The Preterm Prediction Study: association between cervical interleukin 6 concentration and spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: The aim of this study was to determine the interrelationship between cervical concentration of interleukin 6 and detection of fetal fibronectin and other risk factors for spontaneous preterm birth. STUDY DESIGN: All patients with spontaneous preterm birth at <35 weeks' gestation (case patients; n = 125) and subjects matched for race, parity, and center delivered at > or = 37 weeks' gestation (n = 125; control subjects) were selected from women enrolled in the National Institute of Child Health and Human Development's Preterm Prediction Study. Interleukin 6 concentrations were determined by enzyme-linked immunosorbent assay in cervical swabs obtained at 22 weeks' to 24 weeks 6 days' gestation. Cutoffs to define an elevated interleukin 6 concentration included the 90th and 95th percentiles for control subjects (>305 and >538 pg/mL, respectively). RESULTS: The mean (+/-SD) interleukin 6 concentration was significantly higher in case patients than in control subjects (212 +/- 339 vs 111 +/- 186 pg/mL; P = .008). With either cutoff value elevated interleukin 6 concentration was significantly associated with spontaneous preterm birth (90th percentile, 20% vs 9.6%; P = .02; 95th percentile, 12% vs 4.8%; P = .04). Cervical interleukin 6 levels were highest within 4 weeks of delivery, and the trend continued until term. Elevated interleukin 6 concentration was not significantly associated with bacterial vaginosis, maternal body mass index <19.8 kg/m2, or a short cervix (< or = 25 mm), but it was significantly associated with a positive cervicovaginal fetal fibronectin test result (90th percentile, odds ratio, 5.5; 95% confidence interval, 2.6-11.9; 95th percentile, odds ratio, 5.3, 95% confidence interval, 2.1-12.9). The mean interleukin 6 concentration among women with a positive fibronectin test result was 373 +/- 406 pg/mL; that among women with a negative fetal fibronectin test result was 130 +/- 239 pg/mL (P = .001). In a regression analysis that adjusted for risk factors significantly associated with spontaneous preterm birth in this population (positive fetal fibronectin test result, body mass index <19.8 kg/m2, vaginal bleeding in the first or second trimester, previous spontaneous preterm birth, and short cervix) elevated cervical interleukin 6 concentration was not independently associated with spontaneous preterm birth (odds ratio, 1.8; 95% confidence interval, 0.8-4.3). CONCLUSIONS: At 24 weeks' gestation cervical interleukin 6 concentration in women who subsequently had a spontaneous preterm birth at <35 weeks' gestation was significantly elevated relative to those who were delivered at term. The association was particularly strong within 4 weeks of testing. A positive fetal fibronectin test result was strongly associated with elevated cervical interleukin 6 concentration, but bacterial vaginosis was not.

Evaluation of a new testing policy for human immunodeficiency virus to improve screening rates.

OBJECTIVE: To assess the effect of a change in human immunodeficiency virus (HIV) testing policy on HIV testing rates in an urban maternity clinic population. METHODS: Since 1995, our institution has provided pretest counseling and voluntary HIV testing to all pregnant women. After the 1999 Institute of Medicine recommendation of HIV testing with patient notification as a routine component of prenatal care, we conducted a prospective study to determine whether this policy would increase our HIV screening rates. The intervention incorporated HIV testing into the routine battery of tests drawn at antenatal care. Not to be tested required active refusal. The intervention group was comprised of all women receiving an initial antenatal visit in one of our eight maternity clinics between August 1, 1999, and July 30, 2000. The control group was comprised of all women presenting for prenatal care in the same clinics during the year before the intervention. RESULTS: The 3415 women in the intervention group and 3778 controls were similar with respect to most demographic and risk factors. After the intervention, HIV testing increased from 75% to 88% (P <.001). Among all women in both years of the study, women who were in the intervention group, less than 20 years of age, or who had a history of substance abuse, were more likely not to refuse testing. CONCLUSION: After implementation of a policy of routine HIV testing with active patient refusal, HIV testing rates increased among pregnant women in our large, urban obstetric clinic population.

The preterm prediction study: quantitative fetal fibronectin values and the prediction of spontaneous preterm birth. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: A cervicovaginal fetal fibronectin value of >/=50 ng/mL has been used to define women at risk of having a preterm birth. We evaluated the relationship between quantitative fetal fibronectin values and spontaneous preterm birth. STUDY DESIGN: Cervical and vaginal specimens for fetal fibronectin were obtained at 24, 26, 28, and 30 weeks' gestation from 2926 women. Quantitative fetal fibronectin values were calculated by using absorbances determined by enzyme-linked immunosorbent assay. The highest fetal fibronectin value (cervical or vaginal) for each woman at each visit was evaluated in relation to spontaneous preterm birth at <35 weeks' gestation. Receiver operating characteristic curves were constructed to determine the optimal cutoff point for fetal fibronectin values to predict spontaneous preterm birth at <35 weeks' gestation and within 4 weeks of testing. RESULTS: The risk of spontaneous preterm birth increased as a function of increasing fetal fibronectin values from approximately 20 to 300 ng/mL. Fetal fibronectin values > or =300 ng/mL were not associated with a further increase in spontaneous preterm birth. Examination of the receiver operating characteristic curve indicates that the optimal cutoff point for a positive fetal fibronectin test result at 24 to 30 weeks' gestation to predict spontaneous preterm birth at <35 weeks is between 45 and 60 ng/mL. CONCLUSION: Increasing levels of cervicovaginal fetal fibronectin up to 300 ng/mL are associated with an increasing risk of spontaneous preterm birth. Nevertheless, at 24 to 30 weeks, the value currently used, 50 ng of fetal fibronectin per milliliter, appears to be a reasonable cutoff point for predicting spontaneous preterm birth at <35 weeks' gestation.

Extra-amniotic saline, laminaria, or prostaglandin E(2) gel for labor induction with unfavorable cervix: a randomized controlled trial.

OBJECTIVE: To determine which of three methods of cervical ripening resulted in the lowest cesarean rate in women with unfavorable cervices and indications for labor induction. METHODS: Consenting women with singleton gestations, vertex presentations, and unfavorable cervices (dilatation under 2 cm and effacement under 75%) were randomly assigned to laminaria and standard intravenous oxytocin, serial doses of intracervical prostaglandin (PG) E(2) gel (Prepidil, Pharmacia & Upjohn, Inc., Kalamazoo, MI) 0.5 microg every 6 hours for two doses followed by oxytocin if indicated, or extra-amniotic saline infusion and oxytocin. RESULTS: An interim analysis after recruitment of 321 subjects, 67% of the planned sample, found similar cesarean rates for the three groups (laminaria 36%; PGE(2) gel 33%; saline infusion 29%; P =.59); however, the mean randomization-to-delivery interval was significantly longer in the PGE(2) group. Stochastic curtailment, as part of the interim analysis, indicated a low likelihood of achieving a statistically significant difference in cesarean rates between PGE(2) gel and the other two groups. Therefore, we completed the study with saline infusion and laminaria. The saline infusion and laminaria groups had similar preinduction characteristics. The cesarean rates were similar (saline infusion 25.4% versus laminaria 30.3%; P =.32), but the mean interval from randomization to delivery was shorter in the saline infusion group (18.0 versus 21.5 hours, P =.002). There were no significant differences in selected maternal and neonatal morbidities. CONCLUSION: Cervical ripening with extra-amniotic saline infusion, PGE(2), or laminaria resulted in comparable cesarean rates in women with an unfavorable cervix and indications for labor induction. Extra-amniotic saline infusion had the shortest randomization-to-delivery interval without increasing maternal or neonatal morbidity.

Obstetrical determinants of neonatal neurological morbidity in < or = 1000-gram infants.

The purpose of this study is to identify obstetrical factors associated with adverse neurological outcome in < or =1000-g infants. In a 1-year (1992-1993) observational study, the NICHD MFMU Network collected obstetrical risk factors for 486 infants who weighed < or =1000 g at birth and who survived > 2 days. Infants' records were abstracted for seizures, intraventricular hemorrhage, and an abnormal neurological evaluation. Seventy-nine (16%) infants had a Grade III or IV intraventricular hemorrhage, 46 (9%) developed seizures and 57 (14%) had an abnormal neurological evaluation. Both lower birth weight and earlier gestational age correlated (P <0.01) with an increasing incidence of all three outcomes. Several other factors appeared to be associated with neurological morbidity, however, after controlling for potential confounders in the multivariate analyses, most of these factors were no longer significant. African-American race, odds ratio (OR) 0.6 (0.3-1.0), and severe preeclampsia, OR 0.2 (0.1-0.7), were protective against intraventricular hemorrhage. Maternal treatment with corticosteroids did not impact neurological outcome in this study population. We conclude that, in a population of < or =1000-g infants, lower birth weight and earlier gestational age were the only consistently significant predictors of all three adverse neurological outcomes.

Choriodecidual inflammation: a potentially preventable cause of perinatal HIV-1 transmission?

The obstetric risk factors for perinatal transmission of HIV-1 include preterm birth, prolonged rupture of the chorioamniotic membranes, and clinical and histological bacterial chorioamnionitis. A chronic chorioamnionitis precedes many cases of preterm labour and spontaneous rupture of membranes, whereas an acute chorioamnionitis is more common after rupture of the membranes at term. Amniotic fluid cytokines are raised in the presence of term and preterm intrauterine bacterial infections, and various cytokines seem able to attract HIV-1-infected leucocytes into the amniotic cavity and to increase replication of HIV-1. We postulate that the association of preterm birth and prolonged rupture of membranes with perinatal transmission of HIV-1 may result from an associated chronic or acute bacterial chorioamnionitis marked by the migration of HIV-1-infected maternal leucocytes into the amniotic cavity. Antibiotic treatment could prevent this sequence of events.

Terbutaline pump maintenance therapy for prevention of preterm delivery: a double-blind trial.

OBJECTIVE: This study's aim was to determine whether maintenance therapy with terbutaline administered by pump prolongs gestation in women after treatment with intravenous magnesium sulfate tocolysis for suspected preterm labor. STUDY DESIGN: Consenting women with a singleton gestation and intact membranes who had uterine contractions and >1 cm cervical dilation, 80% effacement, or progressive cervical change and whose contractions were successfully arrested with intravenous magnesium were randomly assigned to receive either terbutaline or normal saline solution placebo by subcutaneous infusion pump. Pump therapy was administered with a standardized protocol. Pump therapy was discontinued and parenteral magnesium was resumed if recurrent preterm labor developed while women were on the therapeutic regimen at <34 weeks' gestation and no contraindication for tocolysis existed. If recurrent labor was arrested, pump therapy was restarted according to the original treatment group. A sample size of 48 women was required to detect a 2-week intergroup difference in mean time to delivery. Analyses were based on intent to treat. RESULTS: Fifty-two women received terbutaline (n = 24) or placebo (n = 28). At random assignment the groups were similar with respect to age, race, parity, previous preterm delivery, gestational age, and cervical examination. Overall there was a 1-day difference in mean time to delivery between the groups (terbutaline 29 +/- 22 days and placebo 28 +/- 23 days, P = .78). There were no differences in the rates of preterm delivery at <34 and <37 weeks' gestation. Neonatal outcomes were similar. CONCLUSIONS: Maintenance terbutaline therapy administered by pump does not prolong gestation in women successfully treated for suspected preterm labor.

Management options in women with preterm uterine contractions: a randomized clinical trial.

OBJECTIVE: Our purpose was to evaluate three management strategies and to assess pregnancy outcomes in women with preterm uterine contractions. STUDY DESIGN: Consenting women seen in our hospital triage area with preterm uterine contractions were randomly assigned to observation alone, intravenous hydration, or one dose of subcutaneous terbutaline sulfate (0.25 mg). Eligible women had a singleton gestation between 20 and 34 weeks, intact membranes, more than three contractions in 30 minutes, and a cervical dilation < or = 1 cm and effacement < 80%. Women who had progressive cervical change at < 34 weeks were treated with intravenous tocolysis. Women with recurrent preterm uterine activity remained in their assigned group during subsequent triage visits. RESULTS: One hundred seventy-nine women were randomized: observation (56), hydration (62), and terbutaline (61). Women in these three groups were similar with respect to maternal age, race, parity, prior preterm births, gestational age at randomization, contraction frequency, and mean cervical dilatation. There were no intergroup differences in the mean days to delivery, the number of repeat triage visits, the incidence of preterm labor at < 34 weeks, or the frequency of preterm deliveries at < 34 weeks and < 37 weeks. Women assigned to terbutaline had contractions stopped and were discharged earlier (terbutaline 4.1 +/- 5.1 hours, observation 5.2 +/- 5.3 hours, hydration 6.0 +/- 5.7 hours; p = 0.006). No complications of therapy were observed. CONCLUSIONS: The use of intravenous hydration in the management of preterm contractions was of no benefit. The use of one dose of subcutaneous terbutaline resulted in the shortest length of triage stay but did not affect pregnancy outcome.

Necrotizing fasciitis after cesarean delivery.

OBJECTIVE: To review our experience with the diagnosis and management of necrotizing fasciitis after cesarean delivery. METHODS: We reviewed medical records of women with serious post-cesarean wound infections at the University of Alabama at Birmingham between 1987 and 1994 to identify women with necrotizing fasciitis. The diagnosis of necrotizing fasciitis required intraoperative identification of necrotic fascia in febrile women undergoing post-cesarean wound debridement. RESULTS: During the study period, 5048 women had cesarean deliveries, nine of which were complicated by necrotizing fasciitis. The mean (+/-standard deviation) maternal age was 27 +/- 6 years, and the mean maternal weight was 199 +/- 64 lb. None of the patients had insulin-dependent diabetes mellitus, and none had known peripheral vascular disease. There were no intraoperative complications at cesarean delivery. The mean time from cesarean delivery to the diagnosis of necrotizing fasciitis and reoperation was 10 +/- 4 days (range 5-17). All patients had surgical debridement upon consideration of the diagnosis, and all received broad-spectrum antimicrobial therapy. Results of wound cultures were available in seven of the women, and all seven were found to have polymicrobial infections. There were two mortalities, one as a result of metastatic breast cancer and another with complications of sepsis. CONCLUSION: Necrotizing fasciitis is infrequent (1.8 per 1000 women) after cesarean delivery at our institution, but it does result in appreciable morbidity and mortality.

Prediction of prematurity.

Preterm birth is the leading cause of perinatal morbidity and mortality. A poor understanding of the underlying pathophysiology of spontaneous preterm labor and preterm premature rupture of membranes has limited our ability to identify those women at highest risk for spontaneous preterm birth. There is increasing evidence that inflammation of the upper genital tract may play a major role in the pathogenesis of preterm labor and preterm premature rupture of membranes. Newer markers of infection and inflammation (e.g. bacterial vaginosis, fetal fibronectin, interleukin-6) may make earlier diagnosis possible and may direct potential therapeutic interventions. A better understanding and more accurate diagnosis of well known risk factors (e.g. cervical dilatation) may also improve treatment options. Additionally, combinations of older risk factors and newer, more sensitive diagnostic methods may greatly increase our ability to predict preterm birth and to identify women who might benefit most from directed intervention strategies.

Estrogen replacement therapy is not conducive of venous thromboembolism.

Continued resistance to the use of hormone replacement therapy in menopausal women persists, in part because of concern over a possible relationship between estrogen use and venous thromboembolism. Numerous studies, both retro- and prospective, have failed to yield any evidence of increased relative risk for thrombosis: specific investigations have consistently failed to link estrogen use to clinically significant adverse changes in coagulation factors. We feel that any linkage of menopausal estrogen use and risk of venous thromboembolism is based on anecdotal comments and medical superstition.