Claudia Holzman

The Development of a Standardized Neighborhood Deprivation Index

Census data are widely used for assessing neighborhood socioeconomic context. Research using census data has been inconsistent in variable choice and usually limited to single geographic areas. This paper seeks to a) outline a process for developing a neighborhood deprivation index using principal components analysis and b) demonstrate an example of its utility for identifying contextual variables that are associated with perinatal health outcomes across diverse geographic areas. Year 2000 U.S. Census and vital records birth data (1998–2001) were merged at the census tract level for 19 cities (located in three states) and five suburban counties (located in three states), which were used to create eight study areas within four states. Census variables representing five socio-demographic domains previously associated with health outcomes, including income/poverty, education, employment, housing, and occupation, were empirically summarized using principal components analysis. The resulting first principal component, hereafter referred to as neighborhood deprivation, accounted for 51 to 73% of the total variability across eight study areas. Component loadings were consistent both within and across study areas (0.2–0.4), suggesting that each variable contributes approximately equally to “deprivation” across diverse geographies. The deprivation index was associated with the unadjusted prevalence of preterm birth and low birth weight for white non-Hispanic and to a lesser extent for black non-Hispanic women across the eight sites. The high correlations between census variables, the inherent multidimensionality of constructs like neighborhood deprivation, and the observed associations with birth outcomes suggest the utility of using a deprivation, index for research into neighborhood effects on adverse birth outcomes.

Factors Linked to Bacterial Vaginosis in Nonpregnant Women

OBJECTIVES The purposes of this study were to test the hypothesis that vaginal douching is linked to bacterial vaginosis in both symptomatic and asymptomatic women and to identify other demographic, reproductive, and lifestyle factors associated with bacterial vaginosis. METHODS In this cross-sectional study involving 3 clinic sites, 496 nonpregnant women completed a self-administered questionnaire. Their vaginal smears were assessed and cross-validated for bacterial vaginosis. RESULTS The prevalence of bacterial vaginosis across clinics ranged from 15% to 30%. In analyses restricted to site 1, adjusted odds ratios (ORs) for bacterial vaginosis remained significant for African American women with 13 or fewer years of education (OR = 5.5, 95% confidence interval [CI] = 2.1, 14.5), hormone use within the past 6 months (OR = 0.5, 95% CI = 0.2, 0.8), and vaginal douching within the past 2 months (OR = 2.9, 95% CI = 1.5, 5.6). CONCLUSIONS Two lifestyle factors emerge as strongly associated with bacterial vaginosis: systemic contraceptives appear protective, whereas douching is linked to an increase in prevalence. The temporal relationship between douching and bacterial vaginosis needs further clarification.

Maternal fish consumption, mercury levels, and risk of preterm delivery.

Background Pregnant women receive mixed messages about fish consumption in pregnancy because unsaturated fatty acids and protein in fish are thought to be beneficial, but contaminants such as methylmercury may pose a hazard. Methods In the Pregnancy Outcomes and Community Health (POUCH) study, women were enrolled in the 15th to 27th week of pregnancy from 52 prenatal clinics in five Michigan communities. At enrollment, information was gathered on amount and category of fish consumed during the current pregnancy, and a hair sample was obtained. A segment of hair closest to the scalp, approximating exposure during pregnancy, was assessed for total mercury levels (70–90% methylmercury) in 1,024 POUCH cohort women. Results Mercury levels ranged from 0.01 to 2.50 μg/g (mean = 0.29 μg/g; median = 0.23 μg/g). Total fish consumption and consumption of canned fish, bought fish, and sport-caught fish were positively associated with mercury levels in hair. The greatest fish source for mercury exposure appeared to be canned fish. Compared with women delivering at term, women who delivered before 35 weeks’ gestation were more likely to have hair mercury levels at or above the 90th percentile (≥ 0.55 μg/g), even after adjusting for maternal characteristics and fish consumption (adjusted odds ratio = 3.0; 95% confidence interval, 1.3–6.7). Conclusion This is the first large, community-based study to examine risk of very preterm birth in relation to mercury levels among women with low to moderate exposure. Additional studies are needed to see whether these findings will be replicated in other settings.

Socioeconomic domains and associations with preterm birth

Neighborhood socioeconomic effects on health have been estimated using multiple variables and indices. This inconsistent estimation approach makes comparison across geographic areas challenging. In this paper, we developed indices representing specific socioeconomic domains that can be reproduced in other areas to estimate elements of the neighborhood socioeconomic environment on health outcomes, specifically preterm birth. Using year 2000 U.S. census data and principal components analysis, socioeconomic indices were developed representing a priori - defined domains of education, employment, housing, occupation, poverty and residential stability. These socioeconomic indices were subsequently used in race-stratified multilevel logistic regression models of preterm birth in eight socioeconomically distinct study areas in the U.S. Maternal residence was obtained from birth records and was geocoded to census tracts. In maternal age and education adjusted models, living in tracts with high unemployment, low education, poor housing, low proportion of managerial or professional occupation and high poverty was associated with increased odds of preterm birth for non-Hispanic white women at most sites. Among non-Hispanic black women, similar associations were noted for tract-level low education, high unemployment, low occupation, and high poverty, but the effect estimates were generally smaller than those seen for white women. Increasing amounts of residential stability were not associated with preterm birth in these analyses. We combined the domain estimates across the eight study sites to produce pooled effect estimates for the socioeconomic domains on preterm birth. The research reported here suggests that specific neighborhood-level socioeconomic features may be especially influential to health outcomes. These socioeconomic domains represent potential targets for intervention or policy efforts designed to improve maternal and child health and reduce health disparities.

Mid-pregnancy circulating cytokine levels, histologic chorioamnionitis and spontaneous preterm birth

Some spontaneous preterm deliveries (PTD) are caused by occult infections of the fetal membranes (histologic chorioamnionitis [HCA]). High levels of infection-related markers, including some cytokines, sampled from maternal circulation in mid-pregnancy have been linked to PTD, but whether these specifically identify HCA has not been established. We have tested associations between 13 Th1, Th2 and Th17 cytokines and PTD with and without HCA in a prospective cohort study. The study sample included 926 Pregnancy Outcomes and Community Health Study subcohort women; women with medically indicated PTD or incomplete data excluded. A panel of cytokines was assessed using a multiplex assay in maternal plasma collected at 15-27 weeks of gestation. Severe HCA was scored by a placental pathologist blinded to clinical variables. Multivariable polytomous logistic regression was used to estimate adjusted odds ratios (OR) per 1 standard deviation (S.D.) increase in cytokine levels using a 5 level outcome variable: PTD <35 weeks with HCA, PTD <35 weeks without HCA, PTD 35-36 weeks with HCA, PTD 35-36 weeks without HCA, and term (referent). Interleukin (IL)-1beta, IL-2, IL-12, interferon-gamma, IL-4, IL-6 and transforming growth factor-beta were all significantly associated with PTD <35 weeks with HCA, with ORs of 1.6-2.3 per S.D. increase. None of these were associated with PTD <35 weeks without HCA or PTD 35-36 weeks with HCA. Although the tissues of origin of circulating cytokines are unclear, the observed elevations across many cytokines among women who later delivered <35 weeks with HCA may represent a robust immune response to infection within gestational tissues. These results suggest that women with HCA could be identified using relatively non-invasive means.

Neighbourhood deprivation and small‐for‐gestational‐age term births in the United States

Residential context has received increased attention as a possible contributing factor to race/ethnic and socio-economic disparities in birth outcomes in the United States. Utilising vital statistics birth record data, this study examined the association between neighbourhood deprivation and the risk of a term small-for-gestational-age (SGA) birth among non-Hispanic whites and non-Hispanic blacks in eight geographical areas. An SGA birth was defined as a newborn weighing <10th percentile of the sex- and parity-specific birthweight distribution for a given gestational week. Multi-level random intercept logistic regression models were employed and statistical tests were performed to examine whether the association between neighbourhood deprivation and SGA varied by race/ethnicity and study site. The risk of term SGA was higher among non-Hispanic blacks (range 10.8-17.5%) than non-Hispanic whites (range 5.1-9.2%) in all areas and it was higher in cities than in suburban locations. In all areas, non-Hispanic blacks lived in more deprived neighbourhoods than non-Hispanic whites. However, the adjusted associations between neighbourhood deprivation and term SGA did not vary significantly by race/ethnicity or study site. The summary fully adjusted pooled odds ratios, indicating the effect of one standard deviation increase in the deprivation score, were 1.15 [95% CI 1.08, 1.22] for non-Hispanic whites and 1.09 [95% CI 1.05, 1.14] for non-Hispanic blacks. Thus, neighbourhood deprivation was weakly associated with term SGA among both non-Hispanic whites and non-Hispanic blacks.

Depressive symptoms in mid-pregnancy, lifetime stressors and the 5-HTTLPR genotype

Few studies of gene–environment interactions for the serotonin transporter promoter polymorphism (5‐HTTLPR), life stressors and depression have considered women separately or examined specific types of stressful life events. None have looked at depression during pregnancy. In the Pregnancy Outcomes and Community Health (POUCH) Study, women were queried about history of stressful life events and depressive symptoms at the time of enrollment (15–27 weeks gestation). Stressful life events were grouped a priori into “subconstructs” (e.g. economic, legal, abuse, loss) and evaluated by subconstruct, total subconstruct score and total stressful life event score. The effect of genotype on the association between stressful life events and elevated depressive symptoms was assessed in 568 white non‐Hispanic participants. The relationship between exposure to abuse and elevated depressive symptoms was more pronounced in the s/s group (OR = 24.5) than in the s/l group (OR = 3.0) and the l/l group (OR = 7.7), but this significant interaction was detected only after excluding 73 (13%) women with recent use of psychotropic medications. There was no evidence of gene–environment interaction in analytic models with other stressful life events subconstructs, total subconstruct score or total stressful life events score. These data offer modest support to other reports of gene–environment interaction and highlight the importance of considering specific stressful life events.

Discrimination and Symptoms of Depression in Pregnancy Among African American and White Women

PURPOSE Depressive symptomatology during pregnancy has been associated with negative health outcomes for both the mother and child. This study examines the potential associations between depression and depressive symptoms in poor women and African-American women and their lifelong experiences of discrimination. METHODS Data from 2,731 African-American and White participants in the Pregnancy Outcomes and Community Health Study were analyzed. Multiple regression analyses were used to investigate relations between depressive symptoms and total discrimination, and between depressive symptoms and 3 discrimination types (gender, race, and socioeconomic). MAIN FINDINGS Initial results showed that African-American women had higher levels of depressive symptoms than White women. Self-reported total discrimination and discrimination types were each positively associated with depressive symptomatology in all women. After adjusting for sociodemographic characteristics (maternal age, education, employment status, partner status, and Medicaid status) and examining significant interactions, the race difference in depressive symptomatology was evident only in employed women. The addition of total discrimination to the multicovariate model eliminated race differences in the adjusted mean level of depressive symptoms. When the 3 discrimination types were modeled simultaneously with all other covariates, only gender and economic discrimination remained positively associated with depressive symptoms in African-American and White women. CONCLUSIONS These results should be cautiously interpreted because of 1) the study design--namely, ascertainment of maternal discrimination and depressive symptoms at a single time point; and 2) limitations of the discrimination measure. Despite these limitations, the study points to potential links between lifetime discrimination and depressive symptoms in pregnancy.

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 IL1β, 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.

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: <10th percentile, Referent: 10th–<70th percentile, High: ≥70th 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.