Odds Of Spontaneous Preterm Birth Research Articles

Prescription Opioid Exposure During Pregnancy and Risk of Spontaneous Preterm Delivery

Opioid exposure during pregnancy has been associated with preterm birth, but prior studies have not differentiated between spontaneous and indicated preterm birth or fully investigated these associations as functions of opioid dose. To determine whether prescription opioid use during pregnancy is associated with spontaneous preterm birth and whether the association is dose-dependent. This case-control study examined a retrospective cohort of pregnant patients enrolled in Tennessee Medicaid. Enrollment files were linked to health care encounters, hospital discharge information, birth certificate data, and prescription fills. Eligible participants were pregnant people ages 15 to 44 years without opioid use disorder who experienced birth of a single fetus at 24 weeks gestation or greater between 2007 and 2019 with linked birth certificate data. Cases of spontaneous preterm birth were matched with up to 10 controls based on pregnancy start date, race, ethnicity, age at delivery within 2 years, and history of prior preterm birth. Cases and matched controls were continuously enrolled in TennCare for at least 90 days prior to the index date (case delivery date). Total opioid MME filled during the 60 days prior to the index date. The primary outcome was spontaneous preterm birth determined by a validated algorithm using birth certificate data. Conditional logistic regression was used to estimate the association between spontaneous preterm birth and total opioid morphine milligram equivalents (MME) dispensed, adjusting for parity, prepregnancy body mass index, education level, tobacco use, hepatitis infections, and pain indications. A total of 25 391 cases (median [IQR] age, 23 [20-28] years; 127 Asian [0.5%], 9820 Black [38.7%], 664 Hispanic [2.6%]; 14 748 non-Hispanic White [58.1%]) with spontaneous preterm birth were identified and matched with 225 696 controls (median [IQR] age, 23 [20-27] years; 229 Asian [0.1%], 89 819 Black [39.8%], 3590 Hispanic [1.6%]; 132 002 non-Hispanic White [58.5%]) (251 087 patients total), with 18 702 patients (7.4%) filling an opioid prescription in the 60 days prior to the index date. Each doubling of nonzero opioid MME was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure (adjusted odds ratio, 1.04; 95% CI, 1.01-1.08). In this case-control study, a positive association was found between total prescription opioid dose dispensed and the odds of spontaneous preterm birth. These findings support guidance to minimize opioid exposure during pregnancy and prescribe the lowest dose necessary.

Risk of spontaneous preterm birth elevated after first cesarean delivery at full dilatation: a retrospective cohort study of over 30,000 women

Having a cesarean delivery at full dilatation has been associated with increased subsequent risk of spontaneous preterm birth. The Aberdeen Maternity and Neonatal Databank provides a rare opportunity to study subsequent pregnancy outcomes after a previous cesarean delivery at full dilatation over 40 years, with an ability to include a detailed evaluation of potential confounding factors. This study aimed to investigate if having an initial cesarean delivery at full dilatation is associated with spontaneous preterm birth or other adverse pregnancy outcomes in the subsequent pregnancy. A retrospective cohort study was conducted including women with a first and second pregnancy recorded within the Aberdeen Maternity and Neonatal Databank between 1976 and 2017, where previous cesarean delivery at full dilatation at term in the first birth was the exposure. The primary outcome was spontaneous preterm birth (defined as spontaneous birth <37 weeks). Multivariate logistic regression was used to investigate any association between cesarean delivery at full dilatation and the odds of spontaneous preterm birth. Cesarean delivery at full dilatation in previous pregnancy was compared with: (1) any other mode of birth, and (2) individual modes of birth, including planned cesarean delivery, cesarean delivery in first stage of labor (<10-cm dilatation), and vaginal birth (including spontaneous vaginal birth, nonrotational forceps, Kielland forceps, vacuum-assisted birth, breech vaginal birth). Other outcomes such as antepartum hemorrhage and mode of second birth were also compared. Of the 30,253 women included, 900 had a previous cesarean delivery at full dilatation in the first pregnancy. Women with previous cesarean delivery at full dilatation had a 3-fold increased risk of spontaneous preterm birth in a second pregnancy (unadjusted odds ratio, 2.63; 95% confidence interval, 1.82-3.81; adjusted odds ratio, 3.31; 95% confidence interval, 2.17-5.05) compared with those with all other modes of first birth, adjusted for maternal age, diabetes mellitus, body mass index, smoking, preeclampsia, antepartum hemorrhage, socioeconomic deprivation (Scottish Index of Multiple Deprivation 2016), year of birth, and interpregnancy interval (in second pregnancy). When compared with women with vaginal births only, women with cesarean delivery at full dilatation had 5-fold increased odds of spontaneous preterm birth (adjusted odds ratio, 5.37; 95% confidence interval, 3.40-8.48). Compared with first spontaneous vaginal birth, first instrumental births (nonrotational forceps, Kielland forceps, and vacuum births) were not associated with increased risk of spontaneous preterm birth in the second birth. After an initial cesarean delivery at full dilatation, 3.7% of women had a repeated cesarean delivery at full dilatation and 48% had a planned cesarean delivery in the second birth. This study is a substantial addition to the body of evidence on the risk of subsequent spontaneous preterm birth after cesarean delivery at full dilatation, and demonstrates a strong association between cesarean delivery at full dilatation in the first birth and spontaneous preterm birth in subsequent pregnancy, although the absolute risk remains small. This is a large retrospective cohort and includes a comprehensive assessment of potential confounding factors, including preeclampsia, antepartum hemorrhage, and lengths of first and second stage of labor. Future research should focus on understanding possible causality and developing primary and secondary preventative measures.

Degree of expression of inflammatory proteins in the amniotic cavity, but not prior obstetric history, is associated with the risk severity for spontaneous preterm birth after rescue cerclage for cervical insufficiency.

To examine whether the severity of spontaneous preterm birth (SPTB) risk after rescue cerclage for acute cervical insufficiency (CI) is linked tothe degree of inflammatory response in the amniotic fluid (AF) based on the concentrations of various inflammatory proteins and prior obstetric history. We conducted a retrospective cohort study of 65 singleton pregnantwomen (17-25weeks) who underwent rescue cerclage following the diagnosis of acute CI and were subjected to amniocentesis. EN-RAGE, IL-6, IL-8, and IP-10 as inflammatory mediators and kallistatin, MMP-2/8, and uPA as extracellular matrix remodeling-related molecules were assayed in the AF using ELISA. The level of each inflammatory mediator was divided into quartiles. Intra-amniotic inflammation (IAI; AF IL-6 level ≥2.6ng/mL) was independently associated with SPTB after cerclage placement. The odds of SPTB at<32weeks, even after adjusting for confounders, increased significantly with each increasing quartile of baseline AF levels for each inflammatory mediator (p for trend<.05). Kaplan-Meier survival curves showed that the cerclage-to-delivery intervals were significantly shorter as the quartiles of AF EN-RAGE and MMP-8 increased (log-rank test, p<.01 each). Neither previous term birth nor prior PTB was associated with SPTB risk or cerclage-to-delivery interval after rescue cerclage. Multiparous women who experience CI after term birth showed significantly elevated levels of MMP-8 and reduced kallistatin levels in the AF. In patients with CI, SPTB risk (especially risk severity) after rescue cerclage is associated with thedegree of the inflammatory response in AF as well as the presence of IAI but not with prior obstetric history.

Spontaneous preterm birth risk among HPV-vaccinated and -unvaccinated women: a nationwide retrospective cohort study of over 240 000 singleton births.

To determine whether prior human papillomavirus (HPV) vaccination contributes to preterm birth risk. Population-based retrospective cohort study. Denmark. A cohort of 243 136 primiparous females born in the period 1961-2004 who had a singleton delivery at >22 weeks of gestation occurring from October 2006 to December 2018. High-quality nationwide registries were linked to provide information on demographics, birth outcomes, HPV vaccination status, smoking, body mass index (BMI), and cervical lesions and treatment history. We assessed the association between HPV vaccination status and spontaneous preterm birth using logistic regression. To address age at vaccination, we performed a stratified analysis by vaccination before and after 17 years of age. In age-adjusted and fully adjusted models, there was a nonsignificant difference in the odds of spontaneous preterm birth between vaccinated and unvaccinated women (OR1.05 (95%CI 0.99-1.12) and OR1.04 (95%CI 0.98-1.10), respectively). There was no difference in the odds of spontaneous preterm birth in relation to time between vaccination and pregnancy. In contrast, compared with unvaccinated women, the odds of preterm birth were lower among women vaccinated before the age of 17 years (fully adjusted OR0.87, 95%CI 0.75-1.00). This association was not present for women vaccinated at ≥17 years of age. In this large, population-based cohort, we found reduced odds of spontaneous preterm birth among women vaccinated against HPV at an early age compared with women who were unvaccinated. It seems conceivable that HPV vaccination may not only reduce the incidence of cervical cancer and severe precursors, but also reduce the risk of preterm birth related to HPV infection.

Birth outcomes across the spectrum of maternal age: dissecting aging effect versus confounding by social and medical determinants

BackgroundGiven the trend of increasing maternal age and associated adverse reproductive outcomes in the US, this study aimed to assess whether this association is due to an independent aging or confounded by sociodemographic, biomedical, or behavioral determinants in a predominantly Black US population.MethodsData was from 8509 women enrolled in the Boston Birth Cohort. Adverse reproductive outcomes included spontaneous preterm delivery, cesarean delivery, and low birth weight. Covariates included sociodemographic (parity, race/ethnicity, education, marital status, income, receipt of public assistance, nativity); biomedical (obesity, hypertensive disorders, diabetes mellitus); and behavioral (consistent intake of multivitamin supplements, support from father of baby, support from family, major stress in pregnancy, cigarette smoking, alcohol intake). Analysis included Lowess and marginal probability plots, crude and adjusted sequential logistic regression models to examine age-outcome associations and to what degree the association can be explained by the above covariables.ResultOverall, the study sample had high levels of spontaneous preterm birth (18%), cesarean delivery (33%) and low birth weight (26%). Unadjusted models showed no significant difference odds of spontaneous preterm birth by maternal age but higher odds of cesarean section (aOR: 1.77, 95% CI: 1.60, 1.95) and low birth weight (aOR: 1.15, 95% CI: 1.04, 1.28) among women 30 years or older. Adjustment for sociodemographic factors, biomedical conditions and behavioral factors revealed higher odds of spontaneous preterm birth: (aOR: 1.30, 95% CI: 1.14, 1.49), cesarean section deliveries (aOR: 1.68, 95% CI: 1.51, 1.87) and low birth weight (aOR: 1.36, 95% CI: 1.21, 1.53). Across all ages, optimal BMI status and consistent multivitamin supplement intake were protective of spontaneous preterm birth and low birth weight.ConclusionIn this high-risk minority population, we demonstrated that the association between increasing maternal age and adverse pregnancy outcomes was due to an independent aging effect and the presence of confounding by sociodemographic, biomedical, and behavioral factors. Some modifiable risk factors to counteract aging effect, include optimizing BMI and consistent intake of multivitamin supplement. A fundamental change in how care is provided to women, particularly low income Black women, is needed with emphasis on the protective role of optimal nutritional status.Trial registrationClinicalTrials.gov Identifier: NCT03228875

Nitrate in Drinking Water during Pregnancy and Spontaneous Preterm Birth: A Retrospective Within-Mother Analysis in California.

Background:Nitrate is a widespread groundwater contaminant and a leading cause of drinking water quality violations in California. Associations between nitrate exposure and select adverse birth outcomes have been suggested, but few studies have examined gestational exposures to nitrate and risk of preterm birth (before 37 wk gestation).Objective:We investigated the association between elevated nitrate in drinking water and spontaneous preterm birth through a within-mother retrospective cohort study of births in California.Methods:We acquired over 6 million birth certificate records linked with Office of Statewide Health Planning and Development hospital discharge data for California births from 2000–2011. We used public water system monitoring records to estimate nitrate concentrations in drinking water for each woman’s residence during gestation. After exclusions, we constructed a sample of 1,443,318 consecutive sibling births in order to conduct a within-mother analysis. We used separate conditional logistic regression models to estimate the odds of preterm birth at 20–31 and 32–36 wk, respectively, among women whose nitrate exposure changed between consecutive pregnancies.Results:Spontaneous preterm birth at 20–31 wk was increased in association with tap water nitrate concentrations during pregnancy of 5 to [odds ratio ; 95% confidence interval (CI): 1.29, 1.67] and (; 95% CI: 1.49, 4.26) compared with (as nitrogen). Corresponding estimates for spontaneous preterm birth at 32–36 wk were positive but close to the null for 5 to nitrate (; 95% CI: 1.02, 1.15) and for nitrate (; 95% CI: 0.85, 1.31) vs. nitrate. Our findings were similar in several secondary and sensitivity analyses, including in a conventional individual-level design.Discussion:The results suggest that nitrate in drinking water is associated with increased odds of spontaneous preterm birth. Notably, we estimated modestly increased odds associated with tap water nitrate concentrations of 5 to (below the federal drinking water standard of ) relative to . https://doi.org/10.1289/EHP8205

Effect of a Nonoptimal Cervicovaginal Microbiota and Psychosocial Stress on Recurrent Spontaneous Preterm Birth.

While select cervicovaginal microbiota and psychosocial factors have been associated with spontaneous preterm birth, their effect on the risk of recurrence remains unclear. It is also unknown whether psychosocial factors amplify underlying biologic risk. This study sought to determine the effect of nonoptimal cervicovaginal microbiota and perceived stress on the risk of recurrent spontaneous preterm birth. This was a secondary analysis of a prospective pregnancy cohort, Motherhood and Microbiome. The Cohen's Perceived Stress Scale (PSS-14) was administered and cervical swabs were obtained between 16 and 20 weeks of gestation. PSS-14 scores ≥30 reflected high perceived stress. We analyzed cervicovaginal microbiota using 16S rRNA sequencing and classified microbial communities into community state types (CSTs). CST IV is a nonoptimal cervicovaginal microbial community characterized by anaerobes and a lack of Lactobacillus. The final cohort included a predominantly non-Hispanic Black population of women with prior spontaneous preterm birth who had recurrent spontaneous preterm birth or term birth and had stress measurements (n = 181). A subanalysis was performed in the subset of these women with cervicovaginal microbiota data (n = 74). Multivariable logistic regression modeled adjusted associations between CST IV and recurrent spontaneous preterm birth, high stress and recurrent spontaneous preterm birth, as well as high stress and CST IV. Among the 181 women with prior spontaneous preterm birth, 45 (24.9%) had high perceived stress. We did not detect a significant association between high stress and recurrent spontaneous preterm birth (adjusted odds ratio [aOR] 1.67, 95% confidence interval [CI]: 0.73-3.85). Among the 74 women with prior spontaneous preterm birth and cervicovaginal microbiota analyzed, 29 (39.2%) had CST IV; this proportion differed significantly among women with recurrent spontaneous preterm birth (51.4%) compared with women with term birth (28.2%) (p = 0.04). In models adjusted for race and marital status, the association between CST IV and recurrent spontaneous preterm birth persisted (aOR 3.58, 95% CI: 1.25-10.24). There was no significant interaction between stress and CST IV on the odds of spontaneous preterm birth (p = 0.328). When both stress and CST IV were introduced into the model, their associations with recurrent spontaneous preterm birth were slightly stronger than when they were in the model alone. The aOR for stress with recurrent spontaneous preterm birth was 2.02 (95% CI: 0.61-6.71) and for CST IV the aOR was 3.83 (95% CI: 1.30-11.33). Compared to women with neither of the two exposures, women with both high stress and CST IV had the highest odds of recurrent spontaneous preterm birth (aOR = 6.01, 95% CI: 1.002-36.03). Among a predominantly non-Hispanic Black cohort of women with a prior spontaneous preterm birth, a nonoptimal cervicovaginal microbiota is associated with increased odds of recurrent spontaneous preterm birth. Adjustment for perceived stress may amplify associations between CST IV and recurrent spontaneous preterm birth. Identification of modifiable social or behavioral factors may unveil novel nonpharmacologic interventions to decrease recurrent spontaneous preterm birth among women with underlying biologic risk. · CST IV, a nonoptimal microbiota, is associated with increased odds of recurrent spontaneous preterm birth.. · Adjustment for perceived stress amplified associations between CST IV and recurrent spontaneous preterm birth.. · Identification of modifiable psychosocial factors may unveil novel nonpharmacologic interventions to decrease recurrent preterm birth..

Association between chorionicity and preterm birth in twin pregnancies: a systematic review involving 29 864 twin pregnancies

The perinatal mortality and morbidity among twins vary by chorionicity. Although it is considered that monochorionicity is associated with an increased risk of preterm birth in twin pregnancies, no systematic review exists evaluating this association. This systematic review was undertaken to assess the association between preterm birth and chorionicity in twin pregnancies. We searched the electronic databases from January 1990 to July 2019 without language restrictions. All studies on twin pregnancies where chorionicity and preterm birth were evaluated were included. Findings are reported as odds ratios with 95% confidence intervals. The estimates are pooled using random-effects meta-analysis. From 13156 citations, we included 39 studies (29864 pregnancies). Monochorionicity was significantly associated with increased risk of preterm birth at ≤28, ≤32, ≤34 and <37weeks in women asymptomatic and symptomatic for preterm labour (odds ratio [OR] 2.14, 95% CI 1.52-3.02, I2 =46%, OR 1.55, 95% CI 1.27-1.89 I2 =68%, OR 1.47, 95% CI 1.27-1.69, I2 =60%, OR 1.66, 95% CI 1.43-1.93, I2 =65%, respectively). Among those asymptomatic for preterm labour, significantly increased odds of preterm birth were seen for monochorionicity at gestations ≤34weeks (OR 1.85, 95% CI 1.42-2.40, I2 =25%) and <37weeks (OR 1.75, 95% CI 1.22-2.53, I2 =61%). Sensitivity analysis showed significantly increased odds of spontaneous preterm birth at ≤34 and <37weeks for monochorionicity (OR 1.25, 95% CI 1.01-1.55, I2 =0% and OR 1.41, 95% CI 1.13-1.78, I2 =0%). Monochorionicity is significantly associated with preterm birth at all gestations. In twin pregnancies, monochorionicity is associated with an increased risk of preterm birth at all gestations.

Oil and gas production and spontaneous preterm birth in the San Joaquin Valley, CA: A case-control study.

Recent studies report an association between preterm birth and exposure to unconventional oil and gas wells. There has been limited previous study on exposure to conventional wells, which are common in California. Our objective was to determine whether exposure to well sites was associated with increased odds of spontaneous preterm birth (delivery at <37 weeks). We conducted a case-control study using data on 27,913 preterm birth cases and 197,461 term birth controls. All births were without maternal comorbidities and were located in the San Joaquin Valley, CA, between 1998 and 2011. We obtained data for 83,559 wells in preproduction or production during the study period. We assessed exposure using inverse distance-squared weighting and, for each birth and trimester, we assigned an exposure tertile. Using logistic regression, we estimated adjusted odds ratios (ORs) for the association between exposure to well sites and preterm birth at 20-27, 28-31, and 32-36 weeks. We observed increased ORs for preterm birth with high exposure to wells in the first and second trimesters for births delivered at ≤31 weeks (adjusted ORs, 1.08-1.14). In stratified analyses, the associations were confined to births to Hispanic and non-Hispanic Black women and to women with ≤12 years of educational attainment. In a secondary analysis, we found evidence that exposure to wells in preproduction is associated with higher concentrations of particulate matter. We found evidence that exposure to oil and gas well sites is associated with increased risk of spontaneous preterm birth.

Cervicovaginal microbial communities deficient in Lactobacillus species are associated with second trimester short cervix

The cervix functions as a barrier to ascending pathogens in pregnancy. Short cervical length and lack of cervicovaginal Lactobacillus species are risk factors for spontaneous preterm birth; however, whether they interact to increase risk remains unknown. We sought to examine the relationship between cervicovaginal microbiota and short cervix as well as their combined impact on spontaneous preterm birth risk. This was a secondary analysis of a prospective nested, case-control pregnancy study. Cervical swabs were collected between 16 and 20 weeks of gestation. Cervical length was measured per standard clinical care during a clinically indicated ultrasound at approximately 20 weeks of gestation. Cervicovaginal microbiota were analyzed with 16S ribosomal RNA gene sequencing and classified into community state types among 67 cases of spontaneous preterm birth, 47 cases of medically indicated preterm birth, and 358 cases of term births. Logistic regression was used to model associations of community state type IV, a community characterized by a paucity of Lactobacillus species and a wide array of anaerobic bacteria, and short cervix (<25 mm) as well as to model the association of a combination of short cervix and community state type IV with the odds of spontaneous preterm birth. Among the 472 women in the data set, there were 38 with short cervix (8.1%) and 177 with community state type IV (37.5%). Short cervix was associated with spontaneous preterm birth (adjusted odds ratio, 15.59; 95% confidence interval, 6.77-35.92). Women with community state type IV had higher odds of short cervix (adjusted odds ratio, 2.17; 95% confidence interval, 1.04-4.53) as well as spontaneous preterm birth (adjusted odds ratio, 1.97; 95% confidence interval, 1.06-3.65). While the interaction of community state type IV and short cervix was not significant (P= .771), women with both short cervix and community state type IV (n= 20) had higher odds of spontaneous preterm birth compared with women with both normal cervical length and community state types I, II, III, or V (n= 277) (adjusted odds ratio, 21.8; 95% confidence interval, 6.78-70.2). Community state type IV, characterized by a diverse set of strict and facultative anaerobes and a paucity of Lactobacillus species, is associated with increased odds of short cervix. Women with both community state type IV and short cervix have higher odds of spontaneous preterm birth than women with either factor alone. Determining the cascade of events leading to premature cervical shortening, including dysbiosis, may be critical in preventing spontaneous preterm birth.

Maternal Iodine Status and Associations with Birth Outcomes in Three Major Cities in the United Kingdom

Severe iodine deficiency in mothers is known to impair foetal development. Pregnant women in the UK may be iodine insufficient, but recent assessments of iodine status are limited. This study assessed maternal urinary iodine concentrations (UIC) and birth outcomes in three UK cities. Spot urines were collected from 541 women in London, Manchester and Leeds from 2004–2008 as part of the Screening for Pregnancy End points (SCOPE) study. UIC at 15 and 20 weeks’ gestation was estimated using inductively coupled plasma-mass spectrometry (ICP-MS). Associations were estimated between iodine status (UIC and iodine-to-creatinine ratio) and birth weight, birth weight centile (primary outcome), small for gestational age (SGA) and spontaneous preterm birth. Median UIC was highest in Manchester (139 μg/L, 95% confidence intervals (CI): 126, 158) and London (130 μg/L, 95% CI: 114, 177) and lowest in Leeds (116 μg/L, 95% CI: 99, 135), but the proportion with UIC <50 µg/L was <20% in all three cities. No evidence of an association was observed between UIC and birth weight centile (−0.2% per 50 μg/L increase in UIC, 95% CI: −1.3, 0.8), nor with odds of spontaneous preterm birth (odds ratio = 1.00, 95% CI: 0.84, 1.20). Given the finding of iodine concentrations being insufficient according to World Health Organization (WHO) guidelines amongst pregnant women across all three cities, further studies may be needed to explore implications for maternal thyroid function and longer-term child health outcomes.

Associations of neighborhood-level racial residential segregation with adverse pregnancy outcomes

Previous analyses utilizing birth certificate data have shown environmental factors such as racial residential segregation may contribute to disparities in adverse pregnancy outcomes. However, birth certificate data are ill equipped to reliably differentiate among small for gestational age, spontaneous preterm birth, and medically indicated preterm birth. We sought to utilize data from electronic medical records to determine whether residential segregation among Black women is associated with an increased risk of adverse pregnancy outcomes. The study population was composed of 4770 non-Hispanic Black women who delivered during the years 2009 through 2013 at a single urban medical center. Addresses were geocoded at the level of census tract, and this tract was used to determine the degree of residential segregation for an individual's neighborhood. Residential segregation was measured using the Gi* statistic, a z-score that measures the extent to which the neighborhood racial composition deviates from the composition of the larger surrounding area. The Gi* statistic z-scores were categorized as follows: low (z < 0), medium (z= 0-1.96), and high (z>1.96). Adverse pregnancy outcomes included overall preterm birth, spontaneous preterm birth, medically indicated preterm birth, and small for gestational age. Hierarchical logistic regression models accounting for clustering by census tract and repeated births among mothers were used to estimate odds ratios of adverse pregnancy outcomes associated with segregation. In high segregation areas, the prevalence of overall preterm birth was significantly higher than that in low segregation areas (15.5% vs 10.7%, respectively; P < .001). Likewise, the prevalence of spontaneous preterm birth and medically indicated preterm birth were higher in high (9.5% and 6.0%) vs low (6.2% and 4.6%) segregation neighborhoods (P<.001 and P= .046, respectively). The associations of high segregation with overall preterm birth (odds ratio, 1.31; 95% confidence interval, 1.02-1.69) and spontaneous preterm birth (odds ratio, 1.37; 95% confidence interval, 1.02-1.85) remained significant with adjustment for neighborhood poverty, insurance status, parity, and maternal medical conditions. Among non-Hispanic Black women in an urban area, high levels of segregation were independently associated with the higher odds of spontaneous preterm birth. These findings highlight one aspect of social determinants (ie, segregation) through which adverse pregnancy outcomes may be influenced and points to a potential target for intervention.

Obstetric History and Likelihood of Preterm Birth of Twins.

The objective of this study was to investigate the relationship between preterm birth in a prior pregnancy and preterm birth in a twin pregnancy. We performed a secondary analysis of a randomized controlled trial evaluating 17-α-hydroxyprogesterone caproate in twins. Women were classified as nulliparous, multiparous with a prior term birth, or multiparous with a prior preterm birth. We used logistic regression to examine the odds of spontaneous preterm birth of twins before 35 weeks according to past obstetric history. Of the 653 women analyzed, 294 were nulliparas, 310 had a prior term birth, and 49 had a prior preterm birth. Prior preterm birth increased the likelihood of spontaneous delivery before 35 weeks (adjusted odds ratio [aOR]: 2.44, 95% confidence interval [CI]: 1.28-4.66), whereas prior term delivery decreased these odds (aOR: 0.55, 95% CI: 0.38-0.78) in the current twin pregnancy compared with the nulliparous reference group. This translated into a lower odds of composite neonatal morbidity (aOR: 0.38, 95% CI: 0.27-0.53) for women with a prior term delivery. For women carrying twins, a history of preterm birth increases the odds of spontaneous preterm birth, whereas a prior term birth decreases odds of spontaneous preterm birth and neonatal morbidity for the current twin pregnancy. These results offer risk stratification and reassurance for clinicians.

Gut microbiome of mothers delivering prematurely shows reduced diversity and lower relative abundance of Bifidobacterium and Streptococcus.

ObjectivePreterm birth is the main reason for neonatal deaths worldwide. We investigate whether maternal gut microbiota may play a previously overlooked role.MethodsThe Norwegian Microbiota Study (NoMIC) is a case control study on preterm birth (<259 days of gestation, calculated primarily based on the last menstrual period), including two consecutively born term infants per infant born prematurely. Eligible mothers were fluent in Norwegian and recruited from the maternity ward at a county hospital in Eastern Norway in the period 2002–2005. Fecal samples were collected at day 4 postpartum, and analyzed using 16S ribosomal RNA gene sequencing. We used samples from 121 mothers giving birth vaginally. Measures of alpha diversity (Shannon, Phylogenetic Diversity and Observed Operational Taxonomic Units) and microbiome composition were combined with information from the Medical Birth Registry, pregnancy journals, and questionnaires.ResultsThe association between maternal gut diversity and preterm delivery was examined using logistic regression. One IQR increase in Shannon diversity was significantly associated with 38% lower odds of spontaneous preterm birth, (95% confident interval (CI): 1%, 61%), and the association was stronger when adjusting for maternal age, marital status, ethnicity, parity, BMI, education, antibiotic use, pets in the household, income and smoking (48% lower odds, 95% CI: 4.2%, 72%). Mothers delivering prematurely also had lower abundance of OTUs belonging to Bifidobacterium and Streptococcus, and of the Clostridiales order.ConclusionAnalysis of maternal gut microbiota using next-generation sequencing shows that low gut diversity, with a distinct microbial composition, is associated with spontaneous preterm delivery.

Association between change in cervical length and spontaneous preterm birth in twin pregnancies

There is a lack of consensus on the optimal transvaginal cervical length for determining risk for spontaneous preterm birth in twin pregnancies. Change in transvaginal cervical length over time may reflect early activation of the parturition process, as has been demonstrated in singleton pregnancies. The association between change in transvaginal cervical length and the risk for spontaneous preterm birth has not yet been described in the population of women with diamniotic twin pregnancies. Our primary objective is to determine whether rate of change in transvaginal cervical length in the midtrimester is associated with spontaneous preterm birth in twin gestations. Our secondary objective is to describe parameters for identifying patients at increased risk for spontaneous preterm birth based on change in transvaginal cervical length over time. This is a retrospective cohort of serial transvaginal cervical length performed for twin pregnancies at a single institution from 2008 through 2015. Women with diamniotic twin pregnancies who had transvaginal cervical length measurements at 18 and 22 weeks' gestation and outcome data available were included. Logistic regression was used to determine the relationship between the rate of change in transvaginal cervical length and the risk for the primary outcome of spontaneous preterm birth <35 weeks as well as spontaneous preterm birth <32 weeks. In all, 527 subjects met inclusion criteria for this study. The average rate of change in transvaginal cervical length for patients with spontaneous preterm birth <35 weeks was -0.21 cm/wk (SD 0.27) vs -0.10 cm/wk (SD 0.24) for patients who delivered ≥35 weeks (P < .01). The rate of change in transvaginal cervical length was associated with spontaneous preterm birth <35 weeks when controlling for initial transvaginal cervical length and other important risk factors for spontaneous preterm birth. Results for spontaneous preterm birth <32 weeks were similar. This association remained significant when the rate of weekly change was treated as a dichotomous variable based on an apparent inflection point in the risk for spontaneous preterm birth: women with rapid change in transvaginal cervical length, ≥-0.2 cm/wk, had 3.45 times the odds of spontaneous preterm birth as those with less rapid change (95% confidence interval, 2.15-5.52) when controlling for initial transvaginal cervical length. Change in transvaginal cervical length in the midtrimester is associated with spontaneous preterm birth, and therefore protocols for serial transvaginal cervical length measurement can provide the clinician with information to identify at-risk patients. A decrease of ≥0.2 cm/wk of transvaginal cervical length identifies patients at increased risk for spontaneous preterm birth <35 weeks.

Relación entre estrés durante el embarazo y nacimiento pretérmino espontáneo

BackgroundPreterm birth occurs before 37 completed weeks, its causes are multifactorial and vary according to the gestational age, ethnicity and geographical context. Although several medical/social factors have been clearly identified, over 50% of cases are unknown or unclear; however, psychopathological components emerge as potentially important risk factors. ObjectiveTo determine the relationship between the presence of stress during pregnancy and spontaneous preterm birth. Material and methodsThrough a study of cases and controls in a level III hospital, with a sample of 360 patients during the period from March to November of 2013, where sociodemographic characteristics were collected. In addition, they were applied scales social adjustment, coping strategies and social support. Logistic regression models were developed; psychological, biological and social. Based on the significant variables in each of these generated a final one. ResultsThe final model was found that stress during pregnancy increases the odds of spontaneous preterm birth 1.91 times (adjusted OR=2.91; 95%CI, 1.67-5.08; P<.05). Other significant variables were: history of preterm delivery, unplanned pregnancy, no emotional support, rural residence, inadequate prenatal care and non-stable partner. ConclusionsThe findings support the hypothesis that stress during pregnancy is associated with spontaneous preterm delivery.

Repeated measures of urinary oxidative stress biomarkers during pregnancy and preterm birth

The purpose of this study was to investigate oxidative stress as a mechanism of preterm birth in human subjects; we examined associations between urinary biomarkers of oxidative stress that were measured at multiple time points during pregnancy and preterm birth. This nested case-control study included 130 mothers who delivered preterm and 352 mothers who delivered term who were originally recruited as part of an ongoing prospective birth cohort at Brigham and Women's Hospital. Two biomarkers that included 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane were measured in urine samples that were collected at up to 4 time points (median 10, 18, 26, and 35 weeks) during gestation. Urinary concentrations of 8-isoprostane and 8-OHdG decreased and increased, respectively, as pregnancy progressed. Average levels of 8-isoprostane across pregnancy were associated with increased odds of spontaneous preterm birth (adjusted odds ratio, 6.25; 95% confidence interval, 2.86-13.7), and associations were strongest with levels measured later in pregnancy. Average levels of 8-OHdG were protective against overall preterm birth (adjusted odds ratio, 0.19; 95% confidence interval, 0.10-0.34), and there were no apparent differences in the protective effect in cases of spontaneous preterm birth compared with cases of placental origin. Odds ratios for overall preterm birth were more protective in association with urinary 8-OHdG concentrations that were measured early in pregnancy. Maternal oxidative stress may be an important contributor to preterm birth, regardless of subtype and timing of exposure during pregnancy. The 2 biomarkers that were measured in the present study had opposite associations with preterm birth; an improved understanding of what each represents may help to identify more precisely important mechanisms in the pathway to preterm birth.

Longitudinal profiling of inflammatory cytokines and C-reactive protein during uncomplicated and preterm pregnancy.

Previous studies have investigated the utility of inflammation markers as predictors of preterm birth, but none have compared trends in levels between uncomplicated and preterm pregnancy. We explored longitudinal changes in plasma cytokines, including IL-1β, IL-6, IL-10, and TNF-α, as well as C-reactive protein in pregnant women from a nested case-control study. IL-6 was associated with increased odds of spontaneous preterm birth, defined by presentation of spontaneous preterm labor and/or preterm premature rupture of the membranes. Associations were strongest later in pregnancy. IL-10 was associated with increased odds of placentally mediated preterm birth, defined by presentation with preeclampsia or intrauterine growth restriction, and odds ratios were also highest near the end of pregnancy. Maternal inflammation markers were associated with increased risk of preterm birth, and relationships differed by etiology of preterm delivery and gestational age at sample collection.

Prior Ultrasound-Indicated Cerclage

INTRODUCTION: To evaluate pregnancy outcomes of women with a history of ultrasound-indicated cerclage for a short cervix who in subsequent pregnancy either were followed by transvaginal ultrasound cervical length screening or received a history-indicated cerclage. METHODS: Retrospective cohort study was performed from 1993 to 2012 involving women with an index singleton pregnancy and history of ultrasound-indicated cerclage. Prior ultrasound-indicated cerclage was defined as cerclage placed for cervical length less than 25 mm before 24 weeks of gestation in women at high risk for preterm birth. At our institution, women with a history of ultrasound-indicated cerclage were managed in their subsequent pregnancy either by transvaginal ultrasound cervical length screening or by history-indicated cerclage, at the physician's discretion (Fig. 1). In the transvaginal ultrasound cervical length group, if cervical length became less than 25 mm before 24 weeks of gestation, an ultrasound-indicated cerclage was performed. In the history-indicated cerclage group, history-indicated cerclage was placed at approximately 12–15 weeks of gestation. Primary outcome was spontaneous preterm birth at less than 35 weeks (Table 1).RESULTS: Twenty-eight women met the inclusion criteria. Of these 28 women, 13 were in the transvaginal ultrasound cervical length group and 15 in the history-indicated cerclage group. Demographics were similar in both the groups, except earliest gestational age of prior spontaneous preterm birth (Table 1). The odds of spontaneous preterm birth at less than 35 weeks of gestation for the two groups was similar (odds ratio 0.54, 95% confidence interval 0.04–6.77). Secondary outcomes were also similar in two groups except birth weight (Table 1). CONCLUSION: Women with prior ultrasound-indicated cerclage have similar outcomes if they are managed in the next pregnancy by either transvaginal ultrasound cervical length screening and ultrasound-indicated cerclage placement if cervical length is less than 25 mm before 24 weeks of gestation or by history-indicated cerclage. Our study results are limited by small sample size. There are currently no other studies evaluating this clinical dilemma.

Rate of sonographic cervical shortening and the risk of spontaneous preterm birth

We hypothesized that change in cervical length (CL) on serial ultrasounds is associated with spontaneous preterm birth (SPTB) <36 weeks for women with a short cervix (CL <25 mm). This was a secondary analysis of a multicenter prospective observational study designed to study predictors of preterm birth. Women from the general obstetric population had serial CL ultrasounds between 20-33 weeks' gestation and were followed up until delivery. Two thousand six hundred ninety five women had sonographic CL measurements. Change in CL was associated with SPTB for women with CL <25 mm (odds ratio, 0.97; 95% confidence interval, 0.96-0.98). Among women with a short cervix, for every 1 mm of cervical shortening between ultrasounds, there was a 3% increase in odds of SPTB. The association between change in CL and SPTB remained significant after controlling for age, race, body mass index, tobacco use, and fetal fibronectin test status. Among women with a sonographically short cervix, the rate of change in CL is associated with SPTB, independent of fetal fibronectin test and other important risk factors for SPTB.