Subgroups of pelvic pain are differentially associated with endometriosis and inflammatory comorbidities: a latent class analysis.

ABSTRACT: Chronic pelvic pain is heterogeneous with potentially clinically informative subgroups. We aimed to identify subgroups of pelvic pain based on symptom patterns and investigate their associations with inflammatory and chronic pain-related comorbidities. Latent class analysis (LCA) identified subgroups of participants (n = 1255) from the Adolescence to Adulthood (A2A) cohort. Six participant characteristics were included in the LCA: severity, frequency, and impact on daily activities of both menstruation-associated (cyclic) and non-menstruation-associated (acyclic) pelvic pain. Three-step LCA quantified associations between LC subgroups, demographic and clinical variables, and 18 comorbidities (10 with prevalence ≥10%). Five subgroups were identified: none or minimal (23%), moderate cyclic only (28%), severe cyclic only (20%), moderate or severe acyclic plus moderate cyclic (9%), and severe acyclic plus severe cyclic (21%). Endometriosis prevalence within these 5 LCA-pelvic pain-defined subgroups ranged in size from 4% in "none or minimal pelvic pain" to 24%, 72%, 70%, and 94%, respectively, in the 4 pain subgroups, with statistically significant odds of membership only for the latter 3 subgroups. Migraines were associated with significant odds of membership in all 4 pelvic pain subgroups relative to those with no pelvic pain (adjusted odds ratios = 2.92-7.78), whereas back, joint, or leg pain each had significantly greater odds of membership in the latter 3 subgroups. Asthma or allergies had three times the odds of membership in the most severe pain group. Subgroups with elevated levels of cyclic or acyclic pain are associated with greater frequency of chronic overlapping pain conditions, suggesting an important role for central inflammatory and immunological mechanisms.

Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes: An Individual Participant Data Meta-analysis.

OBJECTIVE: To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016. METHODS OF STUDY SELECTION: Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis. TABULATION, INTEGRATION, AND RESULTS: We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8). CONCLUSION: Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016035711.

Maternal Serum Antioxidants in Mid Pregnancy and Risk of Preterm Delivery and Small for Gestational Age Birth: Results from a Prospective Pregnancy Cohort.

Background: Preterm delivery (PTD) and poor fetal growth are major contributors to neonatal mortality and morbidity that can extend from birth onward. Although overt maternal nutrient deficiencies are associated with adverse pregnancy outcomes, such deficiencies are rare in developed countries. However, some evidence suggests that even within the normal range, higher levels of antioxidant nutrients are protective against adverse pregnancy outcomes. Materials and Methods: Using data from the prospective Pregnancy Outcomes and Community Health (POUCH) Study (n = 301 preterm; n = 246 term), we examined associations between maternal blood levels of selected antioxidants and pregnancy outcomes. Serum collected at 16-27 weeks' gestation was analyzed for carotenoids, retinol, and α- and γ-tocopherol. Using weighted polytomous regression, these nutrient concentrations were assessed in relation to (1) PTD (<37 weeks gestation) overall and grouped as spontaneous or medically indicated; and (2) small for gestational age (SGA) defined as birthweight-for-gestational age <10th percentile of a national reference population. Results: Women with total serum carotenoids in the upper quartile (Q4) had significantly lower odds of medically indicated PTD compared with women in the lower quartiles (Q1-Q3) even after adjustment for maternal characteristics (aOR = 0.4; 95% CI: 0.2-0.9). Odds ratios for SGA were consistently ≤0.5 among women with any of the serum nutrients in Q4 as compared with Q1-Q3, but final models did not reach statistical significance. Conclusion: Results support the possibility that high maternal serum antioxidants and/or the larger dietary or lifestyle pattern they represent may play a protective role in preventing adverse pregnancy outcomes.

Working Towards a Reproducible Method for Quantifying Placental Syncytial Knots.

Prominent syncytial knots (SK) in placentas signal advanced gestation or placental malperfusion, reflecting exposures that adversely affect placental development and pregnancy outcomes. Molecular-level interrogations of syncytiotrophoblast have altered perceptions of and raised questions about the function and disposition of SK. Quantifying SK and achieving acceptable levels of interrater reliability have been challenging. Our objective was to develop a simple, reproducible protocol for counting SK and demonstrate interrater reliability overall and within 3 parameters, ie, preterm vs term delivery, presence vs absence of diffuse prominent SK (DPSK), and SK relationship with a lesion, all of which could influence measurement reproducibility and interpretation. Criteria for defining SK and a grid system drawn on glass slides were developed for counting percentage of villi with SK. One disc section each from 151 placentas, sampled from 8 groups defined by the 3 parameters, was assessed by 2 pretrained pathologists. The resulting weighted kappa statistic for overall interrater agreement was 0.60 (very good) and Spearman correlation coefficient for ranking quartiles was >0.70. Agreement was best for preterm placentas, kappa  =  0.61, and those only showing DPSK associated with a lesion, kappa  =  0.67. Agreement was low in the absence of DPSK, kappa  =  0.22, or when DPSK was present in a placenta not associated with a lesion, kappa  =  0.32. The proposed method offers a potentially reliable approach for categorizing SK counts as normal vs abnormal or providing continuous measure counts. More extensive pretraining, focused on placentas with few SK and those without an associated lesion, is recommended to improve agreement.

Maternal mid-pregnancy lipids and birthweight.

OBJECTIVE: To describe associations between maternal lipids and birthweight and to determine whether pre-pregnancy body mass index (BMI) modifies these associations. DESIGN: Cohort study. SETTING: Multiple communities in Michigan, USA. POPULATION: Participants were a sub-cohort of women from the multi-community Pregnancy Outcomes and Community Health (POUCH) study (1998-2004). METHODS: Maternal total cholesterol, high-density lipoprotein (HDLc), and low-density lipoprotein (LDLc) cholesterol, and triglycerides were assessed at 16-27 weeks' gestation. Women were classified as having normal (< 25 kg/m(2) ) or overweight/obese (≥ 25 kg/m(2) ) pre-pregnancy BMI. MAIN OUTCOME MEASURES: Sex- and gestational-age-specific body weight z-score (BWz). RESULTS: Regression models examined associations among lipids (low: 1st quartile, referent: middle quartiles, high: 4th quartile) and BWz for the total sample and stratified by pre-pregnancy BMI. In adjusted analyses (n = 1207), low HDLc was associated with lower BWz (ß = -0.23, 95% CI -0.40 to -0.06), whereas high triglycerides were associated with higher BWz (ß = 0.23, 95% CI 0.06-0.41). Once stratified by pre-pregnancy BMI, low total cholesterol was associated with lower BWz in normal BMI women (ß = -0.25, 95% CI -0.47 to -0.03), whereas in overweight/obese BMI women, high HDLc was inversely (ß = -0.29, 95% CI -0.54 to -0.04) and high triglycerides were directly associated with BWz (ß = 0.32, 95% CI 0.07-0.54). Removing women with gestational diabetes/hypertensive disorders did not alter the results. CONCLUSIONS: The associations between maternal lipids and BWz vary by lipid measure and pre-pregnancy BMI. Future work should examine whether lipids and pre-pregnancy BMI make unique contributions to the fetal programming of disease.

Inflammation biomarkers in vaginal fluid and preterm delivery.

STUDY QUESTION: Which inflammation biomarkers detected in the vaginal fluid are most informative for identifying preterm delivery (PTD) risk? SUMMARY ANSWER: Elevated interleukin (IL)-6 at mid-trimester was associated with increased odds of spontaneous PTD at <35 weeks and with PTD plus histologic chorioamnionitis (HCA), and had the greatest sensitivity for detecting these two PTD subtypes. WHAT IS KNOWN ALREADY: Maternal and/or fetal inflammation play a role in some preterm deliveries, therefore inflammation biomarkers might help to identify women at greater risk. STUDY DESIGN, SIZE, DURATION: We examined 1115 women from the Pregnancy Outcomes and Community Health Study, a cohort study conducted from September 1998 through June 2004, for whom data were available on mid-pregnancy inflammatory biomarkers. PARTICIPANTS/MATERIALS, SETTING, METHODS: At enrollment at 16-27 weeks gestation, vaginal fluid samples were collected from a swab and 15 eluted biomarkers were measured using the Meso Scale Discovery multiplex electrochemiluminescence platform. Associations of biomarkers with PTD were examined, according to clinical circumstance, week at delivery and presence/absence of HCA. Weighted logistic regression was used to determine odds ratios (OR) and 95% confidence intervals (CI) adjusted for race. Sensitivity and specificity were compared between individual and multiple biomarkers, identified by a bootstrapping method. MAIN RESULTS AND THE ROLE OF CHANCE: Elevated IL-6 (>75th percentile) displayed the strongest association with spontaneous PTD <35 weeks (OR 2.3; CI 1.3-4.0) and PTD with HCA (OR 2.8; CI 1.4-6.0). The sensitivity of IL-6 to detect spontaneous PTD <35 weeks or PTD with HCA was 0.43 and 0.51, respectively, while specificity was 0.74 and 0.75, respectively. IL-6 plus IL1ß, IL-6r, tumor necrosis factor-alpha or granulocyte-macrophage colony-stimulating factor increased specificity (range 0.84-0.88), but decreased sensitivity (range 0.28-0.34) to detect both PTD subtypes. Results were similar when a combination of IL-6 and bacterial vaginosis (BV) was explored. Thus, the use of multiple biomarkers did not detect PTD subtypes with a greater sensitivity than IL-6 alone, and IL-6 is a specific but non-sensitive marker for the detection of spontaneous PTD. LIMITATIONS, REASONS FOR CAUTION: Our ability to find small effect size associations between PTD and inflammation biomarkers (OR <2.0) might have been limited by the modest number of less common PTD subtypes in our population (e.g. spontaneous delivery <35 weeks, PTD accompanied by HCA) and by relatively higher variability for some cytokines, for example tumor necrosis factor-α, IL-12p70, IL-10 and granulocyte-macrophage colony-stimulating factor, that are less stable and commonly undetectable or detectable at low levels in human vaginal secretions. WIDER IMPLICATIONS OF THE FINDINGS: Larger studies are needed to further explore a role of inflammation biomarkers in combination with other risk factors, including specific BV-associated organisms, for the prediction of PTD subtypes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Institute of Child Health and Human Development, National Institute of Nursing, March of Dimes Foundation, Thrasher Research Foundation and Centers for Disease Control and Prevention. The authors have no conflicts of interest.

C-reactive protein and preterm delivery: clues from placental findings and maternal weight.

To study the association between maternal C-reactive protein (CRP) and preterm delivery (PTD) pathways, CRP was measured in maternal plasma collected at mid-pregnancy (n = 1310). PTD was subdivided into spontaneous (sPTD) or medically indicated (MI-PTD). Histologic chorioamnionitis (HCA) was determined by placental histopathology (n = 1076). Adjusted CRP levels were elevated for sPTD (5.5 µg/mL) versus term deliveries (4.8 µg/mL) and higher in sPTD with HCA (6.3 µg/mL). After removing HCA, an interaction between body mass index (BMI) and sPTD in relation to CRP was noted. In BMI-stratified models, an association between CRP and sPTD among women with prepregnancy BMI >25 (8.9 µg/mL for sPTD; 7.2 µg/mL for term) was absent among women with lower BMI. We propose that this remaining association in overweight/obese women suggests that CRP may mark an obesity/inflammation PTD pathway that is distinct from the pathway indicated by HCA.

Maternal lipids at mid-pregnancy and the risk of preterm delivery.

OBJECTIVE: This study examined associations between maternal lipid levels at mid-pregnancy and preterm delivery, medically indicated or spontaneous. DESIGN: Prospective cohort study. SETTING: Women were recruited from 52 clinics in five Michigan, USA communities (1998-2004). POPULATION: Pregnant women were enrolled at 15-27 weeks' gestation and followed to delivery (n=3019). METHODS: A single blood sample was obtained at study enrollment. Blood lipids, i.e. total cholesterol (TC), high-density lipoprotein (HDLc), low-density lipoprotein (LDLc) cholesterol, and triglycerides (TG), were measured on a sub-cohort (n=1309). MAIN OUTCOME MEASURES: There were 221 spontaneous, 100 medically indicated preterm deliveries and 988 term deliveries. Polytomous logistic regression models examined relationships among cholesterol levels (Low: <10(th) percentile, Referent: 10(th) -<70(th) percentile, High: ≥70(th) percentile), quartiles of TG (Referent: first quartile) and delivery outcome (Referent: term). RESULTS: Odds of medically indicated preterm delivery were increased among women with low TC (adjusted odds ratio (aOR)=2.04, 95% confidence interval (CI): 1.12, 3.72), low HDLc (aOR=1.89, 95%CI: 1.04, 3.42) or low LDLc (aOR=1.96, 95%CI: 1.09, 3.54). Odds of spontaneous preterm delivery were increased among women with high TC (aOR=1.51, 95%CI: 1.06, 2.15), high LDLc (aOR=1.42, 95%CI: 0.99, 2.04) or high TG (aOR=1.90, 95%CI: 1.21, 2.97 and aOR=1.72, 95%CI: 1.06, 2.78 for third and fourth quartiles, respectively). CONCLUSIONS: Extremely low TC, HDLc, and LDLc were associated with a modest increase in risk of medically indicated preterm delivery, whereas high TC, LDLc and TG modestly increased the risk of spontaneous preterm delivery. Further research is needed to uncover explanations for these associations and to identify optimal ranges for maternal lipids.

Mid-pregnancy levels of angiogenic markers as indicators of pathways to preterm delivery.

OBJECTIVE: To determine whether mid-pregnancy levels of angiogenic markers were associated with increased risk of preterm delivery (PTD). METHODS: We studied a subcohort from the Pregnancy Outcomes and Community Health Study for whom mid-pregnancy angiogenic markers (soluble fms-like tyrosine kinase-1 [sFlt-1], soluble endoglin [sEng] and placental growth factor [PlGF]) and covariate data were available (N = 1301). Angiogenic marker levels were grouped as high/not high (sFlt-1 and sEng), low/not low (PlGF) and high/intermediate/low (sFlt-1). Associations between levels of angiogenic markers and PTD/PTD subtype were determined for women who were nonsmokers during pregnancy (N = 933). RESULTS: Low PlGF and high sEng were associated with medically-indicated PTD and PTD <35 weeks, largely due to preeclampsia (PE). Excluding PE and small-for-gestational-age infants, low sFlt-1 was positively associated with medically-indicated PTD. CONCLUSIONS: Among nonsmokers, mid-pregnancy levels of angiogenic markers may mark multiple pathways leading to PTD, only one attributable to PE.

Leisure-time physical activity in pregnancy and the birth weight distribution: where is the effect?

BACKGROUND: Leisure-time physical activity (LTPA) is recommended during pregnancy and has been associated with lower risk of delivering a large infant. We sought to characterize the effect of LTPA across the entire birth weight distribution. METHODS: Women enrolled in the Pregnancy Outcomes and Community Health (POUCH) Study (1998-2004) were followed-up in 2007. Follow-up efforts were extensive for a subcohort and minimal for the remainder (nonsubcohort). Thus, 596 subcohort and 418 nonsubcohort women who delivered at term participated. Offspring were categorized as small-, appropriate-, or large-for-gestational-age (SGA, AGA, and LGA, respectively) based on gender and gestational age-specific birth weight z-scores (BWz). At follow-up, women recalled pregnancy LTPA and were classified as inactive, insufficiently active or meeting LTPA recommendations. Linear, logistic, and quantile regression analyses were conducted separately by subcohort status. RESULTS: Meeting LTPA recommendations decreased odds of LGA significantly among the nonsubcohort (aOR = 0.30, 95% CI: 0.14-0.64) and nonsignificantly among the subcohort (aOR = 0.68, 95% CI: 0.34-1.34). In quantile regression, meeting LTPA recommendations reduced BWz among the upper quantiles in the nonsubcohort. CONCLUSIONS: LTPA during pregnancy lowered odds of LGA and reduced BWz among the upper quantiles, without shifting the entire distribution. LTPA during pregnancy may be useful for reducing risks of large fetal size.

Life stressors and 5-HTTLPR interaction in relation to midpregnancy depressive symptoms among African-American women.

OBJECTIVE: In earlier analyses of nonHispanic White women we found a stronger relation between abuse history and midpregnancy elevated depressive symptoms in women with the serotonin transporter (5-HTTLPR) S/S genotype. Here, we focus on African-American women (N=698). Our inquiry is motivated by racial differences in depression diagnosis/treatment, stressors, and frequency of major 5-HTTLPR alleles (S, LA, LG). MATERIALS AND METHODS: Stressful life events (lifetime) and depressive symptoms (current) were ascertained at 15-27 weeks gestation. A Center for Epidemiological Studies Depression Score of more than or equal to 18 was considered 'elevated'. Life events were scored together and separated into six subconstructs. 5-HTTLPR genotypes were grouped as follows: (i) L and S alleles, (ii) S-LG equivalence ('triallelic to biallelic'), and (iii) LA/LA, all others, S/S ('high/intermediate/low'). Odds ratios (OR) for 'elevated' depressive symptoms-life events (total and subconstructs) relations were calculated for each genotype grouping. RESULTS: The prevalence of 'elevated' depressive symptoms did not vary by genotype. The relation between stressful life events and 'elevated' depressive symptoms was stronger in S/S compared with LA/LA genotype (interaction P=0.11). Of the six subconstructs, only abuse showed a statistically significant gene-environment interaction. The OR for the abuse-'elevated' depressive symptoms association was greater for S/S vs. LA/LA genotype (interaction P=0.03) and in the 'triallelic to biallelic' grouping (interaction P=0.04). In the 'high/intermediate/low' grouping, 'low' (S/S) had a higher OR (5.5) than both 'intermediate' and 'high' (ORs≤2.3) (interaction P=0.10). CONCLUSIONS: These results show the importance of examining racial groups, specific stressful events, and different 5-HTTLPR genotype groupings when exploring gene-environment interactions in depression.

Midpregnancy levels of angiogenic markers in relation to maternal characteristics.

OBJECTIVE: The purpose of this study was to describe relations among maternal demographic and lifestyle characteristics and midpregnancy levels of angiogenic markers (soluble Fms-like tyrosine kinase-1, placental growth factor, soluble endoglin). STUDY DESIGN: In a large pregnancy cohort, linear models were used to evaluate relations among maternal characteristics and midpregnancy angiogenic markers with and without covariate adjustment. Associations were examined in a subcohort that included term and preterm deliveries (n = 1302) and among "normal" term pregnancies (n = 668). RESULTS: Concentrations of all factors declined with increasing maternal body mass index. Multiparous women had lower soluble Fms-like tyrosine kinase-1 levels than primiparous women. Higher placental growth factor and slightly lower soluble endoglin levels were observed among women who smoked at enrollment, but not among those women who quit before enrollment. African American women had higher levels of all markers. CONCLUSION: Understanding relations among maternal characteristics and levels of angiogenic factors may improve studies that use these markers to examine etiology and/or to predict adverse pregnancy outcome.

Blood cadmium levels in women of childbearing age vary by race/ethnicity.

The heavy metal cadmium (Cd) is long-lived in the body and low-level cumulative exposure, even among non-smokers, has been associated with changes in renal function and bone metabolism. Women are more susceptible to the adverse effects of Cd and have higher body burdens. Due to increased dietary absorption of Cd in menstruating women and the long half-life of the metal, reproductive age exposures are likely important contributors to overall body burden and disease risk. We examined blood Cd levels in women of reproductive age in the US and assessed variation by race/ethnicity. Blood Cd concentrations were compared among female NHANES participants aged 20-44, who were neither pregnant nor breastfeeding. Sample size varied primarily based on inclusion/exclusion of smokers (n=1734-3121). Mean Cd concentrations, distributions and odds ratios were calculated using SUDAAN. For logistic regression Cd was modeled as high (the upper 10% of the distribution) vs. the remainder. Overall, Mexican Americans had lower Cd levels than other groups due to a lower smoking prevalence, smoking being an important source of exposure. Among never-smokers, Mexican Americans had 1.77 (95% CI: 1.06-2.96) times the odds of high Cd as compared to non-Hispanic Whites after controlling for age and low iron (ferritin). For non-Hispanic Blacks, the odds were 2.96 (CI: 1.96-4.47) times those of non-Hispanic Whites in adjusted models. Adjustment for relevant reproductive factors or exposure to environmental tobacco smoke had no effect. In this nationally representative sample, non-smoking Mexican American and non-Hispanic Black women were more likely to have high Cd than non-Hispanic White women. Additional research is required to determine the underlying causes of these differences.

Polymorphisms in thrombophilia and renin-angiotensin system pathways, preterm delivery, and evidence of placental hemorrhage.

OBJECTIVE: The purpose of this study was to analyze functional polymorphisms in candidate genes (methylenetetrahydrofolate reductase [MTHFR]677C>T, MTHFR1298A>C, factor 5 1691G>A [FVL], and angiotensinogen (AGT)-6G>A) in relation to a hypothesized placental hemorrhage pathway to preterm delivery (PTD). STUDY DESIGN: We assessed maternal genotypes, pregnancy outcomes, and placental pathologic evidence among 560 white and 399 black women who were recruited at mid trimester into a prospective cohort study (1998-2004). Odds of dominant genotypes were calculated for PTDs with (n = 56) or without (n = 177) evidence of placental hemorrhage (referent = term) with the use of race-stratified polytomous logistic regression models. RESULTS: Among white women, FVL GA/AA and AGT(-6) GA/AA were both associated with hemorrhage-related PTDs (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.6-14.2 and OR, 3.8; 95% CI, 1.3-10.5, respectively), but not other PTDs (ORs, 1.2 and 0.9, respectively). FVL GA/AA was associated with placental abruption (OR, 5.8; 95% CI, 1.1-30) among white women. All results were null for MTHFR genotypes. CONCLUSION: FVL and AGT variant genotypes were associated specifically with hemorrhage-related PTDs.

Midpregnancy vaginal fluid defensins, bacterial vaginosis, and risk of preterm delivery.

OBJECTIVE: To assess relations among midpregnancy vaginal defensin levels, a component of the host innate immune response, bacterial vaginosis, and risk of preterm delivery. These relations are compared across race groups because previous studies have repeatedly shown that the prevalence of bacterial vaginosis and the risk of preterm delivery are greater in African-American women compared with that in white women. METHODS: Data are from a prospective study that enrolled pregnant women from 52 clinics in five Michigan communities. In the study subcohort, defensins (human neutrophil peptides 1, 2 and 3) and bacterial vaginosis (Nugent criteria) were measured in vaginal fluid collected at enrollment (15th through 27th week of pregnancy) from 1,031 non-Hispanic white and African-American women (787 term, 244 preterm). Preterm deliveries were categorized by clinical circumstances, ie, spontaneous and medically indicated. RESULTS: Among African Americans, vaginal human neutrophil peptides 1-3 levels greater than or equal to the median were associated with bacterial vaginosis and specifically with spontaneous preterm delivery only (adjusted odds ratio 2.3, 95% confidence interval 1.2-4.3). Once African-American women were stratified by human neutrophil peptide 1-3 levels, bacterial vaginosis added nothing to the prediction of spontaneous preterm delivery risk. None of the above associations were observed in non-Hispanic whites. CONCLUSION: The relations among human neutrophil peptide 1-3 levels, bacterial vaginosis, and preterm delivery vary by race group. In African Americans, midpregnancy human neutrophil peptide 1-3 levels were more informative to preterm delivery risk than was bacterial vaginosis, suggesting an important role for host response. In addition, elevated human neutrophil peptide 1-3 levels may be a marker for particular high-risk vaginal milieus that are not distinguished by the current bacterial vaginosis Nugent scoring system.

Hostility and anomie: links to preterm delivery subtypes and ambulatory blood pressure at mid-pregnancy.

Underlying maternal vascular disease has been implicated as one of several pathways contributing to preterm delivery (PTD) and psychosocial factors such as hostility, anomie, effortful coping, and mastery may be associated with PTD by affecting maternal vascular health. Using data from the Pregnancy Outcomes and Community Health (POUCH) study, we included 2018 non-Hispanic White and 743 African American women from 52 clinics in five Michigan, USA communities. Women were interviewed at 15-27 weeks' gestation and followed to delivery. We found that relations between psychosocial factors and PTD subtypes (i.e. medically indicated, premature rupture of membranes, spontaneous labor) varied by race/ethnicity and socio-economic position (Medicaid insurance status). Among African American women not insured by Medicaid, anomie levels in mid-pregnancy were positively associated with medically indicated PTD after adjusting for maternal age and education. Among all women not insured by Medicaid, hostility levels were positively associated with spontaneous PTD after adjusting for maternal race/ethnicity, age, and education. Failure to detect links between psychosocial factors and PTD risk in poorer women may be due to their excess risk in multiple PTD pathways and/or a more complex web of contributing risk factors. In a subset of 395 women monitored for blood pressure, anomie scores were positively associated with systolic blood pressure and heart rate and hostility scores were positively associated with systolic and diastolic blood pressure, heart rate and mean arterial pressure in models that included time, awake/asleep, race/ethnicity, and age as covariates. Further adjustment for body mass index and smoking attenuated the anomie-vascular relations but had little effect on the hostility-vascular relations. Overall this study of pregnant women provides some physiologic evidence to support findings linking levels of anomie and hostility with risk of PTD.

Assessing mid-trimester salivary cortisol levels across three consecutive days in pregnant women using an at-home collection protocol.

The Pregnancy Outcomes and Community Health (POUCH) Study enrolled women in their 15th to 27th week of pregnancy from 52 prenatal clinics located in five communities. After the study began, an at-home protocol to measure maternal stress was added, which included collection of urine and saliva twice a day (waking = AM, bedtime = PM) for three consecutive days, and completion of a daily diary. The at-home protocol was in place for 2852 POUCH participants at enrollment, and 81.3% (n = 2318) consented and returned samples and diary. For these analyses, salivary cortisol was analysed in a subset of 846 women who delivered at term. Day-to-day correlation coefficients for AM cortisol (0.45-0.55) exceeded those for PM cortisol (0.31-0.43). Study diaries indicated that there was variation in the time interval between waking and sample collection. Analyses of discrete intervals showed the same awakening response pattern in cortisol levels that has been reported in studies with serial AM sampling. The adjusted mean AM cortisol (microg/dL) was 0.506 at 0-15 min post-waking, 0.544 at 16-30 min (P < 0.05), 0.582 at 31-60 min (P < 0.01), and 0.515 at >60 min post-waking. In addition, adjusted mean AM cortisol in samples collected at or before 9 a.m. was higher than that in samples collected after 9 a.m. (0.564 vs. 0.510 microg/dL, P < 0.01). Among working women, adjusted mean AM cortisol was higher on work days than non-work days (0.564 vs. 0.489 microg/dL, P < 0.01), and in multiparae compared with primiparae (0.551 vs. 0.502 microg/dL, P = 0.07). The parity effect was not evident in non-working women. The adjusted mean PM cortisol significantly increased as week of pregnancy at sampling increased, but was not significantly related to time of collection, work day and parity. Factors influencing AM and PM cortisol levels in pregnancy appear to differ. In studies of AM cortisol levels, it is important to gather data on time of sample collection, interval from waking to sample collection, parity and work.