Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: A randomized controlled trial.

CONTEXT: The practice of administering weekly courses of antenatal corticosteroids to pregnant women at risk of preterm delivery is widespread, but no randomized trial has established the efficacy or safety of this practice. OBJECTIVES: To evaluate the efficacy of weekly administration of antenatal corticosteroids compared with a single course in reducing the incidence of neonatal morbidity and to evaluate potential complications of weekly treatment. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled intention-to-treat trial conducted in 13 academic centers in the United States from February 1996 through April 2000. PARTICIPANTS: A total of 502 pregnant women between 24 and 32 completed weeks' gestation who were at high risk of preterm delivery. INTERVENTION: All patients received a complete single course of antenatal corticosteroids (either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses, or dexamethasone, 6 mg intramuscularly repeated every 12 hours for 4 doses). Participants who had not delivered 1 week after receipt of the single course were randomly assigned to receive either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses every week until 34 weeks' gestation or delivery, whichever came first (n = 256), or a similarly administered placebo (n = 246). MAIN OUTCOME MEASURE: Composite neonatal morbidity (including severe respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, proven sepsis, necrotizing enterocolitis, or perinatal death). RESULTS: Composite morbidity occurred in 22.5% of the weekly-course group vs 28.0% of the single-course group (unadjusted relative risk, 0.80; 95% confidence interval, 0.59-1.10). Neither group assignment nor the number of treatment courses was associated with a reduction in composite morbidity. CONCLUSIONS: Weekly courses of antenatal corticosteroids did not reduce composite neonatal morbidity compared with a single course of treatment. Weekly courses of antenatal corticosteroids should not be routinely prescribed for women at risk of preterm delivery.

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.

Value of perinatal autopsy.

OBJECTIVE: To determine how often a perinatal autopsy identified the cause of death, and how frequently this information changed recurrence risk estimates or altered parental counseling. METHODS: We reviewed all autopsies of fetal stillbirths and briefly viable neonates performed by one perinatal pathologist at the University of Alabama Hospital from 1992 to 1994. RESULTS: Four hundred sixteen fetal and early neonatal deaths occurred at our hospital from January 1, 1992, to June 1, 1994. Consent for an autopsy examination was granted for 139 of these (33%), and all autopsies were performed by a single perinatal pathologist. Abnormalities likely to be the cause of death were identified in 130 of 139 cases (94%). Ninety-one subjects did not have structural anomalies: In 14 cases autopsy revealed previously unsuspected pathology that altered parental counseling; in 68 cases autopsy findings were consistent with the clinical obstetrical diagnosis; and in nine cases the cause of death could not be identified. Forty-eight subjects were anomalous. Thirty-seven of these (79%) had been evaluated by antenatal ultrasonography, and autopsy identified additional abnormalities in 51% (19 of 37). In the 11 deaths evaluated neonatally, a previously unsuspected diagnosis likely to be the cause of death was identified in three. Overall, autopsy findings changed recurrence risk estimates and/or parental counseling in 36 of 139 cases (26%). CONCLUSION: The cause of fetal or perinatal death was determined by autopsy in 94% of cases in our series. Counseling and recurrence risk estimates were altered by autopsy findings in 26%.

Calciuria in symptom-free primigravid women remote from term: is the response to an oral calcium challenge predictable?

OBJECTIVE: This study was undertaken to compare the calciuric response in symptom-free primigravid women to an oral calcium load between those with normal urinary calcium excretions and those with relatively low urinary calcium excretions. STUDY DESIGN: This was a prospective clinical trial. Eligible primigravid women between 16 and 20 weeks' gestation provided a 24-hour urine sample for determination of urinary calcium/urinary creatinine ratio. On the basis of these results the patients were divided into 2 groups: a relatively hypocalciuric group, in which the urinary calcium excretion was 3.4 mg. kg-1. 24 h-1. All participants undertook a 3-day low calcium dietary regimen. On the fourth day women underwent an oral calcium challenge. A 2-hour urine sample was collected before ingestion of 1 g calcium carbonate (preload). One hour after ingestion the women again collected a 2-hour urine sample (postload). The urinary calcium/urinary creatinine ratios in the preload and postload samples were determined and compared within and between the groups. RESULTS: The mean change (+/-SD) between the preload and postload urinary calcium/urinary creatinine ratios in the relatively hypocalciuric group was 0.60 +/- 1.44 (P =.04); that in the normocalciuric group was 3.09 +/- 2.26 (P =.11 ). There was a 5-fold difference in the response to calcium load between the hypocalciuric women and the normocalciuric women (0.60 vs 3.09), although this difference was not statistically significant (P =.20). CONCLUSIONS: Both hypocalciuric and normocalciuric women responded to an oral calcium challenge by an increase in the calcium excretion. The cause of the hypocalciuria in women at increased risk for preeclampsia is therefore not simply poor absorption of calcium.

Relationship of gestational age and cervical dilation to the timing of delivery.

OBJECTIVE: To determine the effect of gestational age and cervical dilation on pregnancy continuation in women with idiopathic preterm labor who were treated with parenteral tocolysis. METHOD: A total of 950 women with singleton gestations, intact membranes and preterm labor treated with tocolysis prior to 34 weeks' gestation were retrospectively studied. These women were identified from the March of Dimes prematurity prevention program database. For analysis, women were categorized into five gestational age groups and three cervical dilation groups. The primary outcomes measured were the percentage of women who remained undelivered at 48 h and at 14 days post-initiation of therapy. RESULT: Overall, 82% of women remained undelivered after 48 h and 65% remained undelivered at 14 days. As cervical dilation advanced, the number of women remaining undelivered at 48 h and 14 days significantly decreased. However, even at > or = 4 cm, 52% of women remained undelivered at 48 h. If the cervix was dilated < 2 cm, gestational age did not influence the number of days gained prior to delivery. However, if the cervix was dilated > or = 2 cm, women at < 25 weeks' gestation were more likely to deliver compared to women at the same dilation but with more advanced gestational ages. CONCLUSION: Overall, 82% of women in preterm labor and 52% of those presenting with > or = 4-cm cervical dilation, delivered after 48 h. Therefore there appears to be ample opportunity for most women in preterm labor with intact membranes, even those at advanced dilations, to receive a complete course of corticosteroid therapy.

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.

Fetal heart rate characteristics at 25 to 28 weeks' gestation.

The objective of this article is to define normative fetal heart rate (FHR) tracing characteristics between 25-28 weeks' gestation in a low-risk population with normal pregnancy outcomes and to determine which criteria best determine FHR reactivity. Continuous FHR tracings were reviewed from 188 low-risk women participating in a trial of the Mammary Stimulation Test (MST) at 25-28 weeks' gestation. A reactive tracing required the presence of > or =two accelerations in 20 min. Different acceleration criteria were evaluated based upon the width of the acceleration (short vs. long) and the amplitude of the acceleration (10 vs. 15 bpm). Seventy-one percent of the FHR tracings were reactive using the higher amplitude (15 bpm), short criteria. This number increased significantly to 92% when the lower amplitude (10 bpm), short criteria were used (p <0.01). As gestational age advanced, there was a trend toward increased reactivity irrespective of which criteria were used, but these differences were not significant. Reducing the acceleration amplitude criteria to 10 bpm in preterm pregnancies will maximize the number of reactive nonstress tests. This is advantageous because it would improve test specificity and decrease the false-positive rate. Our findings need to be prospectively validated in a high-risk population.

A randomized trial of misoprostol and extra-amniotic saline infusion for cervical ripening and labor induction.

OBJECTIVE: To compare the cesarean rates in women undergoing induction of labor with unfavorable cervices who receive either misoprostol or extra-amniotic saline infusion. METHODS: We assigned 250 women undergoing indicated induction of labor randomly to misoprostol (50 microg every 4 hours for three doses with or without oxytocin) or extra-amniotic saline infusion and oxytocin. Each eligible subject had a singleton gestation, vertex presentation, intact membranes, cervical dilation no more than 2 cm, and effacement no more than 50%. RESULTS: Two hundred forty-eight women were studied after two exclusions; 120 were assigned to misoprostol, and 128 to extra-amniotic saline infusion. This sample size ensured an 80% chance of detecting an intergroup difference in cesarean rates of at least two-fold. The groups were similar in age, race, parity, indication for induction, and gestational age. The extra-amniotic saline infusion group had a significantly lower median initial dilation; however, at 12 hours, this group was significantly more dilated. The groups also were similar in epidural use, chorioamnionitis rates, endometritis rates, birth weights, and neonatal outcomes. Overall, 23% of women underwent cesarean deliveries, 18% and 27% for the misoprostol and extra-amniotic saline infusion groups, respectively (P = .12). There were no significant differences in the median time to either vaginal or cesarean delivery between the two groups. Eighty-one percent of women were delivered in less than 24 hours from initiation of induction; 78% in the misoprostol group, and 84% in the extra-amniotic saline infusion group (P = .19). CONCLUSION: Both methods of labor induction appear to be equally effective in this group of women at high risk for cesarean delivery and prolonged induction of 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.

Risk factors for the development of preterm premature rupture of the membranes after arrest of preterm labor.

OBJECTIVE: Our purpose was to determine risk factors predictive of preterm premature rupture of the membranes in women treated for preterm labor with intact membranes. STUDY DESIGN: Women with intact membranes participating in a National Institute of Child Health and Human Development multicenter randomized trial of adjunctive antibiotic therapy for preterm labor (24 to 34 weeks) were studied (n = 275). After randomization, 22 women continued to have contractions and were delivered of their infants. The remaining 253 women whose contractions had ceased composed our study population. Preterm premature rupture of the membranes was diagnosed if ruptured membranes occurred > or = 1 hour before the onset of recurrent preterm labor. As part of the study protocol, most women underwent amniocentesis on admission. RESULTS: Preterm premature rupture of the membranes developed in 44% women (17.4%). Women who had preterm premature rupture of the membranes were more likely to be black (p = 0.004), to be multiparous (p = 0.014), to have a history of abortion(s) (p = 0.001), to have had a preterm birth(s) (p = 0.036), to have early onset preterm labor (p = 0.04), to have more advanced cervical dilatation (p = 0.0001), to have one or more amniotic fluid markers suggestive of infection (p = 0.01, odds ratio 4.2), and to have positive amniotic fluid cultures (p = 0.0007, odds ratio 27). Assignment to antibiotic therapy did not prevent preterm premature rupture of the membranes in the 253 women randomized or in the 16 women with a positive amniotic fluid marker(s) of infection. CONCLUSION: Black race, multiparity, a history of abortion or preterm birth, advanced dilatation, and a positive amniotic fluid marker(s) are associated with preterm premature rupture of the membranes in women with preterm labor. Antibiotic treatment did not prevent preterm premature rupture of the membranes.

Prediction of preterm birth in nulliparous patients.

OBJECTIVE: Our goal was to determine whether the mammary stimulation test combined with a risk scoring system and cervical examination at 26 to 28 weeks' gestation could effectively identify private nulliparous patients at risk for spontaneous preterm birth. STUDY DESIGN: The mammary stimulation test was performed by 267 nulliparous patients with singleton gestations at 26 to 28 weeks. Risk scores were determined by the method of Creasy et al. and cervical examinations were performed at the first prenatal visit and at 26 to 28 weeks. Summary predictive values were calculated for each test, and a stepwise discriminate analysis was performed. RESULTS: Spontaneous preterm birth occurred at < 37 weeks in 26 of 265 (9.8%) patients. The following variables were independently associated with spontaneous preterm birth: positive result of mammary stimulation test, risk score > or = 10, soft cervix at 26 to 28 weeks, bacteriuria, and current smoking. The best discriminate model included positive result of mammary stimulation test, soft cervix, bacteriuria, current smoking, and prior spontaneous abortion(s). This model identified 19 patients as being at risk for spontaneous preterm birth with sensitivity of 35%, specificity of 96%, and positive predictive value of 47%. CONCLUSION: Combining the mammary stimulation test with a cervical examination at 26 to 28 weeks' gestation and routinely obtained prenatal data correctly identified 35% of spontaneous preterm births in nulliparous patients with a positive predictive value of 47%. Prospective validation of this model is warranted.

Mammary stimulation test predicts preterm birth in nulliparous women.

OBJECTIVE: This prospective clinical trial was designed to assess the ability of the mammary stimulation test to predict preterm birth in a private nulliparous population. STUDY DESIGN: The mammary stimulation test was performed between 26 and 28 weeks' gestation by 267 nulliparous women with singleton pregnancies. Test results were blinded to both patient and referring physician. Pregnancy outcome data were collected from the perinatal database and medical records. RESULTS: The mammary stimulation test was positive in 45 of 266 (17%) patients. Delivery occurred at < 37 weeks in 27 patients (10.2%) and at < 34 weeks in five (1.9%). The mammary stimulation test demonstrated a sensitivity of 37%, a specificity of 84%, a positive predictive value of 20%, and a negative predictive value of 92% for delivery at < 37 weeks' gestation. For delivery at < 34 weeks' gestation the mammary stimulation test had a sensitivity of 60%, a specificity of 82%, a positive predictive value of 6%, and a negative predictive value 99%. The odds ratio for delivery at < 37 weeks was 3.0 (95% confidence interval 1.3, 7.1), and for delivery at < 34 weeks the odds ratio was 7.0 (95% confidence interval 1.1, 43.0). One third of preterm deliveries were secondary to idiopathic preterm labor, and the mammary stimulation test was positive in 77.8% (seven of nine) of these pregnancies. Patients with a positive test were more likely to require observation in labor and delivery for preterm uterine contractions (34% vs 4.3%, p < 0.01), and they were more likely to demonstrate change at cervical examination (14% vs 2%, p < 0.01). CONCLUSION: In this population traditionally considered to be at low risk for preterm birth a positive mammary stimulation test was useful in identifying patients at risk for preterm uterine activity and preterm birth. Equally important was the identification of women who were at low risk for preterm birth.