Preterm prediction study: comparison of the cervical score and Bishop score for prediction of spontaneous preterm delivery.

OBJECTIVE: To prospectively compare digital cervical score with Bishop score as a predictor of spontaneous preterm delivery before 35 weeks of gestation. METHODS: Data from a cohort of 2,916 singleton pregnancies enrolled in a multicenter preterm prediction study were available. Patients underwent digital cervical examinations at 22-24 and 26-29 weeks of gestation for calculation of Bishop score and cervical score. Relationships between Bishop score, cervical score, and spontaneous preterm delivery were assessed with multivariable logistic regression analysis, McNemar test, and receiver operating characteristic (ROC) curves to identify appropriate diagnostic thresholds and predictive capability. RESULTS: One hundred twenty-seven of 2,916 patients (4.4%) undergoing cervical examination at 22-24 weeks had a spontaneous preterm delivery before 35 weeks. Eighty-four of the 2,538 (3.3%) reexamined at 26-29 weeks also had spontaneous preterm delivery. Receiver operating characteristic curves indicated that optimal diagnostic thresholds for Bishop score were at least 4 at 22-24 weeks, at least 5 at 26-29 weeks, and less than 1.5 at both examinations for cervical score. At 22-24 weeks, areas under the ROC curve favored Bishop score. At 26-29 weeks, there was no significant difference in areas under the ROC curve; however, a cervical score less than 1.5 (sensitivity 35.7%, false positive rate 4.8%) was superior to a Bishop score of 5 or more (P<.001). CONCLUSION: Both cervical evaluations are associated with spontaneous preterm delivery in a singleton population; however, predictive capabilities for spontaneous preterm delivery were modest among women with low event prevalence. Although Bishop score performed better in the mid trimester, by 26-29 weeks a cervical score less than 1.5 was a better predictor of spontaneous preterm delivery before 35 weeks than a Bishop score of at least 5.

The Preterm Prediction Study: toward a multiple-marker test for spontaneous preterm birth.

OBJECTIVE: The Preterm Prediction Study evaluated 28 potential biologic markers for spontaneous preterm birth in asymptomatic women at 23 to 24 weeks gestational age. This analysis compares those markers individually and in combination for an association with spontaneous preterm birth at <32 and <35 weeks gestational age. STUDY DESIGN: With the use of a nested case-control design from an original cohort study of 2929 women, results of tests from 50 women with a spontaneous preterm birth at <32 weeks and 127 women with a spontaneous preterm birth at <35 weeks were compared with results from matched-term control subjects. RESULTS: In the univariate analysis, the most potent markers that are associated with spontaneous preterm birth at <32 weeks by odds ratio were a positive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) and <10th percentile cervical length (odds ratio, 5.8), and in serum, >90th percentiles of alpha-fetoprotein (odds ratio, 8.3) and alkaline phosphatase (odds ratio, 6.8), and >75th percentile of granulocyte colony-stimulating factor (odds ratio, 5.5). Results for spontaneous preterm birth at <35 weeks were generally similar but not as strong. Univariate and multivariate logistic regression analyses demonstrated little interaction among the tests in their association with spontaneous preterm birth. Combinations of the 5 markers were evaluated for their association with <32 weeks spontaneous preterm birth. Ninety-three percent of case patients had at least 1 positive test result versus 34% of control subjects (odds ratio, 24.0; 95% CI, 6.4-93.4). Among the case patients, 59% had >or=2 positive test results versus 2.4% of control subjects (odds ratio, 56.5; 95% CI, 7.1-451.7). If a cutoff of 3 positive test results was used, 20% of case patients and none of the control subjects had positive test results (P < .002). With the use of only the 3 serum tests (alkaline phosphatase, alpha-fetoprotein, and granulocyte colony-stimulating factor), any positive test identified 81% of cases versus 22% of control subjects (odds ratio, 14.7; 95% CI, 5.0-42.7). For spontaneous preterm birth at <35 weeks gestation, any 2 positive tests identified 43% of cases and 6% of control subjects (odds ratio, 11.2; 95% CI, 4.8-26.2). CONCLUSION: Overlap among the strongest biologic markers for spontaneous preterm birth is small. This suggests that the use of tests such as maternal serum alpha-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor as a group or adding their results to fetal fibronectin test and cervical length test results may enhance our ability to predict spontaneous preterm birth and that the development of a multiple-marker test for spontaneous preterm birth is feasible.

The preterm prediction study: can low-risk women destined for spontaneous preterm birth be identified?

OBJECTIVE: Half of all preterm births occur in women without clinical risk factors. Our goal was to assess fetal fibronectin assay, Bishop score, and cervical ultrasonography as screening tests to predict which low-risk pregnancies will end in preterm birth. STUDY DESIGN: We performed a secondary analysis of data collected at 22 to 24 weeks' gestation from low-risk subjects enrolled in the Preterm Prediction Study, an observational study of risk factors for preterm birth conducted by the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Analysis was limited to primigravid women and to women who did not have a history of preterm birth or spontaneous pregnancy loss at <20 weeks' gestation. Bishop score (> or =4), fetal fibronectin level (> or =50 ng/mL), and cervical length (< or =25 mm) at 24 weeks' gestation were evaluated alone and in sequence as tests to predict spontaneous delivery before 35 weeks' gestation. RESULTS: Of the 2929 subjects enrolled in the original study, 2197 (1207 primigravid women and 900 low-risk multiparous women) met criteria for this analysis. There were 64 spontaneous births before 35 weeks' gestation (3.04%). All three tests were significantly related to birth before 35 weeks' gestation (high Bishop score: relative risk, 3.6; 95% confidence interval, 2.1-6.3; fetal fibronectin detection: relative risk, 8.2; 95% confidence interval, 4.8-13.9; short cervical length: relative risk, 6.9; 95% confidence interval, 4.3-11.1). However, the sensitivities of the tests alone were low (23.4% for high Bishop score, 23.4% for fetal fibronectin detection, and 39.1% for short cervix), as were the sensitivities for Bishop score followed by cervical ultrasonography (14.1%) and fetal fibronectin assay followed by cervical scan (15.6%). CONCLUSION: In the setting of low-risk pregnancy, fetal fibronectin assay and cervical ultrasonography have low sensitivity for preterm birth before 35 weeks' gestation. Sequential screening with Bishop score or fetal fibronectin assay followed by cervical ultrasonography further decreased sensitivity to only 15% among low-risk women.

Occupational fatigue and preterm premature rupture of membranes. National Institute of Child Health and Human Development Maternal-Fetal Medicine, Units Network.

OBJECTIVE: The aim of this study was to prospectively determine the relationship between occupational fatigue and spontaneous preterm delivery segregated into the etiologically distinct categories of spontaneous preterm labor, preterm premature rupture of membranes, and indicated preterm delivery. STUDY DESIGN: A total of 2929 women with singleton pregnancies at 22 to 24 weeks' gestation were enrolled in a multicenter (10 sites) Preterm Prediction Study. Patients reported the number of hours worked per week and answered specific questions designed to determine the following 5 sources of occupational fatigue described by Mamelle et al: posture, work with industrial machines, physical exertion, mental stress, and environmental stress. Fatigue was quantified (0-5 index) according to the number of these sources positively reported. Simple and Mantel-Haenszel chi2 tests were used to test the univariate association and hypothesis of a linear trend between sources of occupational fatigue and spontaneous preterm delivery. Covariables were considered by multivariate logistic regression analysis. Women who did not work outside the home were considered separately from those who worked but did not report any sources of occupational fatigue. RESULTS: Each source of occupational fatigue was independently associated with a significantly increased risk of preterm premature rupture of membranes among nulliparous women but not among multiparous women. The risk of preterm premature rupture of membranes increased (P = .002) with an increasing number of sources of occupational fatigue-not working outside the home, 2.1%; working but not reporting fatigue, 3.7%; working with 1 source of fatigue, 3.2%; working with 2 sources of fatigue, 5.2%; working with 3 sources of fatigue, 5.1%; and working with 4 or 5 sources of fatigue, 7.4%. There was also a significant relationship (P = .01) between preterm premature rupture of membranes and an increasing number of hours worked per week among nulliparous women. Neither spontaneous preterm labor nor indicated preterm delivery was significantly associated with occupational fatigue among either nulliparous or multiparous women. CONCLUSION: The occupational fatigue index of Mamelle et al discriminated a group of nulliparous women at increased risk for preterm premature rupture of membranes. The relationship between preterm premature rupture of membranes and occupational fatigue or hours worked may provide guidelines according to which nulliparous women and their employers can be advised.

Preterm delivery in women with pregestational diabetes mellitus or chronic hypertension relative to women with uncomplicated pregnancies. The National institute of Child health and Human Development Maternal- Fetal Medicine Units Network.

OBJECTIVE: The purpose of this study was to compare the rates of indicated and spontaneous preterm delivery among women with chronic hypertension or pregestational diabetes mellitus with the rates among healthy women. STUDY DESIGN: This was a secondary analysis of data from healthy women with singleton gestations enrolled in a prospective observational study for prediction of preterm delivery (control group, n = 2738), women with pregestational diabetes mellitus requiring insulin therapy (n = 461), and women with chronic hypertension (n = 761). The two latter groups were enrolled in a randomized multicenter trial for prevention of preeclampsia. The main outcome measures were rates of preterm delivery, either spontaneous (preterm labor or rupture of membranes) or indicated (for maternal or fetal reasons), and neonatal outcomes. RESULTS: The overall rates of preterm delivery were significantly higher among women with diabetes mellitus (38%) and hypertension (33.1%) than among control women (13.9%). Rates were also significantly higher for delivery at <35 weeks' gestation. Women with diabetes mellitus had significantly higher rates of both indicated preterm delivery (21.9% vs 3.4%; odds ratio, 8.1; 95% confidence interval, 6.0-10.9) and spontaneous preterm delivery (16.1% vs 10.5%; odds ratio, 1.6; 95% confidence interval, 1.2-2.2) than did women in the control group. In addition, they had significantly higher rates of both indicated preterm delivery (odds ratio, 4.8; 95% confidence interval, 3.0-7.5) and spontaneous preterm delivery (odds ratio, 2.1; 95% confidence interval, 1.4-3.0) at <35 weeks' gestation than did control women. Compared with control women those with chronic hypertension had higher rates of indicated preterm delivery at both <37 weeks' gestation (21.9% vs 3.4%; odds ratio, 8.1; 95% confidence interval, 6.2-10.6) and at <35 weeks' gestation (12.1% vs 1.6%; odds ratio, 8.2; 95% confidence interval, 5.7-11.9), but there were no differences in rates of spontaneous preterm delivery. CONCLUSION: The increased rate of preterm delivery among women with chronic hypertension relative to control women was primarily an increase in indicated preterm delivery, whereas the rates of both spontaneous and indicated preterm delivery were increased among women with pregestational diabetes mellitus.

The impact of digital cervical examination on expectantly managed preterm rupture of membranes.

OBJECTIVE: The purpose of this study was to examine the effects of digital cervical examination on maternal and neonatal outcomes among women with preterm rupture of membranes. STUDY DESIGN: This analysis includes data from a previously reported trial of antibiotic treatment during expectant management of rupture of membranes at 24 to 32 weeks' gestation in singleton and twin gestations. Patients from both the randomized trial (n = 299 in the antibiotic group and n = 312 in the placebo group) and the observational component (n = 183) are included in this analysis. The groups were divided into those with one (n = 161) or two digital cervical examinations (n = 27) and those with no digital cervical examinations (n = 606). RESULTS: The gestational ages at enrollment were similar in the two groups (29 +/- 2 weeks' gestation for one or two examinations vs 29 +/- 2 weeks' gestation for no examinations; P =.85). There were no differences in chorioamnionitis (27% vs 29%; P =.69), endometritis (13% vs 11%; P =.5), or wound infection (0.5% vs 1%; P >.999) between the group with one or two examinations and the no-examination group. Infant outcomes were also similar in the two groups, including early sepsis (6% vs 5%; P =.68), respiratory distress syndrome (51% vs 45%; P =.18), intraventricular hemorrhage (7% vs 7%; P =.67), necrotizing enterocolitis (5% vs 3%; P =.19), and perinatal death (7% vs 5%; P =.45). A composite outcome made up of these neonatal outcomes was not different (56% vs 48%; P =.10) between the group with one or two examinations and the no-examination group. The time from rupture to delivery was shorter in the digital examination group (median value, 3 vs 5 days; P <. 009). Multivariable analysis to adjust for antibiotic study group, group B streptococcal culture status, race, and maternal transfer did not modify these results. CONCLUSION: Performance of one or two digital cervical examinations during the course of expectant management of rupture of membranes between 24 and 32 weeks' gestation was associated with shorter latency but did not appear to worsen either maternal or neonatal outcome.

The Preterm Prediction Study: prediction of preterm premature rupture of membranes through clinical findings and ancillary testing. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: Our objective was to determine the relative importance of demographic characteristics, clinical risk factors, and ancillary screening tests in the prediction of preterm birth as a result of premature rupture of membranes. STUDY DESIGN: A total of 2929 women were evaluated in 10 centers at 23 to 24 weeks' gestation. Demographic and clinical characteristics were ascertained. Cervicovaginal fetal fibronectin and bacterial vaginosis were evaluated. Cervical length was measured by vaginal ultrasonography. Patients were evaluated for spontaneous preterm birth caused by preterm premature rupture of membranes at <37 and <35 weeks' gestation. Multivariate analyses were performed separately for nulliparous women and multiparous women. RESULTS: Premature rupture of membranes at <37 weeks' gestation complicated 4.5% of pregnancies, accounting for 32.6% of preterm births. Univariate analysis revealed low body mass index, pulmonary disease, contractions within 2 weeks, short cervix (

Preterm prediction study: is socioeconomic status a risk factor for bacterial vaginosis in Black or in White women?

Bacterial vaginosis (BV), an important risk factor for preterm birth, is a more common infection in Black compared with White pregnant women. Because Black women in the United States are more likely to have lower measures of socioeconomic status (SES), this study examined the hypothesis that BV is associated with low SES. The project evaluated data from the Preterm Prediction Study of 2,929 women prospectively followed during their pregnancies. The women, who were screened for BV at 24 and 28 weeks of gestation, underwent a structured interview to evaluate demographic factors, SES, home and work environment, drug or alcohol use, and prior medical history. Black women in the study had many measures of lower SES compared with the White women, and reported less use of tobacco, alcohol and drugs. In neither the Black nor White women was an association found between BV and measures of SES (with the sole exception of "absence of a home telephone"). Most measures of SES do not explain the difference in rates of BV in Black and in White pregnant women.

The preterm prediction study: granulocyte colony-stimulating factor and spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: Granulocyte colony-stimulating factor is elevated in the amniotic fluid and plasma of women with chorioamnionitis and active preterm labor. We investigated the relationship between plasma granulocyte colony-stimulating factor and subsequent spontaneous preterm birth in pregnant women without symptoms. STUDY DESIGN: We performed a nested case-control study involving 194 women who had a singleton spontaneous preterm birth and 194 matched term control subjects from the patient pool (n = 2929) enrolled in the Preterm Prediction Study. Plasma collected at 24 and 28 weeks' gestation was analyzed for granulocyte colony-stimulating factor, and the results were compared with subsequent spontaneous preterm birth. RESULTS: Compared with term control subjects, women who were delivered of their infants spontaneously at <28 weeks' gestation had increased mean granulocyte colony-stimulating factor values at 24 weeks' gestation (84.7 +/- 38.4 vs 67.7 +/- 28.6 pg/mL; P =.049), and women who were delivered of their infants at <32 weeks' gestation had increased mean plasma granulocyte colony-stimulating factor values at 28 weeks' gestation (80.4 +/- 24.1 vs 55.9 +/- 16.5 pg/mL; P =. 001). At 24 weeks' gestation a granulocyte colony-stimulating factor value >75th percentile in control subjects (approximately 80 pg/mL) was found in 48.9% (23/47) of all women delivered of their infants at <32 weeks' gestation versus 14.9% (7/47) of the term control subjects (adjusted odds ratio, 6.2; 95% confidence interval, 1.8-20. 8). At 28 weeks' gestation a granulocyte colony-stimulating factor value >75th percentile was found in 36.8% (7/19) of women delivered of their infants at <32 weeks' gestation versus 5.3% (1/19) of term control subjects (adjusted odds ratio, 25.7; 95% confidence interval, 1.5-470.4). When measured at 24 or 28 weeks' gestation, granulocyte colony-stimulating factor did not predict spontaneous preterm birth at 32 to 34 weeks' gestation or at 35 to 36 weeks' gestation. CONCLUSION: In pregnant women without symptoms at 24 and 28 weeks' gestation, elevated plasma granulocyte colony-stimulating factor levels are associated with subsequent early (<32 weeks' gestation) spontaneous preterm birth, especially within the next 4 weeks, but not with late spontaneous preterm birth. These data provide further evidence that early spontaneous preterm birth is associated with an inflammatory process that is identifiable by the presence of a cytokine in maternal plasma several weeks before the early spontaneous preterm birth; however, later spontaneous preterm birth is not associated with this process.

The Preterm Prediction Study: sequential cervical length and fetal fibronectin testing for the prediction of spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVES: This study was undertaken to further elucidate the pathogenesis of preterm birth by means of traditional risk factors and new markers for preterm birth derived from the Preterm Prediction Study. STUDY DESIGN: A total of 3076 women (2929 with singleton gestations and 147 with twin pregnancies) were categorized according to the presence of risk factors including black race, low body mass index, the presence of bacterial vaginosis, and previous preterm birth. At 24 and 28 weeks' gestation cervical length was measured and categorized as short (25 mm). Vaginal and cervical fetal fibronectin concentrations were measured at 24, 26, 28, and 30 weeks' gestation and results were categorized as positive (>/=50 ng/mL) or negative (<50 ng/mL). RESULTS: At 24 to 26 weeks' gestation women with each of the risk factors were more likely to have positive fibronectin test results or to have a short cervix. Among women with negative fetal fibronectin results at 24 to 26 weeks' gestation those with a short cervix were more likely to have positive fetal fibronectin results at 28 to 30 weeks' gestation, and among those with normal cervical length those women who had positive fetal fibronectin results were more likely to have a short cervix at later evaluation. Most women who had positive fetal fibronectin results at 24 to 26 weeks' gestation had negative results at 28 to 30 weeks' gestation, whereas most but not all women who had a short cervix at 24 to 26 weeks' gestation still had a short cervix at 28 to 30 weeks' gestation. In each period women with both a positive fetal fibronectin result and a short cervix were at substantially increased risk of spontaneous preterm birth; women with either marker alone had intermediate and approximately equal risks of spontaneous preterm birth, and women without either marker had a low risk of spontaneous preterm birth. CONCLUSION: Regardless of other risk factors, a short cervix predicts a subsequent positive fetal fibronectin result, and a positive fetal fibronectin result predicts subsequent cervical shortening. These data do not support a single sequence of events leading to spontaneous preterm birth.

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.

The preterm prediction study: effect of gestational age and cause of preterm birth on subsequent obstetric outcome. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: We sought to evaluate the association between prior spontaneous preterm delivery and subsequent pregnancy outcome. STUDY DESIGN: A total of 1711 multiparous women with singleton gestations were prospectively evaluated at 23 to 24 weeks' gestation. Prior pregnancies were coded for the presence or absence of a prior spontaneous preterm delivery. If a prior spontaneous preterm delivery had occurred, the gestation of the earliest prior delivery (13-22, 23-27, 28-34, and 35-36 weeks' gestation) was recorded. Current gestations were categorized as spontaneous preterm delivery at <28, <30, <32, <35, or <37 weeks' gestation. The risk of spontaneous preterm delivery in the current gestation was determined on the basis of the occurrence, gestational age, and cause of the earliest prior spontaneous preterm delivery. RESULTS: The incidences of spontaneous preterm delivery before 28, 30, 32, 35, and 37 weeks' gestation were 0.8%, 1.1%, 1.9%, 5.1%, and 11.9%, respectively. Those with a prior spontaneous preterm delivery carried a 2.5-fold increase in the risk of spontaneous preterm delivery in the current gestation over those with no prior spontaneous preterm delivery (21. 7% vs 8.8%; P

Fetal membrane histology in preterm premature rupture of membranes: comparison to controls, and between antibiotic and placebo treatment. The National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network, Bethesda, MD, USA.

The objectives of this study were to test the hypotheses that antibiotic therapy will alter the histologic appearance of fetal membranes in preterm premature rupture of membranes (pPROM), and that the membrane histology will demonstrate distinct differences between term and preterm rupture of membranes. We also wished to test interobserver variability of pathologists. Placental membranes were sampled from 268 women participating in a randomized placebo-controlled trial of antibiotic therapy for pPROM at 24-32 weeks of gestation (cases) and from 4 control groups who were not in the randomized trial: (1) preterm labor without pPROM (n = 21), (2) term labor (n = 65), (3) term PROM (n = 21), and (4) term cesarean section (n = 27). The cases and controls were scored for 40 histologic features by pathologists blinded to the identity of each sample (case or control). pPROM histology of samples from patients receiving antibiotics and those receiving placebo was compared using a chi-squared test and with control groups using logistic regression. There were no histological differences between pPROM cases treated with antibiotic and those receiving placebo, nor with respect to duration of membrane rupture greater or less than 48 h. Concordance among pathologists was low for features other than acute inflammation. Logistic regression analysis controlled for race and pathologist, and demonstrated that all of the control groups had significantly fewer common markers of acute inflammation when compared with the pPROM cases. This study suggests that histopathologic evidence of infection is seen more frequently with pPROM than in preterm or term controls. The histologic features used in this study cannot be used to determine the effectiveness of antibiotic therapy.

Plasma ferritin, premature rupture of membranes, and pregnancy outcome.

OBJECTIVE: The objective of this study was to determine whether plasma ferritin levels predict maternal or neonatal outcomes in women with preterm rupture of membranes at <32 weeks' gestation. METHODS: Plasma from 223 women with premature rupture of membranes at <32 weeks' gestation who had participated in a randomized antibiotic trial were analyzed for ferritin at random assignment and at delivery, and the results were compared with the development of clinical chorioamnionitis, latency until delivery, neonatal sepsis, and a composite adverse neonatal outcome variable. RESULTS: The mean plasma ferritin level rose from 19.2 +/- 29.1 microgram/L on admission to 38.3 +/- 54.3 microgram/L at delivery, with a mean latency of 9.3 +/- 14.6 days. Plasma ferritin levels were significantly higher at both times in mothers whose infants acquired sepsis than in those whose infants did not, especially at delivery (68.5 +/- 96.3 microgram/L vs 32.5 +/- 40.5 microgram/L, P =.01), and neonatal sepsis was 2 to 3 times more common among women with plasma ferritin levels above the median than among those with levels below the median. CONCLUSIONS: Among women with premature rupture of membranes at <32 weeks' gestation, plasma ferritin levels were significantly associated with neonatal sepsis. These data suggest that higher plasma ferritin levels may serve as a marker of infection among women with premature rupture of membranes; however, the clinical utility of plasma ferritin levels in predicting neonatal outcome appears limited.

The Preterm Prediction Study: recurrence risk of spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: We sought to estimate the risk of spontaneous preterm birth in parous women by use of obstetric history, fetal fibronectin, and sonographic cervical length. STUDY DESIGN: The probability of spontaneous preterm birth before 35 weeks' gestation was estimated from a logistic regression model with data from 1282 parous women analyzed according to gestational age at the most recent prior delivery (prior preterm birth at 18 to 26 weeks, 27 to 31 weeks, 32 to 36 weeks, and > or = 37 weeks' gestation), fetal fibronectin status (positive = > or = 50 ng/dl), and cervical length by percentile groups (< or = 10th = < or = 25 nm, 10th to 50th = 26 to 35 mm, and > 50th = > 35 mm) measured at 22 to 24 weeks' gestation. Fibronectin and cervical length results were blinded for clinical care. RESULTS: Among fetal fibronectin positive women with a prior preterm birth, the estimated recurrence risk of preterm birth < 35 weeks' gestation was approximately 65% when the cervix was < or = 25 mm, 45% when the cervix was 26 to 35 mm, and 25% when the cervix was > 35 mm at 24 weeks' gestation. For fetal fibronectin negative women with a prior preterm birth, the recurrence risk was 25% when the cervix was < or = 25 mm, 14% when the cervix was 26 to 35 mm, and 7% when the cervix was > 35 mm. The risk of preterm birth was increased among women with a history of preterm delivery but was not influenced by the gestational age at delivery of the most recent preterm birth. CONCLUSION: The recurrence risk of spontaneous preterm birth varies widely according to fetal fibronectin and cervical length. Cervical length and fetal fibronectin results had distinct and significant effects on the recurrence risk of preterm birth. Predicted recurrence risk is increased by twofold to fourfold in women with a positive compared with a negative fetal fibronectin, and it increases as cervical length shortens in both fetal fibronectin-positive and fetal fibronectin-negative women. These data may be useful to care for women with a history of preterm birth and to design studies to prevent recurrent premature delivery.

A randomized trial of nurse intervention to reduce preterm and low birth weight births.

OBJECTIVE: To test the effect of telephone calls from registered nurses to low-income pregnant women on the rates of low birth weight (LBW) and preterm births. METHODS: A total of 1554 women receiving prenatal care in a public clinic who met study criteria and who consented were assigned randomly to intervention and control groups. Women in the intervention group received telephone calls from a registered nurse, one or two times weekly from 24 weeks' through 37 weeks' gestation. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated. RESULTS: Low birth weight rates were 10.9% in the intervention group and 14.0% in the control group (RR 0.75; 95% CI 0.55, 1.03; P = .072). For gestational age less than 37 weeks, rates were 9.7 in the intervention group and 11.0 in the control group (RR .87; 95% CI 0.62, 1.22; P = .415). In the subgroup of low-income black women 19 years of age and older, a statistically significant difference was found in preterm birth rates before 37 weeks (8.7% in the intervention group versus 15.4% in the controls [RR 0.56; 95% CI 0.38, 0.84; P = .004]). CONCLUSION: There was no difference in LBW or preterm births between intervention and control groups in the total sample. In a secondary analysis of black subjects 19 years of age and older, there was a significant difference in preterm birth rates.

The preterm prediction study: risk factors for indicated preterm births. Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development.

OBJECTIVE: Preterm births occur for many different reasons. Most efforts to identify risk factors for preterm births either ignore cause and consider preterm births as a single entity or examine risk factors for spontaneous preterm births. We performed this study to examine risk factors for indicated preterm births, which constitute more than one quarter of all preterm births. STUDY DESIGN: The study included 2929 women evaluated at 24 weeks' gestation at 10 centers. Information was gathered about demographic factors, socioeconomic status, home and work environments, drug and alcohol use, and medical history. In addition vaginal samples were evaluated for fetal fibronectin and bacterial vaginosis and cervical length was measured by transvaginal ultrasonography. Associations with indicated preterm birth were evaluated by univariate tests and by multivariable analysis with logistic regression. RESULTS: Of the women studied at 24 weeks' gestation 15.3% were delivered of their infants at <37 weeks' gestation. Of these deliveries, 27.7% were indicated preterm births. Risk factors in the final multivariable model were, in order of decreasing odds ratios, mullerian duct abnormality (odds ratio 7.02), proteinuria at <24 weeks' gestation (odds ratio 5.85), history of chronic hypertension (odds ratio 4.06), history of previous indicated preterm birth (odds ratio 2.79), history of lung disease (odds ratio 2.52), previous spontaneous preterm birth (odds ratio 2.45), age >30 years (odds ratio 2.42), black ethnicity (odds ratio 1.56), and working during pregnancy (odds ratio 1.49). Alcohol use in pregnancy was actually associated with a lower risk of indicated preterm birth (odds ratio 0.35). CONCLUSION: The risk factors found in this analysis tend to be different from those associated with spontaneous preterm birth.

Intrauterine infection and the risk of cerebral palsy in very low-birthweight infants.

Very low-birthweight infants constitute more than one-quarter of all new cases of cerebral palsy. We performed a case-control study of associations between antenatal maternal infection and cerebral palsy in very low-birthweight infants. Cases and controls were selected from a cohort of 1238 consecutive infants who: (1) had birthweights between 500 and 1500 g and no major congenital anomaly; (2) were born 1 January 1986 to 31 December 1993 to a mother residing in 1 of 17 counties in north-west North Carolina; and (3) were delivered at the only tertiary obstetric referral centre in those same 17 counties. A total of 984 of these infants (79%) survived to 1 year of age (adjusted for degree of prematurity) and were scheduled for a multidisciplinary examination; 815 (83%) came as scheduled. Excluding two cases attributable to post-neonatal events, 62 cases of cerebral palsy were identified. Controls were the two infants, without cerebral palsy, born closest in time to each case. Medical records were reviewed by a nurse who was not aware of which subjects were cases. Among possible markers of intra-amniotic infection, those associated most strongly with cerebral palsy were chorioamnionitis diagnosed by an obstetrician (odds ratio [OR] adjusted for gestational age [95% confidence limits] = 2.6 [1.0, 6.5]), antepartum maternal temperature > 37.8 degrees C (OR = 2.6 [1.1, 6.0]), uterine tenderness (OR = 2.6 [0.8, 9.3]), maternal receipt of antibiotics (OR = 2.2 [1.0, 4.7]) and neonatal sepsis in the first week of life (OR = 2.9 [0.9, 8.9]). All of these associations were stronger for diplegia than the other clinical subtypes of cerebral palsy. The association with chorioamnionitis and spastic diplegia persisted when adjusted for maternal magnesium sulphate receipt, maternal betamethasone receipt, method of delivery (vaginal vs. abdominal), acidosis on the neonate's initial arterial blood gas, systolic blood pressure < 30 mmHg and the diagnosis of major neonatal neurosonographic abnormality.

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.