Association of maternal prepregnancy BMI with metabolomic profile across gestation.

BACKGROUND/OBJECTIVES: Elevated prepregnancy body mass index (pBMI) and excess gestational weight gain (GWG) constitute important prenatal exposures that may program adiposity and disease risk in offspring. The objective of this study is to investigate the influence of pBMI and GWG on the maternal metabolomic profile across pregnancy, and to identify associations with birth weight. SUBJECTS/METHODS: This is a longitudinal prospective study of 167 nondiabetic women carrying a singleton pregnancy. Women were recruited between March 2011 and December 2013 from antenatal clinics affiliated to the University of California, Irvine, Medical Center. Seven women were excluded from analyses because of a diagnosis of diabetes during pregnancy. A total of 254 plasma metabolites known to be related to obesity in nonpregnant populations were analyzed in each trimester using targeted metabolomics. The effects of pBMI and GWG on metabolites were tested through linear regression and principle component analysis, adjusting for maternal sociodemographic factors, diet, and insulin resistance. A Bonferroni correction was applied for multiple comparison testing. RESULTS: pBMI was significantly associated with 40 metabolites. Nonesterified fatty acids (NEFA) showed a strong positive association with pBMI, with specificity for mono-unsaturated and omega-6 NEFA. Among phospholipids, sphingomyelins with two double bonds and phosphatidylcholines containing 20:3 fatty acid chain, indicative of omega-6 NEFA, were positively associated with pBMI. Few associations between GWG, quality and quantity of the diet, insulin resistance and the maternal metabolome throughout gestation were detected. NEFA levels in the first and, to a lesser degree, in the second trimester were positively associated with birth weight percentiles. CONCLUSIONS: Preconception obesity appears to have a stronger influence on the maternal metabolic milieu than gestational factors such as weight gain, dietary intake and insulin resistance, highlighting the critical importance of preconception health. NEFA in general, as well as monounsaturated and omega-6 fatty acid species in particular, represent key metabolites for a potential mechanism of intergenerational transfer of obesity risk.

Newborn insula gray matter volume is prospectively associated with early life adiposity gain.

BACKGROUND: The importance of energy homeostasis brain circuitry in the context of obesity is well established, however, the developmental ontogeny of this circuitry in humans is currently unknown. Here, we investigate the prospective association between newborn gray matter (GM) volume in the insula, a key brain region underlying energy homeostasis, and change in percent body fat accrual over the first six months of postnatal life, an outcome that represents among the most reliable infant predictors of childhood obesity risk. METHODS: A total of 52 infants (29 male, 23 female, gestational age at birth=39(1.5) weeks) were assessed using structural MRI shortly after birth (postnatal age at MRI scan=25.9(12.2) days), and serial Dual X-Ray Absorptiometry shortly after birth (postnatal age at DXA scan 1=24.6(11.4) days) and at six months of age (postnatal age at DXA scan 2=26.7(3.3) weeks). RESULTS: Insula GM volume was inversely associated with change in percent body fat from birth to six-months postnatal age and accounted for 19% of its variance (ß=-3.6%/S.D., P=0.001). This association was driven by the central-posterior portion of the insula, a region of particular importance for gustation and interoception. The direction of this effect is in concordance with observations in adults, and the results remained statistically significant after adjusting for relevant covariates and potential confounding variables. CONCLUSIONS: Altogether, these findings suggest an underlying neural basis of childhood obesity that precedes the influence of the postnatal environment. The identification of plausible brain-related biomarkers of childhood obesity risk that predate the influence of the postnatal obesogenic environment may contribute to an improved understanding of propensity for obesity, early identification of at-risk individuals, and intervention targets for primary prevention.

Prospective association between maternal allostatic load during pregnancy and child mitochondrial content and bioenergetic capacity.

BACKGROUND: Mitochondria are multifunctional energy-producing and signaling organelles that support life and contribute to stress adaptation. There is a growing understanding of the dynamic relationship between stress exposure and mitochondrial biology; however, the influence of stress on key domains of mitochondrial biology during early-life, particularly the earliest phases of intra-uterine/prenatal period remains largely unknown. Thus, the goal of this study was to examine the impact of fetal exposure to stress (modeled as the biological construct allostatic load) upon mitochondrial biology in early childhood. METHODS: In n = 30 children (range: 3.5-6 years, 53% male), we quantified mitochondrial content via citrate synthase (CS) activity and mtDNA copy number (mtDNAcn), and measured mitochondrial bioenergetic capacity via respiratory chain enzyme activities (complexes I (CI), II (CII), and IV (CIV)) in platelet-depleted peripheral blood mononuclear cells (PBMCs). In a cohort of healthy pregnant women, maternal allostatic load was operationalized as a latent variable (sum of z-scores) representing an aggregation of early-, mid- and late-gestation measures of neuroendocrine (cortisol), immune (interleukin-6, C-reactive protein), metabolic (homeostasis model assessment of insulin resistance, free fatty acids), and cardiovascular (aggregate systolic and diastolic blood pressure) systems, as well as an anthropometric indicator (pre-pregnancy body mass index [BMI]). RESULTS: An interquartile increase in maternal allostatic load during pregnancy was associated with higher mitochondrial content (24% and 15% higher CS and mtDNAcn), and a higher mitochondrial bioenergetic capacity (16%, 23%, and 25% higher CI, CII and CIV enzymatic activities) in child leukocytes. The positive association between maternal allostatic load during pregnancy and child mitochondrial content and bioenergetic capacity remained significant after accounting for the effects of key pre- and post-natal maternal and child covariates (p's < 0.05, except CI p = 0.073). CONCLUSION: We report evidence that prenatal biological stress exposure, modeled as allostatic load, was associated with elevated child mitochondrial content and bioenergetic capacity in early childhood. This higher mitochondrial content and bioenergetic capacity (per leukocyte) may reflect increased energetic demands at the immune or organism level, and thus contribute to wear-and-tear and pathophysiology, and/or programmed pro-inflammatory phenotypes. These findings provide potential mechanistic insight into the cellular processes underlying developmental programming, and support the potential role that changes in mitochondrial content and bioenergetic functional capacity may play in altering life-long susceptibility for health and disease.

Time-dependent effect of non-Hodgkin's lymphoma grade on disease-free survival of relapsed/refractory patients treated with high-dose chemotherapy plus autotransplantation.

Evaluation of time to event outcomes usually is examined by the Kaplan-Meier method and Cox proportional hazards models. We developed a modified statistical model based on histologic grade and other variables to describe the time-dependent outcome for autologous stem cell transplant (autotransplant) performed for non-Hodgkin's lymphoma (NHL) based on histologic grade and other variables. One hundred and fourteen relapsed or refractory NHL patients were treated using BCNU 600 mg/m2, etoposide 2400 mg/m2, and cisplatin 200 mg/m2 IV followed by autotransplant. Median age was 53.5 (range: 25-70) years, 78 patients had aggressive NHL and 36 indolent NHL. Seventy-five patients received involved-field radiotherapy just prior to transplant. At a median follow-up of 33 (range: 3 to 118) months, the estimated 5-year Kaplan-Meier probabilities of overall survival and disease-free survival were 61% and 51%, respectively. Cox proportional hazards model analysis showed that proportionality did not hold for lymphoma grade, indicating that the relationship between the grade and disease-free survival differed over time. By piece-wise Cox model, the relative risk for experiencing relapse or death after 1 year in patients with indolent compared with patients with aggressive NHL was 2.81 (p=0.019) with 95% confidence interval (1.19, 6.65). The time-dependent effect of lymphoma grade on disease-free survival suggests the need for early (within first year) incorporation of novel therapeutic approaches in management of patients with indolent NHL undergoing autotransplant.

Influence of maternal thyroid hormones during gestation on fetal brain development.

Thyroid hormones (THs) play an obligatory role in many fundamental processes underlying brain development and maturation. The developing embryo/fetus is dependent on maternal supply of TH. The fetal thyroid gland does not commence TH synthesis until mid gestation, and the adverse consequences of severe maternal TH deficiency on offspring neurodevelopment are well established. Recent evidence suggests that even more moderate forms of maternal thyroid dysfunction, particularly during early gestation, may have a long-lasting influence on child cognitive development and risk of neurodevelopmental disorders. Moreover, these observed alterations appear to be largely irreversible after birth. It is, therefore, important to gain a better understanding of the role of maternal thyroid dysfunction on offspring neurodevelopment in terms of the nature, magnitude, time-specificity, and context-specificity of its effects. With respect to the issue of context specificity, it is possible that maternal stress and stress-related biological processes during pregnancy may modulate maternal thyroid function. The possibility of an interaction between the thyroid and stress systems in the context of fetal brain development has, however, not been addressed to date. We begin this review with a brief overview of TH biology during pregnancy and a summary of the literature on its effect on the developing brain. Next, we consider and discuss whether and how processes related to maternal stress and stress biology may interact with and modify the effects of maternal thyroid function on offspring brain development. We synthesize several research areas and identify important knowledge gaps that may warrant further study. The scientific and public health relevance of this review relates to achieving a better understanding of the timing, mechanisms and contexts of thyroid programing of brain development, with implications for early identification of risk, primary prevention and intervention.

Association of ultrasound-based measures of fetal body composition with newborn adiposity.

BACKGROUND: Newborns exhibit substantial variation in gestational age-adjusted and sex-adjusted fat mass proportion. The antecedent characteristics of fetal body composition that are associated with newborn fat mass proportion are poorly understood. OBJECTIVE: The aim of this study was to determine whether a composite measure of fetal fat mass is prospectively associated with newborn adiposity. METHODS: In a longitudinal study of 109 low-risk pregnancies, fetal ultrasonography was performed at approximately 12, 20 and 30 weeks gestation. Estimated fetal adiposity (EFA) was derived by integrating cross-sectional arm and thigh per cent fat area and anterior abdominal wall thickness. Newborn per cent body fat was quantified by Dual Energy X-Ray Absorptiometry. The association between EFA and newborn per cent body fat was determined by multiple linear regression. RESULTS: After controlling for confounding factors, EFA at 30 weeks was significantly associated with newborn per cent body fat (standardized ß = 0.41, p < 0.001) and explained 24.0% of its variance, which was substantially higher than that explained by estimated fetal weight (8.1%). The observed effect was driven primarily by arm per cent fat area. CONCLUSIONS: A composite measure of fetal adiposity at 30 weeks gestation may constitute a better predictor of newborn per cent body fat than estimated fetal weight by conventional fetal biometry. Fetal arm fat deposition may represent an early indicator of newborn adiposity. After replication, these findings may provide a basis for an improved understanding of the ontogeny of fetal fat deposition, thereby contributing to a better understanding of its intrauterine determinants and the development of potential interventions.

The neurobiology of stress in human pregnancy: implications for prematurity and development of the fetal central nervous system.

Adverse early experience, including prenatal maternal psychosocial stress, has the potential to negatively influence developmental processes through both physiological and behavioral mechanisms. This in turn may have adverse consequences for the mental and physical health, well-being and aging of the individual throughout the entire life-span. We have initiated a program of research on humans to examine the consequences of maternal stress and related factors in pregnancy on the length of gestation, fetal growth, and brain development. We have also investigated the physiological mechanisms that are involved. In this chapter we outline the theoretical rationale for this work and give an overview of our findings to date. These findings support a significant and independent role for behavioral processes such as maternal prenatal stress in the etiology of prematurity-related outcomes, and suggest that these effects are mediated, in part, by the maternal-placental-fetal neuroendocrine axis; specifically by placental corticotropin-releasing hormone. Using a fetal challenge paradigm as a novel method for quantifying fetal neurologic maturity in utero, we have found that the maternal environment exerts a significant influence on the fetal autonomic nervous system and on central nervous system processes related to recognition, memory and habituation. Finally, our findings provide preliminary evidence to support the notion that the influence of prenatal stress and maternal-placental hormones on the developing fetus may persist after birth, as assessed by measures of temperament and behavioral reactivity in the first 3 years of postnatal life. The implications of these studies for life-span development and health are discussed.

Maternal stress, HPA activity, and fetal/infant outcome.

Preliminary conclusions from our research include the possibility that each of the HPA products evaluated, even though correlated (e.g., ACTH and beta E), may be linked to unique and specific outcomes. Maternal stress during the 28-30 weeks of gestation is associated with birth outcome. Increased levels of psychosocial stress were significantly related to gestational age at birth and infant birth weight. Maternal stress during the third trimester was associated with increased maternal plasma levels of ACTH and cortisol. This finding is consistent with possible mechanisms whereby psychosocial stress influences birth outcome. CRH controls the timing of labor and delivery. Precocious elevation of CRH is related to the risk of preterm delivery. This system may be "stress-sensitive." Even though pregnant women may be immunized from stress, the stress signal that is transmitted (release of ACTH and cortisol) is amplified by the placental release of CRH. This possibility has at least two consequences: (1) influencing the timing of delivery and (2) desensitization of hypophyseal corticotrophs and further "protection" of the pregnant women from the results of stress (i.e., release of ACTH and beta E). Beta E appears to influence fetal learning and perhaps the developing nervous system.

Third trimester POMC disregulation predicts use of anesthesia at vaginal delivery.

In a prospective study, third trimester plasma levels of BE and ACTH were determined in 58 women who delivered vaginally. Peptide regulation was compared between subjects who used conduction anesthesia at delivery and subjects who did not. Third trimester levels of maternal BE and ACTH were significantly related; however, the relationship was significant only in subjects who did not receive conduction anesthesia (n = 24) at delivery. The normal co-release pattern between BE and ACTH in subjects receiving conduction anesthesia (n = 34) during birth was uncoupled. The use of conduction analgesia during vaginal delivery was significantly related to a disregulation index created to quantify the BE-ACTH release pattern. Uncoupled ACTH and BE patterns may result from modified control of pro-opiomelanocortin (POMC) expression during pregnancy or unique proteolytic processing of POMC, and may alter pain tolerance during delivery.

Psychological adaptation and birth outcomes: the role of personal resources, stress, and sociocultural context in pregnancy.

Prenatal psychosocial predictors of infant birth weight and length of gestation were investigated in a prospective study of 120 Hispanic and 110 White pregnant women. Hypotheses specifying that personal resources (mastery, self-esteem, optimism), prenatal stress (state and pregnancy anxiety), and sociocultural factors (income, education, ethnicity) would have different effects on birth outcomes were tested using structural equation modeling. Results confirmed that women with stronger resources had higher birth weight babies (beta = .21), whereas those reporting more stress had shorter gestations (beta = -.20). Resources were also associated with lower stress (beta = -.67), being married, being White, having higher income and education, and giving birth for the first time. There was no evidence that resources buffered the effects of stress. The importance of personal resources in pregnancy is highlighted along with implications for understanding the etiology of adverse birth outcomes.

The association between prenatal stress and infant birth weight and gestational age at birth: a prospective investigation.

OBJECTIVE: The aim was to test a model of the influence of maternal prenatal psychosocial stress on birth outcomes after controlling for biomedical risk. STUDY DESIGN: In a prospective study a sociodemographically homogeneous sample of 90 women was assessed during the third trimester with standard, reliable questionnaires that measured episodic and chronic stress, strain (response to stress), and pregnancy-related anxiety. Birth outcomes included infant birth weight, gestational age at birth, and intrapartum complications. Parity and biomedical (antepartum) risk was also coded. Bivariate and multivariate analyses were performed after controlling for the effects of biomedical risk factors. RESULTS: Independent of biomedical risk, each unit increase of prenatal life event stress (from a possible sample range of 14.7 units) was associated with a 55.03 gm decrease in infant birth weight and with a significant increase in the likelihood of low birth weight (odds ratio 1.32), and each unit increase of prenatal pregnancy anxiety (from a possible sample range of 5 units) was associated with a 3-day decrease in gestational age at birth. CONCLUSION: Independent of biomedical risk, maternal prenatal stress factors are significantly associated with infant birth weight and with gestational age at birth.

Maternal corticotropin-releasing hormone levels in the early third trimester predict length of gestation in human pregnancy.

OBJECTIVE: Corticotropin releasing hormone, a hypothalamic neuropeptide, plays a major role in regulating pituitary-adrenal function and the physiologic response to stress. During pregnancy corticotropin-releasing hormone is synthesized in large amounts by the placenta and released into the maternal and fetal circulations. Various endocrine, autocrine, and paracrine roles have been suggested for placental corticotropin-releasing hormone. The aim of this study was to prospectively assess the relationship between maternal plasma concentrations of corticotropin-releasing hormone in the early third trimester of pregnancy and the length of gestation in two groups of deliveries, with and without spontaneous labor. STUDY DESIGN: In a sample of 63 women with singleton intrauterine pregnancies, maternal plasma samples were collected between 28 and 30 weeks' gestation and corticotropin-releasing hormone concentrations were determined by radioimmunoassay. Each pregnancy was dated on the basis of last menstrual period and early ultrasonography. Parity, antepartum risk conditions, presence or absence of spontaneous labor, and birth outcomes were abstracted from the medical record. RESULTS: Maternal corticotropin-releasing hormone levels between 28 and 30 weeks' gestation significantly and negatively predicted gestational length (P < .01) after adjustment for antepartum risk. Moreover, subjects who were delivered preterm had significantly higher corticotropin-releasing hormone levels in the early third trimester (P < .01) than did those who were delivered at term. In deliveries preceded by spontaneous onset of labor, maternal third-trimester corticotropin-releasing hormone levels significantly and independently predicted earlier onset of labor (P < .01) and preterm labor (P < .05), whereas in deliveries effected by induction of labor or cesarean delivery, maternal corticotropin-releasing hormone levels were a marker of antepartum risk but not a statistically independent predictor of gestational length. CONCLUSION: These findings support the premise that placental corticotropin-releasing hormone is potentially implicated in the timing of human delivery in at least two ways. First, placental corticotropin-releasing hormone may play a role in the physiology of parturition. Premature or accelerated activation of the placental corticotropin-releasing hormone system, as reflected by precocious elevation of maternal corticotropin-releasing hormone levels, may therefore be associated with earlier onset of spontaneous labor and resultant delivery. Second, placental corticotropin-releasing hormone may be a marker of antepartum risk for preterm delivery and therefore an indirect predictor of earlier delivery. The implications of these findings are discussed in the context of the neuroendocrinology of placental corticotropin-releasing hormone and human parturition. Furthermore, the role of corticotropin-releasing hormone as a possible effector of prenatal stress in producing alterations in the timing of normal delivery is detailed.

Prenatal psychosocial factors and the neuroendocrine axis in human pregnancy.

OBJECTIVE: Physiological processes including neuroendocrine function have been proposed as mediators of the relationship between prenatal psychological state and pregnancy outcome; however, there are virtually no human studies that have systematically assessed such mechanisms. Neuroendocrine processes are significantly altered during pregnancy, and are characterized by the evolution of a transient neuroendocrine system, the placenta, and modifications in endocrine control mechanisms. Because these alterations have implications for neuroendocrine responsivity to exogenous conditions, the aim of the present study was to examine the cross-sectional association between prenatal psychosocial factors and stress-related neuroendocrine parameters during human pregnancy. METHOD: Fifty-four adult women with a singleton, intrauterine pregnancy were recruited before 28 weeks of gestation. Maternal antecubital venous blood samples were withdrawn at 28 weeks of gestation for bioassays of adrenocorticotropin hormone (ACTH), beta-endorphin (beta E), and cortisol. Measures of prenatal stress, social support, and personality were collected using a two-part, self-report questionnaire administered at 28 and 30 weeks of gestation. Biomedical data were obtained from the medical record. Factors known to influence neuropeptide and hormone levels during pregnancy were controlled, including gestational age, circadian variation, and obstetric risk. RESULTS: In the present sample, prenatal psychosocial stress, social support, and personality variables were associated with neuroendocrine parameters in two primary ways. First, certain psychosocial factors were significantly associated with plasma levels of ACTH, beta E, and cortisol, and second, psychosocial factors were associated with a measure of disregulation of the normal relationship between two pro-opiomelanocortin (POMC) derivatives, ACTH and beta E. Furthermore, a combination of the maternal psychosocial and sociodemographic factors during pregnancy accounted for 36% of the variance in ACTH, 22% of the variance in the ACTH-beta E disregulation index, 13% of the variance in cortisol, and 3% of the variance in beta E. CONCLUSIONS: The present findings are consistent with the premise that maternal-placental-fetal neuroendocrine parameters are significantly associated, both in magnitude and specificity, with features of maternal psychosocial functioning in pregnancy despite the systemic alterations associated with the endocrinology of pregnancy. These findings provide a basis for further investigations of the role of the neuroendocrine system as a putative mediating pathway between prenatal psychosocial factors and birth outcome, and possibly also as a mechanism linking features of the maternal psychosocial environment to fetal/infant brain development.

Maternal social support predicts birth weight and fetal growth in human pregnancy.

OBJECTIVE: Low birth weight is a primary cause of infant mortality and morbidity. Results of previous studies suggest that social support may be related to higher birth weight through fetal growth processes, although the findings have been inconsistent. The purpose of this investigation was to test a model of the association between a latent prenatal social support factor and fetal growth while taking into account relations between sociodemographic and obstetric risk factors and birth weight. METHOD: A prospective study was conducted among 247 women with a singleton, intrauterine pregnancy receiving care in two university-affiliated prenatal clinics. Measures of support included support from family, support from the baby's father, and general functional support. Sociodemographic characteristics were also assessed. Birth outcome and obstetric risk information were abstracted from patients' medical charts after delivery. RESULTS: Structural equation modeling analyses showed that a latent social support factor significantly predicted fetal growth (birth weight adjusted for length of gestation) with infant sex, obstetric risk, and ethnicity in the model. Marital status and education were indirectly related to fetal growth through social support. The final model with social support and other variables accounted for 31% of the variance in fetal growth. CONCLUSIONS: These findings suggest that prenatal social support is associated with infant birth weight through processes involving fetal growth rather than those involving timing of delivery. Biological and behavioral factors may contribute to the association between support and fetal growth, although these mechanisms need to be further explored. These results pave the way for additional research on fetal growth mechanisms and provide a basis for support intervention research.

Stress and preterm birth: neuroendocrine, immune/inflammatory, and vascular mechanisms.

A growing literature suggests that maternal psychological and social stress is a significant and independent risk factor for a range of adverse reproductive outcomes including preterm birth. Several issues remain to be addressed about stress and vulnerability to stress during pregnancy. Of these, perhaps one of the most important questions relates to biologic plausibility. Parturition, the process that results in birth, is a biological phenomenon. Very little empirical research to date, however, has examined the role of biological processes, if any, as mediators of the relationship between stress and preterm birth. In this paper we discuss the maternal, placental, and fetal neuroendocrine, immune/inflammatory, and vascular processes that may bridge the experience of social adversity before and during pregnancy and the biological outcome of preterm birth.

Maternal corticotropin-releasing hormone and habituation in the human fetus.

Elevated concentrations of maternal corticotrophin-releasing hormone (CRH) during the 2nd and early 3rd trimester of human pregnancy are associated with spontaneous preterm birth, but the effects of maternal CRH on the fetus are unknown. Maternal plasma was collected for analysis of CRH concentration, m = 156.24 +/- 130.91 pg/ml, from 33 pregnant women during Weeks 31-33 of gestation. Immediately after collection of plasma, fetal heart rate (FHR) measures were obtained in response to a challenge with a series of vibroacoustic stimuli. Fetuses of mothers with highly elevated CRH did not respond significantly to the presence of a novel stimulus in a repeated series, p = 0.016. These effects on the FHR response were not related to parity, fetal gender, medical (antepartum) risk, or eventual birth outcomes. Impaired dishabituation in these fetuses of mothers with high concentrations of CRH suggests that neurological systems rich with CRH receptors that support learning and memory, such as parahippocampal regions, may be targets for maternal/placental CRH, with implications for fetal neurological development.

When stress happens matters: effects of earthquake timing on stress responsivity in pregnancy.

OBJECTIVE: The purpose of the study was to assess the effects of the timing of stress during pregnancy on emotional responses and birth outcome. We hypothesized that as pregnancy advanced women would become increasingly resistant to the adverse effects of stress, and so early stress would have more profound effects than later stress. STUDY DESIGN: Forty pregnant women who had experienced an earthquake during pregnancy or shortly afterward were identified. Using regression analyses we determined whether the timing of the earthquake was related to an affective response to this event and to length of gestation. RESULTS: The earthquake was rated as more stressful when it occurred early in pregnancy compared with late in pregnancy, and postpartum ratings were similar to first-trimester ratings (r (quad) =.39; P <.05). Stress experienced early in pregnancy was associated with shorter gestational length (r =.35; P <.05). CONCLUSIONS: As pregnancy advances, women become decreasingly sensitive to the effects of stress. This decrease in vulnerability may reflect increasing protection of the mother and fetus from adverse influences during pregnancy.

Maternal stress is associated with bacterial vaginosis in human pregnancy.

OBJECTIVES: Maternal infection, particularly bacterial vaginosis (BV) in pregnancy, is one of the leading causes of adverse perinatal outcomes. The determinants of individual differences in susceptibility, or vulnerability, to maternal infections are poorly understood. This study examines whether chronic maternal stress predisposes women to infection during pregnancy, and if so, whether the effects of chronic stress on infection are independent of other established risk factors. METHODS: We conducted a cross-sectional, clinical prevalence study of chronic maternal stress and BV status in a sample of 454 pregnant women at 14.3+/-0.3 weeks gestation (+/-SEM). BV was diagnosed by Gram-stain of vaginal fluid samples; chronic maternal stress was assessed using the Cohen Perceived Stress Scale. Other established risk factors for BV, including maternal age, race/ethnicity, marital status, SES, and behaviors related to feminine hygiene, sexual practices, and substance use, were measured using a structured interview. RESULTS: Of the 454 women enrolled in this study, 224 (49%) were BV positive (Nugent score 7-10), 64 (14%) had intermediate vaginal flora (Nugent score 4-6), and 166 (37%) were BV negative (Nugent score 0-3). BV+ women had significantly higher chronic stress levels than BV- women (24.6+/-0.5 vs. 22.2+/-0.6 units (+/-SEM), respectively; t = 3.19; p < .01). Maternal sociodemographic variables (African-American race/ethnicity) and behavioral characteristics (vaginal douching, number of lifetime sexual partners, and use of illicit drugs) also were significantly associated with the presence of BV. After controlling for the effects of these variables, using a multivariable logistic regression model, chronic maternal stress remained a significant and independent predictor of BV status. Women in the moderate-stress group (third quartile) and high-stress (fourth quartile) group were 2.3 times (95% CI = 1.2-4.3) and 2.2 times (95% CI = 1.1-4.2) more likely to be BV+ than women in the low-stress group (bottom quartile). CONCLUSIONS: High levels of chronic stress during pregnancy are associated with bacterial vaginosis. The effect of chronic maternal stress is independent of the effects of other established sociodemographic and behavioral risk factors for BV.