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The purpose of this study was to examine the utility of a single second-trimester plasma corticotropin-releasing hormone measurement as a marker for preterm delivery in women at high risk for preterm delivery.This is an analysis of data from a multicenter placebo-controlled trial designed to evaluate the role of 17 alpha hydroxyprogesterone caproate (17P) in the prevention of recurrent preterm birth. Women with a documented history of a previous spontaneous preterm birth at37 weeks were enrolled (16-20 wks) and randomly assigned in a 2 to 1 ratio to weekly injections of 17P or matching placebo. Blood was collected before treatment in 170 patients (113 assigned 17P and 57 placebo) who were enrolled at 11 of the 19 centers. Plasma levels of corticotropin-releasing hormone were compared between those who delivered preterm and those delivering at term. Data were analyzed using the Wilcoxon rank-sum test.The overall rates of preterm birth in this cohort of 170 patients were 35.9% at37 weeks (31.9% progesterone, 43.9% placebo), and 19.4% at35 weeks (18.6% vs 21.1%). The median levels of corticotropin-releasing hormone were similar between those delivering at37 weeks and those deliveringor = 37 weeks (0.39 ng/mL vs 0.37 ng/mL, P = .08). In addition, there were no differences in corticotropin-releasing hormone levels among those who delivered at35 weeks oror = 35 weeks (0.36 vs 0.38, P = .90). Moreover, there were no differences in corticotropin-releasing hormone levels among those in the placebo group who delivered at37 oror = 37 weeks (0.40 vs 0.41, P = .72) and at35 oror = 35 weeks (P = .64).A single measurement of corticotropin-releasing hormone at 16 to 20 weeks' gestation is not a good biomarker for recurrent preterm delivery in patients at high risk for this complication.

Objective To examine how demographic and pregnancy characteristics can affect the risk of recurrent preterm delivery and the how the effectiveness of progesterone treatment for prevention alters these relationships. Methods This was a secondary analysis of a randomized trial of 17alpha-hydroxyprogesterone caproate to prevent recurrent preterm delivery in women at risk. Associations of risk factors for preterm delivery (less than 37 completed weeks of gestation) were examined separately for the women in the 17alpha-hydroxyprogesterone caproate (n = 310) and placebo (n = 153) groups. Results Univariate analysis found that the number of previous preterm deliveries and whether the penultimate delivery was preterm were significant risk factors for preterm delivery in both the placebo and progesterone groups. High body mass index was protective of preterm birth in the placebo group. Multivariate analysis found progesterone treatment to cancel the risk of more than 1 previous preterm delivery, but not the risk associated with the penultimate pregnancy delivered preterm. Obesity was associated with lower risk for preterm delivery in the placebo group but not in the women treated with progesterone. Conclusion The use of 17alpha-hydroxyprogesterone caproate in women with a previous preterm delivery reduces the overall risk of preterm delivery and changes the epidemiology of risk factors for recurrent preterm delivery. In particular, these data suggest that 17alpha-hydroxyprogesterone caproate reduces the risk of a history of more than 1 preterm delivery. Level of evidence I.

Objective This study was undertaken to determine rates of recurrent preterm birth according to number of prior preterm births, 1 versus 2 or more and cervical length by endovaginal ultrasound at 22 0 to 24 6 weeks, less than 25 mm versus more than 25 mm. Study design We retrospectively analyzed data from charts of women with prior spontaneous preterm birth seen in a Prematurity Prevention Clinic from 1998 through 2004. Women with a history of 1 or more spontaneous preterm births (18 0 -36 6 weeks) were included. Women with multiple gestations, uterine anomalies, and prior cervical surgery were excluded. Transvaginal sonography was used to evaluate each woman's cervical length at 22 0 to 24 6 weeks. Cerclage, bed rest, tocolysis, and steroids were used when clinically appropriate. Primary outcome was gestational age at delivery less than 32 and less than 35 weeks. Data were analyzed according to number of prior preterm births (1 vs ≥2) and sonographic cervical length at 22 0 to 24 6 weeks ( Results A total of 188 eligible women were evaluated. Median gestational age of earliest preterm birth was 26.3 weeks. Of the total 188, 118 (62.8%) women had 1 prior and 70 (37.2%) had 2 or more preterm births. Thirty-eight (20.2%) of the women had a cervical length less than 25 mm and 150 (79.8%) had a cervical length 25 mm or greater. A higher percentage of women with a cervical length less than 25 mm and 2 or more preterm births delivered less than 32 weeks compared with women with 1 prior preterm birth, although this did not reach statistical significance (21.5% vs 12.5%, P =.47). Rates of delivery less than 35 weeks in women with a cervical length less than 25 mm were similar in those with a history of 1 and 2 or more preterm births. Women who had 2 or more prior preterm births were analyzed separately to identify if a cervical length greater than 30 mm or greater than 35 mm could be reassuring for decreasing the risk of recurrent preterm birth. Conclusion Rates of preterm birth less than 32 and less than 35 weeks were similar in women whose cervical length was less than 25 mm at 22 0 to 24 6 weeks, regardless of number of prior preterm births. Women with 2 prior preterm births and a cervix greater than 35 mm were at low risk for subsequent preterm birth less than 35 weeks.

The purpose of this study was to compare perinatal outcomes among women with conservatively treated preterm premature rupture of membranes at 24 to 32 weeks of gestation in the presence or absence of vaginal bleeding.This is a secondary analysis of 581 women with and without vaginal bleeding within 1 week of admission with preterm premature rupture of membranes at 24 to 32 weeks of gestation who were enrolled in a multicenter trial of antibiotic therapy during conservative treatment. The main outcome was latency to delivery. Other outcome variables included clinical abruptio placentae, amnionitis, perinatal death, severe intraventricular hemorrhage, and respiratory distress syndrome.Outcome data were available for 581 patients (n=50 with bleeding). Latency to delivery was not affected by the presence or absence of bleeding. In general, a history of bleeding was associated with higher frequencies of subsequently diagnosed abruptio placentae (12% vs 3.5%; P=.01), perinatal death (16% vs 4.9%; P=.006), intraventricular hemorrhage (14.3% vs 5.9%; P=.03), and respiratory distress syndrome (69.4% vs 40.4%; P.0001), when compared with those women with nonbleeding events. Women with bleeding were less likely to be black (42% vs 60%; P=.002) and had a lower mean gestational age at preterm premature rupture of membranes (27.6 vs 28.5 weeks; P=.02) when compared with white, Hispanic, and other. After an adjustment of data was made for potentially confounding factors, women with recent bleeding were more likely to be diagnosed with abruptio placentae at delivery (odds ratio, 2.8; 95% CI, 1.03-7.8; P=.04), and their infants were more likely to have respiratory distress syndrome (odds ratio, 3.1; 95% CI, 1.5-6.6; P=.004).Vaginal bleeding before preterm premature rupture of membranes is associated with increased rates of neonatal respiratory distress syndrome and abruptio placentae, but not with reduced latency to delivery.

The purpose of this study was to compare the frequency of uterine contractions in asymptomatic pregnant women with and without a short cervix (25 mm) on transvaginal ultrasound (TVU) and to determine the additive risk of contractions on the risk of preterm birth.The study involved secondary analysis of a blinded observational study of asymptomatic singleton pregnancies who were at high risk for preterm birth and who received both home uterine activity monitoring daily and transvaginal ultrasound of the cervix at 22 to 24 and 27 to 28 weeks of gestation. Thresholds for the maximum frequency of uterine contractions of 4 per hour and transvaginal ultrasound cervical length of 25 mm were used for analysis. Contraction frequency was compared in women with cervical length25 mm andor =25 mm and was correlated with the risk of spontaneous preterm birth at35 weeks of gestation.Of the 303 women whose pregnancy was evaluated at 22 to 24 weeks of gestation, the 39 women (13%) with a cervical length of25 mm had 1.6 +/- 2.7 versus 1.2 +/- 2.0 contractions per hour in the 264 women (87%) with a cervical length ofor =25 mm (P=.37). At 27 to 28 weeks of gestation (n=295 women), contraction frequency was 3.2 +/- 3.7 versus 2.8 +/- 3.1 contractions per hour in women with a cervical length of25 mm (n=59 women; 20%) versus those with a cervical length ofor =25 mm (n=236 women; 80%; P=.34). Among women with a short cervix, the relative risks for spontaneous preterm birth were 2.0 (95% CI, 0.95-4.2) and 2.1 (95% CI, 1.06-4.3) for women withor =4 contractions per hour compared with women with4 contractions per hour at 22 to 24 and 27 to 28 weeks of gestation, respectively. Results were confirmed by logistic regression analysis.The frequency of uterine contractions in asymptomatic women was not related significantly to cervical length of25 mm versusor =25 mm. Among women with a cervical length of25 mm at 22 to 24 or 27 to 28 weeks of gestation, there was a trend toward a 2-fold increased risk of spontaneous preterm birth when the maximum contraction frequency wasor =4 per hour, compared to4 per hour.

Very low birth weight (VLBW

Background Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery. Methods We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle. Results Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 1...

When extremely preterm birth is anticipated, a reliable estimate of neonatal outcome is essential for the parents and health care providers who face difficult management decisions. Estimates of birth weight and gestational age are most commonly used for this purpose. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (NICHD MFMU) Network performed an observational study of data available before delivery of infants with birth weights1000 g. Ultrasonographic variables (estimated fetal weight, obstetrically estimated gestational age, femur length, and biparietal diameter) and clinical variables (maternal race, antenatal care, substance abuse, medical treatment, reason for delivery, fetal gender, and presentation) were studied as predictors of intrapartum stillbirth, neonatal death, survival to 120 days after birth or to discharge, and with markers of "serious" morbidity (high-grade intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, oxygen dependence at discharge or 120 days, and seizures). Survival without serious morbidity was considered "intact." Logistic regression was used to evaluate the influence of the obstetrician's opinion of viability and willingness to perform cesarean delivery for fetal distress, birth weight, growth, gender, presentation, and ethnicity on outcomes. Fetal femur length and estimated gestational age predicted survival better than did biparietal diameter or estimated fetal weight. Antenatal ultrasound and clinical data did not distinguish those infants who would suffer serious morbidity or be considered intact. Willingness to perform cesarean delivery was associated with increased likelihood of both survival and intact survival by virtually eliminating intrapartum stillbirth and reducing neonatal mortality. However, such practice was associated with an increased chance of serious morbidity among survivors below 800 g or 26 weeks'. 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 in survivors at that gestational age.

The Preterm Prediction Study conducted by the Maternal Fetal Medicine Network between 1993 and 1996 studied a large number of risk factors for preterm birth in more than 3,000 women at 10 centers. The goals of the study were to better understand the strength of one risk factor versus another and to explore interactions among the predictors looking for combinations of factors that were more predictive of preterm birth than any single factor used alone. The most potent factors that were associated with spontaneous preterm birth at32 weeks were a positive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) andl0th 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), and75th percentile of granulocyte colony-stimulating factor (odds ratio, 5.5). Results for spontaneous preterm birth at35 weeks were generally similar but not as strong. The overlap among the strongest biologic markers for predicting spontaneous preterm birth was small. This suggests that the use of tests such as maternal alpha-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor as a group or adding their results to fetal fibronectin 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.

Uterine contractions, decidual activation, and cervical competence comprise the fundamental components in contemporary models of the spontaneous preterm birth syndrome, but their relative importance and interactive pathways remain poorly defined. Moreover, the traditional concept that the cervix is either competent or incompetent has been challenged because cervical competence more likely functions along a biologic continuum. Cervical incompetence is a clinical diagnosis characterized by recurrent painless dilation and spontaneous midtrimester birth. Although the efficacy of cerclage for cervical incompetence has never been fully confirmed in randomized clinical trials, the role of cerclage has been expanded to include women with "risk factors" for spontaneous preterm birth or nonreassuring sonographic cervical findings in the mid trimester. Evidence from randomized trials suggests that cerclage has limited efficacy in women with risk factors for cervical incompetence. Results of both retrospective cohort series and randomized trials of cerclage in women with shortened cervical length are inconclusive. We believe that women with a prior early spontaneous preterm birth and shortened midtrimester cervical length represent an ideal population for the conduct of a randomized trial of cerclage, which is currently underway.

OBJECTIVE: To estimate the mean levels of fetal fibronectin in cervicovaginal secretions of women with preeclampsia and compare them with levels in normotensive controls. METHODS: Cervicovaginal swabs were obtained before digital examination from women who presented to labor and delivery for evaluation of preeclampsia and compared with fetal fibronectin levels from a group of control subjects with a similar gestational age. Fetal fibronectin was assayed by a specific enzyme-linked immunoassay. A concentration greater than 50 ng/mL was considered a positive result. RESULTS: Forty women with preeclampsia (17 mild and 23 severe) and 31 normotensive women were analyzed. The control group had 9.7% positive fetal fibronectins, whereas the preeclampsia group had 15% positive, P = .72, with 80% power to detect a 22% difference. The majority of the quantitative values in both groups were less than 20 ng/mL. There was not a significant difference between the two groups in quantitative cervicovaginal fetal fibronectin, P = .72, nor was there a difference between the women with severe preeclampsia and the controls, P = 1.0, or between the nulliparous women with preeclampsia versus the nulliparous controls, P = .3. CONCLUSION: Fetal fibronectin is not elevated in cervicovaginal secretions of women with preeclampsia.

High levels of a number of analytes are found in maternal blood; alkaline phosphatase,alpha-fetoprotein, and corticotropin-releasing hormone have been associated with spontaneous preterm birth. We investigated the relationship between 8 potential blood markers and subsequent spontaneous preterm birth in asymptomatic pregnant women.We performed a nested case control study that involved 127 women who were enrolled in the preterm prediction study and who had a singleton spontaneous preterm birth at35 weeks and 127 women who had a term birth and served as matched (age, parity, center) controls. Serum that was collected at 24 and 28 weeks was analyzed for alkaline phosphatase, alpha-fetoprotein, corticotropin-releasing hormone, and 5 other analytes.Alkaline phosphatase, alpha-fetoprotein, and corticotropin-releasing hormone, but not other analytes, were significantly elevated in pregnancies that ended in spontaneous preterm birth. For alkaline phosphatase at 24 weeks, the odds ratio for spontaneous preterm birth at32 weeks was 6.8 (range, 1.4-32.8) and for spontaneous preterm birth at35 weeks 5.1 (range, 1.7-15.6). Similar results were found at 28 weeks. For alpha-fetoprotein at 24 weeks, the odds ratio for spontaneous preterm birth at32 weeks was 8.3 (range,2.2-30.9) and for spontaneous preterm birth at35 weeks was 3.5 (range, 1.8-6.7). The levels at 28 weeks were still predictive but less so than at 24 weeks. Corticotropin-releasing hormone, at 28 weeks but not at 24 weeks, was predictive for spontaneous preterm birth at35 weeks, with an odds ratio 3.4 (range, 1.0-10.9).Elevated alkaline phosphatase and alpha-fetoprotein are associated with subsequent spontaneous preterm birth in asymptomatic pregnant women at 24 and 28 weeks. Elevated corticotropin-releasing hormone levels at 28 weeks are associated with spontaneous preterm birth at35 weeks.

OBJECTIVE: Low serum ferritin levels correlate with low iron stores, whereas high levels are associated with an acute-phase reaction. Our objective was to determine whether elevated levels of ferritin in the genital tract may be a potent marker to identify patients at risk for spontaneous preterm delivery. STUDY DESIGN: We performed a nested case-control study involving 182 women who had spontaneous preterm delivery and 182 term control subjects matched for race, parity, and recruitment center, and selected from 2929 women enrolled in the Preterm Prediction Study of the National Institute of Child Health and Development Maternal-Fetal Medicine Units Network. Cervical fluid ferritin was measured by use of radioimmunoassay. RESULTS: Cervical ferritin levels were significantly higher in women who subsequently had spontaneous early preterm delivery ( P =.002; and P =.004) than in term controls. A cervical ferritin of >75th percentile in the controls (>35.5 ng/mL) was found in 52.9% (9/17) of the women delivered CONCLUSIONS: Elevated cervical ferritin levels at 22 to 24 weeks of gestation in asymptomatic women are associated with subsequent spontaneous preterm birth. The strong correlation of cervical ferritin with other inflammatory markers provides support for the hypothesis of infection as a mediator of preterm delivery. (Am J Obstet Gynecol 2002;186:458-63.)

The measurement of the frequency of uterine contractions has not been useful for reducing the rate of preterm delivery in randomized trials. Nonetheless, ambulatory monitoring of contractions continues to be used in clinical practice.We assessed the frequency of uterine contractions as a predictor of the risk of spontaneous preterm delivery before 35 weeks of gestation. We enrolled women with singleton pregnancies between 22 and 24 weeks of gestation. The women used a contraction monitor at home to record contraction frequency twice daily on 2 or more days per week from enrollment to delivery or 37 weeks of gestation.We obtained 34,908 hours of successful monitoring recordings from 306 women. Although more contractions were recorded from women who delivered before 35 weeks than from women who delivered at 35 weeks or later, we could identify no threshold frequency that effectively identified women who delivered preterm infants. The sensitivity and positive predictive value of a maximal hourly frequency of contractions of four or more between 4 p.m. and 3:59 a.m. were 9 percent and 25 percent, respectively, at 22 to 24 weeks and 28 percent and 23 percent at 27 to 28 weeks. Other proposed screening tests, such as digital and ultrasound evaluations of the cervix and assays for fetal fibronectin in cervicovaginal secretions, also had low sensitivity and positive predictive value for preterm labor.Although the likelihood of preterm delivery increases with an increased frequency of uterine contractions, measurement of this frequency is not clinically useful for predicting preterm delivery.

Background Experimental and epidemiologic data suggest that among nonpregnant adults, sleep duration may be an important risk factor for chronic disease. Although pregnant women commonly report poor sleep, few studies objectively evaluated the quality of sleep in pregnancy or explored the relationship between sleep disturbances and maternal and perinatal outcomes. Objective Our objective was to examine the relationship between objectively assessed sleep duration, timing, and continuity (measured via wrist actigraphy) and maternal cardiovascular and metabolic morbidity specific to pregnancy. Study Design This was a prospective cohort study of nulliparous women. Women were recruited between 16 0/7 and 21 6/7 weeks' gestation. They were asked to wear a wrist actigraphy monitor and complete a daily sleep log for a period of 7 consecutive days. The primary sleep exposure variables were the averages of the following over the total valid nights (minimum 5, maximum 7 nights): short sleep duration during the primary sleep period ( 5 am), and top quartile of minutes of wake time after sleep onset and sleep fragmentation index. The primary outcomes of interest were a composite of hypertensive disorders of pregnancy (mild, severe, or superimposed preeclampsia; eclampsia; or antepartum gestational hypertension) and gestational diabetes mellitus. We used χ 2 tests to assess associations between sleep variables and categorical baseline characteristics. Crude odds ratios and 95% confidence intervals were estimated from univariate logistic regression models to characterize the magnitude of the relationship between sleep characteristics and hypertensive disorders of pregnancy and gestational diabetes. For associations significant in univariate analysis, multiple logistic regression was used to explore further the association of sleep characteristics with pregnancy outcomes. Results In all, 901 eligible women consented to participate; 782 submitted valid actigraphy studies. Short sleep duration and a later sleep midpoint were associated with an increased risk of gestational diabetes (odds ratio, 2.24; 95% confidence interval, 1.11–4.53; and odds ratio, 2.58; 95% confidence interval, 1.24–5.36, respectively) but not of hypertensive disorders. A model with both sleep duration and sleep midpoint as well as their interaction term revealed that while there was no significant interaction between these exposures, the main effects of both short sleep duration and later sleep midpoint with gestational diabetes remained significant (adjusted odds ratio, 2.06; 95% confidence interval, 1.01–4.19; and adjusted odds ratio, 2.37; 95% confidence interval, 1.13–4.97, respectively). Additionally, after adjusting separately for age, body mass index, and race/ethnicity, both short sleep duration and later sleep midpoint remained associated with gestational diabetes. No associations were demonstrated between the sleep quality measures (wake after sleep onset, sleep fragmentation) and hypertensive disorders or gestational diabetes. Conclusion Our results demonstrate a relationship between short sleep duration and later sleep midpoint with gestational diabetes. Our data suggest independent contributions of these 2 sleep characteristics to the risk for gestational diabetes in nulliparous women.

Importance Spontaneous preterm birth is a leading cause of infant mortality. Prediction, largely based on prior pregnancy outcomes, is not possible in women pregnant for the first time. Objective To assess the accuracy of universal screening to predict spontaneous preterm birth in nulliparous women using serial measurements of vaginal fetal fibronectin levels and cervical length. Design, Settings, and Participants A prospective observational cohort study of nulliparous women with singleton pregnancies, from 8 clinical sites across the United States between October 2010 and May 2014. Women and clinicians were blinded to results unless cervical shortening less than 15 mm was identified. Exposures Transvaginal cervical length and quantitative vaginal fetal fibronectin levels were reviewed at 2 study visits 4 or more weeks apart. Main Outcomes and Measures Spontaneous preterm birth at less than 37 weeks was the primary outcome. Cervical length and quantitative fetal fibronectin were considered independently and together at each visit. Measurement distributions were compared for spontaneous preterm birth vs all other births. Spontaneous preterm birth before 32 weeks was a secondary outcome. Results The study included 9410 women (median age, 27.0 [interquartile range, 9.0] years; 60.7% non-Hispanic white, 13.8% non-Hispanic black, 16.5% Hispanic, 4.0% Asian, and 5.1% other), of whom 474 (5.0%) had spontaneous preterm births, 335 (3.6%) had medically indicated preterm births, and 8601 (91.4%) had term births. Among women with spontaneous preterm birth, cervical length of 25 mm or less occurred in 35 of 439 (8.0%) at 16 to 22 weeks’ gestation and in 94 of 403 (23.3%) at 22 to 30 weeks’ gestation. Fetal fibronectin levels of 50 ng/mL or greater at 16 to 22 weeks identified 30 of 410 women (7.3%) with spontaneous preterm birth and 31 of 384 (8.1%) at 22 to 30 weeks. The area under the receiver operating characteristic curve for screening between 22 and 30 weeks for fetal fibronectin level alone was 0.59 (95% CI, 0.56-0.62), for transvaginal cervical length alone was 0.67 (95% CI, 0.64-0.70), and for the combination as continuous variables was 0.67 (95% CI, 0.64-0.70). Conclusions and Relevance Among nulliparous women with singleton pregnancies, quantitative vaginal fetal fibronectin and serial transvaginal ultrasound cervical length had low predictive accuracy for spontaneous preterm birth. These findings do not support routine use of these tests in such women.

This study aims to evaluate whether magnesium sulfate administration for neuroprotection prolongs latency in women with preterm premature rupture of membranes (PPROM) between 24 and 31(6/7) weeks' gestation.This is a secondary analysis of a randomized controlled trial of magnesium sulfate for prevention of cerebral palsy. Gravid women with a singleton pregnancy between 24 and 31(6/7) weeks' gestation with PPROM without evidence of labor were randomized to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour up to 12 hours, or placebo. Maternal outcomes for this analysis were delivery in less than 48 hours and in less than 7 days from randomization. Neonatal outcomes included a composite of respiratory distress syndrome, interventricular hemorrhage grades 3 or 4, periventricular leukomalacia, sepsis, necrotizing enterocolitis, retinopathy of prematurity, or death.A total of 1,259 women were included. The rate of delivery48 hours was not different in the magnesium sulfate and the placebo groups (22.2 and 20.7%, p = 0.51). Delivery7 days was similar between groups (55.4 and 51.4%, p = 0.16). Median latency was also similar between groups (median [interquartile range], 6.0 days [range, 2.4-13.8 days] and 6.6 days [range, 2.4-15.1 days], p = 0.29). Composite neonatal outcomes did not differ between groups.Magnesium sulfate administration given for neuroprotection in women with a singleton gestation with PPROM and without labor before 32 weeks does not impact latency.

To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD).Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences.Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI.Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD.

Objective The purpose of this study was to determine whether hospital differences in the frequency of adverse obstetric outcomes are related to differences in care. Study Design The Assessment of Perinatal EXcellence cohort comprises 115,502 women and their neonates who were born in 25 hospitals in the United States between March 2008 and February 2011. Hierarchical logistic regression was used to quantify the amount of variation in postpartum hemorrhage, peripartum infection, severe perineal laceration, and a composite adverse neonatal outcome among hospitals that is explained by differences in patient characteristics, hospital characteristics, and obstetric care provided. Results The study included 115,502 women. For most outcomes, 20-40% of hospital differences in outcomes were related to differences in patient populations. After adjusting for patient-, provider-, and hospital-level factors, multiple care processes were associated with the predefined adverse outcomes; however, these care processes did not explain significant variation in the frequency of adverse outcomes among hospitals. Ultimately, 50-100% of the interhospital variation in outcomes was unexplained. Conclusion Hospital differences in the frequency of adverse obstetric outcomes could not be explained by differences in frequency of types of care provided.

To evaluate whether progestin prophylaxis influenced the odds of recurrent spontaneous preterm birth among pregnant women with a previous preterm birth.A retrospective cohort study was performed evaluating outcomes of pregnant women with one or more previous preterm births who received prenatal care in a single academic prematurity clinic. Care algorithms were determined and revised by a single supervising physician. Progestin prophylaxis was adopted in 2004 with accelerated access to the first clinic visit adopted in 2008. Rates of preterm birth before 37, 35, and 32 weeks of gestation were compared over time.One thousand sixty-six women with a history of one or more spontaneous preterm births received care in the prematurity clinic and were delivered between January 1, 1998, and June 30, 2012. The gestational age at initiation of prenatal care declined significantly after adoption of an accelerated appointment process (median of 19.1 weeks before 2003, 16.2 weeks from 2004 to 2007, and 15.2 weeks from 2008 to 2012, P.01), and progestin use increased from 50.8% in 2004-2007 to 80.3% after 2008 (P.01). After adjustment for race, smoking, cerclage, and number of prior preterm deliveries, we noted a statistically significant decreased odds of spontaneous preterm birth in years 2008-2012 compared with 1998-2007 before 37 (adjusted odds ratio [OR] 0.75, 95% confidence interval [CI] 0.58-0.97) and 35 (adjusted OR 0.70, 95% CI (.52-0.94) weeks of gestation.Adoption of prophylactic progestin treatment was associated with a decreased odds of recurrent preterm birth before 37 or 35 weeks of gestation after adoption of an aggressive program to facilitate early initiation of progestin treatment.II.

Objectives To evaluate the accuracy of sonographic classification of chorionicity in a large cohort of twins and investigate which factors may be associated with sonographic accuracy. Methods We conducted a secondary analysis of a randomized trial of preterm birth prevention in twins. Sonographic classification of chorionicity was compared with pathologic examination of the placenta. Maternal (age, body mass index, diabetes, and hypertension), obstetric (prior cesarean delivery, gestational age at the first sonographic examination, and antepartum bleeding), and sonographic (oligohydramnios, polyhydramnios, and twin-twin transfusion syndrome) factors were assessed for their possible association with accuracy. Results A total of 545 twin sets in which chorionicity was classified by sonography before 20 weeks' gestation were included; 455 were dichorionic and 90 were monochorionic based on pathologic examination. Sonography misclassified 35 of 545 twin pregnancies (6.4%): 18 of 455 dichorionic twins (4.0%) and 17 of 90 monochorionic twins (19.0%). The sensitivity and specificity of sonographic diagnosis of monochorionicity were 81.1% and 96.0%, respectively. In a multivariable analysis, pregnancies with initial sonographic examinations before 14 weeks' gestation were less likely to have misclassified chorionicity than those with sonographic examinations at 15 to 20 weeks (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.23-0.96). For each week increase in gestational age, the odds of misclassification rose by 10% (OR, 1.10; 95% CI, 1.01-1.2). In the multivariable analysis, maternal age, body mass index, parity, and prior cesarean delivery were not associated with sonographic accuracy. Conclusions Sonography before 20 weeks incorrectly classified chorionicity in 6.4% of twin gestations. Those with first sonographic examinations performed at earlier gestational ages had improved chorionicity diagnosis.

Objective 17-alpha hydroxyprogesterone caproate 250 mg weekly reduces recurrent spontaneous preterm birth in women with a prior spontaneous preterm birth by 33%. The dose is not based on pharmacologic considerations. A therapeutic concentration has not been determined hampering any attempt to optimize treatment. This study evaluated the relationship between 17-alpha hydroxyprogesterone caproate plasma concentrations and the rate of spontaneous preterm birth in women with singleton gestation. Study Design A single blood sample was obtained between 25 and 28 weeks' gestation from 315 women with a spontaneous preterm birth who participated in a placebo-controlled, prospective, randomized clinical trial evaluating the benefit of omega-3 supplementation in reducing preterm birth. All women in the parent study received 17-alpha hydroxyprogesterone caproate and 434 received omega-3 supplementation and 418 received a placebo. Plasma from 315 consenting women was analyzed for 17-alpha hydroxyprogesterone caproate concentration. Results There were no differences between placebo and omega-3 supplemented groups in demographic variables, outcomes or in mean 17-alpha hydroxyprogesterone caproate concentration. Plasma concentrations of 17-alpha hydroxyprogesterone caproate ranged from 3.7-56 ng/mL. Women with plasma concentrations of 17-alpha hydroxyprogesterone caproate in the lowest quartile had a significantly higher risk of spontaneous preterm birth ( P = .03) and delivered at significantly earlier gestational ages ( P = .002) than did women in the second to fourth quartiles. The lowest preterm birth rates were seen when median 17-alpha hydroxyprogesterone caproate concentrations exceeded 6.4 ng/mL. Conclusion Low plasma 17-alpha hydroxyprogesterone caproate concentration is associated with an increased risk of spontaneous preterm birth. This finding validates efficacy of this treatment but suggests that additional studies are needed to determine the optimal dosage.

Accurate diagnosis of preterm labor remains a problematic issue. New techniques such as transvaginal cervical sonography and fetal fibronectin are increasingly important in diagnosis and intervention planning. Neither test can, at present, be recommended for screening of the general population since there is no effective intervention for a positive test. Future directions in research include development of new tocolytic agents such as COX-2 inhibitors and clarification of the best use of adjunctive therapies such as betamethasone for lung maturity.

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 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 Results: In the univariate analysis, the most potent markers that are associated with spontaneous preterm birth at 90th percentiles of α-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 P Conclusion: Overlap among the strongest biologic markers for spontaneous preterm birth is small. This suggests that the use of tests such as maternal serum α-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. (Am J Obstet Gynecol 2001;185:643-51.)

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.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.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).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.

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.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 at20 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.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%).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.

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 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

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 χ 2 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. (Am J Obstet Gynecol 2001;184:438-46.)

Objective:The risk of spontaneous preterm birth has been related to decreased cervical length and to increased serum relaxin. To explore a relationship between these findings, we used data collected from two prior studies to correlate relaxin levels with cervical length and risk of spontaneous preterm birth in women with twin pregnancies.Methods:In a secondary analysis of data collected in two previous observational studies of risk factors for preterm birth, relaxin levels in maternal serum and cervical length were measured at 24 (n = 188) and 28 (n = 145) weeks in women with spontaneous twin pregnancies. Relaxin, as a continuous variable, was related by logistic regression analysis to risk of spontaneous preterm birth before 37, 35, and 32 weeks' gestation, and by Spearman correlation coefficients to cervical length at 24 and 28 weeks. Cervical length at 24 week was known to be correlated with spontaneous preterm birth before 37, 35, and 32 week (P = .03, .01, and .002, respectively) in this study popula...

Objective The aim of the article is to determine whether prior spontaneous abortion (SAB) or induced abortion (IAB), or the interpregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. Methods We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios (ORs) for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared with primigravid participants. Results Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (adj. OR, 1.5; 95% CI, 1.1–2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (PTB) (adj. OR, 2.6, 95% CI, 1.7–4.0), preterm premature rupture of membranes (PROM) (adj. OR, 2.9; 95% CI, 1.6–5.3), and perinatal death (adj. OR, 2.8; 95% CI, 1.5–5.3). Women with one previous IAB had higher rates of spontaneous PTB (adj. OR, 1.4; 95% CI, 1.0–1.9) and preterm PROM (OR, 2.0; 95% CI, 1.4–3.0). An interpregnancy interval less than 6 months after SAB was not associated with adverse outcomes. Conclusion Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes.

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 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 ≥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 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

Objective: This study was undertaken to determine the relationship among cervical lactoferrin concentration, other cervical markers potentially related to infection, and spontaneous preterm birth. Study Design: Cervical lactoferrin concentrations obtained at 22 to 24 weeks' gestation among 121 women who had a spontaneous preterm birth Results: Cervical lactoferrin concentrations ranged from not measurable (19% of the concentrations were below the threshold for this assay) to a titer of ≥1:64. There was no significant difference in the overall distributions of lactoferrin concentrations between the case patients and control subjects ( P =.18). Only when the highest titers of lactoferrin were considered were there more women in the spontaneous preterm birth group (6/121 vs 0/121; P =.03). According to Spearman correlation analyses the cervical lactoferrin concentrations were strongly related to interleukin 6 concentration ( r =.51; P =.0001), sialidase activity ( r =.38; P =.0001), and bacterial vaginosis ( r =.38; P =.0001), were weakly related to fetal fibronectin ( r =. 16; P =.01), and were not related to cervical length. With the 90th percentile (a dilution of 1:32) used as a cutoff to establish a dichotomous variable, lactoferrin concentration had the following odds ratios and 95% confidence intervals for associations with other potential markers of infection: bacterial vaginosis odds ratio, 4.8 (95% confidence interval, 2.2-10.3); interleukin 6 concentration odds ratio, 2.8 (95% confidence interval, 1.2-6.5); sialidase activity odds ratio, 5.5 (95% confidence interval, 2.2-13.7); fetal fibronectin concentration odds ratio, 0.6 (95% confidence interval, 0.2-2.0); chlamydiosis odds ratio, 2.3 (95% confidence interval, 0.8-6.9); and short cervix odds ratio, 0.5 (95% confidence interval, 0.2-1.4). Conclusions: Lactoferrin found in the cervix correlated well with other markers of lower genital tract infection. High lactoferrin levels were associated with spontaneous preterm birth but had a very low predictive sensitivity. (Am J Obstet Gynecol 2000;182:631-5.)

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) or normal (>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 ( 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. (Am J Obstet Gynecol 2000;182:636-43.)

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 2929 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.

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 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 ≤ .001). Gravid women with an early prior spontaneous preterm delivery (23-27 weeks' gestation) had a higher risk of recurrent spontaneous preterm delivery (27.1% vs 8.8%; P ≤ .001). Prior spontaneous preterm delivery was more closely associated with subsequent early spontaneous preterm delivery at P Conclusion: Prior spontaneous preterm delivery is highly associated with recurrence in the current gestation. An early prior spontaneous preterm delivery is more predictive of recurrence and is most highly associated with subsequent early spontaneous preterm delivery. (Am J Obstet Gynecol 1999;181:1216-21.)

Objective: Our objective was to determine any associations among midtrimester cervical fluid sialidase activity, bacterial vaginosis, and subsequent spontaneous preterm birth. Study Design: In this nested case-control study all patients (n = 126) with spontaneous preterm birth at Results: The mean ± SD sialidase activities were similar in case patients and control subjects (0.64 ± 1.60 vs 0.41 ± 0.94 nmol · mL –1 · min –1 , P = .21). Neither sialidase activity above the 90th percentile (10.3% vs 9.5%, P = .8) nor sialidase activity above the 95th percentile (7.9% vs 4.8%, P = .3) of control specimens (>1.43 and >2.23 nmol · mL –1 · min –1 , respectively) was associated with spontaneous preterm birth. The frequency of combinations of bacterial vaginosis and elevated sialidase activity was similar ( P ≥ .63 with either cutoff) in case patients and control subjects. Sialidase activity was significantly higher among women with bacterial vaginosis than among those without bacterial vaginosis (1.35 ± 1.87 vs 0.03 ± 0.14 nmol · mL –1 · min –1 , P Conclusions: Elevated cervical fluid sialidase activity at 22 to 24 weeks' gestation did not distinguish women at increased risk for spontaneous preterm birth, nor did it discriminate a subgroup of patients who had bacterial vaginosis associated with spontaneous preterm birth. (Am J Obstet Gynecol 1999;180:1151-4.)

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/=1000 g at birth.Maternal data available before the birth of singleton infants with birth weights/=1000 g who were delivered at the 11 tertiary perinatal centers of the National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Research Units were studied. Births that followed extramural delivery, antepartum stillbirths, multiple gestations, induced abortions, infants with major malformations, and fetuses delivered at20 weeks' gestation were excluded. Ultrasonographic variables, including estimated fetal weight, obstetrically estimated gestational age, femur length, and biparietal diameter, and clinical variables, such as maternal race, antenatal care, substance abuse, medical treatment, reason for delivery, fetal gender, and presentation, were studied with logistic regression as predictors of neonatal outcome, including intrapartum stillbirth, neonatal death, and survival to 120 days after birth or to discharge from the hospital with or without the presence of markers of major morbidity.Eight hundred eight infants met enrollment criteria; 63 were excluded because of incomplete data and 32 were excluded because of malformations, leaving 713 for analysis, 386 of whom had an ultrasonographic examination within 3 days of delivery that recorded femur length, biparietal diameter, and estimated fetal weight. Forty-two percent of births were the result of preterm labor, 22% were the result of preterm ruptured membranes, 12% were the result of preeclampsia or eclampsia, 9% were the result of fetal distress, 4% were the result of placenta previa or abruptio placentae, and 2% were the result of intrauterine growth restriction. Perinatal mortality before 24 weeks' gestation exceeded 81% (19% stillbirths and 62% neonatal deaths) but declined sharply thereafter. Most survivors born before 26 weeks' gestation had serious morbidity. Fetal femur length and estimated gestational age predicted survival better than did biparietal diameter or estimated fetal weight. Infants who survived with markers of serious long-term morbidity could not be distinguished from those who survived without morbidity markers before delivery by ultrasonography or clinical data. Threshold values for ultrasonographic measurements of biparietal diameter and femur length were developed to distinguish fetuses with no chance of survival.Ultrasonographic assessment of either fetal femur length or gestational age predicts neonatal mortality better than do other antenatal tests. No tests accurately predicted neonatal morbidity in infants weighing/=1000 g at birth.

The aim of the study was to determine the effects of antenatal maternal corticosteroid treatment on selected neonatal outcomes in infants weighing/=1000 g at birth after preterm rupture of membranes.In a 1-year (1992-1993) prospective observational study, the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network collected outcome data for 766 infants who did not have a major fetal anomaly and who had a birth weight/=1000 g (378 were born after preterm rupture of membranes). Only fetuses deemed potentially viable by the obstetrician were included in our analysis. Selected neonatal outcomes were compared between mothers who did and did not receive antenatal corticosteroids. Logistic regression variables included birth weight, sex, race, amnionitis, tocolytic therapies, mode of delivery, and surfactant use.Two hundred fourteen of the 378 infants whose mothers had preterm rupture of membranes were deemed potentially viable; 62 of these mothers received antenatal steroids and 152 did not. Groups were similar with respect to gestational age, birth weight, race, amnionitis, and delivery mode. Women who received antenatal steroids were more likely to have received tocolysis (P.001). Univariate and regression analyses controlling for multiple confounders confirmed no neonatal benefits of maternal corticosteroid use.Corticosteroid treatment in women with preterm rupture of membranes was of no apparent benefit to neonates weighing/=1000 g.

This article summarizes the role of endocrine and paracrine mediators of human parturition. Gonadal steroids (17s—estradiol and progesterone) mediate many of the decidual and uterine contractile functions during early events in labor. Proinflammatory cytokines and chemokines orchestrate many of the events triggering or sustaining active labor at term and in the preterm setting. Several autacoids (prostaglandins, platelet-activating factor) serve proximal activities such as uterine contractility and remodeling of the cervical extracellular matrix leading to dilatation and effacement. As the biochemical participants during parturition become more clearly understood, it will be possible to develop improved surveillance, management, and treatment strategies for preterm labor.

To estimate the frequency of severe maternal morbidity, assess its underlying etiologies, and develop a scoring system to predict its occurrence.Supplemental Digital Content is Available in the Text.This was a secondary analysis of a Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network cohort of 115,502 women and their neonates born in 25 hospitals across the United States over a 3-year period. Women were classified as having severe maternal morbidity according to a scoring system that takes into account the occurrence of red blood cell transfusion (more than three units), intubation, unanticipated surgical intervention, organ failure, and intensive care unit admission. The frequency of severe maternal morbidity was calculated and the underlying etiologies determined. Multivariable analysis identified patient factors present on admission that were independently associated with severe maternal morbidity; these were used to develop a prediction model for severe maternal morbidity.Among 115,502 women who delivered during the study period, 332 (2.9/1,000 births, 95% confidence interval 2.6-3.2) experienced severe maternal morbidity. Postpartum hemorrhage was responsible for approximately half of severe maternal morbidity. Multiple patient factors were found to be independently associated with severe maternal morbidity and were used to develop a predictive model with an area under the receiver operating characteristic curve of 0.80.Severe maternal morbidity occurs in approximately 2.9 per 1,000 births, is most commonly the result of postpartum hemorrhage, and occurs more commonly in association with several identifiable patient characteristics.: II.

The care of women with preterm labor has focused predominantly on inpatient therapy: tocolysis, antibiotics, and steroid administration. The emphasis is slowly but surely shifting to secondary prevention and outpatient therapy. Our goal should be toward primary prevention of preterm labor in all women. Then and only then will a true reduction in spontaneous prematurity rates be seen.

Group B streptococcal infection is the most common cause of neonatal sepsis and is responsible for significant neonatal morbidity and mortality. Group B streptococcus is also the causative agent in 50,000 maternal infections per year. Approximately 30% of women have asymptomatic group B streptococcal colonization at some time during pregnancy, but the neonatal attack rate is only about 2 per 1,000 deliveries. Maternal and neonatal risk factors contribute to the rates of vertical transmission and symptomatic neonatal disease. Options that have been investigated for prevention of neonatal group B streptococcal disease include identification of at-risk pregnancies as well as antenatal, intrapartum, and neonatal treatment. The intrapartum treatment of women at risk for vertical transmission of group B streptococcus to their neonates unequivocally has been shown to decrease the rate of neonatal colonization. Practitioners should implement one of two strategies that incorporate intrapartum prophylaxis for prevention of perinatal group B disease.

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 ≥37 weeks' gestation), fetal fibronectin status (positive = ≥50 ng/dl), and cervical length by percentile groups (≤10th = ≤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 mm at 24 weeks' gestation. For fetal fibronectin negative women with a prior preterm birth, the recurrence risk was 25% when the cervix was ≤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. (Am J Obstet Gynecol 1998;178:1035-40.)

Objective: Our purpose was to evaluate whether maternal weight and body mass index measured either before or during pregnancy are associated with an increased risk of cesarean delivery. Study design: Maternal weight and height were prospectively collected on 2929 women in the National Institutes of Health Maternal-Fetal Medicine Units Network Preterm Prediction Study. Prepregnancy and 27- to 31-week maternal weight and height were used to calculate the body mass index, and its contribution to the risk of cesarean delivery was determined. Women with prenatally diagnosed congenital anomalies ( n = 89) and pregestational diabetes ( n = 31) were excluded from analysis. Results: Univariate analysis of risk factors for cesarean delivery in the 2809 eligible women revealed a decreased risk of cesarean delivery with maternal age 35 years and a male fetus. Increases in either prepregnancy or 27- to 31-week maternal weight (5-pound units) or body mass index (1.0 kg/m 2 units) were significantly associated with an increased odds of cesarean delivery ( p = 0.0001). Each unit increase in prepregnancy or 27- to 31-week body mass index resulted in a parallel increase in the odds of cesarean delivery of 7.0% and 7.8%, respectively. Multivariable stepwise logistic regression analysis confirmed the association of male fetus, age, nulliparity, and body mass index as significant variables contributing to cesarean delivery risk. Conclusions: The risk of cesarean delivery is associated with incremental changes in maternal weight and body mass index before and during pregnancy after adjustment for potential confounding factors. Prepregnancy counseling about optimizing maternal weight and monitoring weight gain during pregnancy to decrease the risk of cesarean delivery are supported by this study. (Am J Obstet Gynecol 1997;177:333-41.)

OBJECTIVE: Our purpose was to determine how various temporal patterns of fetal fibronectin positivity from 24 to 30 weeks predict subsequent fetal fibronectin test results and spontaneous preterm delivery. STUDY DESIGN: A total of 2929 women had vaginal and cervical fetal fibronectin tests obtained at least once at 24, 26, 28, or 30 weeks, and 1870 women had tests performed at all four gestational ages. Fetal fibronectin values ≥50 ng/ml were considered positive. Various patterns of positive and negative tests were evaluated for prediction of (1) whether the next fetal fibronectin test would be positive or negative and (2) the percent of women with a spontaneous preterm delivery ≥4 weeks after the last fetal fibronectin test at RESULTS: Women with previous negative test results had only a 3% chance of a subsequent positive test result; however, if the last test result was positive, 29% of the next tests were positive. Of the 1870 women with tests at 24, 26, 28, and 30 weeks, 89% had all negative results, 8.4% had one positive result, 1.8% had two positive results, and 0.8% had three or four positive results. The higher the percent of positive tests at 24 to 26 weeks, at 28 to 30 weeks, or at 24 to 30 weeks, the greater the risk of subsequent spontaneous preterm birth. As an example, the risk of spontaneous preterm birth at CONCLUSION: The presence of a positive cervical or vaginal fetal fibronectin test result predicts subsequent positive fetal fibronectin positivity and subsequent spontaneous preterm birth. The greater the percent of positive results, the higher is the risk of spontaneous preterm birth. After a positive test result, two negative results are required before the risk of spontaneous preterm birth returns to baseline.(Am J Obstet Gynecol 1997;177:8-12.)

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 ≤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 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. (Am J Obstet Gynecol 1997;176:960-6.)