Preconception insulin resistance and neonatal birth weight in women with obesity: role of bile acids.

RESEARCH QUESTION: Does maternal preconception insulin resistance affect neonatal birth weight among women with obesity? Is insulin resistance associated with circulating bile acids? Do bile acids influence the association between maternal preconception insulin resistance and neonatal birth weight? DESIGN: An exploratory post-hoc analysis of the LIFEstyle randomized controlled trial comparing lifestyle intervention with conventional infertility treatment in women with a BMI of ≥29 kg/m2. Fasting blood samples were collected at randomization and after 3 and 6 months in 469 women. Insulin resistance was quantified using the homeostasis model assessment of insulin resistance (HOMA-IR). Bile acid sub-species were determined by liquid chromatography with tandem mass spectrometry. Singletons were included (n = 238). Birth weight Z-scores were adjusted for age, offspring gender and parity. Multilevel analysis and linear regressions were used. RESULTS: A total of 913 pairs of simultaneous preconception HOMA-IR (median [Q25; Q75]: 2.96 [2.07; 4.16]) and total bile acid measurements (1.79 [1.10; 2.94]) µmol/l were taken. Preconception HOMA-IR was positively associated with total bile acids (adjusted B 0.15; 95% CI 0.09 to 0.22; P < 0.001) and all bile acid sub-species. At the last measurement before pregnancy, HOMA-IR (2.71 [1.91; 3.74]) was positively related to birth weight Z-score (mean ± SD 0.4 ± 1.1; adjusted B 0.08; 95% CI 0.01 to 0.14; P = 0.03). None of the preconception bile acids measured were associated with birth weight. CONCLUSION: Maternal preconception insulin resistance is an important determinant of neonatal birth weight in women with obesity, whereas preconception bile acids are not.

Childhood adversity and women's cardiometabolic health in adulthood: associations with health behaviors, psychological distress, mood symptoms, and personality.

BACKGROUND: We tested whether childhood adversity is associated with poor cardiometabolic health in adulthood among a sample of overweight or obese Dutch women of reproductive age. Health behaviors, psychological distress, mood symptoms, or personality traits were included as potential mediators. METHODS: Data came from a follow-up visit (N = 115), carried out in 2016/2017, of a randomized controlled lifestyle intervention trial in 577 obese infertile women. The associations between total adversity exposure score and cardiometabolic health were tested with regression models. Sleep, smoking and eating behavior, symptoms of depression, anxiety and stress, and personality traits were potential mediators. RESULTS: Childhood adversity scores were not associated with cardiometabolic outcomes but were associated with poorer sleep quality score (M = 7.2 (SD = 3.5) for those with ≥2 types of events versus 4.8 (2.9) for those with no events; p = 0.022), higher external eating score (26.4 (8.7) versus 21.8 (10.3); p = 0.038), higher perceived stress score (17.1 (6.8) versus 12.3 (4.5); p = 0.016), post-traumatic stress score (1.9 (1.5) versus 0.6 (1.1); p < 0.001), and lower agreeableness score (28.2 (4.2) versus 30.3 (3.1); p = 0.035). CONCLUSION: Childhood adversity was associated with poorer health behaviors including sleep and eating behavior, and more stress-related symptoms, but not with women's cardiometabolic health.

Long-term effects of a preconception lifestyle intervention on cardiometabolic health of overweight and obese women.

BACKGROUND: The global prevalence of obesity in women keeps increasing. The preconception period may be a window of opportunity to improve lifestyle, reduce obesity and improve cardiometabolic health. This study assessed the effect of a preconception lifestyle intervention on long-term cardiometabolic health in two randomized controlled trials (RCTs). METHODS: Participants of the LIFEstyle and RADIEL preconception lifestyle intervention studies with a baseline body mass index (BMI) ≥29 kg/m2 were eligible for this follow-up study. Both studies randomized between a lifestyle intervention targeting physical activity, diet and behaviour modification or usual care. We assessed cardiometabolic health 6 years after randomization. RESULTS: In the LIFEstyle study (n = 111) and RADIEL study (n = 39), no statistically significant differences between the intervention and control groups were found for body composition, blood pressure, arterial stiffness, fasting glucose, homeostasis model assessment of insulin resistance, HbA1c, lipids and high sensitive C-reactive protein levels 6 years after randomization. Participants of the LIFEstyle study who successfully lost ≥5% bodyweight or reached a BMI <29 kg/m2 during the intervention (n = 22, [44%]) had lower weight (-8.1 kg; 99% CI [-16.6 to -0.9]), BMI (-3.3 kg/m2; [-6.5 to -0.8]), waist circumference (-8.2 cm; [-15.3 to -1.3]), fasting glucose (-0.5 mmol/L; [-1.1 to -0.0]), HbA1c (-4.1 mmol/mol; [-9.1 to -0.8]), and higher HDL-C (0.3 mmol/L; [0.1-0.5]) compared with controls. CONCLUSION: We found no evidence of improved cardiometabolic health 6 years after a preconception lifestyle intervention among overweight and obese women in two RCTs. Women who successfully lost weight during the intervention had better cardiometabolic health 6 years later, emphasizing the potential of successful preconception lifestyle improvement.

Exploring the similarities and differences of burn registers globally: Results from a data dictionary comparison study.

INTRODUCTION: Pooling and comparing data from the existing global network of burn registers represents a powerful, yet untapped, opportunity to improve burn prevention and care. There have been no studies investigating whether registers are sufficiently similar to allow data comparisons. It is also not known what differences exist that could bias analyses. Understanding this information is essential prior to any future data sharing. The aim of this project was to compare the variables collected in countrywide and intercountry burn registers to understand their similarities and differences. METHODS: Register custodians were invited to participate and share their data dictionaries. Inclusion and exclusion criteria were compared to understand each register population. Descriptive statistics were calculated for the number of unique variables. Variables were classified into themes. Definition, method, timing of measurement, and response options were compared for a sample of register concepts. RESULTS: 13 burn registries participated in the study. Inclusion criteria varied between registers. Median number of variables per register was 94 (range 28 - 890), of which 24% (range 4.8 - 100%) were required to be collected. Six themes (patient information, admission details, injury, inpatient, outpatient, other) and 41 subthemes were identified. Register concepts of age and timing of injury show similarities in data collection. Intent, mechanism, inhalational injury, infection, and patient death show greater variation in measurement. CONCLUSIONS: We found some commonalities between registers and some differences. Commonalities would assist in any future efforts to pool and compare data between registers. Differences between registers could introduce selection and measurement bias, which needs to be addressed in any strategy aiming to facilitate burn register data sharing. We recommend the development of common data elements used in an international minimum data set for burn injuries, including standard definitions and methods of measurement, as the next step in achieving burn register data sharing.

Impact of hair type, hair sample weight, external hair exposures, and race on cumulative hair cortisol.

The biomarker cortisol assesses the impact of biopsychosocial stressors that activate the stress response system. Hair has emerged as a valid and non-invasive means of gauging cumulative cortisol deposited over month-long periods of time. Established protocols for the extraction of hair cortisol are being validated and refined in humans, yet methodological information about hair characteristics on cortisol remains limited. In addition to external hair exposures (e.g. dye, time spent outside), we examined hair categorization or type (e.g. kinky, straight) by extending a hair typing methodology for scientific use that is currently popular among hair care professionals. We then examined the interaction between hair type and race on cortisol levels with a hair questionnaire. Three studies were pooled to investigate how sample weight, hair type, race, heat exposures, and hair treatments impacted cumulative hair cortisol concentrations. Study 1 consisted of Adult Kenyan Medical Workers (N = 44); Study 2 Mexican and Mexican Americans (N = 106); and Study 3 American Youth (N = 107). We found significantly higher cortisol in 5 mg of hair when compared to larger sample weights, and higher cortisol in those who spent more time outdoors. Cortisol concentrations differed between racial groups and varied by hair type; moreover, there were directional differences in cumulative cortisol from straighter to curlier hair types which depended on racial group. In addition to demonstrating the impact of relatively novel control factors like hair sample weight, outdoor exposure, and hair type, the present study illustrates the importance of disentangling hair type and race to understand variability in cumulative hair cortisol. These influences should be included in future studies that measure hair cortisol.

A lifestyle intervention randomized controlled trial in obese women with infertility improved body composition among those who experienced childhood adversity.

Previous research indicates that tailoring lifestyle interventions to participant characteristics optimizes intervention effectiveness. Our objective was to assess whether the effects of a preconception lifestyle intervention in obese infertile women depended on women's exposure to adversity in childhood. A follow-up of a preconception lifestyle intervention randomized controlled trial (the LIFEstyle study) was conducted in the Netherlands among 577 infertile women (age 18-39 years) with a body mass index (BMI) ≥29 kg/m2 at time of randomization; N = 110 (19%) consented to the follow-up assessment, 6 years later. A 6-month preconception lifestyle intervention aimed weight loss through improving diet and increasing physical activity. The control group received care as usual. Outcome measures included weight, BMI, waist and hip circumference, body fat percentage, blood pressure and metabolic syndrome. The potential moderator, childhood adversity, was assessed with the Life Events Checklist-5 questionnaire. Among the 110 women in our follow-up study, n = 65 (59%) reported no childhood adverse events, n = 28 (25.5%) reported 1 type of childhood adverse events and n = 17 (15.5%) reported ≥2 types of childhood adverse events. Regression models showed significant interactions between childhood adversity and effects of lifestyle intervention at the 6-year follow-up. Among women who experienced childhood adversity, the intervention significantly reduced weight (-10.0 [95% CI -18.5 to -1.5] kg, p = 0.02), BMI (-3.2 [-6.1 to -0.2] kg/m2 , p = 0.04) and body fat percentage (-4.5 [95% CI -7.2 to -1.9] p < 0.01). Among women without childhood adversity, the intervention did not affect these outcomes (2.7 [-3.9 to 9.4] kg, p = 0.42), (0.9 [-1.4 to 3.3] kg/m2 , p = 0.42) and (1.7 [95% CI -0.3 to 3.7] p = 0.10), respectively. Having a history of childhood adversity modified the effect of a preconception lifestyle intervention on women's body composition. If replicated, it may be important to consider childhood adversity as a determinant of lifestyle intervention effectiveness.

The Effect of Lifestyle Intervention on Systemic Oxidative Stress in Women with Obesity and Infertility: A Post-Hoc Analysis of a Randomized Controlled Trial.

We aimed to study whether lifestyle intervention could reduce systemic oxidative stress (OS) and the association between OS and cardiometabolic outcomes in women with obesity and infertility. From 2009 to 2012, infertile women with a BMI ≥ 29 kg/m2 were randomly assigned to a six-month lifestyle intervention followed by infertility treatment (N = 289) or to prompt infertility treatment (N = 285). Fasting serum free thiols (FT) concentrations were determined by colorimetry at baseline, at three and six months after randomization. Generalized estimating equations and restricted cubic spline regressions were used to estimate mean differences in serum FT levels between groups and to explore associations between serum FT levels and cardiometabolic outcomes. Baseline serum FT levels did not differ between the two groups (N = 203 in the intervention group vs N = 226 in the control group, 222.1 ± 48.0 µM vs 229.9 ± 47.8 µM, p = 0.09). Body weight decreased by 3.70 kg in the intervention group compared with the control group at six months (95% confidence interval [CI]: -7.61 to 0.21, p = 0.06). No differences in serum FT levels were observed between groups at either three months (N = 142 vs N = 150, mean differences: -1.03 µM, 95% CI: -8.37 to 6.32, p = 0.78) or six months (N = 104 vs N = 96, mean differences: 2.19 µM, 95% CI: -5.90 to 10.28, p = 0.60). In a pooled analysis of all available measurements, triglycerides (crude B: 5.29, 95% CI: 1.08 to 9.50, p = 0.01), insulin (crude B: 0.62, 95% CI: 0.26 to 0.98, p = 0.001), and homeostasis model assessment of insulin resistance (crude B: 2.50, 95% CI: 1.16 to 3.38, p < 0.001) were positively associated with serum FT levels. High-sensitivity C-reactive protein (hs-CRP) was negatively associated with serum FT levels (crude B: -0.60, 95% CI: -1.11 to -0.10, p = 0.02). The change in hs-CRP during the lifestyle intervention was strongly and inversely associated with serum FT levels (crude B: -0.41, 95% CI: -0.70 to -0.13, p = 0.005). No significant deviations from linear associations were observed between serum FT and hs-CRP. We do not observe an improvement in systemic OS in women with obesity and infertility with modest weight loss. There were potential associations between OS and biomarkers of cardiometabolic health. Trial registration: This trial was registered on 16 November 2008 at the Dutch trial register (NTR1530).

Sex-specific associations between person and environment-related childhood adverse events and levels of cortisol and DHEA in adolescence.

BACKGROUND: Person and environment-related childhood adverse events have been demonstrated to increase the risk of impaired mental health in later life differently for boys and girls. Altered hypothalamic pituitary adrenal (HPA)-axis functioning has been suggested as a key mechanism underlying this association. Cortisol and dehydroepiandrosterone (DHEA) are both output hormones of the HPA-axis. DHEA may have a protective function against long-term exposure to increased levels of cortisol, but has been little investigated in relation to childhood adversity. OBJECTIVE: We aimed to test the associations between person-, and environment-related childhood adversity and levels of cortisol, DHEA and cortisol/DHEA ratio in adolescent boys and girls. METHODS: A total of 215 Dutch adolescents participated in the study and filled out the 27-item Adverse Life Events Questionnaire for the assessment of childhood adversity, which was split up in separate scores for person-related and environment-related events. Cortisol and DHEA concentrations and cortisol/DHEA ratio were determined in proximal 3 cm long hair segments. Additionally, saliva samples were collected immediately and 30 minutes after waking up, at noon and at 8 pm. Multiple linear regression analyses were used to test associations between childhood adversity and cortisol and DHEA concentrations, for boys and girls separately, with age, BMI and pubertal development as covariates. RESULTS: Data were available for 74 boys and 116 girls with a mean age of 15.7 years (SD = 2.0). Higher levels of person-related childhood adversity were associated with higher hair DHEA levels in girls and with higher hair cortisol levels in boys. A trend towards a significant association was observed between higher levels of environment-related childhood adversity and higher DHEA levels in boys. Neither person- nor environment related childhood adversity was associated with cortisol/DHEA ratio. A trend was observed for environment-related childhood adversity and lower daily cortisol output in boys. CONCLUSION: We found differential associations between childhood adversity and cortisol and DHEA levels in girls and boys, for respectively person-related and environment-related childhood adversity. Our findings suggest that different types of childhood adversity are not only linked to levels of cortisol, but also to DHEA concentrations, in a sex-specific manner, with possible future implications for mental health.

Hypothalamic-pituitary-adrenal axis and autonomic nervous system reactivity in children prenatally exposed to maternal depression: A systematic review of prospective studies.

Depression is a common condition affecting up to 20% of all pregnant women, and is associated with subsequent developmental and behavioral problems in children, such as conduct disorder and ADHD. One proposed mechanism underlying these associations is modification of the fetal hypothalamic pituitary adrenal (HPA)-axis and the autonomic nervous system (ANS), resulting in altered responses to stress. This review examined the evidence regarding altered HPA-axis and ANS reactivity in children prenatally exposed to high maternal depressive symptoms. A systematic search was conducted in the electronic databases MEDLINE, EMBASE and PsycINFO, for studies published till 25 July 2017. A total of 13 studies comprising 2271 mother-infant dyads were included. None of the studies were suitable for meta-analysis. Risk of bias assessment showed low risk for four studies. Only three studies described an independent association between exposure to high maternal prenatal depressive symptoms and altered stress reactivity in children. There is limited evidence of an independent association between prenatal exposure to maternal depression and altered HPA or ANS reactivity in children.

Earlier age of sex and substance use initiation is associated with unique hormone profiles during social evaluative threat in Mexican American adolescents.

Latinx adolescents are at a disproportional risk for poor sexual and reproductive health outcomes (STIs, adolescent pregnancy) compared to other ethnic groups. They also report high rates of alcohol and drug use that are similar to non-Hispanic White youth. The hormonal underpinnings of the emergence of sex and substance use behaviors among Latinx adolescents remain understudied however. Pubertal shifts in motivation and reward-seeking in social situations are closely tied to the emergence of risky sexual and substance use behaviors. The experience of developing earlier or later than same age peers may increase stress (cortisol) reactivity during social evaluative situations leading to more risky behavior. Further, testosterone can be responsive to social evaluative threat (SET) and is linked to status-seeking behavior, including risk-taking. The current study sought to unravel the complex relationship between cortisol and testosterone responsivity to social evaluative threat, pubertal status, and the emergence of sex and drug use among US-born Mexican-origin youth growing up in an agricultural community. Mexican American 14-year olds (N = 234, 54% female) from the Center for Health Assessment of Mothers and Children (CHAMACOS) participated in the Trier Social Stress Test. Cortisol and testosterone were assayed from saliva. At 16, youth reported on age at vaginal and oral sex initiation, and alcohol and marijuana use initiation. Hierarchical regressions examined cortisol and testosterone reactivity, and pubertal status within each sex to predict the onset of these risky behaviors. Results indicated that boys who were less developed than their same-aged peers or with lower testosterone reactivity and elevated cortisol reactivity to the TSST reported the earliest sex and substance use initiation. For girls, higher cortisol reactivity predicted earlier alcohol use initiation, and higher testosterone reactivity predicted earlier oral sex. Our results suggests it is important for health care providers to not overlook Latinx boys who may look younger in discussions about mitigating risk. Latinx girls under increased stress may be more likely to try to self-medicate with alcohol, and potentially other drugs.

The effects of a pre-conception lifestyle intervention in women with obesity and infertility on perceived stress, mood symptoms, sleep and quality of life.

BACKGROUND: Obesity is an increasing problem worldwide and is associated with serious health risks. Obesity not only reduces physical health, but can also negatively affect levels of perceived stress, mood symptoms, sleep quality and quality of life (QoL), which may lead to further weight gain. We have previously shown that a pre-conception lifestyle intervention reduced weight and improved physical QoL in the short term. In the current study, we assessed the effects of this intervention in women with obesity and infertility on perceived stress, mood symptoms, sleep quality and QoL five years after randomization. METHODS AND FINDINGS: We followed women who participated in the LIFEstyle study. This is a multi-center randomized controlled trial comparing a six-month lifestyle intervention to improve diet and increase physical activity followed by infertility treatment, versus prompt infertility treatment. Participants were 577 women with infertility between 18 and 39 years of age with a body mass index (BMI) ≥ 29 kg/m2. For the current study we measured perceived stress, mood symptoms, sleep quality and QoL in 178 women five years after randomization. T-tests and linear regression models were used to assess differences between the intervention and control groups. Five years after randomization, no differences were observed for perceived stress, mood symptoms, sleep quality and QoL between the intervention (n = 84) and control groups (n = 94). There was selective participation: women who did not participate in the follow-up had lower baseline mental QoL, and benefitted more from the intervention in terms of improved physical QoL during the original LIFEstyle intervention. CONCLUSIONS: We found no evidence that a pre-conception lifestyle intervention improved female well-being five years after randomization.

Effect of a lifestyle intervention in obese infertile women on cardiometabolic health and quality of life: A randomized controlled trial.

BACKGROUND: The prevalence of obesity, an important cardiometabolic risk factor, is rising in women. Lifestyle improvements are the first step in treatment of obesity, but the success depends on factors like timing and motivation. Women are especially receptive to advice about lifestyle before and during pregnancy. Therefore, we hypothesize that the pre-pregnancy period provides the perfect window of opportunity to improve cardiometabolic health and quality of life of obese infertile women, by means of a lifestyle intervention. METHODS AND FINDINGS: Between 2009-2012, 577 infertile women between 18 and 39 years of age, with a Body Mass Index of ≥ 29 kg/m2, were randomized to a six month lifestyle intervention preceding infertility treatment, or to direct infertility treatment. The goal of the intervention was 5-10% weight loss or a BMI < 29 kg/m2. Cardiometabolic outcomes included weight, waist- and hip circumference, body mass index, systolic and diastolic blood pressure, fasting glucose and insulin, HOMA-IR, hs-CRP, lipids and metabolic syndrome. All outcomes were measured by research nurses at randomization, 3 and 6 months. Self-reported quality of life was also measured at 12 months. Three participants withdrew their informed consent, and 63 participants discontinued the intervention program. Intention to treat analysis was conducted. Mixed effects regression models analyses were performed. Results are displayed as estimated mean differences between intervention and control group. Weight (-3.1 kg 95% CI: -4.0 to -2.2 kg; P < .001), waist circumference (-2.4 cm 95% CI: -3.6 to -1.1 cm; P < .001), hip circumference (-3.0 95% CI: -4.2 to -1.9 cm; P < .001), BMI (-1.2 kg/m2 95% CI: -1.5 to -0.8 kg/m2; P < .001), systolic blood pressure (-2.8 mmHg 95% CI: -5.0 to -0.7 mmHg; P = .01) and HOMA-IR (-0.5 95% CI: -0.8 to -0.1; P = .01) were lower in the intervention group compared to controls. Hs-CRP and lipids did not differ between groups. The odds ratio for metabolic syndrome in the intervention group was 0.53 (95% CI: 0.33 to 0.85; P < .01) compared to controls. Physical QoL scores were higher in the lifestyle intervention group (2.2 95% CI: 0.9 to 3.5; P = .001) while mental QoL scores did not differ. CONCLUSIONS: In obese infertile women, a lifestyle intervention prior to infertility treatment improves cardiometabolic health and self-reported physical quality of life (LIFEstyle study: Netherlands Trial Register: NTR1530).

Emotional, neurohormonal, and hemodynamic responses to mental stress in Tako-Tsubo cardiomyopathy.

Tako-Tsubo cardiomyopathy (TTC) is characterized by apical ballooning of the left ventricle and symptoms and signs mimicking acute myocardial infarction. The high catecholamine levels in the acute phase of TTC and common emotional triggers suggest a dysregulated stress response system. This study examined whether patients with TTC show exaggerated emotional, neurohormonal, and hemodynamic responses to mental stress. Patients with TTC (n = 18; mean age 68.3 ± 11.7, 78% women) and 2 comparison groups (healthy controls, n = 19; mean age 60.0 ± 7.6, 68% women; chronic heart failure, n = 19; mean age 68.8 ± 10.1, 68% women) performed a structured mental stress task (anger recall and mental arithmetic) and low-grade exercise with repeated assessments of negative emotions, neurohormones (catecholamines: norepinephrine, epinephrine, dopamine, hypothalamic-pituitary-adrenal axis hormones: adrenocorticotropic hormone [ACTH], cortisol), echocardiography, blood pressure, and heart rate. TTC was associated with higher norepinephrine (520.7 ± 125.5 vs 407.9 ± 155.3 pg/ml, p = 0.021) and dopamine (16.2 ± 10.3 vs 10.3 ± 3.9 pg/ml, p = 0.027) levels during mental stress and relatively low emotional arousal (p <0.05) compared with healthy controls. During exercise, norepinephrine (511.3 ± 167.1 vs 394.4 ± 124.3 pg/ml, p = 0.037) and dopamine (17.3 ± 10.0 vs 10.8 ± 4.1 pg/ml, p = 0.017) levels were also significantly higher in patients with TTC compared with healthy controls. In conclusion, catecholamine levels during mental stress and exercise were elevated in TTC compared with healthy controls. No evidence was found for a dysregulated hypothalamic-pituitary-adrenal axis or hemodynamic responses. Patients with TTC showed blunted emotional arousal to mental stress. This study suggests that catecholamine hyper-reactivity and not emotional hyper-reactivity to stress is likely to play a role in myocardial vulnerability in TTC.