after preterm premature rupture of membranes. Patients with preterm premature rupture of membranes were categorized into 3 groups on the basis of the following betamethasone exposures: (1) none (control subjects), (2) two 12-mg doses in a 24-hour interval on admission (single course), and (3) weekly administration after the initial single course (multiple courses). All included patients received prophylactic antibiotics for group B streptococci. Discrete data were tested for significance with the chi(2) test. Continuous data were tested for significance with an analysis of variance. Multiple logistic regression analysis was performed to determine the confounding effect of the multiple variables that were considered risk factors for early-onset neonatal sepsis. All P values of <.05 were considered significant. RESULTS: Three hundred seventy-four patients with preterm premature rupture of membranes were included, 203 of whom were evaluated in the control group, 99 in the single-course group, and 72 in the group receiving multiple courses of betamethasone. Early-onset neonatal sepsis was significantly associated with multiple courses of corticosteroids (P <.001) and gestational age (P =.002). Multiple courses of antenatal betamethasone were significantly associated with chorioamnionitis (P =.004) and endometritis (P =.004). Single-course corticosteroid administration was not significantly associated with any maternal or neonatal infectious complications. CONCLUSIONS: Multiple courses of antenatal betamethasone administered to patients with preterm premature rupture of membranes is associated with an increased risk of early-onset neonatal sepsis development.

A randomized, double-blind, placebo-controlled trial of 5-fluorouracil for the treatment of cervicovaginal human papillomavirus.

OBJECTIVE: To compare intravaginal 5-fluorouracil (5-FU) and placebo for the treatment of cervical and/or vaginal human papillomavirus (HPV). METHODS: A randomized, placebo-controlled trial was performed. Women with HPV detected visually or by Papanicolaou (Pap) test and confirmed by colposcopic biopsy were randomized to receive either intravaginal 5-FU cream or an intravaginal placebo cream. Women with cervical or vaginal intraepithelial neoplasia were excluded. The primary outcome measure was cytologic regression of HPV as determined by Pap test screening 4 to 6 months after treatment. The secondary outcome was cytologic evidence of disease progression at both the 4-6-month and 12-month follow-up evaluations. Data were analyzed using the Chi square test with significance established at P < 0.05. RESULTS: A total of forty patients were randomized, and thirty patients had a follow-up Pap test 4 to 6 months after treatment. Of those patients treated with 5-FU, 28% demonstrated regression of HPV on cytologic evaluation, compared with 69% of those treated with placebo (P < 0.05). Twelve-month follow-up cytology was available from 18 of the study participants. There were no significant differences in the frequency of cytologic progression or regression between groups at 12 months. CONCLUSION: Four to six months post treatment, the use of intravaginal 5-FU for the treatment of cervical or vaginal HPV is associated with a lower rate of regression than the use of placebo.

The effect of indomethacin tocolysis on fetal ductus arteriosus constriction with advancing gestational age.

OBJECTIVE: Our purpose was to determine whether continuing exposure to indomethacin tocolysis is associated with an increased incidence of constriction of the human fetal ductus arteriosus with advancing gestational age. STUDY DESIGN: Fetal echocardiograms were reviewed in 61 cases in which the pregnant women were treated for preterm labor with indomethacin (25 mg orally every 6 hours). Density function analysis and regression analysis were used to assess the effect of indomethacin tocolysis on ductal constriction with advancing gestational age. RESULTS: A total of 193 fetal echocardiograms were obtained for 72 fetuses. Ductal constriction developed in 50% of the fetuses ranging from 24.7 to 35.0 weeks' gestation. Fetuses with indomethacin-induced ductal constriction demonstrated a greater increase in systolic flow velocities with advancing gestational age compared with the nonconstricted group (p < 0.05). Constriction was detected at a mean gestational age of 30.9 +/- 2.3 weeks at an average of 5.1 +/- 6.0 days after initiation of therapy. Ductal constriction occurred by 31 weeks' gestation in 70% of the affected fetuses. After discontinuation of indomethacin therapy, all follow-up echocardiograms demonstrated a return to nonconstricted ductal flow velocities. No significant adverse neonatal outcomes were attributed to indomethacin use. CONCLUSIONS: A dramatic yet reversible increase in the incidence of indomethacin-induced ductal constriction occurs at 31 weeks' gestation. However, ductal constriction can occur at any gestational age. With indomethacin tocolysis, weekly fetal echocardiography is warranted for the duration of therapy.