Vaginal progesterone is associated with decreased group B streptococcus colonisation at term: a retrospective cohort study.

OBJECTIVE: To investigate whether women using intravaginal progesterone suppositories for preterm birth prevention during pregnancy will have lower rates of group B streptococcus (GBS) colonisation at term, compared with women receiving intramuscular 17-alpha-hydroxyprogesterone caproate. DESIGN: This was a retrospective observational cohort study of women who were prescribed a progestogen during their pregnancy for preterm birth prevention, and who delivered at term. SETTING: A tertiary referral hospital in central Ohio. POPULATION: Patients who were prescribed a progestogen during their pregnancy for preterm birth prevention between 2004 and 2017 were included in the study. Patients who delivered at <37 weeks of pregnancy, switched progestogen type during the pregnancy, or had a pessary or cerclage placed were excluded. METHODS: Baseline characteristics were compared using Mann-Whitney U-test or Chi-square test as appropriate. The association between type of progestogen and GBS colonisation was assessed using bivariate and multivariable analyses. MAIN OUTCOME MEASURES: The primary outcome was GBS colonisation. RESULTS: In all, 565 patients were included in the study, of whom 173 received intravaginal progesterone, and 392 17-alpha-hydroxyprogesterone caproate. Patients receiving intravaginal progesterone were less likely to be colonised with GBS (19.7 versus 28.1%). After adjustments for potential confounders were made in a multivariable logistic regression analysis, receiving intravaginal progesterone suppositories (adjusted odds ratio [OR] 0.61, 95% CI 0.39-0.95) was associated with reduced GBS colonisation. CONCLUSIONS: Intravaginal progesterone is associated with a decreased prevalence of rectovaginal GBS colonisation at term. TWEETABLE ABSTRACT: Vaginal progesterone is associated with a lower incidence of rectovaginal GBS colonisation, compared with 17α-hydroxyprogesterone caproate.

Cervical funneling or intra-amniotic debris and preterm birth in nulliparous women with midtrimester cervical length less than 30 mm.

OBJECTIVE: To evaluate whether the presence of cervical funneling or intra-amniotic debris identified in the second trimester is associated with a higher rate of preterm birth (PTB) in asymptomatic nulliparous pregnant women with a midtrimester cervical length (CL) less than 30 mm (i.e. below the 10th percentile). METHODS: This was a secondary cohort analysis of data from a multicenter trial in nulliparous women between 16 and 22 weeks' gestation with a singleton gestation and CL less than 30 mm on transvaginal ultrasound, randomized to treatment with either 17-alpha-hydroxyprogesterone caproate or placebo. Sonographers were centrally certified in CL measurement, as well as in identification of intra-amniotic debris and cervical funneling. Univariable and multivariable analysis was performed to assess the associations of cervical funneling and intra-amniotic debris with PTB. RESULTS: Of the 657 women randomized, 112 (17%) had cervical funneling only, 33 (5%) had intra-amniotic debris only and 45 (7%) had both on second-trimester ultrasound. Women with either of these findings had a shorter median CL than those without (21.0 mm vs 26.4 mm; P < 0.001). PTB prior to 37 weeks was more likely in women with cervical funneling (37% vs 21%; odds ratio (OR), 2.2 (95% CI, 1.5-3.3)) or intra-amniotic debris (35% vs 23%; OR, 1.7 (95% CI, 1.1-2.9)). Results were similar for PTB before 34 and before 32 weeks' gestation. After multivariable adjustment that included CL, PTB < 34 and < 32 weeks continued to be associated with the presence of intra-amniotic debris (adjusted OR (aOR), 1.85 (95% CI, 1.00-3.44) and aOR, 2.78 (95% CI, 1.42-5.45), respectively), but not cervical funneling (aOR, 1.17 (95% CI, 0.63-2.17) and aOR, 1.45 (95% CI, 0.71-2.96), respectively). CONCLUSIONS: Among asymptomatic nulliparous women with midtrimester CL less than 30 mm, the presence of intra-amniotic debris, but not cervical funneling, is associated with an increased risk for PTB before 34 and 32 weeks' gestation, independently of CL. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Timing of umbilical cord clamping among infants born at 22 through 27 weeks' gestation.

OBJECTIVE: To investigate the safety, feasibility and efficacy of delayed cord clamping (DCC) compared with immediate cord clamping (ICC) at delivery among infants born at 22 to 27 weeks' gestation. STUDY DESIGN: This was a pilot, randomized, controlled trial in which women in labor with singleton pregnancies at 22 to 27 weeks' gestation were randomly assigned to ICC (cord clamped at 5 to 10 s) or DCC (30 to 45 s). RESULTS: Forty mother-infant pairs were randomized. Infants in the ICC and DCC groups had mean gestational ages (GA) of 24.6 and 24.4 weeks, respectively. No differences were observed between the groups across all available safety measures, although infants in the DCC group had higher admission temperatures than infants in the ICC group (97.4 vs. 96.2 °F, P=0.04). During the first 24 h of life, blood pressures were lower in the ICC group than in the DCC group (P<0.05), despite a threefold greater incidence of treatment for hypotension (45% vs. 12%, P<0.01). Infants in the ICC group had increased numbers of red blood transfusions (in first 28 days of life) than infants in DCC group (4.1±3.9 vs. 2.8±2.2, P=0.04). CONCLUSION: Among infants born at an average GA of 24 weeks', DCC appears safe, logistically feasible, and offers hematological and circulatory advantages compared with ICC. A more comprehensive appraisal of this practice is needed.

Can the optimal cervical length for placing ultrasound-indicated cerclage be identified?

OBJECTIVE: To assess a continuum of cervical length (CL) cut-offs for the efficacy of ultrasound-indicated cerclage in women with previous spontaneous preterm birth (PTB). METHODS: This was a planned secondary analysis of a multicenter randomized clinical trial of ultrasound-indicated cerclage for the prevention of PTB in high-risk women. The efficacy of cerclage for preventing recurrent PTB < 35, < 32 and < 24 weeks' gestation was assessed using multivariable logistic regression analysis. Odds ratios (ORs) and CIs were estimated for a range of CL cut-offs using bootstrap regression. The 2.5(th) and 97.5(th) percentiles of bootstrapped ORs determined the CIs. Results were illustrated using smoothed curves superimposed on estimated ORs by CL cut-off. RESULTS: Of 301 women with a CL < 25 mm, 142 underwent ultrasound-indicated cerclage and 159 did not have cerclage placement. The few cases with CL < 10 mm limited the evaluation to CL cut-offs between < 10 mm and < 25 mm. For PTB < 35 weeks, ORs in women with a cerclage and CL < 25 mm were statistically significantly lower than in those without cerclage, and efficacy was maintained at smaller CL cut-offs. Results were similar for PTB < 32 weeks. For PTB < 24 weeks, results differed, with ORs increasing toward unity (no benefit), with wide CIs, for CL cut-offs between < 10 mm and < 15 mm, attributed to the small number of births < 24 weeks. CONCLUSIONS: The efficacy of ultrasound-indicated cerclage in women with previous spontaneous PTB varies by action point CL cut-off and by PTB gestational age of interest. Cerclage significantly reduces the risk of PTB < 35 and < 32 weeks, at CL cut-offs between < 10 mm and < 25 mm, with the greatest reduction at shorter CL, affirming that women with prior spontaneous PTB and a short CL are appropriate candidates for ultrasound-indicated cerclage. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids.

OBJECTIVE: The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. STUDY DESIGN: This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. RESULTS: CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. CONCLUSION: Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.

The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth: a case-control study.

OBJECTIVE: To determine whether ß2 -adrenoceptor (ß2 AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester. DESIGN: A case-control ancillary study to a multicentre randomised controlled trial. SETTING: Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. POPULATION: Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length. METHODS: Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. ß2 AR genotype was determined at positions encoding for amino acid residues 16 and 27. MAIN OUTCOME MEASURES: Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks. RESULTS: Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited. CONCLUSIONS: ß2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with ß2 AR genotype do not appear to involve a short cervix pathway.

Association between body mass index and pregnancy outcome in a randomized trial of cerclage for short cervix.

OBJECTIVE: To evaluate whether increasing body mass index (BMI) alters the efficacy of ultrasound-directed cerclage in women with a history of preterm birth. METHODS: This was a planned secondary analysis of a multicenter trial in which women with a singleton gestation and prior spontaneous preterm birth (17 to 33 + 6 weeks' gestation) were screened for a short cervix by serial transvaginal ultrasound evaluations between 16 and 22 + 6 weeks. Women with a short cervix (cervical length < 25 mm) were randomly assigned to cerclage or not. Linear and logistic regression were used to assess the relationship between BMI and continuous and categorical variables, respectively. RESULTS: Overall, in the screened women (n = 986), BMI was not associated with cervical length (P = 0.68), gestational age at delivery (P = 0.12) or birth at < 35 weeks (P = 0.68). For the cerclage group (n = 148), BMI had no significant effect. For the no-cerclage group (n = 153), BMI was associated with a decrease in gestational age at delivery, with an estimated slope of - 0.14 weeks per kg/m(2) (P = 0.03; including adjustment for cervical length). This result was driven primarily by several women with BMI > 47 kg/m(2) . CONCLUSION: In women at high risk for recurrent preterm birth, BMI was not associated with cervical length or gestational age at birth. BMI did not appear to adversely affect ultrasound-indicated cerclage.

Vitamin D status and recurrent preterm birth: a nested case-control study in high-risk women.

OBJECTIVE: To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption. DESIGN: A nested case-control study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. SETTING: Fourteen academic health centres in the USA. POPULATION: Women with prior spontaneous preterm birth. METHODS: In 131 cases (preterm delivery at <35 weeks of gestation) and 134 term controls, we measured serum 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) from samples collected at baseline (16-22 weeks of gestation). Logistic regression models controlled for study centre, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment. MAIN OUTCOME MEASURES: Recurrent preterm birth at <37 and <32 weeks of gestation. RESULTS: The median mid-gestation serum 25(OH)D concentration was 67 nmol/l, and 27% had concentrations of <50 nmol/l. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR 1.33; 95% CI 0.48-3.70 for lowest versus highest quartiles). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/l, or higher, with those with <50 nmol/l generated an odds ratio of 0.80 (95% CI 0.38-1.69). Contrary to our expectation, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (-0.18, P < 0.01). CONCLUSIONS: In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth.

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.

Midpregnancy genitourinary tract infection with Chlamydia trachomatis: association with subsequent preterm delivery in women with bacterial vaginosis and Trichomonas vaginalis.

OBJECTIVE: The objective of the study was to estimate whether midpregnancy genitourinary tract infection with Chlamydia trachomatis is associated with an increased risk of subsequent preterm delivery. STUDY DESIGN: Infection with C. trachomatis was determined using a ligase chain reaction assay (performed in batch after delivery) of voided urine samples collected at the randomization visit (16(0/7) to 23(6/7) weeks' gestation) and the follow-up visit (24(0/7) to 29(6/7) weeks) among 2470 gravide women with bacterial vaginosis or Trichomonas vaginalis infection enrolled in 2 multicenter randomized antibiotic treatment trials (metronidazole versus. placebo). RESULTS: The overall prevalence of genitourinary tract C. trachomatis infection at both visits was 10%. Preterm delivery less than 37 weeks' or less than 35 weeks' gestational age was not associated with the presence or absence of C. trachomatis infection at either the randomization (less than 37 weeks: 14% versus 13%, P=.58; less than 35 weeks: 6.4% versus 5.5%, P=.55) or the follow-up visit (less than 37 weeks: 13% versus 11%, P=.33; less than 35 weeks: 4.4% versus 3.7, P=.62). Treatment with an antibiotic effective against chlamydia infection was not associated with a statistically significant difference in preterm delivery. CONCLUSION: In this secondary analysis, midtrimester chlamydia infection was not associated with an increased risk of preterm birth. Treatment of chlamydia was not associated with a decreased frequency of preterm birth.

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.

The preterm prediction study: maternal serum relaxin, sonographic cervical length, and spontaneous preterm birth in twins.

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 weeks was known to be correlated with spontaneous preterm birth before 37, 35, and 32 weeks (P =.03,.01, and.002, respectively) in this study population. RESULTS: Cervical length did not correlate with relaxin levels at 24 (P=.601) or 28 (P=.304) weeks. Relationships between relaxin and spontaneous preterm birth were observed at 24 weeks for births before 37 weeks (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.00, 2.44; P=.05), and at 28 weeks for births before 35 weeks (OR 1.97, 95% CI 1.05, 3.70; P=.034) and 32 weeks (OR 2.43, 95% CI 1.01, 5.83; P=.048). CONCLUSION: The absence of an association between relaxin and cervical length suggests that increased relaxin does not explain the inverse correlation between cervical length and spontaneous preterm birth in women with spontaneous twin pregnancies.

The diagnosis and management of preterm labor.

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.

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.

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.

Vaginal fetal fibronectin measurements from 8 to 22 weeks' gestation and subsequent spontaneous preterm birth.

OBJECTIVE: We sought to determine the range of fetal fibronectin values in the vagina from 8 to 22 weeks' gestation, the factors associated with both low and high values, and whether high values are associated with gestational age at birth. STUDY DESIGN: Vaginal fetal fibronectin was quantitatively determined in a prospective cohort study of 13,360 women being evaluated for participation in the National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit treatment trials for bacterial vaginosis and Trichomonas vaginalis. Fetal fibronectin values were correlated with gestational age at screening, race, the presence of bacterial vaginosis and Trichomonas vaginalis, and gestational age at delivery. RESULTS: Vaginal fetal fibronectin values at each gestational age ranged from unmeasurable to >1000 ng/mL, with median values always being <10 ng/mL. Fetal fibronectin values declined progressively with increasing gestational age at sampling. Bacterial vaginosis and black race were associated with higher values, whereas nulliparity was associated with lower values. High values after 13 weeks' gestation were associated with a 2- to 3-fold increased risk of subsequent spontaneous preterm birth overall and a 4-fold increased risk of very early preterm birth. CONCLUSION: Elevated vaginal fetal fibronectin levels from 13 to 22 weeks' gestation are associated with a significantly increased risk of spontaneous preterm birth.

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.