Prenatal mood and anxiety disorders and associated cytokine changes.

BACKGROUND: We examined whether women with prenatal mood and anxiety disorders would exhibit differential pro- and anti-inflammatory marker trajectories during the prenatal and postpartum periods compared to women without these disorders. METHODS: Approximately 179 pregnant women participated in a longitudinal study conducted in two urban areas. Blood samples for inflammatory markers were collected at six study visits. The Structured Clinical Interview for the DSM-IV (SCID) was administered to participants scoring above cutoffs on anxiety and depression. Pregnant women with SCID Axis I diagnoses of mood and/or anxiety disorders were compared to other participants on inflammatory markers. Multilevel modeling tested associations between SCID diagnoses and within-person interleukin (IL)6 and IL10 trajectories. RESULTS: Prenatal SCID diagnoses were associated with linear, quadratic and cubic change in IL6 from prenatal to postpartum timepoints. Women with a prenatal SCID diagnosis had steeper decreases and increases in IL6 during prenatal and postpartum periods. SCID diagnoses were associated with lower IL10 in mid-pregnancy to postpartum (b = -0.078, SE = 0.019; p = .015). LIMITATIONS: Future studies would benefit from a larger sample size and a larger number of participants with SCID diagnoses. Future research should also examine whether different prenatal Axis 1 diagnoses are associated with different patterns of immune response in pregnancy. CONCLUSIONS: Pregnant women with prenatal mood and anxiety disorders had greater fluctuations in IL6 across prenatal and postpartum periods and lower IL10 through pregnancy and postpartum. They may have different proinflammatory states that remain after birth without a reciprocal anti-inflammatory response.

Partner relationship quality and IL-6:IL-10 trajectories from pregnancy to a year after-birth.

BACKGROUND: Inflammatory activity during pregnancy and the postpartum period shifts systematically due to pregnancy progression, delivery, and postpartum recovery. Factors that deregulate inflammatory activity increase the risk for adverse pregnancy outcomes and slower postpartum recovery. The IL-6:IL-10 or TNF-α:IL-10 ratio is potentially one way to capture peripheral inflammatory regulation; higher values indicate that anti-inflammatory IL-10 is less effective at regulating pro-inflammatory TNF-α or IL-6, skewing towards maladaptive pro-inflammatory profiles. Associations between partner relationship quality and IL-6:IL-10 or TNF-α:IL-10 trajectories during pregnancy and the postpartum period have not been assessed. The purpose of this study was to test whether partner relationship quality (support, conflict) is associated with attenuated IL-6, IL-10, TNF-α, TNF-α:IL-10 or IL-6:IL-10 trajectories from the third trimester to the postpartum period. METHODS: A sample of 162 women from the Healthy Babies Before Birth study reported on partner relationship quality (support and conflict) using the Social Support Effectiveness Questionnaire during the third trimester. Plasma samples were collected in the third trimester and at 1-, 6- and 12-months postpartum, and assayed for TNF-α, IL-6 and IL-10. Associations between both indicators of relationship quality (support and conflict) and TNF-α, IL-6, IL-10, IL-6:IL-10, TNF-α:IL-10 trajectories were tested using multi-level modelling, controlling for sociodemographic, pregnancy and health variables. RESULTS: Partner support interacted with time to predict IL-6:IL-10 trajectories, linear: b = -0.176, SE = 0.067, p =.010, quadratic: b = 0.012, SE = 0.005, p =.009. Lower partner support was associated with steeper increases in IL-6:IL-10 from the third trimester to 6 months postpartum, followed by steeper decreases in IL-6:IL-10 from 6 months postpartum to a year after birth. Partner conflict was not associated with IL-6:IL-10 levels at study entry, b = 0.233, SE = 0.219, p =.290, or over time, p's > 0.782. Neither indicator of partner relationship quality was associated with TNF-α, IL-6, IL-10, or TNF-α:IL-10 trajectories, p's > 0.205. CONCLUSION: Lower partner support may be associated with reduced moderation of IL-6 by IL-10 between pregnancy and a year postpartum, with possible consequences for maternal health and well-being.

Pregnancy-specific anxiety and gestational length: The mediating role of diurnal cortisol indices.

BACKGROUND: Preterm birth or shorter gestation is a common adverse pregnancy outcome. Pregnancy-specific anxiety is robustly associated with risk for shorter gestation. Hypothalamic-pituitary-adrenal (HPA) dysregulation, indicated by diurnal cortisol index variability [slope, area-under-the-curve (AUC) or cortisol awakening response (CAR)], could mediate associations between pregnancy-specific anxiety and shorter gestation. The purpose of this study was to explore whether diurnal cortisol index variability mediates associations between pregnancy-specific anxiety and gestational length. METHODS: A sample of 149 women from the Healthy Babies Before Birth study reported pregnancy-specific anxiety in early pregnancy. Saliva samples were taken at three times during pregnancy, for two days each, at wake, 30 min post wake, noon, and evening. Diurnal cortisol indices were calculated using standard approaches. Pregnancy cortisol index variability was calculated across pregnancy timepoints. Gestational length was derived from medical charts. Covariates were sociodemographics, parity and obstetric risk. Mediation models were tested using SPSS PROCESS. RESULTS: There was a significant indirect effect of pregnancy-specific anxiety on gestational length via CAR variability, b(SE)= -0.102(0.057), .95CI [- 0.227,- 0.008]. Higher pregnancy-specific anxiety was associated with lower CAR variability, b(SE)= -0.019(0.008), p = .022, and lower CAR variability was associated with shorter gestation, b(SE)= 5.29(2.64), p = .047. Neither AUC or slope variability mediated associations between pregnancy-specific anxiety and gestational length. CONCLUSION: Lower CAR variability during pregnancy mediated the association between higher pregnancy-specific anxiety and shorter gestational length. Pregnancy-specific anxiety could dysregulate HPA axis activity, as indicated by lower CAR variability, demonstrating the importance of the HPA axis system in regulating pregnancy outcomes.

Maternal anxiety, depression and stress affects offspring gut microbiome diversity and bifidobacterial abundances.

Uncovering mechanisms underlying fetal programming during pregnancy is of critical importance. Atypical neurodevelopment during the pre- and immediate postnatal period has been associated with long-term adverse health outcomes, including mood disorders and aberrant cognitive ability in offspring. Maternal factors that have been implicated in anomalous offspring development include maternal inflammation and tress, anxiety, and depression. One potential mechanism through which these factors perturb normal offspring postnatal development is through microbiome disruption. The mother is a primary source of early postnatal microbiome seeding for the offspring, and the transference of a healthy microbiome is key in normal neurodevelopment. Since psychological stress, mood disorders, and inflammation have all been implicated in altering maternal microbiome community structure, passing on aberrant microbial communities to the offspring that may then affect developmental outcomes. Therefore, we examined how maternal stress, anxiety and depression assessed with standardized instruments, and maternal inflammatory cytokine levels in the pre- and postnatal period are associated with the offspring microbiome within the first 13 months of life, utilizing full length 16S sequencing on infant stool samples, that allowed for species-level resolution. Results revealed that infants of mothers who reported higher anxiety and perceived stress had reduced alpha diversity. Additionally, the relative taxonomic quantitative abundances of Bifidobacterium dentium and other species that have been associated with either modulation of the gut-brain axis, or other beneficial health outcomes, were reduced in the offspring of mothers with higher anxiety, perceived stress, and depression. We also found associations between bifidobacteria and prenatal maternal pro-inflammatory cytokines IL-6, IL-8, and IL-10. In summary, specific microbial taxa involved in maintaining proper brain and immune function are lower in offspring born to mothers with anxiety, depression, or stress, providing strong evidence for a mechanism by which maternal factors may affect offspring health through microbiota dysregulation.

Anxiety in pregnancy and length of gestation: Findings from the healthy babies before birth study.

OBJECTIVES: Anxiety is prevalent in pregnancy and predicts risk of adverse birth outcomes. Many instruments measure anxiety in pregnancy, some of which assess pregnancy anxiety defined as maternal concerns about a current pregnancy (e.g., baby, childbirth). The present study examined covariance among four anxiety or distress measures at two times in pregnancy and tested joint and individual effects on gestational length. We hypothesized that the common variance of the measures in each trimester would predict earlier delivery. METHOD: Research staff interviewed 196 women in first and third trimester utilizing a clinical screener of anxiety severity/impairment, two instruments measuring pregnancy anxiety, and one on prenatal distress. Birth outcomes and medical risk factors were obtained from medical records after birth. Structural equation modeling fit latent factors for each trimester from the four measures. Subsequent models tested whether the latent factors predicted gestational length, and unique effects of each measure. RESULTS: The third-trimester pregnancy anxiety latent factor predicted shorter gestational length adjusting for mother's age, education, parity, and obstetric risk. Scores on a four-item pregnancy-specific anxiety measure (PSAS) in third trimester added uniquely to prediction of gestational length. In first trimester, scores on the clinical screener (OASIS) uniquely predicted shorter gestational length whereas the latent factor did not. CONCLUSION: These results support existing evidence indicating that pregnancy anxiety is a reliable risk factor for earlier birth. Findings point to possible screening for clinically significant anxiety symptoms in the first trimester, and pregnancy-specific anxiety thereafter to advance efforts to prevent earlier delivery. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Pregnancy anxiety, placental corticotropin-releasing hormone and length of gestation.

OBJECTIVE: High pregnancy anxiety is a consistent predictor of earlier labor and delivery. Placental corticotropin-releasing hormone (pCRH) predicts earlier delivery consistently and it has been identified as a biological mediator of the association between pregnancy anxiety and gestational length. However, studies have not examined whether changes in pregnancy anxiety are associated with earlier birth as mediated by changes in pCRH during pregnancy. Accordingly, this study tests whether linear changes in pregnancy anxiety are associated with length of gestation indirectly through nonlinear increases in pCRH over pregnancy. METHODS: A sample of pregnant women (n=233) completed prenatal assessments in early pregnancy, second trimester, and third trimester that included a 4-item assessment of pregnancy anxiety and collection of blood samples assayed for pCRH using radioimmunoassay. Length of gestation was abstracted from medical records after birth. RESULTS: Increases in pregnancy anxiety from early pregnancy to third trimester predicted shorted length of gestation, as did nonlinear increases in pCRH over pregnancy. However, there was no evidence of an indirect effect of changes in pregnancy anxiety on length of gestation via changes in pCRH. CONCLUSIONS: These results indicate that linear changes in pregnancy anxiety and nonlinear changes in pCRH during pregnancy are independent risk factors for shortened gestational length. This study adds to a small but growing body of work on biopsychological processes in pregnancy and length of gestation. Modeling changes in psychological and biological processes during pregnancy could provide more insight into understanding risk for adverse pregnancy outcomes.

Inflammatory and immune marker trajectories from pregnancy to one-year post-birth.

BACKGROUND: Pregnancy is an immunomodulatory state, with reported systematic changes in inflammatory and immune activity by pregnancy stage. Published data are inconsistent as to how inflammatory and immune markers change and recover across pregnancy and the postpartum period, or the sociodemographic, health and pregnancy-related factors that could affect biomarker trajectories. The purpose of this study is to describe inflammatory and immune marker trajectories from pregnancy to a year post-birth, and to test associations with sociodemographic, health and pregnancy-related variables. METHODS: A sample of 179 pregnant women were assessed three times during pregnancy (between 8 and 36 weeks gestation) and three times during the postpartum period (between 1 and 12 months). Maternal sociodemographic characteristics, health, and pregnancy factors were obtained at study entry. Blood samples from each assessment were assayed for interleukin(IL)-6, tumor necrosis factor(TNF)α, IL-8, IL-10, and interferon(IFN)γ. Multilevel modelling was used to characterize biomarker trajectories and associations with sociodemographic and health variables. RESULTS: Distinct trajectories over time emerged for each biomarker. Male pregnancies were associated with higher TNFα, IL-10, and IFNγ; higher pre-pregnancy BMI was associated with higher IL-6 and IFNγ. Nulliparity was associated with greater increases in IL-6 and TNFα. CONCLUSIONS: Patterns observed for inflammatory and immune markers from pregnancy to a year postpartum support the hypothesis that the maternal immune system changes systematically across pregnancy and through an extended postpartum period. Parity, pre-pregnancy BMI and child sex are associated with inflammatory marker patterns over time. These results contribute to our understanding of how immune system activity changes from pregnancy to the post-birth period, and the factors that could affect those changes.

Association between diagnosed perinatal mood and anxiety disorders and adverse perinatal outcomes.

PURPOSE: To determine whether a diagnosis of a perinatal mood and anxiety disorder (PMAD) is associated with adverse perinatal outcomes. METHODS: Mental health symptom screening and diagnostic data from 82 women with single gestation in the Healthy Babies Before Birth study conducted from 2013 to 2018 were obtained by clinic interview. If a woman scored over 10 on the Patient Health Questionnaire (PHQ-9) or endorsed the suicidality item; or scored over 7 on the Overall Anxiety Severity and Impairment Scale (OASIS), a Structured Clinical Interview for DSM-IV (SCID) Axis I Disorders was administered. An adverse perinatal outcome was operationalized as a diagnosis of gestational diabetes mellitus, intrauterine growth restriction, preeclampsia, chorioamnionitis, hemorrhage, fetal death, preterm birth, or a low birthweight baby, and abstracted from the medical records. RESULTS: Women were between 22.0 and 45.0 years old (Mean age = 33.1 ± 4.3). Mean BMI was 24.7 ± 5.6 (Range 16.8 to 47.1). Nineteen percent (16) of the 82 women had a SCID diagnosis of a PMAD. Thirty-seven percent (30) had a diagnosed adverse perinatal outcome. Multiple logistic regression was conducted with these predictors: SCID diagnosis of a PMAD, maternal age, BMI. All predictors were significant with respective odds ratios as follows: OR = 3.58, 95% CI 1.03-12.44, p = .045; OR = 2.30, 95% CI 1.21-4.38, p = .011; OR = 1.69, 95% CI 1.06-2.69, p = .027. CONCLUSIONS: A PMAD diagnosis was associated with 3.5 times higher odds of having an adverse perinatal outcome. For every 5 years a woman aged or every five units her BMI increased her odds of having an adverse perinatal outcome increased. Older age and increased BMI are well established adverse perinatal outcome risk factors. These results suggest that mental illness risk should also be consistently assessed in obstetric settings.

The moderating role of resilience resources in the association between stressful life events and symptoms of postpartum depression.

BACKGROUND: One in seven women experience postpartum depression, posing a serious public health concern. One of the most robust predictors of elevated postpartum depressive symptoms is major stressful life events that occur during pregnancy. Having greater resilience resources that promote successful adaptation to stressful demands may be protective in the face of stress during pregnancy. The current study tested whether three resilience resources- mastery, dispositional optimism, and spirituality- each predicted early symptoms of postpartum depression and moderated the hypothesized association between experiencing stressful life events during pregnancy and symptoms of postpartum depression. METHODS: The sample included 233 women who participated in a prospective longitudinal study from pregnancy through postpartum. Depressive symptoms were assessed at approximately 4 to 8 weeks after birth, whereas resilience resources and stressful life events were measured in pregnancy. Multiple linear regressions were used to test hypotheses. RESULTS: Stressful life events predicted greater symptoms of depression postpartum. Mastery and optimism predicted fewer symptoms of depression postpartum. Mastery moderated the association between stressful life events and symptoms of depression when controlling for previous psychiatric history, t(231) = -1.97, p=.0497. LIMITATIONS: There was some attrition among study participants across timepoints, which was accounted for in analyses with multiple imputation. CONCLUSIONS: These findings point to the protective nature of a mother's sense of mastery in the face of major life stressors during pregnancy and suggest this is an important construct to target in interventions addressing postpartum depression.

Postpartum sleep loss and accelerated epigenetic aging.

BACKGROUND: Insufficient sleep has been linked to accelerated biological aging in adults, providing a possible mechanism through which sleep may influence disease risk. In the current paper, we test the hypothesis that short sleep in postpartum would predict older biological age in women one year post birth, as indicated by accelerated epigenetic aging. METHODS: As part of a larger study of pregnancy and postpartum health (Healthy Babies Before Birth, HB3), 33 mothers provided blood samples for epigenetic aging clock estimates. intrinsic epigenetic age acceleration (IEAA), extrinsic apigenetic age acceleration, phenotypic epigenetic age acceleration (PEAA), GrimAge, DNAmPAI-1, and DNAm telomere length (TL) were calculated using established protocols. Sleep duration was categorized as insufficient sleep (<7 hours per night) or healthy sleep duration (7+ hours per night). Sleep quality was determined using the Pittsburgh Sleep Quality Index (Global score >5). RESULTS: Maternal postpartum sleep duration at 6 months, but not 12 months, following a birth was predictive of older 12-month IEAA, B (SE) = 3.0 (1.2), P = .02, PEAA, B (SE) = 7.3 (2.0), P = .002, and DNAmTL, B (SE) = -0.18 (0.07), P = .01, but not other indices, all P> .127. Self-reported poor sleep quality at 6 and 12 months was not significantly related to epigenetic age. CONCLUSIONS: These findings suggest that insufficient sleep duration during the early postpartum period is associated with accelerated biological aging. As the sample size is small, additional research is warranted with a larger sample size to replicate these findings.

Low Prenatal Vitamin D Metabolite Ratio and Subsequent Postpartum Depression Risk.

Background: Depression is a common complication of pregnancy and vitamin D deficiency is one biological risk factor for postpartum depression (PPD). Materials and Methods: We evaluated the ratio of 24,25(OH)2D and 25(OH)D serum concentrations referred to as the Vitamin D Metabolite Ratio (VMR), a new candidate biomarker during pregnancyand its relationship with PPD. Women were enrolled in the first trimester of pregnancy and followed through four timepoints. Results: A total of 89 women had complete depression, biomarker and demographic data and 34% were at risk for PPD (CES-D≥16). Stepwise multiple logistic regression models for PPD risk were carried out with eight predictors. Results showed that only lower VMR, OR = 1.43, 95% CI 1.10-1.86, p = 0.007, and Hispanic/Latina identification, OR = 3.83, 95% CI 1.44-10.92, p = 0.007 were significantly associated with higher PPD risk. Conclusion: Routine prenatal screening for vitamin D metabolites, particularly in Hispanic/Latina women, may identify women at risk for PPD.

Maternal prenatal anxiety trajectories and infant developmental outcomes in one-year-old offspring.

A longitudinal study of a sample of women and their offspring from two urban areas (N = 233) was conducted to test whether maternal prenatal anxiety trajectories from early to late pregnancy are associated with 12-month infant developmental outcomes, independent of maternal postpartum anxiety symptoms, prenatal and postpartum depressive symptoms, parity, birth outcomes and maternal education. Three types of maternal anxiety trajectories over the course of pregnancy were identified and labeled increasing, decreasing, and stable-low. Only increasing maternal prenatal anxiety was associated with 12-month infant outcomes, specifically lower Bayley-III scores on receptive language and gross motor skills. Maternal anxiety measured at each individual timepoint in pregnancy was not associated with infant Bayley-III outcomes, highlighting the importance of examining trajectories of maternal affect.

Epigenetic age and pregnancy outcomes: GrimAge acceleration is associated with shorter gestational length and lower birthweight.

BACKGROUND: Advanced biological aging, as measured by epigenetic aging indices, is associated with early mortality and morbidity. Associations between maternal epigenetic aging indices in pregnancy and pregnancy outcomes, namely gestational length and birthweight, have not been assessed. The purpose of this study was to examine whether epigenetic age during pregnancy was associated with gestational length and birthweight. RESULTS: The sample consisted of 77 women from the Los Angeles, CA, area enrolled in the Healthy Babies Before Birth study. Whole blood samples for DNA methylation assay were obtained during the second trimester (15.6 ± 2.15 weeks gestation). Epigenetic age indices GrimAge acceleration (GrimAgeAccel), DNAm PAI-1, DNAm ADM, and DNAm cystatin C were calculated. Gestational length and birthweight were obtained from medical chart review. Covariates were maternal sociodemographic variables, gestational age at blood sample collection, and pre-pregnancy body mass index. In separate covariate-adjusted linear regression models, higher early second trimester GrimAgeAccel, b(SE) = - .171 (.056), p = .004; DNAm PAI-1, b(SE) = - 1.95 × 10-4 (8.5 × 10-5), p = .004; DNAm ADM, b(SE) = - .033 (.011), p = .003; and DNAm cystatin C, b(SE) = 2.10 × 10-5 (8.0 × 10-5), p = .012, were each associated with shorter gestational length. Higher GrimAgeAccel, b(SE) = - 75.2 (19.7), p < .001; DNAm PAI-1, b(SE) = - .079(.031), p = .013; DNAm ADM, b(SE) = - 13.8 (3.87), p = .001; and DNAm cystatin C, b(SE) = - .010 (.003), p = .001, were also associated with lower birthweight, independent of gestational length. DISCUSSION: Higher maternal prenatal GrimAgeAccel, DNAm PAI-1, DNAm ADM, and DNAm cystatin C were associated with shorter gestational length and lower birthweight. These findings suggest that biological age, as measured by these epigenetic indices, could indicate risk for adverse pregnancy outcomes.

Immune epigenetic age in pregnancy and 1 year after birth: Associations with weight change.

PROBLEM: Epigenetic age indices are markers of biological aging determined from DNA methylation patterns. Accelerated epigenetic age predicts morbidity and mortality. Women tend to demonstrate slower blood epigenetic aging compared to men, possibly due to female-specific hormones and reproductive milestones. Pregnancy and the post-partum period are critical reproductive periods that have not been studied yet with respect to epigenetic aging. The purpose of this paper was to examine whether pregnancy itself and an important pregnancy-related variable, changes in body mass index (BMI) between pregnancy and the post-partum period, are associated with epigenetic aging. METHOD OF STUDY: A pilot sample of 35 women was recruited as part of the Healthy Babies Before Birth (HB3) project. Whole blood samples were collected at mid-pregnancy and 1 year post-partum. DNA methylation at both time points was assayed using Infinium 450K and EPIC chips. Epigenetic age indices were calculated using an online calculator. RESULTS: Paired-sample t-tests were used to test differences in epigenetic age indices from pregnancy to 1 year after birth. Over this critical time span, women became younger with respect to phenotypic epigenetic age, GrimAge, DNAm PAI-1, and epigenetic age indices linked to aging-related shifts in immune cell populations, known as extrinsic epigenetic age. Post-partum BMI retention, but not prenatal BMI increases, predicted accelerated epigenetic aging. CONCLUSION: Women appear to become younger from pregnancy to the post-partum period based on specific epigenetic age indices. Further, BMI at 1 year after birth that reflects weight retention predicted greater epigenetic aging during this period.

Interactions between race/ethnicity, poverty status, and pregnancy cardio-metabolic diseases in prediction of postpartum cardio-metabolic health.

Background: Prenatal health disparities exist for African Americans and low socioeconomic status (SES) individuals when compared to non-Hispanic Whites and people of higher SES, particularly in cardio-metabolic diseases. Furthermore, having had a pregnancy-specific cardio-metabolic disease, e.g. preeclampsia, increases risk for future cardio-metabolic disease. Although these factors (race, SES and pregnancy cardio-metabolic disease) are interrelated, studies have rarely considered their combined effect on postpartum cardio-metabolic risk. The purpose of this study was to assess whether SES, race/ethnicity, and prenatal cardio-metabolic disease interact in the prediction of postpartum cardio-metabolic risk. Methods: A sample of 1,753 low-income women of African American, Latina, non-Hispanic White race/ethnicity was recruited after a birth in 5 US sites. Household income was used to categorize poverty status as Poor (< Federal Poverty Level; FPL), near poor (100-200% FPL), or low/middle income (> 200% FPL). Three prenatal cardio-metabolic disease diagnoses (preeclampsia, gestational hypertension, gestational diabetes) were identified from medical records. Four biomarkers (mean arterial pressure, glycosylated haemoglobin, total cholesterol:HDL ratio, and waist-hip ratio) were collected at 6 and 12 months postpartum, and combined into an average postpartum cardio-metabolic risk index. Maternal age, pre-pregnancy body mass index, parity, health behaviors and employment status were covariates. Results: Analyses revealed interactions of race/ethnicity, poverty status, and prenatal cardio-metabolic diseases in the prediction of postpartum cardio-metabolic risk. African American women had higher postpartum cardio-metabolic risk, which was exacerbated following a prenatal cardio-metabolic disease. Low/middle income African American women had higher cardio-metabolic risk compared to poor African American, and all Latina and White women. Conclusions: African American women, and especially those who experienced pregnancy complications, emerged as vulnerable, and greater household income did not appear to confer protection against worse postpartum cardio-metabolic risk for this group. These results highlight the complex interplay between socioeconomic status and race/ethnicity with respect to understanding health disparities.

Pro-inflammatory immune cell gene expression during the third trimester of pregnancy is associated with shorter gestational length and lower birthweight.

PROBLEM: Altered maternal immune function predicts risk for shorter gestation and low birthweight. Few studies examine associations between prenatal immune cell gene expression and gestational length or birthweight. No studies examine which cell types drive associations. The purpose of this study is to explore associations between peripheral blood immune cell gene expression and gestational length and birthweight, using transcript origin analysis. METHOD OF STUDY: Eighty-nine women were drawn from the Community Child Health Network cohort. Third trimester maternal dried blood spots were used for genome-wide transcriptional (mRNA) profiling. Gestational length and birthweight were obtained from medical charts. Covariates were age, race/ethnicity, pre-pregnancy body mass index, smoking, gestational age at blood sampling, and pregnancy infections. Associations between gene expression profiles and gestational length and birthweight were tested using general linear models. The Transcription Element Listening System (TELiS) bioinformatics analysis quantified upstream transcription factor activity. Transcript origin analysis identified leukocyte subsets mediating observed effects. RESULTS: Shorter gestation was predicted by increased NF-kB (TFBM ratio = -0.582 ± 0.172, P < .001) and monocyte activity (diagnosticity score = 0.172 ± 0.054, P < .001). Longer gestation was associated with increased dendritic cell activity (diagnosticity score = 0.194 ± 0.039, P < .001). Increased AP-1 activity predicted lower birthweight (TFBM ratio = -0.240 ± 0.111, P = .031). Dendritic cells and CD4+ and CD8+ T cells predicted birthweight-related gene expression differences (diagnosticity score P's < 0.021). CONCLUSION: Higher third trimester pro-inflammatory gene expression predicted shorter gestation and lower birthweight. Variations in monocyte and dendritic cell biology contributed to both effects, and T-cell biology contributed to higher birthweight. These analyses clarify the role of myeloid/lymphoid lineage immune regulation in pregnancy outcomes.

History of the establishment of the Preterm Birth international collaborative (PREBIC).

INTRODUCTION: The primary aim of PREBIC is to assess the underlying mechanisms and developing strategies for preterm birth (PTB) prevention. MATERIALS AND METHODS: We used concept mapping and logic models to track goals. This paper reviews our progress over 13 years using working group activities, research developments, guest speakers, and publications. RESULTS: Using interactions between genetics, environment, and behaviors we identified complex interactions between biological systems. PREBIC determined that epidemiology and biomarkers should be an initial focus. In 2005, we initiated presentations by young investigators, yearly satellite meetings, working groups including nutrition and inflammation, assessment of clinical trials, and accepted an invitation by the WHO to begin yearly meetings in Geneva. DISCUSSION: PREBIC used epidemiology to identify PTB factors and complex pathways. Candidate genes are associated with the environment, behavior (stress), obesity, inflammation and insulin resistance. Epigenetic changes and production of proteins can be used as biomarkers to define risk. Subsequently, we found risk factors for PTB that were also associated with the risk of cardiovascular disease (CVD) of the mother. Tanz et al. (2017) found that a history of PTB is independently predictive of CVD later in life and suggested that a modest proportion of PTB-CVD association was accounted by CVD risk factors, many of which have been identified in this paper. CONCLUSION: Our findings support a relationship between genes, environment, behaviors and risk of CVD in women. The next several years must assess which factors are modifiable early in life and before pregnancy to prevent PTB.

Pregnancy anxiety predicts shorter gestation in Latina and non-Latina white women: The role of placental corticotrophin-releasing hormone.

OBJECTIVE: Previous research has shown that a woman's anxiety about her pregnancy predicts gestational length. Placental corticotrophin-releasing hormone (CRH) is a stress-responsive peptide proposed as a mechanism. We examined placental CRH as a physiological mediator of the association between pregnancy anxiety and gestational length in Latina and non-Latina White women to replicate evidence of associations between pregnancy anxiety, placental CRH and gestational length; to test whether placental CRH levels or changes mediate effects of pregnancy anxiety on gestational length; to examine ethnic differences in pregnancy anxiety, placental CRH, and gestational length; and to explore whether the effects of pregnancy anxiety on gestational length as mediated by placental CRH vary by ethnicity. METHODS: In a prospective study of 337 pregnant Latina and non-Latina White women, participants completed in-person interviews that included a 10-item measure of pregnancy anxiety and provided blood samples assayed using radioimmunoassay at three timepoints (19, 25, and 31 weeks gestation). RESULTS: Pregnancy anxiety at 19 and 31 weeks and levels of placental CRH at 31 weeks predicted gestational length. Tests of indirect effects were consistent with mediation such that both pregnancy anxiety at 19 weeks and increases from 19 to 31 weeks predicted placental CRH at 31 weeks, which in turn predicted gestational length. Tests of moderated mediation by ethnicity showed that the mediated effect of placental CRH at 31 weeks was significant for Latinas only. CONCLUSIONS: These findings add to growing evidence of the involvement of pregnancy anxiety in the timing of birth, address mechanisms, and suggest possible ethnic differences.

Cardiovascular and Metabolic Risk in Women in the First Year Postpartum: Allostatic Load as a Function of Race, Ethnicity, and Poverty Status.

OBJECTIVE: Allostatic load (AL) represents multisystem physiological "wear-and-tear" reflecting emerging chronic disease risk. We assessed AL during the first year postpartum in a diverse community sample with known health disparities. STUDY DESIGN: The Eunice Kennedy Shriver National Institute for Child Health and Human Development Community Child Health Network enrolled 2,448 predominantly low-income African-American, Latina, and White women immediately after delivery of liveborn infants at ≥20 weeks' gestation, following them over time with interviews, clinical measures, and biomarkers. AL at 6 and 12 months postpartum was measured by body mass index, waist:hip ratio, blood pressure, pulse, hemoglobin A1c, high-sensitive C-reactive protein, total cholesterol and high-density lipoprotein, and diurnal cortisol slope. RESULTS: Adverse AL health-risk profiles were significantly more prevalent among African-American women compared with non-Hispanic Whites, with Latinas intermediate. Breastfeeding was protective, particularly for White women. Complications of pregnancy were associated with higher AL, and disparities persisted or worsened through the first year postpartum. CONCLUSION: Adverse AL profiles occurred in a substantial proportion of postpartum women, and disparities did not improve from birth to 1 year. Breastfeeding was protective for the mother.

Poor sleep quality increases symptoms of depression and anxiety in postpartum women.

This study evaluated the relationship between sleep quality and symptoms of depression and anxiety in women studied in pregnancy and postpartum. Scores on standardized measures of sleep (PSQI) at 6 months postpartum, and symptoms of anxiety and depression (OASIS, the PHQ9, and EPDS) were assessed by structured interviews in 116 women in pregnancy and/or postpartum. Poor sleep quality was significantly associated with greater symptoms of depression and anxiety. Women who had significantly higher OASIS (anxiety) scores (ß = .530, p < .001), PHQ9 (depression) scores (ß = .496, p < .001), and EPDS (postpartum depression and anxiety) scores (ß = .585, p < .001) also had elevated total PSQI scores after adjustment for covariates, including prenatal depression and anxiety scores. Though inferences about causality are not feasible, these results support emerging research showing sleep quality is a risk factor for negative maternal affect in the postpartum period. Assessment of maternal sleep hygiene is worth consideration as a component of identifying women at risk for postpartum depression and anxiety.