The association between early life adversity and bacterial vaginosis during pregnancy




Objective


The purpose of this study was to examine associations between chronic preconception psychosocial and socioeconomic stress with bacterial vaginosis (BV) during pregnancy.


Study Design


Using univariate and multivariate logistic regression, childhood abuse and neglect, chronic discrimination, childhood socioeconomic status, potential confounders, and BV were assessed at 14-16 and 19-22 weeks’ gestation in a cohort of 312 pregnant women.


Results


Persistent BV (BV positive at both time points vs no BV at either time point) was associated with childhood sexual abuse (CSA), chronic discrimination, and lack of parental home ownership. These associations were still present after covarying for current perceived stress, socioeconomic status, and other potential confounders.


Conclusion


There is evidence that BV during pregnancy is independently linked with early life psychosocial adversity, suggesting that a life-course perspective may be important in elucidating determinants of perinatal outcomes.


Bacterial vaginosis (BV) is the most common reproductive tract infection in women of child-bearing age, with a prevalence of 10-40% during pregnancy. Although various risk factors have been identified, including African American race, marital status, low socioeconomic status (SES), young age, douching, substance use, and sexual practices, a large proportion of the variance remains unexplained. Studies have consistently shown that BV is associated with a 2-fold increased risk of preterm birth and higher risks associated with early preterm birth. Because preterm birth is the leading cause of infant mortality and childhood disability, research pertaining to mediators such as BV is a public health priority. Such research is especially important because antibiotic trials have not shown consistent reductions for the risk of preterm birth.


A potential risk factor that is a biologically plausible cause of BV is stress. A large body of literature from animal and human studies has established that psychosocial stress has an impact on immune and endocrine function and can increase susceptibility to infection. Although pregnancy-specific evidence is more limited, some studies report that women with increased levels of psychosocial stress have elevated levels of serum proinflammatory cytokines and cortisol. Furthermore, behavioral sequelae of psychosocial stress, such as smoking, are risk factors for BV. Other stressors, such as those of a socioeconomic nature, have also been consistently associated with BV. The stress-BV association is of particular interest because stress is an increasingly recognized risk factor for preterm birth, and it has been postulated that infection and/or immune pathways may mediate this association.


Despite the plausibility of a relationship between stress and BV, pregnancy-specific literature remains inconclusive. Among nonpregnant women, perceived stress has been associated with incident BV. However, no studies among pregnant women have clearly established a temporal relationship between various measures of stress and the development of BV, and the results of cross-sectional studies are mixed. Regarding perceived stress, 1 study reported a significant positive association, whereas 2 other studies did not replicate this finding. Other stress-related constructs, including state and trait anxiety, life events, social support, and hassles have not been independently associated with BV. Few studies have explicitly examined stressors of a chronic nature, although Culhane et al examined community stressors and reported that residing in neighborhoods with high homelessness rates was associated with BV.


In interpreting this literature, it may be relevant to consider that the timing and chronicity of a given stressor may influence the strength of its relationship to perinatal outcomes. Regarding timing, psychological and physiological reactivity to stressors has been shown to progressively decrease as gestation advances. This implies that stress exposures before pregnancy or early in pregnancy may exert greater effects than those later in gestation. Also, childhood SES may make unique contributions to or interact with adversity during adulthood to explain adult health outcomes, including perinatal outcomes. Regarding chronicity, there is evidence that immune and endocrine alterations in the context of chronic stress are different from those of acute stress, specifically that acute stress may lead to heightened immune responses, whereas chronic stress may lead to immune suppression.


Given the limited literature specifically concerning chronic stressors, particularly those pertaining to the preconception period, the goal of this study was to assess their association with BV during pregnancy. It was hypothesized that stressors of a chronic nature with an onset in early life are more strongly associated with bacterial vaginosis than acute psychosocial or socioeconomic stress during pregnancy.


Materials and Methods


Participants


Participants were self-identified African American, Hispanic, or non-Hispanic white women 16 years old or older with singleton pregnancies recruited from 2 sites in southern California: the University of California, Irvine, Medical Center in Orange, CA, and Cedars-Sinai Medical Center in Los Angeles, CA, between September 2004 and July 2007. All participants provided written informed consent and study procedures were approved by the institutional review boards of the 2 respective institutions.


Women with cord, placental, or uterine anomalies, fetal congenital malformations, conditions that may dysregulate neuroendocrine and/or immune function, those who had received corticosteroid therapy in the 3 months preceding enrollment, or those whose pregnancies ended in a spontaneous abortion were ineligible for the study.


Procedures


Study visits occurred at approximately 14-16 weeks (T1: mean gestational age [GA] 15.2 weeks, SD 0.81) and 19-22 weeks (T2: mean GA 20.5 weeks, SD 0.84) of gestation. Study assessments included structured psychosocial and medical interviews; questionnaire administration; fetal biometry ultrasound; a speculum examination for collection of vaginal fluid and BV assessment; and the collection of venous blood, saliva and urine. Gestational age was determined through a combination of last menstrual period and obstetric ultrasonographic biometry before 16 weeks of GA, using standard clinical criteria.


Measures


BV measure


BV status was assessed by microscopic evaluation of air dried vaginal fluid slides, using Nugent scoring, the epidemiologic gold standard for assessing BV. All slides were read by a single expert reviewer (Janice French, CNM, MSN), who was blinded to participant characteristics. For these analyses, BV was dichotomized into present (score 7-10) vs absent (score 0-6). Exclusion of intermediate scores (score 4-6) from the absent category yielded similar results. Because there was greater a priori interest in chronic exposures rather than acute exposures, the outcome of interest was persistent BV, which compares women who were BV positive at both time points vs those who were BV negative at the 2 assessments. Furthermore, very few women changed BV status between time points, limiting analyses of incident and remissive BV.


Psychosocial and socioeconomic measures


Various measures were used to capture the domains of psychosocial and socioeconomic stress. First, childhood trauma was measured with the Childhood Trauma Questionnaire Short Form. This widely utilized scale assesses 5 domains of childhood trauma: physical abuse, emotional abuse, sexual abuse, physical neglect, and emotional neglect. Each item is measured on a 5 point Likert scale, measuring the frequency or severity of each exposure. Each trauma type was dichotomized into present vs absent based on cut points suggested to minimize the false identification of trauma.


Another measure of chronic stress was operationalized as discrimination, based on the Everyday Discrimination Scale. This 9 item scale measures the frequency of day-to-day experiences of unfair treatment on a 6 point Likert scale (range: 0, never, to 6, almost every day). Questions are asked without reference to race or ethnicity; rather the measure assesses generalized unfair treatment. Although commonly used in homogeneous minority samples, this scale has also been used in ethnically diverse studies.


A contrasting measure of more recently experienced stress was measured with the 14 item version of Cohen’s Perceived Stress Scale (PSS) at both study assessments, which assesses the degree to which situations in the previous month are viewed as stressful on a 5 point Likert scale (range: 1, never, to 5, very often).


All scales demonstrated good internal validity (Cronbach’s alpha: T1 PSS, 0.86; T2 PSS, 0.86; discrimination, 0.85; childhood emotional abuse, 0.85; childhood physical abuse, 0.85; childhood sexual abuse, 0.94; childhood emotional neglect, 0.90; childhood physical neglect, 0.71). Scales other than the childhood trauma questionnaire were examined as both continuous and dichotomous exposures, in which the upper 25th percentile was chosen to distinguish between elevated vs low/normal levels.


Childhood SES was measured as parental home ownership before age 16 years (yes/no). This specific measure was chosen because compared with other retrospective assessments of SES such as income, adults are generally able to recall whether their parents owned homes when they were growing up. Current SES was assessed with household income in the last year, measured on an 11 point ordinal scale ranging from less than $5000 to $100,000 or more; adjusting for the number of persons in the household yielded similar point estimates. Current SES was also measured as education, categorized as less than high school, high school degree with or without vocational education, some college, and bachelor’s degree or higher.


Covariates


Covariates and potential confounders were identified from a literature review. Measures collected through maternal self-report included race/ethnicity, age, marital status, parity, illicit drug use during pregnancy, lifetime number of sexual partners, age at first sexual intercourse, frequency of sexual intercourse during pregnancy, and antibiotic use from the beginning of pregnancy through the second study assessment. Current maternal SES (ie, education and income as described previously) was also considered as a covariate/potential confounder, in addition to a main effect. Smoking status during pregnancy was determined by self-report and cotinine assays. Prenatal antibiotic use was ascertained through self-report and prenatal medical record abstraction. Continuous and categorical classifications based on literature-defined cut points were considered; also, the distribution of each variable and collinearity considerations influenced categorizations for multivariate modeling.


Statistical analyses


The modeling strategy used several steps. First, the distribution of each variable was examined and values were checked for normality and plausibility. Second, relationships between persistent BV, stressors, and covariates were examined using χ 2 and Fisher’s exact tests as appropriate. Crude and adjusted associations between persistent BV and stressors were quantified as odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate unconditional logistic regression; statistical significance was inferred for CIs not containing the value 1. Due to the relatively large number of considered covariates, variable screening was used by examining the relationship between each individual covariate/confounder and persistent BV. Covariates associated with persistent BV at P < .15 were considered for inclusion in multivariate models. Furthermore, covariates not significantly associated with BV were added to models to see whether they changed the point estimate by more than 10%.


Collinearity was assessed by computation of condition indices and variance decomposition proportions (VDPs), using condition indices less than 20 and VDPs greater than 0.5 as an indication of a collinearity problem. Goodness of fit was assessed with the Hosmer-Lemeshow test. Analyses were conducted in SAS 9.2 (SAS Institute, Cary, NC) and SPSS 15.0 (SPSS Inc, Chicago, IL).




Results


BV was slightly more prevalent at T1 than T2 (17.3% vs 15.9%, respectively; difference not statistically significant). Among those who had BV data from both visits, BV status remained highly stable. Thirty-seven women (13.0%) were BV positive at T1 and T2 and 229 women (80.4%) were BV negative at both assessments. Only 8 women acquired BV from T1 to T2, and 11 women experienced remission of BV. Participants who were missing BV data at either time point (n = 27) did not have significantly different baseline characteristics from those with BV data at both time points.


The distribution of exposures and a description of the study population are included in Tables 1 and 2 , respectively. The largest proportion of participants was Hispanic, followed by non-Hispanic whites and then African Americans. Approximately half were married, with nearly equal numbers of unmarried participants in the 2 cohabitation categories. Participants averaged 28.8 years of age (SD 5.9) and were mostly parous, and there were few substance users. PSS scores were similar for both study assessments. A substantial minority of participants’ parents did not own a home and reported exposure to each of the 5 categories of childhood trauma.



TABLE 1

Distribution of exposures a




































































Exposure n/mean % exposed/SD
Discrimination score Mean 6.0 SD 6.2
Childhood sexual abuse b 54 18.7
Childhood physical abuse 49 16.9
Childhood emotional abuse 46 15.8
Childhood physical neglect 46 15.8
Childhood emotional neglect 52 17.9
Parental homeownership 181 61.1
T1 PSS score Mean 34.0 SD 8.1
T2 PSS score Mean 34.2 SD 8.2
Yearly household income Median $40,000-50,000/y
Education
Less than high school 30 9.7
High school or vocational school 88 28.5
Some college 101 32.7
Bachelor’s degree or above 90 29.1

BV , bacterial vaginosis; PSS , Perceived Stress Scale.

Cammack. Early life adversity and bacterial vaginosis during pregnancy. Am J Obstet Gynecol 2011.

a Sample sizes may not total 312 (total number of subjects with BV data) because of missing data;


b Eighteen subjects were missing data on all childhood abuse/neglect exposures.



TABLE 2

Overall distribution of covariates and bivariate associations between covariates and persistent BV

























































































































































































Variable n (%) a Number with persistent BV (%) b χ 2 test statistic
Race/ethnicity 29.8 c , d
Non-Hispanic white 113 (36.2) 4/101 (4)
African American 73 (23.4) 19/53 (35.9)
Hispanic 126 (40.4) 14/112 (12.5)
Parity 0.25
0 108 (34.6) 13/93 (14)
1 115 (36.9) 15/100 (15)
≥2 89 (28.5) 9/73 (12.3)
Age, y 10.7 c
≤29 (median) 165 (52.9) 28/135 (20.7)
>29 147 (47.1) 9/131 (6.9)
Cohabitation status 25.2 c
Married or cohabiting 243 (78.4) 18/213 (8.4)
Not married, not cohabiting 67 (21.6) 18/51 (35.3)
Smoking status during pregnancy
Smoker 25 (8.4) 6/23 (26.1) 3.2
Nonsmoker 271 (91.6) 29/230 (12.6)
Drug use during pregnancy
Drug use 11 (3.6) 4/8 (50) 9.1 c , d
No drug use 293 (96.4) 32/253 (12.7)
Antibiotic use during pregnancy
Antibiotic use since beginning of pregnancy 61 (20.8) 5/52 (9.6) 0.9
No antibiotic use since beginning of pregnancy 233 (79.2) 31/210 (14.8)
Lifetime sexual partners 1.8
<4 (median) 142 (49.3) 15/132 (11.4)
≥4 146 (50.7) 22/128 (17.2)
Age at first sexual intercourse, y 7.8 e , f
<14 17 (5.8) 5/14 (35.7)
14-17 167 (57.0) 23/149 (15.4)
≥18 109 (37.2) 9/100 (9)
Frequency of sexual intercourse during pregnancy 1.9
Less than once a month 49 (17.2) 8/43 (18.6)
1-3 times per month 80 (28.1) 11/74 (14.9)
1-2 times per wk 109 (38.2) 10/95 (10.5)
>2 times per wk 47 (16.5) 5/43 (11.6)

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May 31, 2017 | Posted by in GYNECOLOGY | Comments Off on The association between early life adversity and bacterial vaginosis during pregnancy

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