Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection.

BACKGROUND: Infection with Trichomonas vaginalis during pregnancy has been associated with preterm delivery. It is uncertain whether treatment of asymptomatic trichomoniasis in pregnant women reduces the occurrence of preterm delivery. METHODS: We screened pregnant women for trichomoniasis by culture of vaginal secretions. We randomly assigned 617 women with asymptomatic trichomoniasis who were 16 to 23 weeks pregnant to receive two 2-g doses of metronidazole (320 women) or placebo (297 women) 48 hours apart. We treated women again with the same two-dose regimen at 24 to 29 weeks of gestation. The primary outcome was delivery before 37 weeks of gestation. RESULTS: Between randomization and follow-up, trichomoniasis resolved in 249 of 269 women for whom follow-up cultures were available in the metronidazole group (92.6 percent) and 92 of 260 women with follow-up cultures in the placebo group (35.4 percent). Data on the time and characteristics of delivery were available for 315 women in the metronidazole group and 289 women in the placebo group. Delivery occurred before 37 weeks of gestation in 60 women in the metronidazole group (19.0 percent) and 31 women in the placebo group (10.7 percent) (relative risk, 1.8; 95 percent confidence interval, 1.2 to 2.7; P=0.004). The difference was attributable primarily to an increase in preterm delivery resulting from spontaneous preterm labor (10.2 percent vs. 3.5 percent; relative risk, 3.0; 95 percent confidence interval, 1.5 to 5.9). CONCLUSIONS: Treatment of pregnant women with asymptomatic trichomoniasis does not prevent preterm delivery. Routine screening and treatment of asymptomatic pregnant women for this condition cannot be recommended.

Safety of labor epidural anesthesia for women with severe hypertensive disease. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: The aim of this study was to determine whether epidural anesthesia during labor increased the frequencies of cesarean delivery, pulmonary edema, and renal failure among women with severe hypertensive disease. STUDY DESIGN: We performed a secondary retrospective analysis of a subgroup population within a multicenter double-blind trial of low-dose aspirin therapy for women at high risk for development of preeclampsia. Subjects in whom severe hypertensive disease developed were selected. The primary outcomes were the overall frequencies of cesarean delivery among women with severe hypertensive disease who had labor with and without epidural anesthesia. Other maternal and neonatal outcomes were also compared between women who did and did not receive epidural anesthesia. RESULTS: Among the women with severe hypertensive disease (n = 444) 327 had labor. Among the women with severe disease who had labor there was no difference in either the overall cesarean delivery rate (32.1% vs 28.0%; P =.44) or the rate of cesarean delivery for fetal distress or failure to progress (27.8% vs 22.0%; P =.26) between women who did and did not receive epidural analgesia. Women with chronic hypertension were more likely to have a cesarean delivery overall if they received epidural anesthesia, but there was otherwise no difference in the frequencies of cesarean delivery for these indications between women with and without epidural anesthesia within each of the high-risk groups. Pulmonary edema was rare and acute renal failure did not develop in any women. CONCLUSION: Epidural anesthesia use did not increase the frequencies of cesarean delivery, pulmonary edema, and renal failure among women with severe hypertensive disease.

Effect of fetal presentation on the amniotic fluid index.

OBJECTIVE: The aim of this study was to determine whether the amniotic fluid index differs according to whether a fetus is in breech or cephalic presentation. STUDY DESIGN: Between January 1995 and April 1996 the amniotic fluid index was measured both immediately before and after attempted external cephalic version. Amniotic fluid indexes were measured by a senior obstetric resident or attending physician. Preprocedure amniotic fluid indexes and change in amniotic fluid index after successful and failed external cephalic version were compared with unpaired and paired Student t tests, respectively. P <.05 was considered statistically significant. RESULTS: Thirty consecutive women between 36 and 40 weeks' gestation with breech presentations were evaluated before undergoing an attempt at external cephalic version. The preprocedure amniotic fluid index was not different (P =.61) between women who had success (12.1 cm) and failure (11.4 cm) of attempts at external cephalic version. Successful external cephalic version was associated with a statistically significant increase (P <.0001) in amniotic fluid index with respect to gestations with a persistent breech presentation (3.14 vs -0.35). CONCLUSION: Successful version from a breech to a cephalic presentation resulted in a significant increase in the amniotic fluid index. This should be considered when a breech presentation with a low normal amniotic fluid index is evaluated. Presentation of the fetus should be considered in evaluating amniotic fluid index distribution curves.

Obstetric determinants of neonatal survival: antenatal predictors of neonatal survival and morbidity in extremely low birth weight infants.

OBJECTIVE: The aim of the study was to compare clinical and ultrasonographic variables obtained before delivery as predictors of neonatal survival and morbidity in infants weighing

The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. NICHD MFMU Network.

OBJECTIVES: This study was undertaken to determine the relationship between fetal fibronectin, short cervix, bacterial vaginosis, other traditional risk factors, and spontaneous preterm birth. METHODS: From 1992 through 1994, 2929 women were screened at the gestational age 22 to 24 weeks. RESULTS: The odds ratios for spontaneous preterm birth were highest for fetal fibronectin, followed by a short cervix and history of preterm birth. These factors, as well as bacterial vaginosis, were more strongly associated with early than with late spontaneous preterm birth. Bacterial vaginosis was more common--and a stronger predictor of spontaneous preterm birth--in Black women, while body mass index less than 19.8 was a stronger predictor in non-Black women. This analysis suggests a pathway leading from Black race through bacterial vaginosis and fetal fibronectin to spontaneous preterm birth. Prior preterm birth is associated with spontaneous preterm birth through a short cervix. CONCLUSIONS: Fetal fibronectin and a short cervix are stronger predictors of spontaneous preterm birth than traditional risk factors. Bacterial vaginosis was found more often in Black than in non-Black women and accounted for 40% of the attributable risk for spontaneous preterm birth at less than 32 weeks.

Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

CONTEXT: Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent. OBJECTIVE: To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. PATIENTS: A total of 614 of 804 eligible gravidas with PPROM between 24 weeks' and 0 days' and 32 weeks' and 0 days' gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization. INTERVENTIONS: Intravenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen. Group B streptococcus (GBS) carriers were identified and treated. Tocolysis and corticosteroids were prohibited after randomization. MAIN OUTCOME MEASURES: The composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth. These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed. RESULTS: In the total study population, the primary outcome (44.1 % vs 52.9%; P=.04), respiratory distress (40.5% vs 48.7%; P=.04), and necrotizing enterocolitis (2.3% vs 5.8%; P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%; P=.03), respiratory distress (40.8% vs 50.6%; P=.03), overall sepsis (8.4% vs 15.6%; P=.01), pneumonia (2.9% vs 7.0%; P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P<.001). CONCLUSIONS: We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity.

Obstetric determinants of neonatal survival: influence of willingness to perform cesarean delivery on survival of extremely low-birth-weight infants. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

OBJECTIVE: Our purpose was to evaluate the relationship between the approach to obstetric management and survival of extremely low-birth-weight infants. STUDY DESIGN: In this prospective observational study we evaluated 713 singleton births of infants weighing < or = 1000 gm during 1 year at the 11 tertiary perinatal care centers of the National Institutes of Child Health and Human Development network of maternal-fetal medicine units. Major anomalies, extramural delivery, antepartum stillbirth, induced abortion, and gestational age < 21 weeks were excluded. The obstetrician's opinion of viability and willingness to perform cesarean delivery in the event of fetal distress were ascertained from the medical record or interview when documentation was unclear. Grade 3 and 4 intraventricular hemorrhage, grade 3 and 4 retinopathy of prematurity, necrotizing enterocolitis requiring surgery, oxygen dependence at discharge or 120 days, and seizures were considered serious morbidity. Survival without serious morbidity was considered intact survival. Logistic regression was used to evaluate the influence of the approach to obstetric management, adjusted for birth weight, growth, gender, presentation, and ethnicity. RESULTS: Willingness to perform cesarean delivery was associated with increased likelihood of both survival (adjusted odds ratio 3.7, 95% confidence interval 2.3 to 6.0) and intact survival (adjusted odds ratio 1.8, 95% confidence interval 1.0 to 3.3). Willingness to intervene for fetal indications appeared to virtually eliminate intrapartum stillbirth and to reduce neonatal mortality. Below 800 gm or 26 weeks, however, willingness to perform cesarean delivery was linked to an increased chance of survival with serious morbidity. Although obstetricians were willing to intervene for fetal indications in most cases by 24 weeks, willingness to perform cesarean delivery was associated with twice the risk for serious morbidity at that gestational age. CONCLUSIONS: The approach to obstetric management significantly influences the outcome of extremely low-birth-weight infants. Above 800 gm or 26 weeks the obstetrician should usually be willing to perform cesarean delivery for fetal indications. Between 22 and 25 weeks willingness to intervene results in greater likelihood of both intact survival and survival with serious morbidity. In these cases patients and physicians should be aware of the impact of the approach to obstetric management and consider the likelihood of serious morbidity and mortality when formulating plans for delivery.

The preterm prediction study: risk factors in twin gestations. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: Our purpose was to determine the association between the presence of bacterial vaginosis, fetal fibronectin, and a short cervix and the risk of spontaneous preterm birth of twins. STUDY DESIGN: We prospectively screened 147 women with twins at 24 and 28 weeks' gestation for more than 50 potential risk factors for spontaneous preterm birth. We also measured cervical length with ultrasound scans and tested for the presence of bacterial vaginosis. Fetal fibronectin level was evaluated every 2 weeks from 24 to 30 weeks' gestation. Outcomes included spontaneous preterm birth at < 32 weeks, < 35 weeks, and < 37 weeks. RESULTS: Among twin as compared with singleton pregnancies, a cervical length < or = 25 mm was more common at both 24 and 28 weeks, a statistically significant difference. There were no significant differences in most other risk factors. Of the factors evaluated by means of univariate analysis at 24 weeks, only a short cervix (< or = 25 mm) was consistently associated with spontaneous preterm birth. The odds ratio and 95% confidence interval for spontaneous preterm birth at < 32 weeks, < 35 weeks, and < 37 weeks were 6.9 (2.0 to 24.2), 3.2 (1.3 to 7.9), and 2.8 (1.1 to 7.7). At 28 weeks, a cervical length < or = 25 mm was not a strong predictor of spontaneous preterm birth. At both 28 weeks (odds ratio, 9.4; confidence interval, 1.0 to 67.7) and 30 weeks (odds ratio 46.1; confidence interval, 4.2 to 1381), a positive fetal fibronectin result was significantly associated with spontaneous preterm birth at < 32 weeks. Bacterial vaginosis at 24 or 28 weeks was not associated with spontaneous preterm birth of twins. Multivariate analysis confirmed the association between cervical length < or = 25 mm at the 24-week visit and spontaneous preterm birth and also confirmed that at 24 weeks the other risk factors were less consistently and often not statistically significantly associated with spontaneous preterm birth. Of the risk factors evaluated at 28 weeks, only a positive fetal fibronectin was associated with a significantly increased risk for spontaneous preterm birth. CONCLUSIONS: Most known risk factors for spontaneous preterm birth were not significantly associated with spontaneous preterm birth of twins. At 24 weeks, cervical length < or = 25 mm was the best predictor of spontaneous preterm birth at < 32 weeks, < 35 weeks, and < 37 weeks. Of the risk factors evaluated at 28 weeks, fetal fibronectin was the only statistically significant predictor of spontaneous preterm birth at < 32 weeks.

A selective aggressive approach to the neonate exposed to meconium-stained amniotic fluid.

OBJECTIVE: We attempted to determine the effect on meconium aspiration syndrome from a selective approach of neonatal endotracheal intubation in meconium-exposed fetuses. STUDY DESIGN: All pregnancies delivered at the Medical College of Virginia in 1990 were included. Meconium was noted at membrane rupture and qualified as thick, moderate, or thin. Neonates underwent suctioning with a DeLee device at delivery. They were observed without endotracheal intubation if they fulfilled the following criteria: vaginal delivery, gestational age > 37 weeks, birth weight > 2500 gm, and anticipated Apgar score > or = 8 at 1 minute. RESULTS: Of 4289 deliveries, 659 were exposed to meconium and 48% of infants were intubated. Birth weights, gestational ages at delivery, and umbilical arterial pH were similar between intubated and nonintubated neonates. Neonatal intensive care unit admissions were significantly higher in intubated neonates. All 9 neonates diagnosed with meconium aspiration syndrome were intubated at birth. CONCLUSIONS: Utilization of this protocol resulted in reduction of neonatal intubation. Meconium aspiration syndrome did not occur in the nonintubated group.

Compound presentation resulting from the forward-roll technique of external cephalic version: a possible mechanism.

Limited reports exist about the frequency of compound presentation after external cephalic version. A compound hand and foot presentation is reported after external cephalic version in a woman desiring vaginal birth after cesarean delivery. We report a mechanism by which a forward roll during external cephalic version may predispose an infant in complete breech position to a compound foot presentation.

Low serum alpha-fetoprotein level and sex chromosome monosomy.

A case of 45,X karyotype in association with low maternal serum alpha-fetoprotein levels is reported. Previous cases of trisomy have been linked to low alpha-fetoprotein levels. Cases of sex chromosome aneuploidy may be included in the group of aneuploidies with low levels of maternal serum alpha-fetoprotein.

Pyelonephritis in pregnancy. The role of in-hospital management and nitrofurantoin suppression.

Acute pyelonephritis remains a frequent complication of pregnancy. Prevention of the potential complications of this disease requires aggressive in-hospital management. However, the high frequency of positive outpatient cultures following discharge has cast doubt on the adequacy of in-hospital care and, at the same time, has concentrated attention on follow-up care. In a randomized, prospective study, we evaluated the effects of in-hospital management and outpatient nitrofurantoin on subsequent urine cultures. The overall frequency of positive cultures following discharge from the hospital was 38%. However, appropriate antibiotic selection, a negative follow-up in-hospital culture and nitrofurantoin suppression reduced the rate to 8% (P less than .01). Nitrofurantoin did not reduce the rate of positive cultures if antibiotic selection was inappropriate or if the in-hospital follow-up culture was positive. These results suggest that more aggressive management of acute pyelonephritis in pregnancy may be indicated and that suppressive therapy cannot compensate for inappropriate in-hospital management.

Office diagnosis of asymptomatic bacteriuria in pregnant women.

Diagnosis and treatment of asymptomatic bacteriuria in pregnant patients can virtually eliminate pyelonephritis, the most common medical cause for antepartum hospitalization. However, the ever-increasing cost of the urine culture has led most clinicians away from routine urine screening. Uricult dip-slide paddles provide an inexpensive, efficient way to screen urine. Clean-catch urine specimens were obtained from 544 consecutive asymptomatic pregnant patients seen in the outpatient obstetric clinic at the Medical University of South Carolina. Specimens were analyzed by both traditional culture techniques and the Uricult dip-slide paddles. By comparison, the Uricult test detected 55 of the 56 significant gram-negative urinary pathogens found by culture. Detection of potential gram-positive pathogens is more difficult. A scheme is proposed that allows reliable, inexpensive surveillance in all pregnant patients. Hopefully, this algorithm will rekindle the obstetrician's interest in urine screening.

The preterm cervix and preterm labor: relative risks, predictive values, and change over time.

The accurate prediction and diagnosis of preterm labor continue to frustrate the clinician. This is partly due to a scarcity of cervical data from the early third trimester. A total of 760 prospective, serial, paired, and blinded pelvic examinations were done at 28 to 34 weeks of gestation for 191 patients without a history of preterm labor. If the cervix was dilated greater than or equal to 1 cm (internal os) or effaced greater than 30%, the relative risk of preterm labor was increased to 1.8 to 4.2. Negative predictive values for cervical status were greater than 92%, but positive predictive values were less than or equal to 18%. Change over time was unusual (dilatation increase greater than or equal to 1 cm or effacement increase greater than or equal to 40%), suggesting that a baseline late second-trimester examination could assist in the early but accurate diagnosis of preterm labor should it be suspected later in gestation. These data suggest that even in the low-risk patient, an early cervical examination could be beneficial.

Evidence of accelerated platelet production and consumption in nonthrombocytopenic preeclampsia.

Platelet size and the distribution of platelet sizes are both increased in preeclamptic patients with normal platelet counts. These changes suggest that accelerated platelet production and consumption are both widespread in preeclampsia.

Predictive value of fibronectin levels in normotensive gravid women destined to become preeclamptic.

The plasma fibronectin concentration was abnormally elevated (greater than 400 micrograms/ml) in 16 of 17 normotensive gravid women who subsequently developed preeclampsia. Of this group, 13 had elevated levels detectable greater than or equal to 4 weeks before the onset of hypertension. Our results indicate that plasma fibronectin levels can be abnormally increased long before the onset of clinical symptoms and that abnormalities of this glycoprotein may be an early indication of this pathologic process.

Preterm rupture of the membranes: combination therapy.

Preterm rupture of the membranes poses perhaps the greatest threat to perinatal survival. Unfortunately, the literature leaves us in a quandry as to the management of the problem. At the Medical University of South Carolina for the past 3 years, aspects of both active and passive management have been used. Vaginal pool phospholipid analysis, the use of corticosteroids whenever appropriate, and tocolysis (in an attempt to gain 48 hours) were used in 96 consecutive patients with premature rupture of the membranes between 26 and 36 weeks' gestation. Decisions about delivery were dictated by spontaneous onset of labor and/or evidence of chorioamnionitis. This regimen prolonged gestation an average of 4.6 days. Maternal and neonatal infectious morbidity was uncommon. Clinical chorioamnionitis was diagnosed in 5.2% of mothers, and only 8.5% of all neonates had evidence of serious infection. Respiratory distress syndrome was seen in 12.8% of neonates. There were only three perinatal deaths, and most babies (92.5%) were discharged without residual problems (average hospital stay, 18.1 days). A detailed analysis of the group by gestational age categories will be presented.

Update on external cephalic version performed at term.

External cephalic version under tocolysis at term was investigated during a prospective study at the Los Angeles County/University of Southern California Medical Center from October 1, 1979 to March 16, 1983. Two hundred twelve patients were considered for attempted version. Forty-one patients were excluded, and 23 patients as previously reported were randomized to the control group. The procedure was successful in 73% (108 of 148). Of the 102 successful versions observed until delivery (six lost to follow-up), 93% (95 of 102) presented in labor with a vertex presentation; seven fetuses reverted to abnormal lies. The cesarean section rate in the success group with a vertex presentation was 24% (23 of 95).