A Computer Simulation of Progesterone and Cox2 Inhibitor Treatment for Preterm Labor

Background: Sufficient information from in vitro and in vivo studies has become available to permit computer modeling of the processes that occur in the myometrium during labor. This development allows the in silico investigation of pathological mechanisms and the trialing of potential treatments. Methods/Results: Based on the human literature, we developed a computer model of the immune-endocrine environment of the myometrial cell. The interactions between molecules are represented by differential equations. The model is designed to simulate the estrogen and progesterone receptor changes during pregnancy and particularly the changes in the progesterone receptor (PR) isoforms A and B that are thought to mediate functional progesterone withdrawal in the human at labor. Parturition is represented by an increase in the PRA to PRB ratio to levels seen in women in labor. Infection is shown by inducing inflammation in the system by increasing phospho-IkB kinase concentration (IKK) levels; which lead to increased NF-kappa B activation, causing an increase in the PRA/PRB ratio. We examined the effects of progesterone or cyclooxygenase 2 (Cox2) inhibitor treatments on the PRA/PRB ratio in silico. The model predicted that high doses of progesterone and Cox2 inhibition would be effective in preventing an NF-kappa B-induced PRA/PRB ratio increase to the levels found during labor. Conclusions: Our data illustrate the use of dynamic biological computer simulations to test the effectiveness of therapeutic interventions. This may allow the early rejection of ineffective therapies prior to expensive field trials

Pregnancy Anxiety and Prenatal Cortisol Trajectories

Pregnancy anxiety is a potent predictor of adverse birth and infant outcomes. The goal of the current study was to examine one potential mechanism whereby these effects may occur by testing associations between pregnancy anxiety and maternal salivary cortisol on 4 occasions during pregnancy in a sample of 448 women. Higher mean levels of pregnancy anxiety over the course of pregnancy predicted steeper increases in cortisol trajectories compared to lower pregnancy anxiety. Significant differences between cortisol trajectories emerged between 30 to 31 weeks of gestation. Results remained significant when adjusted for state anxiety and perceived stress. Neither changes in pregnancy anxiety over gestation, nor pregnancy anxiety specific to only a particular time in pregnancy predicted cortisol. These findings provide support for one way in which pregnancy anxiety may influence maternal physiology and contribute to a growing literature on the complex biological pathways linking pregnancy anxiety to birth and infant outcomes

Prenatal Stress and Stress Physiology Influences Human Fetal and Infant Development

Prenatal stress has been proposed as a risk factor that may have developmental consequences persisting throughout the lifespan. Exposing rodents to stress during pregnancy has consequences for brain development, stress regulation, learning, emotionality (increased anxiety), and social behavior (increased withdrawal) of the offspring (Weinstock, 2001; Chapillon et al., 2002). Additionally, non-human primates who experience stress during pregnancy have offspring with enhanced behavioral reactivity to stressors later in life (Clarke et al., 1994), lowered levels of motor behavior (Schneider, 1992), compromised neuromotor responses (Schneider and Coe, 1993), irritable temperament (Schneider et al., 1992), and attentional problems (Schneider et al., 1999).https://digitalcommons.chapman.edu/psychology_books/1014/thumbnail.jp

Prenatal Beta-Endorphin as an Early Predictor of Postpartum Depressive Symptoms in Euthymic Women

After delivery, many women experience symptoms of postpartum depression (PPD), and early identification of women at risk is therefore important. The opioid peptide [beta]-endorphin has been implicated in non-puerperal depression but its role in the development of PPD is unknown

Elevated Corticotropin-Releasing Hormone in Human Pregnancy Increases the Risk of Postpartum Depressive Symptoms

Postpartum depression (PPD) is common and has serious implications for the mother and her newborn. A possible link between placental corticotropin-releasing hormone (pCRH) and PPD incidence has been discussed, but there is a lack of empirical evidence

Timing of Fetal Exposure to Stress Hormones: Effects on Newborn Physical and Neuromuscular Maturation

The purpose of the study was to determine the specific periods during pregnancy in which human fetal exposure to stress hormones affects newborn physical and neuromuscular maturation. Blood was collected from 158 women at 15, 19, 25, and 31 weeks\u27 gestation. Levels of placental corticotropin-releasing hormone (CRH) and maternal cortisol were determined from plasma. Newborns were evaluated with the New Ballard Maturation Score. Results indicated that increases in maternal cortisol at 15, 19, and 25 weeks and increases in placental CRH at 31 weeks were significantly associated with decreases in infant maturation among mates (even after con trolling for length of gestation). Results also suggested that increases in maternal cortisol at 31 weeks were associated with increases in infant maturation among females, although these results were not significant after controlling for length of gestation. Findings suggest that stress hormones have effects on human fetal neurodevelopment that are independent of birth outcome

Lifetime Racism and Blood Pressure Changes During Pregnancy: Implications for Fetal Growth

Objective: Research suggests that exposure to racism partially explains why African American women are 2 to 3 times more likely to deliver low birth weight and preterm infants. However, the physiological pathways by which racism exerts these effects are unclear. This study examined how lifetime exposure to racism, in combination with maternal blood pressure changes during pregnancy, was associated with fetal growth. Methods: African American pregnant women (n = 39) reported exposure to childhood and adulthood racism in several life domains (e.g., at school, at work), which were experienced directly or indirectly, meaning vicariously experienced when someone close to them was treated unfairly. A research nurse measured maternal blood pressure at 18 to 20 and 30 to 32 weeks gestation. Standardized questionnaires and trained interviewers assessed maternal demographics. Neonatal length of gestation and birth weight data were collected from medical charts. Results: Childhood racism interacted with diastolic blood pressure to predict birth weight. Specifically, women with two or more domains of indirect exposure to racism in childhood and increases in diastolic blood pressure between 18 and 32 weeks had lower gestational age adjusted birth weight than the other women. A similar pattern was found for direct exposure to racism in childhood. Conclusions: Increases in diastolic blood pressure between the second and third trimesters predicted lower birth weight, but only when racism exposure in childhood (direct or indirect) was relatively high. Understanding pregnant African American women’s lifetime direct and indirect experiences with racism in combination with prenatal blood pressure may improve identification of highest risk subgroups within this population

Stress and Blood Pressure During Pregnancy: Racial Differences and Associations With Birthweight

OBJECTIVE: To extend findings that African American women report greater stress during pregnancy, have higher blood pressure (BP), and are twice as likely to have low birthweight infants relative to white women. This study examines a) racial differences in associations between stress and BP during pregnancy, and b) the combined effects of stress and BP on infant birthweight in a sample of 170 African American and white women. METHODS: A prospective, longitudinal study of pregnant women was conducted in which measures of BP, stress, and other relevant variables were collected. Multiple measures of systolic and diastolic BP were taken at each of three points during pregnancy (18-20, 24-26, and 30-32 weeks gestation). RESULTS: Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were positively associated with stress in pregnant African American women and not in pregnant white women. In analyses of birthweight, there were no main effects of BP or stress. However, a significant interaction demonstrated that, when stress was high, DBP was negatively associated with birthweight and a combination of high stress and high DBP predicted the lowest birthweight in the sample. Furthermore, African American women were twice as likely as white women to have a combination of high stress and high DBP. CONCLUSIONS: Racial differences in relationships between stress and BP, and the interactive effect of stress and DBP on birthweight together suggest that a high stress-high BP profile may pose a risk for lower birthweight among African American women, in particular, and possibly for all pregnant women

Explaining racial and ethnic inequalities in postpartum allostatic load: Results from a multisite study of low to middle income woment

AbstractBackgroundRacial and ethnic inequalities in women's health are widely documented, but not for the postpartum period, and few studies examine whether neighborhood, psychosocial, and biological factors explain these gaps in women's health.MethodsUsing prospective longitudinal data collected from 1766 low to middle income women between 2008 and 2012 by the Community Child Health Network (CCHN), we tested the extent to which adjustment for neighborhood, economic, psychological, and medical conditions following a birth explained differences between African American, Latina, and White women in an indicator of physiological dysregulation allostatic load (AL), at one year postpartum as measured by 10 biomarkers: Body Mass Index, Waist Hip Ratio, systolic and diastolic blood pressure, high sensitivity C-reactive protein, Hemoglobin A1c, high-density lipoprotein and cholesterol ratio, and diurnal cortisol.ResultsMean postpartum AL scores were 4.65 for African American, 4.57 for Latina and 3.86 for White women. Unadjusted regression estimates for high AL for African American women (with White as the reference) were 0.80 (SD = 0.11) and 0.53 (SD = 0.15) for Latina women. Adjustment for household poverty, neighborhood, stress, and resilience variables resulted in a reduction of 36% of the excess risk in high AL for African Americans versus Whites and 42% of the excess risk for Latinas compared to Whites.ConclusionsRacial and ethnic inequalities in AL were accounted for largely by household poverty with additional contributions by psychological, economic, neighbourhood and medical variables. There remained a significant inequality between African American, and Latina women as compared to Whites even after adjustment for this set of variables. Future research into health inequalities among women should include a fuller consideration of the social determinants of health including employment, housing and prepregnancy medical conditions

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