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Objective: Limited data are available from low- and middle-income countries (LMICs) on the relationship of haemoglobin levels to adverse outcomes at different times during pregnancy. We evaluated the association of haemoglobin levels in nulliparous women at two times in pregnancy with pregnancy outcomes., Design: ASPIRIN Trial data were used to study the association between haemoglobin levels measured at 6 +0 -13 +6  weeks and 26 +0 -30 +0  weeks of gestation with fetal and neonatal outcomes., Setting: Obstetric care facilities in Pakistan, India, Kenya, Zambia, The Democratic Republic of the Congo and Guatemala., Population: A total of 11 976 pregnant women., Methods: Generalised linear models were used to obtain adjusted relative risks and 95% CI for adverse outcomes., Main Outcome Measures: Preterm birth, stillbirth, neonatal death, small for gestational age (SGA) and birthweight <2500 g., Results: The mean haemoglobin levels at 6 +0 -13 +6  weeks and at 26-30 weeks of gestation were 116 g/l (SD 17) and 107 g/l (SD 15), respectively. In general, pregnancy outcomes were better with increasing haemoglobin. At 6 +0 -13 +6  weeks of gestation, stillbirth, SGA and birthweight <2500 g, were significantly associated with haemoglobin of 70-89 g/l compared with haemoglobin of 110-129 g/l The relationships of adverse pregnancy outcomes with various haemoglobin levels were more marked at 26-30 weeks of gestation., Conclusions: Both lower and some higher haemoglobin concentrations are associated with adverse fetal and neonatal outcomes at 6 +0 -13 +6  weeks and at 26-30 weeks of gestation, although the relationship with low haemoglobin levels appears more consistent and generally stronger., Tweetable Abstract: Both lower and some higher haemoglobin concentrations were associated with adverse fetal and neonatal outcomes at 6-13 weeks and 26-30 weeks of gestation., (© 2021 John Wiley & Sons Ltd.)

Background: Preterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation., Methods: ASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks' gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with ClinicalTrials.gov, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970., Findings: From March 23, 2016 to June 30, 2018, 14 361 women were screened for inclusion and 11 976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks' gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (<34 weeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups., Interpretation: In populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality., Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Preterm birth (PTB) remains the leading cause of neonatal mortality and long term disability throughout the world. Though complex in its origins, a growing body of evidence suggests that first trimester administration of low dose aspirin (LDA) may substantially reduce the rate of PTB., Methods: Hypothesis: LDA initiated in the first trimester reduces the risk of preterm birth. Study Design Type: Prospective randomized, placebo-controlled, double-blinded multi-national clinical trial conducted in seven low and middle income countries. Trial will be individually randomized with one-to-one ratio (intervention/control) Population: Nulliparous women between the ages of 14 and 40, with a singleton pregnancy between 6 0/7 weeks and 13 6/7 weeks gestational age (GA) confirmed by ultrasound prior to enrollment, no more than two previous first trimester pregnancy losses, and no contraindications to aspirin., Intervention: Daily administration of low dose (81 mg) aspirin, initiated between 6 0/7 weeks and 13 6/7 weeks GA and continued to 36 0/7 weeks GA, compared to an identical appearing placebo. Compliance and outcomes will be assessed biweekly., Outcomes: Primary outcome: Incidence of PTB (birth prior to 37 0/7 weeks GA). Secondary outcomes Incidence of preeclampsia/eclampsia, small for gestational age and perinatal mortality., Discussion: This study is unique as it will examine the impact of LDA early in pregnancy in low-middle income countries with preterm birth as a primary outcome. The importance of developing low-cost, high impact interventions in low-middle income countries is magnified as they are often unable to bear the financial costs of treating illness., Trial Registration: ClinicalTrials.gov identifier: NCT02409680 Date: March 30, 2015.

Objective  This study aims to evaluate the association between prepregnancy body mass index (BMI) and adverse pregnancy outcomes in women with type 1 diabetes mellitus (DM). Methods  This is a secondary analysis of a cohort of 426 pregnancies in women with type 1 DM recruited before 20 weeks gestation. Women were categorized according to prepregnancy BMI: low BMI (< 20 kg/m 2 ), normal BMI (20 to < 25 kg/m 2 ), and high BMI (≥ 25 kg/m 2 ). The outcomes of interest were: spontaneous abortion (delivery < 20 weeks gestation); preeclampsia; emergent delivery for maternal indications (hypertension or placental abruption); and preterm delivery (< 37 weeks gestation). Analyses included proportional hazards and multiple logistic regression models with covariates: age, age at diagnosis of type 1 DM, previous spontaneous abortion, microvascular disease (nephropathy or retinopathy), and glycohemoglobin A 1 concentrations. Results  Low BMI was associated with preterm delivery. High BMI was associated with emergent delivery for maternal indications. Glycemic control as measured by glycohemoglobin A 1 was associated with increased risk of spontaneous abortion, attenuating the association with low prepregnancy weight. Conclusion  Prepregnancy BMI is a risk factor to be considered when caring for women with type 1 DM, in particular for preterm delivery (low BMI) and emergent delivery for maternal indications (high BMI)., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Antenatal corticosteroids are commonly used to reduce neonatal mortality, but most research to date has been in high-resource settings and few studies have evaluated its impact on stillbirth. In the Antenatal Corticosteroids Trial (ACT), a multi-country trial to assess impact of a multi-faceted intervention including antenatal corticosteroids to reduce neonatal mortality associated with preterm birth, we found an overall increase in 28-day neonatal mortality and stillbirth associated with the intervention., Methods: The ACT was a cluster-randomized trial conducted in 102 clusters across 7 research sites in 6 countries (India [2 sites], Pakistan, Zambia, Kenya, Guatemala and Argentina), comparing an intervention to train birth attendants at all levels of the health system to identify women at risk of preterm birth, administer corticosteroids and refer women at risk. Because of inadequate gestational age dating, the <5(th) percentile birth weight was used as a proxy for preterm birth. A pre-specified secondary outcome of the trial was stillbirth., Results: After adjusting for the pre-trial imbalance in stillbirth rates, the ACT intervention was associated with a non-significant increased risk of stillbirth (aRR 1.08, 95 % CI, 0.99-1.17, p-0.073). Additionally, the stillbirth rate was higher in the term births (1.20 95 % CI 1.06-1.37, 0.004) and among those with signs of maceration (RR 1.18 (1.04-1.35), p = 0.013) in the intervention vs. control clusters. Differences in obstetric care favored the control clusters and maternal infection was likely more common in the intervention clusters., Conclusions: In this pragmatic trial, limited data were available to identify the causes of the increase in stillbirths in the intervention clusters. A higher rate of stillbirth in the intervention clusters prior to the trial, differences in obstetric care and an increase in maternal infection are potential explanations for the observed increase in stillbirths in the intervention clusters during the trial., Trial Registration: clinicaltrials.gov (NCT01084096).

The Global Network's Antenatal Corticosteroids Trial (ACT), was a multi-country, cluster-randomized trial to improve appropriate use of antenatal corticosteroids (ACS) in low-resource settings in low-middle income countries (LMIC). ACT substantially increased ACS use in the intervention clusters, but the intervention failed to show benefit in the targeted < 5th percentile birth weight infants and was associated with increased neonatal mortality and stillbirth in the overall population. In this issue are six papers which are secondary analyses related to ACT that explore potential reasons for the increase in adverse outcomes overall, as well as site differences in outcomes. The African sites appeared to have increased neonatal mortality in the intervention clusters while the Guatemalan site had a significant reduction in neonatal mortality, perhaps related to a combination of ACS and improving obstetric care in the intervention clusters. Maternal and neonatal infections were increased in the intervention clusters across all sites and increased infections are a possible partial explanation for the increase in neonatal mortality and stillbirth in the intervention clusters, especially in the African sites. The analyses presented here provide guidance for future ACS trials in LMIC. These include having accurate gestational age dating of study subjects and having care givers who can diagnose conditions leading to preterm birth and predict which women likely will deliver in the next 7 days. All study subjects should be followed through delivery and the neonatal period, regardless of when they deliver. Clearly defined measures of maternal and neonatal infection should be utilized. Trials in low income country facilities including clinics and those without newborn intensive care seem to be of the highest priority.

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., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: We sought to identify serum markers of subsequent spontaneous preterm birth (SPTB) in asymptomatic women prior to labor., Study Design: Serum proteomics was applied to sera from 80 pregnant women sampled at 24 weeks and an additional 80 pregnant women sampled at 28 weeks. Half had uncomplicated pregnancies and half had SPTB., Results: Three specific peptides arising from inter-alpha-trypsin inhibitor heavy chain 4 protein were significantly reduced in women at 24 and 28 weeks having subsequent SPTB. The most discriminating peptide had a sensitivity of 65.0% and specificity of 82.5%; odds ratio, 8.8; and 95% confidence interval, 3.1-24.8. A combination of the 3 new biomarkers and 6 previously studied biomarkers increased sensitivity to 86.5%, with a specificity of 80.6% at 28 weeks., Conclusion: Three novel serum markers of SPTB have been identified using serum proteomics. Using a combination of these new markers with additional markers, women at risk of SPTB can be identified weeks prior to SPTB., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: The truncated mitochondrial progesterone receptor (PR-M) is homologous to nuclear PRs with the exception of an amino terminus hydrophobic membrane localization sequence, which localizes PR-M to mitochondria. Given the matrilineal inheritance of both spontaneous preterm birth (SPTB) and the mitochondrial genome, we hypothesized that (a) PR-M is polymorphic and (b) PR-M localization sequence polymorphisms could result in variable progesterone-mitochondrial effects and variable responsiveness to progesterone prophylaxis., Methods: Secondary analysis of DNA from women enrolled in a multicenter, prospective, study of 17 alpha-hydroxyprogesterone caproate (17OHPC) versus placebo for the prevention of recurrent SPTB. DNA was extracted from stored saliva., Results: The PR-M localization sequence was sequenced on 344 patients. Sequences were compared with the previously published 48 base-pair sequence, and all were identical., Conclusions: We did not detect genetic variation in the mitochondrial localization sequence of the truncated PR-M in a group of women at high risk for SPTB.

Elevated concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloproteinase-9 (MMP-9) in fetal and neonatal compartments have been associated with an increased risk for preterm birth (PTB) and/or neonatal morbidity. The purpose of this study was to determine if the maternal serum concentration of IL-6, CRP, and MMP-9 in women at risk for PTB, who are not in labor and have intact membranes, are associated with an increased risk for PTB <32 weeks and/or neonatal morbidity. Maternal serum samples collected from 475 patients enrolled in a multicenter randomized controlled trial of single versus weekly corticosteroids for women at increased risk for preterm delivery were assayed. Serum was collected at randomization (24 to 32 weeks' gestation). Maternal serum concentrations of IL-6, CRP, and MMP-9 were subsequently determined using enzyme-linked immunoassays. Multivariate logistic regression analysis was performed to explore the relationship between maternal serum concentrations of IL-6, CRP, and MMP-9 and PTB <32 weeks, respiratory distress syndrome (RDS), chronic lung disease (CLD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and any sepsis. Maternal serum concentrations of IL-6 and CRP, but not MMP-9, above the 90th percentile at the time of randomization were associated with PTB <32 weeks. In contrast, there was no significant relationship between RDS and NEC and the maternal serum concentration of IL-6, CRP, or MMP-9 (univariate analysis). The development of CLD was associated with a high (above 90th percentile) IL-6 and CRP in maternal serum, even after adjustment for gestational age (GA) at randomization and treatment group. However, when GA at delivery was added to the model, this finding was nonsignificant. Neonatal sepsis was more frequent in neonates born to mothers with a high maternal serum concentration of CRP (>90th percentile). However, there was no significant association after adjustment for GA at randomization and treatment group. Logistic regression analysis for each analyte indicated that high maternal serum concentrations of IL-6 and CRP, but not MMP-9, were associated with an increased risk of IVH (odds ratio [OR] 4.60, 95% confidence interval [CI] 1.86 to 10.68; OR 4.07, 95% CI 1.63 to 9.50) after adjusting for GA at randomization and treatment group. Most babies (25/30) had grade I IVH. When GA at delivery was included, elevated IL-6 remained significantly associated with IVH (OR 2.77, 95% CI 1.02 to 7.09). An elevated maternal serum concentration of IL-6 and CRP are risk factors for PTB <32 weeks and subsequent development of neonatal IVH. An elevated maternal serum IL-6 appears to confer additional risk for IVH even after adjusting for GA at delivery., (Copyright Thieme Medical Publishers.)

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.

Objective: To determine if women with a history of a previous preterm cesarean delivery experienced an increased risk of subsequent uterine rupture compared with women who had a previous nonclassic term cesarean delivery., Methods: A prospective observational study was performed in singleton gestations that had a previous nonclassic cesarean delivery from 1999 to 2002. Women with a history of a previous preterm cesarean delivery were compared with women who had a previous term cesarean delivery. Women who had both a preterm and term cesarean delivery were included in the preterm group., Results: A prior preterm cesarean delivery was significantly associated with an increased risk of subsequent uterine rupture (0.58% compared with 0.28%, P<.001). When women who had a subsequent elective cesarean delivery were removed (remaining n=26,454) women with a previous preterm cesarean delivery were still significantly more likely to sustain a uterine rupture (0.79% compared with 0.46%, P=.001). However, when only women who had a subsequent trial of labor were included, there was still an absolute increased risk of uterine rupture, but it was not statistically significant (1.00% compared with 0.68%, P=.081). In a multivariable analysis controlling for confounding variables (oxytocin use, two or more previous cesarean deliveries, a cesarean delivery within the past 2 years, and preterm delivery in the current pregnancy), patients with a previous preterm cesarean delivery remained at an increased risk of subsequent uterine rupture (P=.043, odds ratio 1.6, 95% confidence interval 1.01-2.50) compared with women with previous term cesarean delivery., Conclusion: Women who have had a previous preterm cesarean delivery are at a minimally increased risk for uterine rupture in a subsequent pregnancy when compared with women who have had previous term cesarean deliveries.

Objective: The purpose of this study was to determine the impact of persistent bacterial vaginosis (BV) on the occurrence of spontaneous preterm birth (SPB) in women who test positive for fetal fibronectin., Study Design: This is a secondary analysis of a subset of pregnant women who tested positive for BV and fetal fibronectin between 16(0/7) and 25(6/7) weeks of gestation and who participated in randomized placebo controlled trials of antibiotic therapy. Nugent's criteria were used for the diagnosis of BV. Patients were reassessed for the presence of BV after treatment. The rate of SPB at <34 weeks of gestation was analyzed on the basis of treatment mode and BV status at the follow-up visit., Results: The primary studies included a total of 3285 women. A subset of 215 women met the criteria for this analysis. Seventy-seven of 100 patients (77%) in the antibiotics group vs 33 of the 115 patients (28.7%) in the placebo group became BV negative (P < .0001). The rate of SPB at <34 weeks of gestation was lower for BV resolution compared with persistent BV (0 vs 5.7%, respectively; P = .01)., Conclusion: In women who tested positive for fetal fibronectin and BV, resolution of BV is associated with less SPB before 34 weeks of gestation.

Objective: To estimate the natural history of funneling in the second trimester by transvaginal ultrasonograms and whether funneling increases the risk of spontaneous birth., Methods: Secondary analysis of a blinded, multi-center observational study of women with at least one prior spontaneous preterm birth at 16.0-31.9 weeks who subsequently carried singleton gestations. Cervical length, funneling (membrane prolapse greater than or equal to 5 mm), funnel shape, and dynamic changes were recorded at 16-18 weeks, and then every 2 weeks until 23.9 weeks. Managing obstetricians were blinded to the ultrasonography results. The primary outcome was gestational age at delivery., Results: Five hundred ninety scans were performed in 183 women, of which 60 (33%) had funneling observed on at least one of the serial evaluations. These 60 women delivered at an earlier gestational age at delivery than the 123 women without funneling (31.7+/-7.9 weeks compared with 36.9+/-4.4 weeks; P<.001). In the 60 women with funneling on at least one evaluation, the progression over time of internal os cervical anatomy from a "T" to a "V" to a "U" shape was associated with earlier gestational age at delivery, whereas resolution of "V" shape funnels was associated with term delivery. Women with a shortened cervical length less than 25 mm (n=60) had a similar gestational age at birth with or without funneling (30.6+/-8.0 weeks compared with 31.9+/-6.6 weeks; P=.59). After controlling for the shortest observed cervical length, largest funnel percent was not a significant independent risk factor., Conclusion: The natural history of second-trimester funneling has significant variability and a significant association with earlier gestational age at delivery. As an independent finding, funneling does not add appreciably to the risk of early gestational age at delivery associated with a shortened cervical length., Level of Evidence: II.

Objective: This study was undertaken to compare uterine contraction frequency in twins versus singletons and to determine if contraction frequency can be an efficient predictor of spontaneous preterm birth in twin gestations., Study Design: Fifty-nine twin and 306 singleton gestations were enrolled between 22 and 24 weeks at 11 centers. Contraction frequency was recorded with a home uterine activity monitor (HUAM) 2 or more times per day on 2 or more days per week until delivery or 36-6/7 weeks. Masked HUAM data were interpreted according to standard protocol. Repeated measures analyses were used to determine whether mean or maximum uterine contraction frequency per hour differed between singleton and twin gestations across gestational age, by time of day, and by delivery before 35 weeks or beyond. Uterine contraction frequency was also evaluated by logistic regression and receiver operator characteristic (ROC) curves as tests to predict spontaneous preterm birth., Results: There were 34,908 hours of HUAM data recorded by the 306 singleton gestations and 5,427 hours by the 59 women with twins. Uterine contraction frequency was significantly greater in twins (P = .002) compared with singletons, regardless of gestational age. Contraction frequency in twins increased significantly with gestational age and time of day (1600-0359 hours); but was not associated with spontaneous preterm birth. Maximum uterine contraction frequency was associated with preterm birth less than 35 weeks but only in the morning (am) recording (0400-1559) and at the 29- to 30-week gestational age interval. This relationship was modest (odds ratio 1-2) and not consistent across gestational age or between the am and afternoon/evening (pm) monitoring sessions. ROC analysis revealed no contraction frequency that efficiently identified twins who delivered prematurely at any 2-week gestational age interval., Conclusion: Mean uterine contraction frequency was significantly higher for twin gestations than singletons throughout the latter half of pregnancy and between 1600 and 0359 hours but was not higher among twins who delivered less than 35 weeks' gestation. Neither maximum am or pm contraction frequency predicted spontaneous preterm birth less than 35 weeks' gestation in twin pregnancies.

Objective: To estimate the impact of sexual behavior on the risk of recurrent spontaneous preterm birth at less than 37 weeks of gestation., Methods: This is a secondary analysis of a multicenter, blinded observational study of endovaginal sonographic examinations performed at 16-18 weeks of gestation on 187 women with singleton gestations who were at high risk for recurrent spontaneous preterm birth (prior spontaneous preterm birth at < 32 weeks of gestation). At the time of enrollment, each woman was interviewed by a research nurse with regard to her sexual history. The patient was asked about the number of sexual partners in her lifetime, the number of sexual partners since the start of her pregnancy, and, on average, the frequency of intercourse per week in the preceding month., Results: A total of 165 pregnancies were available for this analysis. The population incidence of spontaneous preterm birth at less than 37 weeks of gestation in the study pregnancy was 36%. An increasing number of sexual partners in a woman's lifetime was associated with an increased risk of spontaneous preterm delivery (one partner 19%, 2-3 partners 29%, >or= 4 partners 44%, P = .007), whereas the number of sexual partners since the start of pregnancy was not (P = .42). Women who reported infrequent sexual intercourse during early pregnancy had an incidence of recurrent spontaneous preterm birth of 28% compared with 38% in those women who reported some intercourse (P = .35)., Conclusion: Self-reported coitus during early pregnancy was not associated with an increased risk of recurrent preterm delivery. There was an association between increasing number of sexual partners in a woman's lifetime and recurrent preterm delivery., Level of Evidence: II-2.

Objective: This study was undertaken to determine whether women with recurrent spontaneous preterm births (rSPBs) have different clinical characteristics or systemic markers than those with isolated preterm (iSPBs) or recurrent term births (rTBs), when assessed remote from delivery., Study Design: We compared clinical characteristics and findings (including cervical ultrasound, bacterial vaginosis, fetal fibronectin), maternal plasma markers obtained at 22 to 24 weeks' gestation (inflammatory cytokines, cortisol, and corticotrophin-releasing hormone), between women with rSPBs (2 or 3 consecutive SPBs and no TBs), iSPBs (1 SPB and 1 or 2 TBs), and rTBs (2 or 3 consecutive TBs and no SPBs)., Results: A total of 1257 women met our inclusion criteria; 47 rSPBs, 241 iSPBs (80 current and 161 prior iSPBs), and 969 rTBs. Before pregnancy, women with rSPBs had lower weights (P < .0001) and body mass indexes (BMIs) (P < .001), and were more likely to be less than 100 lbs (P = .008) or less than 19.8 kg/m2 BMI (P = .001). At 22 to 24 weeks those with rSPBs remained lighter and leaner, and had more advanced Bishop scores than iSPBs and rTBs. Ultrasound demonstrated progressive decrease in cervical length for those with rTBs, prior iSPBs, current iSPBs, and rSPBs, and also progressively more frequent short cervixes with worsening history (P < .001). Cervical length was shorter for women of lower pregravid weight and BMI, but not with shorter height. At 22 to 24 weeks, women with rSPBs had more common uterine contractions and tocolytic agents, but not more infections or antibiotic therapy. Those with an SPB in the current gestation had higher fetal fibronectin levels and more frequent vaginal bleeding, regardless of prior outcome. Maternal cortisol and corticotrophin-releasing hormone were higher in women with iSPBs and rSPBs than in rTB controls, (P = .001 and .0027), a finding more apparent with SPB in the current pregnancy. However, maternal cytokines were not increased with either iSPBs or rSPBs., Conclusion: Women with rSPBs are leaner, contract more, have shorter cervixes, and have more advanced Bishop scores than women with iSPBs or rTBs.

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.

Objective: Preterm birth occurs in 1 of 8 pregnancies and may result in significant morbidity and mortality. 17-alpha hydroxyprogesterone caproate (17-OHP caproate) has been found to be efficacious in reducing the risk of subsequent preterm delivery in women who have had a previous spontaneous preterm birth (sPTB). This analysis was undertaken to evaluate if 17-OHP caproate therapy works preferentially depending on the gestational age at previous spontaneous delivery. We hypothesized that treatment with 17-OHP caproate is more effective in prolonging pregnancy depending on the gestational age of the earliest previous preterm birth (20-27.9, 28-33.9 vs 34-36.9 weeks)., Study Design: This was a secondary analysis of 459 women with a previous sPTB enrolled in a randomized controlled trial evaluating 17-OHP caproate versus placebo. Effectiveness of 17-OHP caproate for pregnancy prolongation was evaluated based on gestational age at earliest previous delivery according to clinically relevant groupings (20-27.9, 28-33.9, and 34-36.9 weeks). Statistical analysis included the chi-square, Fisher exact, and Kruskal-Wallis tests, logistic regression, and survival analysis using proportional hazards., Results: Gestational age at earliest previous delivery was similar between women treated with 17-OHP caproate or placebo (P = .1). Women with earliest delivery at 20 to 27.9 weeks and at 28 to 33.9 weeks delivered at significantly more advanced gestational age if treated with 17-OHP caproate than with placebo (median 37.3 vs 35.4 weeks, P = .046 and 38.0 vs 36.7 weeks, P = .004, respectively) and were less likely to deliver <37 weeks (42% vs 63%, P = .026 and 34% vs 56%, P = .005, respectively). Those with earliest delivery at 34 to 36.9 weeks were not significantly different between 17-OHP caproate or control., Conclusion: 17-OHP caproate therapy given to prevent recurrent PTB is associated with a prolongation of pregnancy overall, and especially for women with a previous spontaneous PTB at <34 weeks.

Objective: 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., Study Design: 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 at <37 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., Results: The overall rates of preterm birth in this cohort of 170 patients were 35.9% at <37 weeks (31.9% progesterone, 43.9% placebo), and 19.4% at <35 weeks (18.6% vs 21.1%). The median levels of corticotropin-releasing hormone were similar between those delivering at <37 weeks and those delivering > or = 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 at <35 weeks or > or = 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 at <37 or > or = 37 weeks (0.40 vs 0.41, P = .72) and at <35 or > or = 35 weeks (P = .64)., Conclusion: 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: The purpose of this study was to evaluate the relationship between prepregnancy maternal body mass index and spontaneous preterm birth and indicated preterm birth., Study Design: This was a secondary analysis of the Maternal-Fetal Medicine Units Network, Preterm Prediction study. Patients were classified into categories that were based on their body mass index. Rates of indicated and spontaneous preterm birth were compared., Results: Five hundred ninety-seven (20.5%) of 2910 women were obese. Obese women had fewer spontaneous preterm births at < 37 weeks of gestation (6.2% vs 11.2%; P < .001) and at < 34 weeks of gestation (1.5% vs 3.5%; P = .012). Women with a body mass index of < 19 kg/m2 had 16.6% spontaneous preterm birth, with a body mass index of 19 to 24.9 kg/m 2 had 11.3% spontaneous preterm birth, with a body mass index of 25 to 29.9 kg/m2 had 8.1% spontaneous preterm birth, with a body mass index of 30 to 34.9 kg/m2 had 7.1% spontaneous preterm birth, and with a body mass index of > or = 35 kg/m2 had 5.2% spontaneous preterm birth (P < .0001). Indicated delivery was responsible for an increasing proportion of preterm births with increasing body mass index (P = .001). Obese women had lower rates of cervical length < 25 mm (5% vs 8%; P = .012). Multivariable regression analysis confirmed a lower rate of spontaneous preterm birth in obese gravid women (odds ratio, 0.57; 95% CI, 0.39-0.83; P = .003)., Conclusion: Obesity before pregnancy is associated with a lower rate of spontaneous preterm birth.

Objective: It is stated commonly that the earlier in pregnancy bacterial vaginosis is diagnosed, the greater is the increase in risk of preterm birth compared with women without bacterial vaginosis. However, this contention is based on small numbers of women., Study Design: In this analysis of 12,937 women who were screened for bacterial vaginosis as part of a previously conducted clinical trial, the odds ratio of preterm birth (<7 weeks of gestation) for asymptomatic bacterial vaginosis-positive versus bacterial vaginosis-negative women was evaluated among women who were screened from 8 to 22 weeks of gestation., Results: The odds ratio of preterm birth among bacterial vaginosis-positive versus bacterial vaginosis-negative women ranged from 1.1 to 1.6 and did not vary significantly according to the gestational age at which bacterial vaginosis was screened. The odds ratio for preterm birth did not vary significantly by gestational age at diagnosis when bacterial vaginosis was subdivided into Gram stain score 7 to 8 or 9 to 10., Conclusion: Although bacterial vaginosis was associated with an increased risk of preterm birth, the gestational age at which bacterial vaginosis was screened for and diagnosed did not influence the increase.