The Multifaceted Effects of Osteocytic TGFß Signaling on the Skeletal and Extraskeletal Functions of Bone.

PURPOSE OF REVIEW: To summarize the fundamental role of transforming growth factor beta (TGFß) signaling in osteocytes and highlight the physiological and pathophysiological conditions stemming from the deregulation of this pathway in osteocytes. RECENT FINDINGS: Osteocytes perform a myriad of skeletal and extraskeletal functions, including mechanosensing, coordinating bone remodeling, local bone matrix turnover, and maintaining systemic mineral homeostasis and global energy balance. Transforming growth factor-beta (TGFß) signaling, which is crucial for embryonic and postnatal bone development and maintenance, has been found to be essential for several osteocyte functions. There is some evidence that TGFß might be accomplishing these functions through crosstalk with the Wnt, PTH, and YAP/TAZ pathways in osteocytes, and a better understanding of this complex molecular network can help identify the pivotal convergence points responsible for distinct osteocyte functions. This review provides recent updates on the interwoven signaling cascades coordinated by TGFß signaling within osteocytes to support their skeletal and extraskeletal functions and highlights physiological and pathophysiological conditions implicating the role of TGFß signaling in osteocytes.

Perceived psychosocial stress and glucose intolerance among pregnant Hispanic women.

AIM: Prior literature suggests a positive association between psychosocial stress and the risk of diabetes in non-pregnant populations, but studies during pregnancy are sparse. We evaluated the relationship between stress and glucose intolerance among 1115 Hispanic (predominantly Puerto Rican) prenatal care patients in Proyecto Buena Salud, a prospective cohort study in Western Massachusetts (2006-2011). METHODS: Cohen's Perceived Stress Scale (PSS-14) was administered in early (mean = 12.3 weeks gestation; range 4.1-18 weeks) and mid- (mean = 21.3 weeks gestation; range 18.1-26 weeks) pregnancy. Participants were classified as having a pregnancy complicated by gestational diabetes mellitus, impaired glucose tolerance, and abnormal glucose tolerance, based on the degree of abnormality on glucose tolerance testing between 24 and 28 weeks of gestation. RESULTS: The prevalence of gestational diabetes mellitus, impaired glucose tolerance, and abnormal glucose tolerance was 4.1%, 7.2%, and 14.5%, respectively. Absolute levels of early or mid-pregnancy stress were not significantly associated with glucose intolerance. However, participants with an increase in stress from early to mid-pregnancy had a 2.6-fold increased odds of gestational diabetes mellitus (95% confidence intervals: 1.0-6.9) as compared to those with no change or a decrease in stress after adjusting for age and pre-pregnancy body mass index. In addition, every one-point increase in stress scores was associated with a 5.5mg/dL increase in screening glucose level (ß=5.5; standard deviation=2.8; P=0.05), after adjusting for the same variables. CONCLUSION: In this population of predominantly Puerto Rican women, stress patterns during pregnancy may influence the risk of glucose intolerance.

Stress and placental resistance measured by Doppler ultrasound in early and mid-pregnancy.

OBJECTIVES: To examine the association between self reports and biomarkers of stress and placental resistance (measured by Doppler ultrasound of the uterine and umbilical arteries), to determine if restriction of blood flow to the placenta is a mechanism by which stress might affect health during pregnancy. METHODS: Eight hundred and seventy-two women had ultrasound examinations of the uterine artery at 15-19 weeks' gestation and the uterine and umbilical arteries at 24-29 weeks, and resistance and pulsatility indices were calculated. Psychosocial stress was measured by telephone interview and self-administered questionnaire using several validated tools twice during the pregnancy. Cortisol and corticotropin-releasing hormone (CRH) were measured twice during the pregnancy. Linear and hierarchical models were used to examine the relationships among reported stress, stress hormones and placental Doppler indices. RESULTS: The umbilical artery resistance index was higher in younger women, those with less education, those who were single and those who smoked. The uterine artery pulsatility index was higher in women with pre-eclampsia, those living alone, those with high body mass index, and those who gained the least weight during pregnancy. A higher CRH level was associated with small increases in uterine artery pulsatility and umbilical artery resistance indices. Psychosocial measures of stress were not consistently associated with higher placental resistance. CONCLUSIONS: Increased CRH levels may be associated with increased placental resistance. Otherwise, these findings do not support the hypothesis that restriction of blood flow to the fetus is a major mechanism by which stress affects infant health.

Psychological and biological markers of stress and bacterial vaginosis in pregnant women.

OBJECTIVES: To determine whether stress is associated with risk of bacterial vaginosis (BV) in pregnant women. DESIGN: Prospective cohort study. SETTING: The prenatal care clinics at the University of North Carolina. The residents' clinic sees mostly government-insured and uninsured women, and the physicians' clinic sees mostly those with private health insurance. POPULATION: A total of 897 women gave samples for BV analysis. Study participants were 22% African-American, 68% white; 24% unmarried and 44% nulliparous. More than half had completed college. METHODS: Women completed two questionnaires and two interviews reporting stress and psychological aspects of their lives. Measurement scales included the Sarason life events questionnaire, the Cohen perceived stress scale, Spielberger state-trait anxiety, the John Henryism coping style and the Medical Outcomes Study social support inventory. Two stress hormones, corticotrophin-releasing hormone and cortisol, were also measured. MAIN OUTCOME MEASURES: BV at 15-19 and 24-29 weeks of gestation was diagnosed by Gram's stain. RESULTS: Women in the highest quartile of stress measures, particularly state anxiety (OR=2.0, 95% CI 1.2-3.3), perceived stress (OR=2.4, 95% CI 1.5-3.9) and total life events (OR=2.0, 95% CI 1.3-3.2), had the highest risk of BV. Adjustment for confounders, especially age, race, and income, reduced these associations (state anxiety: OR=1.3, 95% CI 0.7-2.4; perceived stress: OR=1.4, 95% CI 0.8-2.5; total life events: OR=1.3, 95% CI 0.7-2.4). No clear pattern of association was seen between stress hormones and BV. CONCLUSIONS: Few associations between stress and BV were seen after adjustment for confounders.

Maternal stress and preterm birth.

This study examined a comprehensive array of psychosocial factors, including life events, social support, depression, pregnancy-related anxiety, perceived discrimination, and neighborhood safety in relation to preterm birth (<37 weeks) in a prospective cohort study of 1,962 pregnant women in central North Carolina between 1996 and 2000, in which 12% delivered preterm. There was an increased risk of preterm birth among women with high counts of pregnancy-related anxiety (risk ratio (RR) = 2.1, 95% confidence interval (CI): 1.5, 3.0), with life events to which the respondent assigned a negative impact weight (RR = 1.8, 95% CI: 1.2, 2.7), and with a perception of racial discrimination (RR = 1.4, 95% CI: 1.0, 2.0). Different levels of social support or depression were not associated with preterm birth. Preterm birth initiated by labor or ruptured membranes was associated with pregnancy-related anxiety among women assigning a high level of negative impact weights (RR = 3.0, 95% CI: 1.7, 5.3). The association between high levels of pregnancy-related anxiety and preterm birth was reduced when restricted to women without medical comorbidities, but the association was not eliminated. The prospective collection of multiple psychosocial measures on a large population of women indicates that a subset of these factors is associated with preterm birth.

Smoking and pregnancy outcome among African-American and white women in central North Carolina.

Despite extensive research on tobacco smoking during pregnancy, few studies address risks among African-American and white women, groups that differ in brand preference and smoking habits. The Pregnancy, Infection, and Nutrition Study is a prospective cohort study that included 2,418 women with detailed information on smoking during pregnancy, including brand, number of cigarettes per day, and changes during pregnancy. We analyzed risk of preterm birth (<37 and <34 weeks' gestation) and small-for-gestational-age deliveries in relation to tobacco use. Pregnant African-American smokers differed markedly from whites in brand preference (95% vs 26% smoked menthol cigarettes) and number of cigarettes per day (1% of African-Americans and 12% of whites smoked 20+ cigarettes per day). Smoking was not related to risk of preterm birth overall, but cotinine measured at the time of delivery was (adjusted odds ratio = 2.2, 95% confidence interval = 1.1-4.5). A clear association and dose-response gradient was present for risk of fetal growth restriction (risk ratio for 20+ cigarettes/day = 2.4, 95% confidence interval = 1.4-4.0). Associations of tobacco use with preterm premature rupture of amniotic membrane resulting in preterm birth were notably stronger than the associations with other types of preterm birth.

Determinants of participation in an epidemiological study of preterm delivery.

We describe the study design and patterns of participation for a cohort study of preterm delivery, focused on genital tract infections, nutrition, tobacco use, illicit drugs and psychosocial stress. Women are recruited at 24-29 weeks' gestation from prenatal clinics at a teaching hospital and a county health department. We recruited 57% of the first 1843 eligible women; 29% refused and 8% could not be contacted. White women were somewhat more likely to participate than African-American women (61% vs. 54% respectively). More notable differences were found comparing teaching hospital and health department clinics (71% vs. 47% participation respectively), with the health department clinic having a greater proportion refuse (24% vs. 33%) and more women who could not be contacted (4% vs. 11%). Participation was affected only minimally by day or timing of recruitment, but inability to contact diminished substantially as the study continued (13-0%). Refusals were largely unrelated to patient attributes. Lower education predicted inability to contact. Risk of preterm delivery was 14% among recruited women, 10% among women who refused, and 15% among women whom we were not able to contact, demonstrating that, overall, risk status was not lower among recruited women.

Male and female occupation in relation to miscarriage and preterm delivery in central North Carolina.

PURPOSE: This study was undertaken to evaluate the role of parental occupation in miscarriage and preterm delivery. Previous studies raise the possibility that both male and female exposures could affect pregnancy. METHODS: Data from a population-based study of miscarriage and preterm delivery in central North Carolina were used to examine potential associations with male and female occupation. Medically treated miscarriage cases (n = 418), preterm delivery cases identified through hospital record review (n = 582), and term, normal birth weight controls (n = 787) were sought for telephone interview. The interview included information on jobs the woman held before and during the pregnancy, reports of her partner's job around the time of pregnancy, and information on potential confounding factors. RESULTS: Female employment overall, or in specific jobs, around the time of conception or early pregnancy was not associated with the risk of miscarriage, whereas working during pregnancy, especially in the seventh month, was inversely associated with risk of preterm delivery. Male employment in several industrial occupations was weakly associated with miscarriage (adjusted odds ratios (OR) of 1.6 to 1.8), and somewhat more strongly associated with preterm delivery, particularly for chemists and sheet metal workers (adjusted OR over 3). Restriction to married men strengthened the associations. CONCLUSIONS: Our results are limited by nonresponse, imprecision, incomplete identification of miscarriages, and lack of detailed occupational exposure information. Nonetheless, we found greater support for further examination of male compared to female jobs in relation to pregnancy outcome.

Birthweight patterns in Harare, Zimbabwe.

Few data on birthweight distributions are available for Zimbabwe. This paper reports a study of 2140 births in Harare, Zimbabwe, occurring in April 1986. Births took place in public facilities, which are estimated to serve 85% of the urban population. Mean birthweight for the entire sample is 2970 g, and for singleton livebirths 3059 g. These data suggest that the proportion of low birthweight in Harare attributable to prematurity falls between the patterns of developed and developing countries.