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Repetitive negative thinking (RNT) is a transdiagnostic feature that predicts increased mental health risks, inflammation, and reduced engagement in health promoting behaviors. Depression, anxiety, stress, inflammation, higher body mass index (BMI), and low engagement in health behaviors are associated with adverse outcomes during pregnancy as well as postpartum. However, there is limited literature on the associations between RNT and these contributing factors in the perinatal period, an at-risk time during which women may benefit from clinical interventions directed at RNT.This study examined the contribution of RNT to inflammation [interleukin (IL)-6] and breastfeeding duration through mediating indicators of mental health and BMI. Behavioral and biological assessments occurred during late pregnancy as well as at 4-6 weeks, 4 months, 8 months, and 12 months postpartum.RNT was positively associated with depressive symptoms, anxiety, and perceived stress (ps ≤ .001) at each assessment timepoint, with the strongest associations observed at the pregnancy assessment and significant, but attenuated, associations during postpartum (ps .01). In modeling of the association between RNT and IL-6, the indirect effect of BMI was significant at each timepoint (95%CIs 0.0013, 0.0052). Women with lower RNT exhibited longer breastfeeding duration (p = .02). These effects were not significantly mediated by mental health indicators.Clinically meaningful relationships, in which RNT predicts mental health, inflammation, and health behavior engagement during pregnancy and postpartum were observed. Clinical interventions to reduce RNT may have unique benefits this time.Further research is warranted to determine if therapies to reduce RNT confer unique benefits for maternal and child health.

Emerging research has connected abundances of specific bacteria to differences in psychosocial behaviors in animals and adult humans. However, research assessing mind-microbiome associations in children is sparse with extant work primarily focused on populations with autism, making it unclear whether links are also present in typically developing children. The current study fills this gap by examining associations between prosocial-self-regulating temperaments (effortful control; EC) and the gut microbiome in typically developing children.Maternal ratings of temperament were assessed in 77 toddlers 18 to 27 months of age (46.7% female, mean age = 23.14 months). Next-generation pyrosequencing of the V1-V3 region of the 16S rRNA gene was used to classify children's gut microbial composition from fecal samples. EC included the following subcategories: cuddliness, attentional focusing, attentional shifting, inhibitory control, and low-intensity pleasure.After adjusting for covariates, EC was positively associated with relative abundances of Akkermansia (Δ R2 = 0.117, b = 0.022, SE = 0.007, p = .002), with cuddliness (i.e., joy and ease of being held) driving the relation. Furthermore, attentional focusing was negatively associated with Alistipes (Δ R2 = 0.062, b = -0.011, SE = 0.005, p = .028). Permutational analysis of variance revealed no significant differences in community structure between high and low EC groups on the phylum level ( R2 = 0.00372, p = .745) or the genus level ( R2 = 0.01559, p = .276).Findings suggest that certain microbes may be linked to prosocial behaviors used to regulate emotion in typically developing children. Further research is needed to test whether these observations replicate in larger samples.

Although Black American mothers and infants are at higher risk for morbidity and mortality than their White counterparts, the biological mechanisms underlying these phenomena remain largely unknown. To investigate the role that lifetime stressor exposure, perceived stressor severity, and systemic inflammatory markers might play, we studied how these factors were interrelated in 92 pregnant Black American women. We also compared inflammatory marker levels for women who did versus did not go on to give birth preterm. During the early third trimester, women completed the Stress and Adversity Inventory for Adults to assess the stressors they experienced over their lifetime. Women also provided blood samples for plasma interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor (TNF)-α quantification. Preterm births were identified by medical record review. Controlling for relevant covariates, there were significant positive associations between average levels of both overall and acute perceived stressor severity and plasma IL-1β levels. Controlling for perceived stress at assessment and exposure to racial discrimination did not affect these results. Mediation models revealed that exposure to more chronic stressors was related to higher plasma IL-1β levels, as mediated by higher average levels of overall perceived stressor severity. Exposure to fewer acute stressors was related to higher plasma IL-1β levels, as mediated by higher average levels of acute perceived stressor severity. Finally, women who went on to give birth preterm had higher levels of plasma IL-6. These data thus highlight the potential importance of assessing and addressing lifetime stressor exposure among mothers before and during maternal-infant care.

Background Depression is the leading cause of disease burden among women worldwide. However, an understanding of symptom profiles among women at risk of mood disorders is limited. We determined distinct profiles of affective symptoms among high risk women, along with their distinguishing characteristics. Methods Women were recruited from 17 clinical sites affiliated with the National Network of Depression Centers. They completed measures of depression (Patient Health Questionnaire – 9) and anxiety (Generalized Anxiety Disorder – 7) as well as questions regarding demographics, reproductive status, behavioral/mental health history, and life stress/adversity. Latent class analysis and multinomial logistic regression were used to identify and characterize symptom profiles. Results 5792 women participated, ages 18 to 90 (M = 38). Three latent classes were identified: generally asymptomatic (48%), elevated symptoms of comorbid anxiety and depression (16%), and somatic symptoms (36%). Financial security and greater social support were protective factors that distinguished asymptomatic women. The profile of the class with elevated anxiety/depressive symptoms constituted a complex mix of adverse social determinants and potentially heritable clinical features, including a diagnosis of Bipolar Disorder. Women in the 3rd latent class were characterized by menstrual irregularity and a stronger expression of neurovegetative symptoms, especially sleep disturbance and fatigue. Limitations Limitations included less than optimal racial diversity of our sample and reliance on self-report. Conclusions Different symptom profiles may reflect distinct subtypes of women at risk of mood disorders. Understanding the etiology and mechanisms underlying clinical and psychosocial features of these profiles can inform more precisely targeted interventions to address women's diverse needs.

Background Among Black Americans, interpersonal racial discrimination is common. Stress, including following discrimination, contributes to pregnancy complications. In this secondary analysis, we provide data on associations among discrimination, stress, and their interaction across the life course and inflammation, perceived stress, and depressive symptoms during pregnancy. Methods During the early third trimester, Black American women (n = 93) completed the Experiences of Discrimination Scale, the Stress and Adversity Inventory, the Perceived Stress Scale, and the Center for Epidemiological Studies Depression Inventory. Plasma interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and IL-β levels were quantified. Associations were examined by linear regression, controlling for demographic, behavioral, and clinical covariates. Results Associations among racial discrimination and plasma IL-8, TNF-α, and IL-β levels depended upon average ratings of life course stress. When stress was low, discrimination in the mid tertile was associated with the highest levels of IL-8, TNF-α, and IL-β. Subscale analyses suggested that findings related to IL-8 were driven by chronic stress whereas findings related to TNF-α and IL-β were driven by acute stress. When examined together, greater discrimination but not greater life course stress was associated with higher prenatal perceived stress. In subscale analyses, the association between discrimination and prenatal perceived stress depended upon average ratings of life course acute stress. When acute stress was low, discrimination in the midtertile was associated with the highest levels of prenatal perceived stress. When acute stress was high, discrimination in the high tertile was associated with the highest levels of prenatal perceived stress. There were also direct associations among greater life course chronic stress, prenatal perceived stress, and prenatal depressive symptoms. Associations were attenuated when discrimination was included as a covariate. Conclusions The current analyses suggest that, among Black Americans, prenatal inflammation, perceived stress, and depressive symptoms may be shaped by racial discrimination and stress across the life course. In many cases, associations among discrimination and prenatal parameters depended upon how stressful exposures to life course stressors had been rated. The data suggest the potential for adaptive plasticity under some stress and highlight the deleterious nature of compounding stress.

As reviewed in Part 1 of this two part review, birth prior to full term is a substantial public health issue. In the US, ˜400,000 babies per year are born preterm ( 1 million are early term (37-386/7 weeks) and remarkable racial disparities in shortened gestation are observed among African Americans as compared to Whites. Biomechanisms linking stressor exposures with birth outcomes are increasingly being explicated. The current paper reviews the mechanistic role of maternal biological functioning in the link between behavioral exposures and birth outcomes. These include the inter-related roles of neuroendocrine function, inflammatory regulation, biological aging, and the microbiome. An integrative approach which addresses both behavioral and biological factors within the same study, carefully considers the role of race/ethnicity, and rigorously defines birth outcomes (e.g., spontaneous versus medically-indicated and inclusive of early term birth) is needed to move research in this field toward better mechanistic understanding and clinical application.

Childhood adversity is associated with a host of mental and physical health problems across the lifespan. Individuals who have experienced childhood adversity (e.g., child abuse and neglect, family conflict, poor parent/child relationships, low socioeconomic status or extreme poverty) are at a greater risk for morbidity and premature mortality than those not exposed to childhood adversity. Several mechanisms likely contribute to the relationship between childhood adversity and health across the lifespan (e.g., health behaviors, cardiovascular reactivity). In this paper, we review a large body of research within the field of psychoneuroimmunology, demonstrating the relationship between early life stress and alterations of the immune system. We first review the literature demonstrating that childhood adversity is associated with immune dysregulation across different indices, including proinflammatory cytokine production (and its impact on telomere length), illness and infection susceptibility, latent herpesvirus reactivation, and immune response to a tumor. We then summarize the growing literature on how childhood adversity may alter epigenetic processes. Finally, we propose future directions related to this work that have basic and applied implications.

Background Despite high prevalence and clinical implications of disturbed sleep during pregnancy, information on changes in sleep across pregnancy and postpartum is incomplete. Moreover, predictors of differential patterns of sleep quality across the perinatal period are poorly defined. Methods This study examined subjective sleep quality using the Pittsburgh Sleep Quality Index during each trimester of pregnancy and at 4-11 weeks postpartum among 133 women inclusive of nulliparous and multiparous African Americans and Whites. Results At any given assessment, 53%-71% of women reported poor overall sleep quality (Pittsburgh Sleep Quality Index total score > 5). Moreover, 92% reported poor overall sleep quality during at least 1 assessment, including 88% at some time during gestation. Compared to nulliparous women, multiparous women reported poorer overall sleep quality, shorter sleep duration, and poorer sleep efficiency during the first trimester; poorer overall sleep quality and longer sleep latency in the second trimester; and more frequent sleep disturbances (eg, night time and early morning awakenings) during the third trimester. Among nulliparous as well as multiparous women, specific aspects of sleep (eg, subjective sleep quality, sleep disturbances, sleep efficiency) were poorer in African American compared to White women at different time points during pregnancy. No effects of race or parity were observed on sleep parameters at postpartum. Conclusions Poor sleep quality during pregnancy as well as early postpartum is highly prevalent among both African American and White women. Both multiparous status and African American race are associated with more disturbed sleep at some time points during pregnancy. These individual differences should be considered in future research and clinical efforts to promote perinatal sleep health.

Elevated proinflammatory cytokines and decreased antiinflammatory cytokines are important in the context of perinatal health, and immune dysregulation has been found among perinatal women with low socioeconomic status (SES). Data examining psychological factors that may contribute to cytokines in pregnancy are lacking. Of importance, these associations may be most evident among women with low SES. This study examined the moderating role of SES on associations among presence of meaning in life and repetitive negative thinking with cytokine levels among 67 pregnant women. A cumulative SES index was calculated using income, education, perceived social class, and receipt of governmental support. Measures included the Perseverative Thinking Questionnaire, Meaning in Life Questionnaire, and serum interleukin (IL)-6 as well as IL-4. Using PROCESS, moderation analyses showed significant interactions between psychological factors and SES in predicting serum cytokines. In the context of high SES only, greater repetitive negative thinking was associated with higher levels of the proinflammatory cytokine IL-6 (p = 0.056) while greater meaning in life was associated with higher levels of the antiinflammatory cytokine IL-4 (p = 0.02). Findings from this study suggest that the benefits of these psychological factors on cytokine levels may be most readily observable among women with greater economic stability. Identifying psychological factors that positively contribute to biological functioning in women experiencing heightened economic distress will be crucial in addressing SES-related disparities in perinatal health.

Appalachian women 18 to 26 years old have high baseline seropositivity rates for at least 1 of the 4 human papillomavirus vaccine–related types, but low vaccine-relevant type infections. Supplemental digital content is available in the text., Background Key informants of the Appalachian community questioned whether their unique environmental stressors would alter their immune response to human papillomavirus (HPV) infections. The primary aim of this study is to determine predictors of HPV seroprevalence to at least 1 of the 4 vaccine-related HPV types before vaccination using a psychoneuroimmunologic model in Appalachian women. Method Women aged 18 to 26 years (n = 185) who had not received HPV vaccination provided cervical HPV DNA and blood samples. Human papillomavirus DNA was identified through Hybrid Capture 2 assay and then genotyped for HPV types 6, 11, 16, and 18 by Roche Linear Array. Competitive Luminex Immunoassay measured the type-specific antibodies to HPV types 6, 11, 16, and 18 in milli-Merck units per milliliter. Nine psychoneuroimmunology scales measuring attributes of stress were self-completed. Results Human papillomavirus DNA was detected in 50% (92/183) of participants, with only 14% (26/183) positive for HPV-6/11/16/18 DNA. Seropositivity for at least one anti–HPV-6/11/16 or 18, on the other hand, was present in 35% (64/183) of women, with only 10% (19/183) concomitantly infected and seropositive for the vaccine-related types. The Perceived Stress Scale was not a strong predictor of HPV seropositivity. Conclusions Both HPV infection and vaccine-related HPV type seropositivity is common among Appalachian women aged 18 to 26 years. The anticipated effect of environmental stressors on HPV seropositivity was not seen when multiple predictors were considered.

The number of US adults identifying as lesbian, gay, bisexual, transgender, or a different sexual identity has doubled since 2008, and about 40 % of the sexual and gender minority population identify as people of color. Minority stress theory posits that sexual and gender minorities are at particular risk for stress via stigma and discrimination at the structural, interpersonal, and individual levels. This stress, in turn, elevates the risk of adverse health outcomes across several domains. However, there remains a conspicuously limited amount of research on the psychoneuroimmunology of stress among sexual and gender minorities. We developed the Biopsychosocial Minority Stress Framework which posits that sexual minority status leads to unique experiences of minority stress which results in adverse health behavioral factors, elevated psychological distress and sleep disturbance, and immune dysregulation. Moderators in the model include both individual differences and intersectional identities. There is a crucial need to understand the biological-psychological axis of stress among the increasingly visible sexual and gender minority population to increase their health, longevity, and quality of life.

Background Influenza immunization during pregnancy provides protection to the mother and the infant. Studies in adults and children with inactivated influenza vaccine have identified changes in immune gene expression that were correlated with antibody responses. The current study was performed to define baseline blood transcriptional profiles and changes induced by inactivated influenza vaccine in pregnant women and to identify correlates with antibody responses. Methods Pregnant women were immunized with inactivated influenza vaccine during the 2013–2014 and 2014–2015 seasons. Blood samples were collected on day 0 (before vaccination) and on days 1 and 7 after vaccination for transcriptional profile analyses, and on days 0 and 30, along with delivery and cord blood samples, to measure antibody titers. Results Transcriptional analysis demonstrated overexpression of interferon-stimulated genes (ISGs) on day 1 and of plasma cell genes on day 7. Prevaccination ISG expression and ISGs overexpressed on day 1 were significantly correlated with increased H3N2, B Yamagata, and B Victoria antibody titers. Plasma cell gene expression on day 7 was correlated with increased B Yamagata and B Victoria antibody titers. Compared with women who were vaccinated during the previous influenza season, those who were not showed more frequent significant correlations between ISGs and antibody titers. Conclusions Influenza vaccination in pregnant women resulted in enhanced expression of ISGs and plasma cell genes correlated with antibody responses. Brief summary: This study identified gene expression profiles of interferon-stimulated genes and plasma cells before vaccination and early after vaccination that were correlated with antibody responses in pregnant women vaccinated for influenza.

During pregnancy, there are significant physiological changes to support a healthy fetus. Parasympathetic activity normatively decreases across pregnancy, and psychological stress can promote even further decreased heart rate variability (HRV). This study evaluated (1) changes in vagally-mediated HRV from pregnancy to postpartum, (2) changes in vagally-mediated HRV from pregnancy to postpartum based on negative partner relationship qualities, and (3) changes in depressive symptoms from pregnancy to postpartum based on negative partner relationship qualities. 78 participants in their 3rd trimester self-reported their relationship quality with their partner at the first visit. Depressive symptoms and vagally-mediated HRV were evaluated at rest at five time points from 3rd trimester to 12 months postpartum. On average, the only significant increase in vagally-mediated HRV occurred between the 3rd trimester and 4–6 weeks postpartum. However, those who reported more negative partner relationship qualities during their 3rd trimester of pregnancy maintained lower vagally-mediated HRV levels across all of the first year postpartum and significantly lower vagally-mediated HRV at both 4 and 8 months postpartum as compared to people who reported fewer negative partner relationship qualities. Across the first year postpartum, people reporting more negative partner relationship qualities experienced more severe depressive symptoms than their counterparts with fewer negative partner relationship qualities; however, there was no difference in the rate of change of depressive symptoms across the first year postpartum based on negative partner relationship qualities. Because lower vagally-mediated HRV is associated with depressive symptoms, future work should explore the temporal relationship between vagally-mediated HRV and depressive symptoms in the postpartum period.

Excessive inflammation in pregnancy predicts adverse birth outcomes, including shortened gestational length and lower birthweight, with African American women at greater risk. As substantial racial disparities in sleep quality, and evidence that African Americans have increased vulnerability for sleep-induced inflammatory dysregulation, sleep may be a critical, modifiable health behavior that contributes to racial disparities in birth outcomes. The present study examined sleep disturbance as a predictor of genome-wide transcriptome profiles of peripheral blood samples from 103 pregnant women (33 African American, 70 white) assessed at 18.7 ± 7.2 weeks gestation. We hypothesized that pregnant women with significant sleep disturbances would have gene expression profiles indicating over-expression of inflammatory pathways, with greater effects among African American compared to white women. Promoter-based bioinformatics analyses of differentially expressed genes indicated greater activation of NF-кB, AP1, and CREB transcription factors among African American women with sleep disturbances (all p < 0.05), and enhanced activation of AP1, but not NF-кB and reduced CREB activity among white women with sleep disturbances (p < 0.05). Differences in glucocorticoid receptor (GR) activity were also observed, in which African American women with sleep disturbances had reduced GR activity (p < 0.05), but white women with sleep disturbances showed a trend for enhanced GR activity (p = 0.11). Similarly, Interferon Response Factor (IRF) activity was reduced in African American women while increased in white women with sleep disturbances (p < 0.05). The current study provides novel evidence for gene expression related to inflammation, glucocorticoids, and anti-viral immunity among pregnant women with sleep disturbances, with differential effects by race. African Americans showed greater breadth and magnitude in these proinflammatory and anti-viral pathways than whites, with divergence in anti-inflammatory glucocorticoid, proinflammatory adrenergic-mediated cAMP, and anti-viral interferon responses. These data elucidate the role of sleep disturbances in intracellular inflammatory and anti-viral immunity in pregnancy and provide a potential target for intervention.

Significant health disparities exist between African Americans (AA) and European Americans (EA) in hypertension and hypertension-related disorders. Evidence suggests that this is due to impaired vasodilation in AAs. Pregnancy is a potent systemic vasodilatory state. However, differences in vasodilation between AAs and EAs have not been investigated in pregnancy. We sought to examine the effects of pregnancy on vasodilation in AA and EA women and how this might be related to discrimination and low birth weight in their offspring. Hemodynamics [blood pressure (MAP), cardiac output (CO), total peripheral resistance (TPR)] and heart rate variability (HF-HRV) were examined at baseline in 40 pregnant AAs (n = 20) and EAs (n = 20) and matched nonpregnant women (n = 40). The Experiences of Discrimination scale and birth weight were also measured in the offspring of the pregnant participants. Whereas pregnancy was associated with decreased MAP independent of race, AAs showed impaired vasodilation independent of pregnancy status as indicated by greater TPR despite greater HF-HRV. In AAs, but not EAs, reports of fewer incidences of discrimination were associated with greater TPR. Finally, the HF-HRV of EA mothers was inversely related to the birth weight of their offspring but was uncorrelated in AAs. We report novel evidence of impaired vasodilation to an endogenous vasodilatory stimulus in AAs. Higher TPR was related to discrimination in AAs and higher HF-HRV was related to low birth weight in EAs. These findings have implications for understanding the intergenerational transmission of impaired vasodilation in AAs.

Women who have experienced significant adversities during childhood and adulthood are at risk for excessive inflammation during pregnancy, but the mechanisms are unclear. Using structural equation modeling, we examined pathways from childhood abuse history and current socioeconomic status (SES) to inflammatory markers through indicators of health risk, recent stressors, and psychological distress in 214 women assessed at mid-pregnancy (5–31 weeks gestation). Self-reported data on socioeconomic indicators, childhood trauma history, pre-pregnancy body mass index (BMI), smoking, sleep quality, interpersonal conflict, recent life events, perceived stress, and depressive symptoms were collected, and serum levels of C-reactive protein (CRP) and interleukin (IL)-6 were determined. In separate models, pre-pregnancy BMI, sleep quality, and interpersonal conflict statistically explained the relationship between adversity and inflammation. These three intermediate variables were then entered into a multiple mediation analysis to examine unique effects. Childhood abuse history and current SES both demonstrated significant indirect effects on CRP through pre-pregnancy BMI, and current SES showed a significant indirect effect on IL-6 through all intermediate variables. When examining each indirect pathway individually, pre-pregnancy BMI and interpersonal conflict emerged as parallel pathways by which low current SES leads to elevated IL-6; the indirect pathway through sleep quality was no longer significant. Pre-pregnancy BMI and interpersonal conflict are two independent mechanisms by which adversity is associated with increased inflammation during pregnancy. Women who have been exposed to significant adversity may be at particular risk for obesity, sleep disruption, and interpersonal conflict, with implications for immune dysregulation during pregnancy.

INTRODUCTION: Compared to women who have given birth before (i.e., multiparas), those giving birth for the first time (i.e., primiparas) show higher cortisol levels. Psychological factors may play a role; hypothalamic-pituitary-adrenal activation is a well-described stress response. Primiparity also predicts greater risk for postpartum depression, which may be related to greater correspondence between cortisol and mood following prenatal cortisol elevations. The current study examined associations among parity, perinatal cortisol adaptation, pregnancy-specific distress, and postpartum mood. METHODS: This longitudinal study assayed serum cortisol levels among 137 women at early, mid-, and late pregnancy and postpartum. Pregnancy-specific distress and depressive symptoms were assessed. Maternal age, race, body mass index, sleep quality, depressive symptoms, and sampling time of day were statistically controlled. RESULTS: Primiparous women showed higher cortisol levels than multiparous women during mid- [Formula: see text] , p < 0.01) and late pregnancy [Formula: see text] , p < 0.01) and higher distress across pregnancy (F(1,126) = 22.1, p < 0.01). Mediation analyses demonstrated that the association between parity and prenatal cortisol (per area under the curve; AUC) was partially accounted for by distress (ab = 1.0, 95%CI [0.05, 2.9]). Prenatal cortisol (per AUC) did not predict postpartum depressive symptoms (b* = 0.03, p = 0.81), with no difference by parity (b* = 0.03, p = 0.91). At postpartum, a significant interaction between parity and cortisol (b* = 0.40, p = 0.03) revealed no significant association between cortisol and mood among multiparas (b* = −0.11, p = 0.28) but a trend toward a positive association among primiparas (b* = 0.24, p = 0.06). DISCUSSION: Cortisol levels and pregnancy-specific distress are higher in primiparas versus multiparas, with pregnancy-specific distress partially mediating the association between parity and cortisol levels. Cortisol levels and mood display correspondence at postpartum in primiparous but not multiparous women. While observational studies must be interpreted with caution due to potential unmeasured confounders, these findings suggest that future studies examining mechanisms underlying perinatal and postpartum hypothalamic-pituitary-adrenal perturbations and designing interventions aimed at preventing related complications should carefully consider potential differences by parity.

Background Postpartum is a period of unique psychosocial stress characterized by sleep disturbance, risk for depressed mood, and heightened parenting stress. However, data on effects of these exposures on inflammatory immune function are limited. Methods This study examined associations among sleep, psychosocial stress (i.e., parenting stress, general perceived stress), mood (i.e., depressive symptoms), serum cytokine levels, and LPS-stimulated proinflammatory cytokine production among 69 women (32 African American, 37 White) assessed at 7–10 weeks postpartum. Results No associations between behavioral measures and serum cytokine levels were observed among women of either race. In African American women, but not Whites, poorer sleep quality, greater parenting stress, and greater depressive symptoms were associated with greater LPS-stimulated IL-6 and IL-8 production (ps ≤ 0.05). Also in African Americans, greater general perceived stress was associated with greater IL-8 production, and greater depressive symptoms with greater stimulated TNF-α production (ps ≤ 0.05). Simple mediation models highlighted the bidirectional relationship between stress and sleep in relation to inflammation among African American women. Conclusions Significant effects of both stress/distress and poor sleep quality on proinflammatory cytokine production during postpartum were observed uniquely among African American women. These data are consistent with an allostatic load model which predicts that conditions of chronic stress impart vulnerability to dysregulated responses to novel stressor exposures. The bidirectional nature of the stress-sleep relationship has clinical relevance. Studies examining whether interventions focused on one or both of these psychological factors during postpartum is beneficial for inflammatory profiles would be informative. In addition, examination of these models in relation to maternal health at postpartum, including delivery related wounds and other infections, is warranted.

Adverse perinatal health outcomes are heightened among women with psychosocial risk factors, including childhood adversity and a lack of social support. Biological aging could be one pathway by which such outcomes occur. However, data examining links between psychosocial factors and indicators of biological aging among perinatal women are limited. The current study examined the associations of childhood socioeconomic status (SES), childhood trauma, and current social support with telomere length in peripheral blood mononuclear cells (PBMCs) in a sample of 81 women assessed in early, mid, and late pregnancy as well as 7-11 weeks postpartum. Childhood SES was defined as perceived childhood social class and parental educational attainment. Measures included the Childhood Trauma Questionnaire, Center for Epidemiologic Studies-Depression Scale, Multidimensional Scale of Perceived Social Support, and average telomere length in PBMCs. Per a linear mixed model, telomere length did not change across pregnancy and postpartum visits; thus, subsequent analyses defined telomere length as the average across all available timepoints. ANCOVAs showed group differences by perceived childhood social class, maternal and paternal educational attainment, and current family social support, with lower values corresponding with shorter telomeres, after adjustment for possible confounds. No effects of childhood trauma or social support from significant others or friends on telomere length were observed. Findings demonstrate that while current SES was not related to telomeres, low childhood SES, independent of current SES, and low family social support were distinct risk factors for cellular aging in women. These data have relevance for understanding potential mechanisms by which early life deprivation of socioeconomic and relationship resources affect maternal health. In turn, this has potential significance for intergenerational transmission of telomere length. The predictive value of markers of biological versus chronological age on birth outcomes warrants investigation.

Background In the US, influenza vaccination is recommended annually to everyone ≥6 months. Prior receipt of influenza vaccine can dampen antibody responses to subsequent vaccination. This may have implications for pregnant women and their newborns, groups at high risk for complications from influenza infection. Objective This study examined effects of prior vaccination on maternal and cord blood antibody levels in a cohort of pregnant women in the US. Study design Influenza antibody titers were measured in 141 pregnant women via the hemagglutination inhibition (HAI) assay prior to receipt of quadrivalent influenza vaccine, 30 days post-vaccination, and at delivery (maternal and cord blood). Logistic regression analyses adjusting for age, BMI, parity, gestational age at vaccination, and year of vaccination compared HAI titers, seroprotection, and seroconversion in women with versus without vaccination in the prior year. Results Compared to those without vaccination in the previous year (n = 50), women with prior vaccination (n = 91) exhibited higher baseline antibody titers and/or seroprotection rates against all four strains after controlling for covariates. Prior vaccination also predicted lower antibody responses and seroconversion rates at one month post-vaccination. However, at delivery, there were no significant differences in antibody titers or seroprotection rates in women or newborns, and no meaningful differences in the efficiency of antibody transfer, as indicated by the ratio of cord blood to maternal antibody titers at the time of delivery. Conclusion In this cohort of pregnant women, receipt of influenza vaccine the previous year predicted higher baseline antibody titers and decreased antibody responses at one month post-vaccination against all influenza strains. However, prior maternal vaccination did not significantly affect either maternal antibody levels at delivery or antibody levels transferred to the neonate. This study is registered with the NIH as a clinical trial (NCT02148874).

Introduction Disrupted sleep and shorter sleep duration is common in pregnancy, due to hormonal changes and physical discomfort, and in postpartum due to new infants. Objective data in this population studied over more than one year are lacking. The current analysis focuses on actigraphy-based and self-reported sleep. We examined the level of correspondence between these two complementary measurement modalities. Methods Pregnant women were enrolled in the Stress and Health in Pregnancy and Postpartum (SHIPP) study. Study visits were conducted from 2016-2019 during the 3rd trimester, 4-6 weeks postpartum, and 4 months, 8 months, and 12 months postpartum. Participants completed the Pittsburgh Sleep Quality Index (PSQI) and provided wrist-actigraphy data (Actiwatch, Philips Respironics) for one week prior to each study visit. Actigraphy-based time in bed (TIB), total sleep time (TST), sleep efficiency (SE), WASO and sleep latency (SL) were calculated. Correlations were conducted between actigraphy-based and self-reported PSQI sleep measures. Results 79 women (28.9±4.6 years) provided complete actigraphy data (≥3 valid days; 6.4±1.0 days) for at least one time point. Objective TST from the 3rd trimester to 12-months postpartum was 7.19, 6.87, 6.86, 6.89, and 6.78 hours, respectively. Actigraphy-based TIB was positively correlated with self-reported TIB at all five visits (r’s: 0.37-0.62, p’s Conclusion Ensuring collection of accurate sleep data during pregnancy and postpartum is important, as poor sleep is associated with negative health outcomes for both mother and child. Self-reported data is common in large, epidemiologic studies yet actigraphy-based measures may capture different aspects of sleep than self-report. Support This study was supported by the National Institutes of Health (R01 NR01366).

Study Objectives Delivery prior to full term affects 37% of US births, including ~400,000 preterm births (1,000,000 early term births (37–38 weeks). Approximately 70% of cases of shortened gestation are spontaneous—without medically-indicated cause. Elucidation of modifiable behavioral factors would have considerable clinical impact. Methods This study examined the role of depressive symptoms and sleep quality in predicting the odds of spontaneous shortened gestation among 317 women (135 black, 182 white) who completed psychosocial assessment in mid-pregnancy. Results Adjusting for key covariates, black women had 1.89 times higher odds of spontaneous shortened gestation compared to White women (OR [95% CI] = 1.89 [1.01, 3.53], p = 0.046). Women who reported only poor subjective sleep quality (PSQI > 6) or only elevated depressive symptoms (CES-D ≥ 16) exhibited no statistically significant differences in odds of spontaneous shortened gestation compared to those with neither risk factor. However, women with comorbid poor sleep and depressive symptoms exhibited markedly higher odds of spontaneous shortened gestation than those with neither risk factor (39.2% versus 15.7% [OR (95% CI) = 2.69 (1.27, 5.70)], p = 0.01). A higher proportion of black women met criteria for both risk factors (23% of black women versus 11% of white women; p = 0.004), with a lower proportion experiencing neither risk factor (40.7% of black versus 64.3% of white women; p < 0.001). Conclusions Additive effects of poor subjective sleep quality and depressive symptoms were observed with markedly higher odds of spontaneous shortened gestation among women with both risk factors. Racial inequities in rates of comorbid exposure corresponded with inequities in shortened gestation. Future empirical studies and intervention efforts should consider the interactive effects of these commonly co-morbid exposures.

Birth prior to full term is a substantial public health issue. In the US, ~400,000 babies per year are born preterm (< 37 weeks), while >1 million are early term (37–38(6/7) weeks). Birth prior to full term confers risk both immediate and long term, including neonatal intensive care, decrements in school performance, and increased mortality risk from infancy through young adulthood. Risk for low birth weight and preterm birth are 1.5–2 times greater among African Americans versus Whites. Psychosocial stress related to being a member of a discriminated racial minority group contributes substantially to these racial disparities. Providing promising targets for intervention, depressed mood, anxiety, and poor sleep are each linked with exposure to chronic stress, including racial discrimination. A rigorous transdisciplinary approach addressing these gaps holds great promise for clinical impact in addressing racial disparities as well as ameliorating effects of stress on perinatal health more broadly. As will be reviewed in a companion paper, the mechanistic roles of physiological sequelae to stress – including neuroendocrine, inflammatory regulation, biological aging, and the microbiome – also require delineation.

Early life, including prenatal development and childhood, is a period of sensitivity, with potential for developmental programming under conditions of adversity. The intergenerational effects of early adversity have received attention, most often studied in relation to fetal development according to maternal exposures. Less often considered but critically important is the effect of early adversity on future prenatal risk (e.g., risk for preeclampsia, preterm birth), which threatens the health of mother and infant. The body's ability to turn collections of genes "on" or "off" across a range of tissues via receptor-driven transcription factors and epigenetic mechanisms (i.e., chemical modifications to the genome) in response to the perceived environment may help to explain such associations. This review aims to summarize discoveries surrounding the effects of early adversity on gene expression, emphasizing prenatal populations. First, we review findings from gene expression studies examining the effects of early adversity on various tissues known to contribute to prenatal health in adulthood. Next, we review several gene regulatory mechanisms thought to underlie differences in gene expression. Finally, we discuss potential implications for prenatal risk among early adversity-exposed mothers according to our current understanding of the biology that contributes to the development of prenatal syndromes.

Sleep is a critical restorative behavior which occupies approximately one third of people’s lives. Extensive data link sleep health with disease and mortality risk in the general population. During pregnancy and following childbirth, unique factors contribute to overall sleep health. In addition, there are unique implications of poor sleep during these time periods. Poor maternal sleep may contribute to risk for adverse birth outcomes as well as poor maternal physical and mental health in pregnancy, postpartum, and longer term during childrearing. Moreover, the extent to which notable racial disparities in sleep contribute to disparities in adverse perinatal health outcomes remains to be fully explicated. Part I of this two-part review details these implications of poor sleep for mental health, physical health outcomes, and relationship functioning, while Part II delves into biological mechanisms as well as treatment approaches.

As described in Part I of this two-part review, maternal sleep has wide-ranging implications for maternal health and overall family functioning. In addition, poor sleep quality and insufficient sleep are highly prevalent and characterized by considerable racial disparities. Part II of this review discusses physiological mechanisms, including inflammation and appetite hormones, by which sleep impacts multiple facets of women’s health during pregnancy and postpartum. These mechanisms are increasingly being delineated, but require further study and better integration with studies of behavioral and physical health outcomes. Further, there are multiple potential strategies for improving maternal sleep, providing the opportunity to tailor treatment approaches to individual needs. Ultimately, as a critical health behavior that is amenable to intervention, sleep provides a promising future direction for measurably impacting clinically relevant health parameters in women of childbearing age.

Objective: The Appalachian population suffers a disparate burden of chronic stress leading to high perceived stress. The study aim was to determine the association between perceived stress and Epstein-Barr virus (EBV) antibody titers, along with the impact of perceived social support, Appalachian self-identify, and health behaviors. Methods: Serum EBV VCA-IgG antibody titer levels from 169 female Appalachian residents (aged 18-26 years) were examined. Perceived stress, perceived social support, Appalachian self-identity, and health behaviors were assessed via self-administered questionnaires. Results: There were 169 of 185 women positive for EBV. Among these women, the median EBV antibody titer level was 404 U/mL (range 101-6,464), and the overall geometric mean was 563.2 (95% CI 486.6-651.9). For a 1-point increase in perceived stress, the EBV antibody titer increased by 1.92% (95% CI 0.04-3.76%). For every point increase in perceived social support, the EBV antibody titer decreased by 1.00% (95% CI 0.06-1.98%). Perceived stress was significantly associated with sleep quality, BMI, and current smoking status, but not with binge-drinking, drug use, or Appalachian self-identity. No mediating effects of sleep quality, BMI, binge-drinking, current drug use, or >4 sexual partners were observed in the relationship between perceived stress and EBV titer level. Conclusion: Young Appalachian women reported high levels of perceived stress that were significantly associated with higher EBV titers. Higher perceived social support was associated with lower EBV titers. Health behaviors and Appalachian self-identity did not impact the relationship between perceived stress and EBV titers.

Pregnancy is a period of considerable physiological adaption in neuroendocrine, cardiovascular, as well as immune function. Understanding of typical changes in inflammatory immune responses during healthy pregnancy is incomplete. In addition, despite considerable racial difference in adverse pregnancy outcomes, data are lacking on potential racial differences in such adaptation. This repeated measures prospective cohort study included 37 Black and 39 White women who provided blood samples during early, mid-, and late pregnancy and 8–10 weeks postpartum. Peripheral blood mononuclear cells were incubated with lipopolysaccharide (LPS) for 24 hours and supernatants assayed by electrochemiluminescence to quantify interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-1β, and IL-8 production. While no changes were observed in IL-8 production over time, significant increases in IL-6, TNF-α, and IL-1β production were observed from early to late pregnancy, with subsequent declines approaching early pregnancy values at postpartum (ps

Background: Pregnant women have an elevated risk of illness and hospitalisation from influenza. Pregnant women are recommended to be prioritised for influenza vaccination during any stage of pregnancy. The risk of seasonal influenza varies substantially throughout the year in temperate climates; however, there is limited knowledge of how vaccination timing during pregnancy impacts the benefits received by the mother and foetus. Objectives: To compare antenatal vaccination timing with regard to influenza vaccine immunogenicity during pregnancy and transplacental transfer to their newborns. Methods: Studies were eligible for inclusion if immunogenicity to influenza vaccine was evaluated in women stratified by trimester of pregnancy. Haemagglutination inhibition (HI) titres, stratified by trimester of vaccination, had to be measured at either pre-vaccination and within one month post-vaccination, post-vaccination and at delivery in the mother, or in cord/newborn blood. Authors searched PubMed, Scopus, Web of Science and EMBASE databases from inception until June 2016 and authors of identified studies were contacted for additional data. Extracted data were tabulated and summarised via random-effect meta-analyses and qualitative methods. Results: Sixteen studies met the inclusion criteria. Meta-analyses found that compared with women vaccinated in an earlier trimester, those vaccinated in a later trimester had a greater fold increase in HI titres (1.33- to 1.96-fold) and higher HI titres in cord/newborn blood (1.21- to 1.64-fold). Conclusions: This review provides comparative analysis of the effect of vaccination timing on maternal immunogenicity and protection of the infant that is informative and relevant to current vaccine scheduling for pregnant women.

As reviewed in Part 1 of this two part review, birth prior to full term is a substantial public health issue. In the US, (~)400, 000 babies per year are born preterm (< 37 weeks), while > 1 million are early term (37–38(6/7) weeks) and remarkable racial disparities in shortened gestation are observed among African Americans as compared to Whites. Biomechanisms linking stressor exposures with birth outcomes are increasingly being explicated. The current paper reviews the mechanistic role of maternal biological functioning in the link between behavioral exposures and birth outcomes. These include the inter-related roles of neuroendocrine function, inflammatory regulation, biological aging, and the microbiome. An integrative approach which addresses both behavioral and biological factors within the same study, carefully considers the role of race/ethnicity, and rigorously defines birth outcomes (e.g., spontaneous versus medically-indicated and inclusive of early term birth) is needed to move research in this field toward better mechanistic understanding and clinical application.

Background: Breastfeeding plays an important role in both maternal and infant health and well-being. While researchers have examined the relationship between postpartum psychological distress and breastfeeding behaviors, few have investigated links between prenatal distress, postpartum distress, and breastfeeding behaviors over time. Research Aim: We aimed to determine if prenatal breastfeeding beliefs and psychological distress during and after pregnancy were associated with initiation and early cessation rates of breastfeeding. Methods: In our secondary data analysis, a nonexperimental longitudinal one-group design was used. We assessed pregnant women ( N = 70) during four perinatal visits (early, mid, and late pregnancy and 7-10 weeks postpartum). Participants completed self-report surveys about psychological distress and depressive symptoms at each visit, breastfeeding beliefs during the third visit, and breastfeeding behaviors at the postpartum visit. Results: Participants who breastfed for ⩾8 weeks had more positive beliefs about breastfeeding prior to delivery than participants with early cessation, who in turn had more positive beliefs than those who never initiated. Participants with early cessation reported heightened levels of pregnancy-specific distress in early pregnancy compared to those who continued breastfeeding or never initiated. Participants who continued breastfeeding for ⩾8 weeks reported less general anxiety and depressive symptoms in postpartum than those who discontinued or never initiated. Conclusions: Prenatal beliefs about breastfeeding, pregnancy-specific distress in early pregnancy, and general anxiety and depressive symptoms in postpartum are associated with breastfeeding initiation and continuation. Of clinical relevance, addressing prenatal and postpartum distress in the implementation of breastfeeding practice interventions could improve breastfeeding rates.

Study objectives Poor sleep promotes inflammation. In turn, inflammation is a causal mechanism in term as well as preterm parturition. In the United States, a persistent racial disparity in preterm birth exists, with African Americans showing ∼1.5 times greater risk. This study examined associations among sleep quality, serum proinflammatory cytokines, and length of gestation in a racially diverse sample of 138 pregnant women. Design Observational. Measurements Women completed the Pittsburgh Sleep Quality Index (PSQI) and other psychosocial and behavioral measures during midpregnancy. Serum levels of interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor (TNF)-α were determined by high-sensitivity assays. Birth outcomes were determined via medical record review. Results Among African American women (n = 79), shorter gestation was predicted by poorer overall sleep (rs = -0.35, P = 0.002) as well the following PSQI subscales: subjective sleep quality (rs = -0.34, P = 0.002), sleep latency (rs = -0.27, P = 0.02), and sleep efficiency (rs = -0.27, P = 0.02). African American women with poor sleep quality (PSQI > 5) had 10.2 times the odds of preterm birth compared to those with good sleep quality. In contrast, among European American women (n = 53), gestational length was not significantly predicted by sleep quality (Ps > 0.12). Bootstrapping analyses showed that, among African Americans, IL-8 significantly mediated the association between sleep quality and length of gestation (indirect effect estimate -0.029; 95% confidence interval -0.06, -0.002). Conclusions The data provide novel evidence that African American women exhibit greater inflammation in response to sleep disturbance than European American women and these effects correspond with length of gestation. Racial differences in susceptibility to sleep induced immune dysregulation may contribute to marked racial disparities in preterm birth.

Though typically mild, side effects to the influenza virus vaccine are common and may contribute to negative perceptions including the belief that the vaccine can cause the flu. However, the extent to which subjective symptoms correspond with biological response indicators is poorly understood.This study examined associations among subjective side effects (soreness at the site of injection and illness-like symptoms), serum proinflammatory cytokines and body temperature a baseline, 1, 2, and 3 days following receipt of trivalent inactivated influenza vaccine (IIV3) in a sample of 56 women 18-40 years in age.In relation to local reactions, women reporting being very sore at the injection site at 1 day post-vaccination exhibited greater increases in serum TNF-α and MIF in the days following vaccination compared to those with no or mild soreness. In addition, higher basal body temperature was observed in this group compared to other groups (98.7°F versus 98.0-98.1°). In relation to systemic reactions, women endorsing illness-like symptoms (headache, fatigue, nausea, sore throat, dizziness, achiness, or mild fever) exhibited marginally higher IL-6 at baseline (p=0.055) and greater increases in serum MIF at 2 days post-vaccination than those reporting no systemic symptoms. Associations of systemic symptoms with inflammatory responses were not accounted for by concomitant local reactions. As expected, antibody responses to the vaccine were highly similar in women regardless of local or systemic symptoms.These results are consistent with the notion that subjective reports of local and systemic reactions following vaccination may be predicted by and correspond with biological indicators of inflammatory status, but are not meaningful predictors of antibody responses. To improve adherence to vaccine recommendations, clinicians should provide assurance that such symptoms may be related to normal mild inflammatory responses to the vaccine and do not reflect immunogenicity.

This study investigated the relationships between various maternal characteristics and child outcomes in preschool age children. Participants included 128 mother-child pairs. Mothers and children participated in two observational tasks, clean-up and Tickle-Me-Elmo, which were coded for expressions of emotion, and mothers completed self-report surveys. A person-centered latent profile analysis was applied, identifying distinct maternal profiles defined by observed positive emotion expression and reported positive and negative emotionality, depressive symptoms, and parenting stress. Four profiles were identified, labeled Happy, Melancholic, Stressed, and Struggling. These profiles were found to be associated with child outcomes, including observed positive and negative emotion expression and problem behaviors. Specifically, the Melancholic and Struggling profiles tended to be negatively related to child emotion expression, while the Stressed and Struggling profiles tended to be related to greater child problem behaviors. The results highlight meaningful distinctions between concurrent, interacting maternal characteristics that contribute to child emotion socialization, and they suggest significant differentiations in the factors that contribute to child risk.

Background: Understanding the dynamics of the gut–brain axis has clinical implications for physical and mental health conditions, including obesity and anxiety. As such disorders have early life antecedents, it is of value to determine if associations between the gut microbiome and behavior are present in early life in humans. Methods: We used next generation pyrosequencing to examine associations between the community structure of the gut microbiome and maternal ratings of child temperament in 77 children at 18–27 months of age. It was hypothesized that children would differ in their gut microbial structure, as indicated by measures of alpha and beta diversity, based on their temperamental characteristics. Results: Among both boys and girls, greater Surgency/Extraversion was associated greater phylogenetic diversity. In addition, among boys only, subscales loading on this composite scale were associated with differences in phylogenetic diversity, the Shannon Diversity index (SDI), beta diversity, and differences in abundances of Dialister, Rikenellaceae, Ruminococcaceae, and Parabacteroides. In girls only, higher Effortful Control was associated with a lower SDI score and differences in both beta diversity and Rikenellaceae were observed in relation to Fear. Some differences in dietary patterns were observed in relation to temperament, but these did not account for the observed differences in the microbiome. Conclusions: Differences in gut microbiome composition, including alpha diversity, beta diversity, and abundances of specific bacterial species, were observed in association with temperament in toddlers. This study was cross-sectional and observational and, therefore, does not permit determination of the causal direction of effects. However, if bidirectional brain–gut relationships are present in humans in early life, this may represent an opportunity for intervention relevant to physical as well as mental health disorders.

Maternal psychosocial stress during pregnancy is associated with risks to maternal health and birth outcomes, as well as adverse health and behavioral outcomes in offspring. Maternal immune dysregulation, particularly disruption of inflammatory processes, is also implicated in adverse perinatal health outcomes, with the greatest evidence in relation to preterm birth. Increasingly, the extent to which psychosocial stress induces dysregulation of inflammatory processes during pregnancy is being considered. In this article, I describe studies linking stress to immune function during pregnancy, with an emphasis on studies from my research group on inflammation. As reviewed here, research utilizing psychoneuroimmunology models in pregnancy is a rapidly developing area with abundant opportunities to address questions of clinical relevance for both maternal and child health.

Objective Childhood trauma is associated with negative perinatal health outcomes including mood disorders and shorter gestation. However, effects of early life exposures on maternal biology are poorly delineated. This study examined associations between childhood trauma and inflammation, as well as the mediating role of obesity in this relationship. Method This study examined a racially diverse sample of 77 pregnant women assessed in early, mid, and late pregnancy. Assessments included the Childhood Trauma Questionnaire, Center for Epidemiologic Studies-Depression Scale, serum CRP, IL-6, and TNF-α, and prepregnancy BMI. Results Per linear mixed models, while no direct relationships were observed between childhood trauma with IL-6 or TNF-α, physical (95% CI: 0.007, 0.080) and emotional (95% CI: 0.005, 0.046) abuse as well as emotional neglect (95% CI: 0.010, 0.051) predicted elevated CRP. Effects remained after adjustment for race, income, education, smoking status, medical conditions, and depressive symptoms. PROCESS analyses showed BMI mediated the relationship between physical abuse and both serum CRP (95% CI: 0.014, 0.062) and IL-6 (95% CI: 0.009, 0.034). Conclusions Exposure to childhood trauma, particularly emotional abuse, physical abuse, and emotional neglect, is associated with inflammation in pregnant women. Obesity served as 1 pathway by which physical abuse contributed to elevations in serum CRP and IL-6. Interventions targeting maternal obesity prior to pregnancy may help mitigate the effects of childhood trauma on perinatal health. These findings have relevance for understanding biological and behavioral pathways by which early life exposures contribute to maternal health. (PsycINFO Database Record