1.
Allostatic load, a measure of chronic physiological stress, is associated with pregnancy outcomes, but not fertility, among women with unexplained infertility.
Barrett, ES, Vitek, W, Mbowe, O, Thurston, SW, Legro, RS, Alvero, R, Baker, V, Bates, GW, Casson, P, Coutifaris, C, et al
Human reproduction (Oxford, England). 2018;(9):1757-1766
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Abstract
STUDY QUESTION Among infertile women undergoing ovarian stimulation, is allostatic load (AL), a measure of chronic physiological stress, associated with subsequent fertility and pregnancy outcomes? SUMMARY ANSWER AL at baseline was not associated with conception, spontaneous abortion or live birth, however, it was significantly associated with increased odds of pre-eclampsia and preterm birth among women who had a live birth in the study. WHAT IS KNOWN ALREADY Several studies have linked AL during pregnancy to adverse outcomes including preterm birth and pre-eclampsia, hypothesizing that it may contribute to well-documented disparities in pregnancy and birth outcomes. However, AL biomarkers change over the course of pregnancy, raising questions as to whether gestational AL assessment is a valid measure of cumulative physiologic stress starting long before pregnancy. To better understand how AL may impact reproductive outcomes, AL measurement in the non-pregnant state (i.e. prior to conception) is needed. STUDY DESIGN, SIZE, DURATION A secondary data analysis based on data from 836 women who participated in Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), a multi-center, randomized clinical trial of ovarian stimulation conducted from 2011 to 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS Ovulatory women with unexplained infertility (ages 18-40) were enrolled and at baseline, biological and anthropometric measures were collected. AL scores were calculated as a composite of the following baseline variables determined a priori: BMI, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, dehydroepiandrosterone sulfate, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, C-reactive protein and HOMA score. Participants received ovarian stimulation for up to four cycles and if they conceived, were followed throughout pregnancy. We fit multi-variable logistic regression models examining AL (one-tailed and two-tailed) in relation to the following reproductive outcomes: conception, spontaneous abortion, live birth, pre-eclampsia, preterm birth and low birthweight. MAIN RESULTS AND THE ROLE OF CHANCE Adjusting for covariates, a unit increase in two-tailed AL score was associated with 62% increased odds of pre-eclampsia (OR: 1.62, 95% CI: 1.14, 2.38) 44% increased odds of preterm birth (OR: 1.44, 95% CI: 1.02, 2.08), and 39% increased odds of low birthweight (OR: 1.39, 95% CI: 0.99, 1.97). The relationship between AL and preterm birth was mediated by pre-eclampsia (P = 0.0003). In one-tailed AL analyses, associations were similar, but slightly attenuated. AL was not associated with fertility outcomes (conception, spontaneous abortion, live birth). LIMITATIONS, REASONS FOR CAUTION Results may not be generalizable to fertile women who conceive naturally or women with other types of infertility. Comparisons to previous, related work are difficult because variables included in AL composite measures vary across studies. AL may be indicative of overall poor health, rather than being specific to chronic physiological stress. WIDER IMPLICATIONS OF THE FINDINGS Our results suggest that chronic physiological stress may not impact success of ovarian stimulation, however, they confirm and extend previous work suggesting that AL is associated with adverse pregnancy outcomes. Physiological dysregulation due to chronic stress has been proposed as a possible mechanism underlying disparities in birth outcomes, which are currently poorly understood. Assessing biomarkers of physiological dysregulation pre-conception or in early pregnancy, may help to identify women at risk of adverse pregnancy outcomes, particularly pre-eclampsia. STUDY FUNDING/COMPETING INTEREST(S): Support for AMIGOS was provided by: U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936 and U10HD055925. Support for the current analysis was provided by T32ES007271, R25HD075737, P30ES001247 and P30ES005022. This research was made possible by funding by American Recovery and Reinvestment Act. The content is solely the responsibility of the authors and does not necessarily represent the official views of NICHD, NIEHS or NIH. E.B., W.V., O.M., R.A., M.R., V.B., G.W.B., C.C., E.E., S.K., R.U., P.C, H.Z., N.S. and S.T. have nothing to disclose. R.L. reported serving as a consultant to Abbvie, Bayer, Kindex, Odega, Millendo and Fractyl and serving as a site investigator and receiving grants from Ferring. K.H. reported receiving grants from Roche Diagnostics and Ferring. R.R. reported a grant from AbbVie. M.D. reported being on the Board of Directors of and a stockholder in Advanced Reproductive Care. TRIAL REGISTRATION NUMBER Clinical Trials.gov number: NCT01044862.
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Beta cell stress in a 4-year follow-up of patients with type 2 diabetes: A longitudinal analysis of the BetaDecline Study.
Russo, GT, Giorda, CB, Cercone, S, De Cosmo, S, Nicolucci, A, Cucinotta, D, ,
Diabetes/metabolism research and reviews. 2018;(6):e3016
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is associated with a progressive deterioration in beta cell function and loss of glycaemic control. Clinical predictors of beta cell failure are needed to guide appropriate therapy. METHODS A prospective evaluation of a large set of potential predictors of beta cell stress, measured as change in the proinsulin/insulin (PI/I) ratio, was conducted in a cohort of 235 outpatients with T2DM on stable treatment with oral hypoglycaemic agents or diet followed up for ~4 years (median value 3.9 years; interquartile range 3.8-4.1 years). RESULTS Overall, metabolic control deteriorated over time, with a significant increase in glycated haemoglobin (HbA1c; P < .0001), proinsulin (P < .0001), and PI/I ratio (P = .001), without significant changes in the homeostatic model assessment of insulin resistance. Multivariate regression analysis showed that for each 1% (10.9 mmol/mol) increase from baseline in HbA1c, the risk of beta cell stress increased by 3.8 times; for each 1% (10.9 mmol/mol) incremental increase in HbA1c during the study, risk of beta cell stress increased by 2.25 times that at baseline. By contrast, baseline anthropometric and clinical variables, lipid profile, inflammatory markers (PCR, IL-6), non-esterified fatty acids, and current therapies did not independently influence PI/I ratio variation during follow-up. CONCLUSIONS In this cohort of patients with T2DM, beta cell function progressively deteriorated despite current therapies. Among a large set of clinical and biochemical predictors, only baseline HbA1c levels and their deterioration overtime were associated with higher beta cell stress over time.
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Behavioral stress is affected by the mode of tube feeding in very low birth weight infants.
Dsilna, A, Christensson, K, Gustafsson, AS, Lagercrantz, H, Alfredsson, L
The Clinical journal of pain. 2008;(5):447-55
Abstract
OBJECTIVE To compare the effect of continuous versus bolus feeding on behavioral responses of stress in very low birth weight infants during early postnatal life. METHODS In a randomized, controlled trial conducted at 3 neonatal units, 70 premature infants with gestational age 24 to 29 weeks and birth weight <1200 g were randomly assigned to 1 of 3 feeding methods: continuous nasogastric feeding, bolus nasogastric feeding, and bolus orogastric feeding. Behavioral responses were video recorded during feeding at 7 and 15 days of postnatal age and at 32 weeks of postmenstrual age. The odds ratio (OR) of manifest behavioral stress was calculated by means of logistic regression. RESULTS A significantly higher risk of a behavioral stress response in bolus-fed infants compared with continuous-fed infants at 15 days of age was observed, [adjusted OR=4.1 (95% confidence interval: 1.1-15.4)]. A similar difference was observed at 32 weeks of postmenstrual age [adjusted OR=4.2 (95% confidence interval: 1.0-17.8)]. In addition, bolus-fed infants showed statistically significant higher need of behavioral and physiologic stabilization during feeding. DISCUSSION This trial suggests that continuous feeding is associated with lower behavioral stress response as compared with bolus feeding among very low birth weight infants, in early postnatal life.
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A double-blind, placebo-controlled, double-centre study of the effects of an oral multivitamin-mineral combination on stress.
Schlebusch, L, Bosch, BA, Polglase, G, Kleinschmidt, I, Pillay, BJ, Cassimjee, MH
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde. 2000;(12):1216-23
Abstract
OBJECTIVES To assess the effects of a multivitamin-mineral combination (Berocca Calmag) treatment on stress in a large sample of South Africans. METHOD This was a multiple-dose, double-blind, placebo-controlled, double-centre study. Patients were drawn from two centres with high stress levels (Durban and Johannesburg), each study recruiting the same number of patients (150) from 1,000 adults with predetermined high stress levels. Dropouts from the study were replaced. Study medication safety was evaluated by recording adverse events. On day 1 (baseline) patients were subjected to an individual in-depth assessment that included a biographical questionnaire, four psychological scales, and collateral information from close relatives. On day 30 (end of the study period) or at the latest 7 days after the last planned medication intake, the assessment was repeated for purposes of pre- and post-response comparison. RESULTS Thirty-three patients dropped out and were replaced, leaving 300 patients who completed the study--151 in group 1 (multivitamin-mineral combination), and 149 in group 2 (placebo). There were no statistically significant differences between the two groups regarding demographics and baseline stress scores at study entry. Both groups improved between baseline and the end of treatment as assessed. The degree of improvement was statistically significant and greatest in group 1 for all psychometric instruments, with this beneficial effect increasing over the course of the day. Subgroup analyses for age (18-44 and 45-65 years), gender and ethnicity showed no general effect on the overall study outcome. CONCLUSIONS The multivitamin-mineral combination tested is well tolerated and can be used as part of a treatment programme for stress-related symptoms at the recommended dose.