Environmental variables as potential modifiable risk factors of preterm birth in Philadelphia, PA.

OBJECTIVE: To examine whether variation in neighborhood context is associated with preterm birth (PTB) outcomes and gestational age (GA) at delivery in Philadelphia, and to determine whether these associations might persist when considering relevant individual-level variables. STUDY DESIGN: We analyzed individual-level data collected for a prospective cohort study of singleton pregnancies with preterm labor. We merged block-group level data to each individual's home address. Unadjusted analyses were performed to determine the association between block-group variables and individual-level outcomes. Block-group variables identified as potential risk factors were incorporated into multivariable individual-level models to determine significance. RESULTS: We analyzed data for 817 women. The prevalence of PTB <37 weeks was 41.5%. Although in unadjusted analyses several block-group variables were associated with PTB and GA at delivery, none retained significance in individual-level multivariable models. CONCLUSION: Block-group level data were not associated with PTB outcomes or GA at delivery in Philadelphia.

Prenatal inflammation is associated with adverse neonatal outcomes.

OBJECTIVE: The purpose of this study was to determine whether prenatal inflammation (as assessed by clinical chorioamnionitis, maternal temperature >38°C, or histologic chorioamnionitis) is associated with a composite adverse neonatal outcome. STUDY DESIGN: We performed a prospective cohort study of women at 22 weeks to 33 weeks 6 days' gestation with symptoms of labor (April 2009 to March 2012). Relevant maternal and neonatal exposures and outcomes were recorded. Multivariable logistic regression was performed to determine the association between prenatal inflammation and neonatal outcomes that were controlled for potential confounders. RESULTS: We analyzed 871 mother-infant pairs. The preterm birth rate was 42.0%. When we controlled for infant sex and modified the data by gestational age at delivery, prenatal inflammation remains a significant risk factor for adverse neonatal outcomes, despite advancing gestational age: clinical chorioamnionitis at 32 weeks' gestation (odds ratio [OR], 3.12; 95% confidence interval [CI], 1.02-9.52], at 36 weeks' gestation (OR, 8.88; 95% CI, 4.32-18.25), and at 40 weeks' gestation (OR, 25.30; 95% CI, 9.25-69.19); maternal temperature >38°C at 32 weeks' gestation (OR, 3.18; 95% CI, 0.66-15.42), at 36 weeks gestation (OR, 8.40; 95% CI, 3.60-19.61), and at 40 weeks gestation (OR, 22.19; 95% CI, 8.15-60.44); histologic chorioamnionitis at 32 weeks gestation (OR, 1.25; 95% CI, 0.64-2.46), at 36 weeks gestation (OR, 2.56; 95% CI, 1.54-4.23), and at 40 weeks gestation (OR, 5.23; 95% CI, 1.95-13.99). CONCLUSION: The protective association with advancing gestational age is diminished when prenatal inflammation is present.

Biomarkers and cervical length to predict spontaneous preterm birth in asymptomatic high-risk women.

OBJECTIVE: To investigate whether biomarkers from different pathways of spontaneous preterm birth (cervical membrane degradation [fetal fibronectin], cervical remodeling [soluble E-cadherin], and inflammation (elafin, surfactant protein-D, interleukin-6 [IL-6]) were superior to one biomarker alone in predicting preterm birth. Our secondary objective was to examine the association of these biomarkers with cervical length in predicting preterm birth. METHODS: We performed a single-center, prospective cohort study from August 2011 to November 2012 of asymptomatic women at risk for spontaneous preterm birth as a result of obstetric and gynecologic history. Cervicovaginal fluid and cervical length measurements were collected at two time points (20-23 6/7 weeks and 24-27 6/7 weeks of gestation). RESULTS: Among the 104 women with complete data, the preterm birth rate was 24.5%. Prior preterm birth (P=.006) and cervical length at visit 1 (P=.003) were significantly associated with preterm birth, whereas fetal fibronectin and median biomarker levels (elafin, soluble E-cadherin, IL-6) were not. Median surfactant protein-D levels at visit 1 by preterm birth status were statistically but not clinically different (0.44 ng/mL compared with 0.40 ng/mL, P<.001). Analyses of biomarkers from more than one pathway were not superior to single biomarker analyses in predicting prematurity. Neither inclusion of biomarkers nor fetal fibronectin improved the predictive ability of cervical length alone. CONCLUSION: Cervical length assessment and obstetric history but not fetal fibronectin or biomarkers were useful in the risk stratification of women identified to be at greatest risk for spontaneous preterm birth. LEVEL OF EVIDENCE: II.

Clinical prediction rules for preterm birth in patients presenting with preterm labor.

OBJECTIVE: To develop prediction rules to identify which women with preterm labor are at greatest risk for delivery within 10 days and before 37 weeks of gestation using demographic and clinical risk factors alone. METHODS: We analyzed data collected for a prospective cohort study of singleton pregnancies at 22-33 6/7 weeks of gestation with preterm labor. Potential risk factors were included in multivariable logistic models for each outcome. Using backwards regression, we identified combinations of risk factors that generated the most parsimonious yet predictive models. Adjusted odds ratios of covariates in the final models were used to estimate weights for each risk factor and were summed to generate a predictive score. The score associated with the highest negative predictive value was defined as a positive test result for each outcome. Bootstrapping techniques internally validated the scoring systems. RESULTS: We include data from 583 women. The risk of delivery within 10 days was 15.4% (n=90) and before 37 weeks of gestation it was 35.0% (n=204). The final model for delivery within 10 days included initial cervical dilatation, no prenatal care, and tobacco use (area under curve=0.75), and for delivery before 37 weeks of gestation it included initial cervical dilatation, obstetric history, and tobacco use (area under the curve=0.73). A positive test result was associated with 84% sensitivity, 51% specificity, 24% positive predictive value, and 95% negative predictive value in predicting delivery within 10 days and 79% sensitivity, 50% specificity, 46% positive predictive value, and 82% negative predictive value in predicting delivery before 37 weeks of gestation. CONCLUSION: Based on their strong negative predictive values, these prediction rules could identify patients who do not require intensive monitoring when they present with preterm labor. LEVEL OF EVIDENCE: II.

The soluble receptor for advanced glycation end products can prospectively identify patients at greatest risk for preterm birth.

OBJECTIVE: Our primary objective was to determine whether there was an association between levels of antenatal maternal serum soluble RAGE (sRAGE), drawn at the time of presentation with preterm labor (PTL), and subsequent preterm birth (PTB). Secondary objectives were to determine whether levels of sRAGE - analyzed from both antenatal maternal serum (MS) and postpartum umbilical cord serum (CS) - were associated with neonatal sepsis. METHODS: Nested case-control analyses were performed within a prospective cohort of patients at risk for PTB. MS was obtained at enrollment and CS at delivery. The sRAGE levels were analyzed. Non-parametric calculations and receiver-operator analyses were performed. RESULTS: Overall, 39.8% of patients delivered < 37 weeks (n=498) and 15% had neonatal sepsis (n=193). In comparing cases and controls, sRAGE was significantly lower in those with than those without an adverse event (PTB: median MS-sRAGE 771.79 versus 948.485 pg/mL, p=0.004; neonatal sepsis: 25-centile CS-sRAGE 1220.49 versus 2244.41 pg/mL, p=0.0013). Adding MS-sRAGE to models of clinical variables significantly enhanced the ability of the model to predict both PTB (area under the curve [AUC] 0.71 versus 0.79, p=0.004) and neonatal sepsis (AUC 0.65 versus 0.75, p=0.04). The negative predictive value of CS-sRAGE for neonatal sepsis was very strong (NPV=0.91). CONCLUSIONS: The sRAGE can be used to help predict adverse perinatal outcomes. Patients with higher levels of sRAGE - who therefore may have an enhanced capability to regulate their immune response - appear less likely to experience PTB and neonatal sepsis.