Women's health and wellbeing: the roles of early life adversity, stress and lifestyle

Cardiovascular disease, including coronary heart disease and stroke, is becoming increasingly prevalent worldwide. Cardiovascular disease is currently the leading cause of death among women, and increasing rates of obesity play a role in the high mortality rates. In this thesis we investigated the association between early life adversity and cardiovascular risk factors in adulthood, and potential underlying hormonal, behavioral and psychological pathways. The effectiveness of lifestyle interventions to improve cardiovascular risk factors and mental wellbeing among obese women of reproductive age was assessed, as well as the role of a history of childhood adversity in the effectiveness of a lifestyle intervention in improving body composition. Early life adversity is associated with poor health behaviors and more stress symptoms, possibly through altered levels of stress hormones, and those behavioral as well as stress related factors may lead to future increased risk of cardiovascular disease. A preconception lifestyle intervention was successful in improving cardiovascular risk factors in the short-term, although we were not able to detect long-term maintenance of these effects. A meta-analysis showed that among overweight and obese women of reproductive age lifestyle interventions improve mental wellbeing. Ongoing research will shed light on the role of childhood adversity in the effectiveness of a lifestyle intervention in improving cardiovascular risk factors

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

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

Funding Information Hartstichting. Grant Number: 2013T085 ZonMw. Grant Number: 50‐50110‐96‐518 European Commission. Grant Number: 633595Peer reviewedPublisher PD

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

Funding: This research was supported by The Netherlands Organization for Health Research and Development (50-50110-96-518), the Dutch Heart Foundation (Grant number: 2013T085), and the European Commission (Horizon2020 project ‘DynaHealth’, 633595). The department of obstetrics and gynaecology from the UMCG receives an unrestricted educational grant from Ferring Pharmaceutical BV the Netherlands, unrelated to the present study.Peer reviewedPublisher PD

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

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 &lt;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.</p

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)