Lifetime stressor exposure, systemic inflammation during pregnancy, and preterm birth among Black American women.

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-1ß, 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-1ß 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-1ß levels, as mediated by higher average levels of overall perceived stressor severity. Exposure to fewer acute stressors was related to higher plasma IL-1ß 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.

A Comparison of Recruitment Methods for a Prospective Cohort Study of Perinatal Psychoneuroimmunology among Black American Women.

Improved understanding of perinatal psychoneuroimmunology is needed, particularly to combat the high rates of maternal and infant mortality witnessed among Black Americans. We compared the success of recruitment by advertisement, in person, or by phone during the course of a prospective cohort study of perinatal psychoneuroimmunology among Black American women. Over 24 months, 363 women were assessed and 96 were enrolled. Women recruited by phone were less likely to complete full screening than women recruited by advertisement (OR = 0.32, p < 0.01) or in person (OR = 0.19, p < 0.01). Women recruited by advertisement were less likely to complete full screening than women recruited in person (OR = 0.60, p = 0.05). Odds of unsuccessful contact were 13.2 and 11.5 times greater among women recruited by phone versus by advertisement or in person, respectively (p values ≤ 0.01). Women recruited by advertisement and in person showed similar odds of unsuccessful contact (OR = 0.87, p = 0.76). Odds of screening decline were similar following recruitment in person or by phone when contact was successful (OR = 0.85, p = 0.76). Focusing on eligible women (n = 142), those recruited in person were significantly less likely to enroll than those recruited by advertisement (OR = 0.28, p < 0.01; Fig. 4). Considering all women (n = 363), odds of enrollment did not significantly differ among the recruitment groups (p values ≥ 0.09). Most (93.8%) enrolled women consented to biological specimen banking. Findings from this brief report provide a starting point for perinatal scientists to critically consider not only how to maximize research efforts but also how research team actions may perpetuate or assuage the research mistrust introduced by long-standing social inequities.

Racial Discrimination and Stress Across the Life Course: Associations With Prenatal Inflammation, Perceived Stress, and Depressive Symptoms.

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-ß 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-ß 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-ß. Subscale analyses suggested that findings related to IL-8 were driven by chronic stress whereas findings related to TNF-α and IL-ß 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.

Stress During Pregnancy and Epigenetic Modifications to Offspring DNA: A Systematic Review of Associations and Implications for Preterm Birth.

Offspring born preterm (ie, before 37 weeks of gestation) are more likely to die or experience long-standing illness than full-term offspring. Maternal genetic variants (ie, heritable, stable variations in the genetic code) and epigenetic modifications (ie, chemical modifications to the genetic code that can affect which genes are turned on or off) in response to stress have been implicated in preterm birth. Fetal genetic variants have been linked to preterm birth though the role of offspring epigenetics in preterm birth remains understudied. This systematic review synthesizes the literature examining associations among stress during pregnancy and epigenetic modifications to offspring DNA, with 25 reports identified. Ten reports examined DNA methylation (ie, addition/removal of methyl groups to/from DNA) across the epigenome. The remainder examined DNA methylation near genes of interest, primarily genes linked to hypothalamic-pituitary-adrenal axis function (NR3C1, FKBP51), growth/immune function (IGF2), and socioemotional regulation (SLC6A4, OXTR). The majority of reports noted associations among stress and offspring DNA methylation, primarily when perceived stress, anxiety, or depression served as the predictor. Findings suggest that differences in offspring epigenetic patterns may play a role in stress-associated preterm birth and serve as targets for novel interventions.

Patterns of DNA methylation as an indicator of biological aging: State of the science and future directions in precision health promotion.

BACKGROUND: A rapidly expanding literature suggests that individuals of the same chronological age show significant variation in biological age. PURPOSE: The purpose of this article is to review the literature surrounding epigenetic age as estimated by DNA methylation, involving the addition or removal of methyl groups to DNA that can alter gene expression without changing the DNA sequence. METHODS: This state of the science literature review summarizes current approaches in epigenetic age determination and applications of aging algorithms. FINDINGS: A number of algorithms estimate epigenetic age using DNA methylation markers, primarily among adults. Algorithm application has focused on determining predictive value for risk of disease and death and identifying antecedents to age acceleration. Several studies have incorporated epigenetic age to evaluate intervention effectiveness. DISCUSSION: As the research community continues to refine aging algorithms, there may be opportunity to promote health from a precision health perspective.

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing: Pathway Analysis Among African American Women.

BACKGROUND: Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests that inflammatory pathways differ by race; however, studies among African American women are lacking. OBJECTIVES: We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1ß production. METHODS: A candidate gene study using a prospective cohort design was used. We collected blood samples at 28-32 weeks of gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN single-nucleotide polymorphism (SNP) rs2637988 was genotyped, and lipopolysaccharide-stimulated IL-1Ra and IL-1ß production was quantified. Medical record review determined timing of birth. RESULTS: Women with GG genotype gave birth earlier than women with AA/AG genotypes (b* = .21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [-0.05, 0.13]). Women with GG genotype showed less inhibition of IL-1ß production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = .93, p = .03). Greater IL-1ß production at 28-32 weeks of pregnancy was marginally associated with earlier birth (b* = .21, p = .05). DISCUSSION: Women with GG genotype may be at risk for earlier birth because of diminished IL-1ß inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions.

Differences in inflammatory markers between nulliparous women admitted to hospitals in preactive vs active labor.

OBJECTIVE: To determine whether labor-associated inflammatory markers differ between low-risk, nulliparous women in preactive vs active labor at hospital admission and over time. STUDY DESIGN: Prospective comparative study of low-risk, nulliparous women with spontaneous labor onset at term (n = 118) sampled from 2 large Midwestern hospitals. Circulating concentrations of inflammatory markers were measured at admission and again 2 and 4 hours later: namely, neutrophil, and monocyte counts; and serum inflammatory cytokines (interleukin -1ß, interleukin-6, tumor necrosis factor-α, interleukin-10) and chemokines (interleukin-8). Biomarker concentrations and their patterns of change over time were compared between preactive (n = 63) and active (n = 55) labor admission groups using Mann-Whitney U tests. RESULTS: Concentrations of interleukin-6 and interleukin-10 in the active labor admission group were significantly higher than concentrations in the preactive labor admission group at all 3 time points. Neutrophil levels were significantly higher in the active group at 2 and 4 hours after admission. The rate of increase in neutrophils and interleukin-10 between admission and 2 hours later was faster in the active group (P < .001 and P = .003, respectively). CONCLUSION: Circulating concentrations of several inflammatory biomarkers are higher and their rate of change over time since admission is faster among low-risk, nulliparous women admitted to hospitals in active labor, as compared with those admitted in preactive labor. More research is needed to determine if progressive changes in inflammatory biomarkers might be a useful adjunct to improving the assessment of labor progression and determining the optimal timing of labor admission.

Inflammatory markers are elevated in early pregnancy, but not late pregnancy, in women with overweight and obesity that later develop preeclampsia.

PROBLEM: Obesity and preeclampsia both involve a pathological inflammatory response, which may be how obesity increases preeclampsia risk. Previous studies have failed to assess robust measurements of inflammatory markers across gestation, specifically in overweight/ obese women in the context of preeclampsia. METHOD OF STUDY: We measured 20 inflammatory markers in plasma via multiplex assay (ThermoFisher Inflammation 20 plex Human ProcartaPlex Panel) across the three trimesters of pregnancy in an existing cohort of overweight and obese women who developed preeclampsia (n = 37) and without preeclampsia (n = 74). Mann-Whitney U tests examined differences in inflammatory marker concentrations between cases and controls. Repeated measures ANOVA tests were used to explore differences in inflammatory marker concentrations over time within cases and controls. RESULTS: Pro-inflammatory markers (IL-1α, IL-1ß, IL-6, IFN-α, IFN-γ, GM-CSF, IL-12p70, IL-17α, TNF-α, IL-8) and anti-inflammatory markers (IL-4, IL-10, IL-13) were higher in the first and second trimester in participants who later developed preeclampsia compared to those who did not (p < .05). Only TNF-α and IL-8 remained elevated in the third trimester. Inflammatory markers did not change across pregnancy in preeclampsia cases but did increase across pregnancy in controls. CONCLUSION: Our findings diverge from prior studies, predominantly of non-obese women, that report lower circulating concentrations of anti-inflammatory cytokines in preeclampsia versus normotensive pregnancy, particularly by late pregnancy. We posit that women with overweight and obesity who develop preeclampsia entered pregnancy with a heightened pro-inflammatory state likely related to obesity, which increased risk for preeclampsia. Further studies are needed to investigate if inflammatory maker profiles differ between obese and non-obese women.

Mothers' Perspectives on a Mother/Infant Dyad Postpartum Primary Care Program Following Gestational Diabetes Mellitus: A Qualitative Pilot Study.

PURPOSE: The purpose of this study is to characterize mothers' experiences within a mother/infant dyad postpartum primary care program (Dyad) following gestational diabetes mellitus (GDM) to inform improvements in the delivery of care. METHODS: A qualitative pilot study of women (n = 10) enrolled in a mother/infant Dyad program was conducted in a primary care practice at a large, urban academic medical center. Respondents were asked a series of open-ended questions about their experience with GDM, the Dyad program, and health behaviors. Interviews were audio-recorded, transcribed verbatim, and analyzed using ground theory with NVivo 12 Plus software. RESULTS: Three key themes emerged: (1) Dyad program experience, (2) implementation of health behavior changes, and (3) acknowledgment of future GDM and type 2 diabetes mellitus (T2DM) health risks. Respondents felt that the program conveniently served mother and infant health care needs in a single appointment. Respondents also valued support from primary care providers when implementing health behavior changes. The Dyad program provided an opportunity for respondents to understand their current and future risk for developing GDM and T2DM. CONCLUSIONS: Postpartum women enrolled in the Dyad program received highly personalized primary care services. The results of our study will help integrate patient-centered strategies into models for GDM care to maintain patient engagement in postpartum clinical services.

Early adversity and the regulation of gene expression: Implications for prenatal health.

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.

Allostatic load in the association of depressive symptoms with incident coronary heart disease: The Jackson Heart Study.

African Americans are at heightened risk for coronary heart disease (CHD), with biologic pathways poorly understood. We examined the role of allostatic load (AL) in the association of depressive symptoms with incident CHD among 2,670 African American men and women in the prospective Jackson Heart Study. Depressive symptoms were quantified using the Center for Epidemiologic Studies Depression Scale (CES-D). Incident CHD was ascertained by self-report, death certificate survey, and adjudicated medical record surveillance. Baseline AL was quantified using biologic parameters of metabolic, cardiovascular, immune, and neuroendocrine subsystems and as a combined meta-factor. Sequential models adjusted for demographic, socioeconomic, and behavioral covariates, stratified to examine differences by sex. Greater depressive symptomatology was associated with greater metabolic, cardiovascular, and immune AL (p-values≤0.036) and AL meta-factor z-scores (p = 0.007), with findings driven by observations among females. Each 1-point increase in baseline depressive symptomatology, and 1-SD increase in metabolic AL, neuroendocrine AL, and AL meta-factor z-scores was associated with 3.3%, 88%, 39%, and 130% increases in CHD risk, respectively (p-values <0.001). Neuroendocrine AL and AL meta-factor scores predicted incident CHD among males but not females in stratified analyses. Metabolic AL partially mediated the association of depressive symptoms with incident CHD (5.79% mediation, p = 0.044), a finding present among females (p = 0.016) but not males (p = 0.840). Among African American adults, we present novel findings of an association between depressive symptomatology and incident CHD, partially mediated by metabolic AL. These findings appear to be unique to females, an important consideration in the design of targeted interventions for CHD prevention.

Racial discrimination and leukocyte glucocorticoid sensitivity: Implications for birth timing.

RATIONALE: Psychological stress-induced cortisol elevations appear to contribute to preterm birth. Yet, some studies suggest that the biological ramifications of racial discrimination-associated stress are unique and may involve development of decreased glucocorticoid sensitivity despite normalized cortisol levels. OBJECTIVE: In this study, we examined the effects of racial discrimination on maternal cortisol output, leukocyte glucocorticoid sensitivity, and the degree of correspondence between cortisol levels and birth timing in an African American cohort. METHOD: A generally healthy prospective cohort was enrolled at 28-32 weeks gestation (n = 91). The Experiences of Discrimination scale was administered, whole blood collected, and plasma cortisol levels, cytokine levels, and leukocyte counts quantified for examination of patterns of endogenous feedback. RESULTS: Racial discrimination in the mid-tertile was associated with greater maternal cortisol levels than the bottom tertile among women reporting internalizing responses (b* = 0.68, p = 0.001). Decreased leukocyte glucocorticoid sensitivity was witnessed at greater frequencies of experiences of racial discrimination, as evidenced by decreased correspondence between maternal cortisol levels and plasma IL-8 levels, monocyte counts, and lymphocyte counts (p values ≤ 0.043). The association between maternal cortisol levels and birth timing differed by discrimination tertile (p values ≤ 0.005), with greater cortisol levels predictive of earlier birth among women without (b* = -0.59, p < 0.001) but not with racial discrimination (ps ≥ 0.497). CONCLUSION: We provide novel evidence of decreased glucocorticoid sensitivity at increasing frequency of exposure to racial discrimination. Our findings suggest that the biology of preterm birth may depend upon racial discriminatory exposures, favoring pathways dependent upon glucocorticoid-induced increases in leukocyte tissue surveillance versus glucocorticoid resistance-associated inflammatory aberrations at increasing levels of exposure. Precision approaches to prenatal care are sorely needed to combat preterm birth, particularly among African American women, with efforts dependent upon further research examining the pathways contributing to the syndrome dependent upon the totality of an individual's exposures.

Maternal parity and perinatal cortisol adaptation: The role of pregnancy-specific distress and implications for postpartum mood.

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- (χ2 = 11.8, p < 0.01) and late pregnancy (χ2 = 18.9, p < 0.01) and higher distress across pregnancy (F1,126 = 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.

Effects of Maternal Vitamin D Supplementation on the Maternal and Infant Epigenome.

INTRODUCTION: Mothers and infants are at high risk for inadequate vitamin D status. Mechanisms by which vitamin D may affect maternal and infant DNA methylation are poorly understood. OBJECTIVE: This study quantified the effects of vitamin D3 supplementation on DNA methylation in pregnant and lactating women and their breastfed infants. MATERIALS AND METHODS: In this randomized controlled pilot study, pregnant women received vitamin D3 400 international units (IU) (n = 6; control) or 3,800 IU (n = 7; intervention) daily from late second trimester through 4-6 weeks postpartum. Epigenome-wide DNA methylation was quantified in leukocytes collected from mothers at birth and mother-infant dyads at 4-6 weeks postpartum. RESULTS: At birth, intervention group mothers showed DNA methylation gain and loss at 76 and 89 cytosine-guanine (CpG) dinucleotides, respectively, compared to controls. Postpartum, methylation gain was noted at 200 and loss at 102 CpGs. Associated gene clusters showed strongest biologic relevance for cell migration/motility and cellular membrane function at birth and cadherin signaling and immune function at postpartum. Breastfed 4-6-week-old infants of intervention mothers showed DNA methylation gain and loss in 217 and 213 CpGs, respectively, compared to controls. Genes showing differential methylation mapped most strongly to collagen metabolic processes and regulation of apoptosis. CONCLUSIONS: Maternal vitamin D supplementation during pregnancy and lactation alters DNA methylation in mothers and breastfed infants. Additional work is needed to fully elucidate the short- and long-term biologic effects of vitamin D supplementation at varying doses, which could hold important implications for establishing clinical recommendations for prenatal and offspring health promotion.

Childhood stress and birth timing among African American women: Cortisol as biological mediator.

Preterm birth (PTB) occurs among 1:11U.S. white women and 1:7.5 African American women and is a significant driver of racial disparities in infant mortality. Maternal stress is the most common clinical phenotype underlying spontaneous PTB. Specific patterns of stress and biological mediators driving PTB remain unclear. We examined the effect of childhood stress on birth timing among African American women and evaluated maternal cortisol elevation as a biological mediator. A prospective observational design was employed, with a single study visit at 28-32 weeks gestation and medical record review. The Stress and Adversity Inventory was administered, which provides a comprehensive estimate of childhood stress, stress in adulthood, and five core characteristic subscales (interpersonal loss, physical danger, humiliation, entrapment, role disruption). Venipuncture was performed between 11:00am and 4:00pm and plasma cortisol quantified by ELISA. Analyses controlled for stress in adulthood. Among a final sample of 89, cumulative childhood stress predicted birth timing (p=0.01). The association was driven by stress related to interpersonal loss and physical danger, with support for maternal cortisol as a biological mediator (ab=0.02, 95% CI [0.001, 0.045]; ab=0.02, 95% CI [0.001, 0.043], respectively). Results were similar, overall, in sub-group analyses among spontaneously laboring women (n=53); however, role disruption arose as an additional predictor, as mediated by cortisol elevations (ab=0.03, 95% CI [0.005, 0.074]). Of note, cortisol was no longer supported as a mediator linking physical danger to birth timing after adjusting for sleep quality and hours awake prior to venipuncture (ab=0.02, 95% CI [-0.0001, 0.046]). We provide preliminary evidence that, independent of stress in adulthood, childhood stress of specific core characteristics may shape birth timing, with cortisol elevation as a biological mediator. Further investigation is warranted and may bolster the development of biologically-informed screening tools for the prediction and targeted prevention of stress-related PTB.

Body Mass Index as a Measure of Obesity: Racial Differences in Predictive Value for Health Parameters During Pregnancy.

BACKGROUND: As a measure of obesity, body mass index (BMI; kg/m2) is an imperfect predictor of health outcomes, particularly among African Americans. However, BMI is used to guide prenatal care. We examined racial differences in the predictive value of maternal BMI for physiologic correlates of obesity, serum interleukin (IL)-6 and C-reactive protein (CRP), as well as cesarean section and infant birth weight. METHODS: One hundred five pregnant women (40 European American, 65 African American) were assessed during the second trimester. BMI was defined as per prepregnancy weight. Electrochemiluminescence and enzyme-linked immunosorbent assays were used to quantify IL-6 and CRP, respectively. Birth outcomes were determined by medical record review. RESULTS: Women of both races classified as obese had higher serum IL-6 and CRP than their normal-weight counterparts (ps ≤ 0.01). However, among women with overweight, elevations in IL-6 (p < 0.01) and CRP (p = 0.06) were observed among European Americans, but not African Americans (ps ≥ 0.61). Maternal obesity was a significantly better predictor of cesarean section among European Americans versus African Americans (p = 0.03) and BMI was associated with infant birth weight among European Americans (p < 0.01), but not African Americans (p = 0.94). Effects remained after controlling for gestational age at delivery, gestational diabetes, and gestational weight gain as appropriate. CONCLUSIONS: BMI may be a less valid predictor of correlates of overweight/obesity among African Americans versus European Americans during pregnancy. This should be considered in epidemiological studies of maternal-child health. In addition, studies examining the comparative validity of alternative/complementary measures to define obesity in pregnancy are warranted to inform clinical care.

Adaptation of the inflammatory immune response across pregnancy and postpartum in Black and White women.

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 24h and supernatants assayed by electrochemiluminescence to quantify interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-1ß, and IL-8 production. While no changes were observed in IL-8 production over time, significant increases in IL-6, TNF-α, and IL-1ß production were observed from early to late pregnancy, with subsequent declines approaching early pregnancy values at postpartum (ps<0.05). Overall, inflammatory response patterns were highly similar among Black versus White women. However, Black women had greater TNF-α production during mid-pregnancy (p=0.002) and marginally lower IL-1ß production at postpartum (p=0.054). These data show a clear trajectory of change in the inflammatory immune response across pregnancy and postpartum. In this cohort of generally healthy women, Black and White women exhibited minimal differences in LPS-stimulated cytokine production across the perinatal period. Future prospective studies in Black and White women with healthy versus adverse outcomes (e.g., preeclampsia, preterm birth) would inform our understanding of the potential role of immune dysregulation in pregnant women and in relation to racial disparities in perinatal health.

Serum brain-derived neurotrophic factor (BDNF) across pregnancy and postpartum: Associations with race, depressive symptoms, and low birth weight.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is implicated as a causal factor in major depression and is critical to placental development during pregnancy. Longitudinal data on BDNF across the perinatal period are lacking. These data are of interest given the potential implications for maternal mood and fetal growth, particularly among Black women who show ∼2-fold greater risk for delivering low birth weight infants. METHODS: Serum BDNF, serum cortisol, and depressive symptoms (per CES-D) were assessed during each trimester and 4-11 weeks postpartum among 139 women (77 Black, 62 White). Low birth weight (<2500g) was determined via medical record. RESULTS: Serum BDNF declined considerably from 1st through 3rd trimesters (ps≤0.008) and subsequently increased at postpartum (p<0.001). Black women exhibited significantly higher serum BDNF during the 1st trimester, 2nd trimester, and postpartum (ps≤0.032) as well as lower serum cortisol during the 2nd and 3rd trimester (ps≤0.01). Higher serum cortisol was concurrently associated with lower serum BDNF in the 2nd trimester only (p<0.05). Controlling for race, serum BDNF at both the 2nd and 3rd trimester was negatively associated with 3rd trimester depressive symptoms (ps≤0.02). In addition, women delivering low versus healthy weight infants showed significantly lower serum BDNF in the 3rd trimester (p=0.004). Women delivering low versus healthy weight infants did not differ in depressive symptoms at any time point during pregnancy (ps≥0.34). CONCLUSIONS: Serum BDNF declines considerably across pregnancy in Black and White women, with overall higher levels in Blacks. Lower serum BDNF in late pregnancy corresponds with higher depressive symptoms and risk for low birth weight in Black and White women. However, the predictive value of serum BDNF in pregnancy is specific to within-race comparisons. Potential links between racial differences in serum BDNF and differential pregnancy-related cortisol adaptation require further investigation.

A proposed bio-panel to predict risk for spontaneous preterm birth among African American women.

Preterm birth (PTB), or birth prior to 37 weeks gestation, impacts 11.5% of U.S. deliveries. PTB results in significant morbidity and mortality among affected children and imposes a large societal financial burden. Racial disparities in PTB are alarming. African American women are at more than 1.5 times the risk for PTB than white women. Unfortunately, the medical community's ability to predict who is at risk for PTB is extremely limited. History of a prior PTB remains the strongest predictor during a singleton gestation. Cervical length and fetal fibronectin measurement are helpful tools. However, usefulness is limited, particularly among the 95% of U.S. women currently pregnant and lacking a history of PTB. Therefore, preventive therapies do not reach a great number of women who may benefit from them. This manuscript, in response to the pressing need for predictors of PTB risk and elimination of racial disparities in PTB, presents a proposed bio-panel for use in predicting risk for spontaneous PTB among African American women. This bio-panel, measured each trimester, includes stimulated production of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-1 receptor antagonist (Ra), soluble(s) TNF receptor(R) 1, and sTNFR2, and cortisol responsiveness. We hypothesize that greater IL-1ß and TNF-α production, decreased IL-1Ra, sTNFR1, and sTNFR2 production, and decreased cortisol responsiveness at each time point as well as a more expedient alignment with this unfavorable profile over time will be associated with PTB. The choice to focus on inflammatory parameters is supported by data highlighting a crucial role for inflammation in labor. Specific inflammatory mediators have been chosen due to their potential importance in preterm labor among African American women. The bio-panel also focuses on inflammatory regulation (i.e., cytokine production upon ex vivo stimulation), which is hypothesized to provide insight into potential in vivo leukocyte responses and potential for initiation of a preterm inflammatory cascade. Production of receptor antagonists is also considered, as pro-inflammatory mediator effects can be greatly influenced by their balance with respective antagonists. Finally, leukocyte responsiveness to cortisol is included as a measure of cortisol's ability to convey anti-inflammatory signals. The development of a bio-panel predictive of risk for spontaneous PTB among African American women would represent a significant advancement. Available preventive therapies, namely progesterone supplementation, could be delivered to women deemed at risk. Further, the identification of biological predictors of PTB may uncover novel targets for preventive therapies.