Abstract
The advent of assisted reproduction has allowed the conception of millions of individuals who otherwise would not have existed. Although most ART children are born healthy, there is ...increasing awareness of the plasticity of the human embryo causing concerns about potential long-term consequences of ART for the growth, development and health of this growing population of individuals. Evidence from studies in animals and humans suggest that physiology and metabolism may be permanently affected by ART. It suggests that ART children may be at increased risk of later cardiometabolic diseases. Part of this increased susceptibility to cardiometabolic diseases seems to be due to parental predisposition, while part of the increased susceptibility seems to be due to the ART procedure itself. Due to the fast development of new techniques in ART, it is unclear whether newer techniques are associated with similar risks. There is evidence to suggest that the newer techniques are safer, but the rapid developments in reproductive medicine and ever increasing indications for ART make it difficult to draw conclusions. Until more is known about the effectiveness and safety of ART for the broader indications in which ART is currently used, caution in using ART is mandatory.
Further progress could be made if long-term follow-up studies were included in the development of new ART techniques. Harmonization of measurements in human and animal studies of ART would allow faster scientific progress and less scientific waste. Also, including more details of the ART procedures in ART registries and allowing follow up of ART children through linking registries with already collected data from perinatal registries, child health clinics and schools would help to provide a better understanding of the growth, development and health of the growing population of ART children. Ultimately, these studies will provide the much needed information on how to provide ART children with the best possible start in life.
This paper describes the findings of studies among men and women who were born around the time of the Dutch famine of 1944-1945, investigating the effects of undernutrition during critical periods of ...development on later health and disease. The Dutch famine was remarkable in several ways and its unique features have allowed scientists to investigate the long-term consequences of prenatal undernutrition in humans. The effects of undernutrition depended on its timing during gestation, and the organs and tissues undergoing critical periods of development at that time. Early gestation appeared to be the most vulnerable. The effects of famine were widespread and affected the structure and function of many organs and tissues, resulted in altered behaviour and increased risks of chronic degenerative diseases, which in turn led to reduced participation in the labour market and increased mortality. Also, the effects of famine were independent of size at birth, which suggests that programming may occur without altering size at birth. Studies in other settings show that those faced with undernutrition during the critical earliest stages of development have increased rates of chronic generative disease in adult life. This suggests that these findings reflect biologically fundamental processes that describe human plasticity. These findings teach us the fundamental importance of a good start in life. Adequately feeding women before and during pregnancy will allow future generations to reach their full potential and lead healthier and more productive lives, ultimately leading to healthier and more equal future.
Background
Although cardiorespiratory fitness (CRF) in childhood and adolescence may be linked to future cardiovascular health, there is currently limited evidence for a longitudinal association.
...Objectives
To provide a systematic review on the prospective association between CRF in childhood and adolescence and cardiovascular disease (CVD) risk factors at least 2 years later.
Methods
Using a systematic search of Medline, Embase, and SPORTDiscus, relevant articles were identified by the following criteria: generally healthy children and adolescents between 3 and 18 years of age with CRF assessed at baseline, and a follow-up period of ≥ 2 years. The outcome measures were CVD risk factors. We appraised quality of the included articles with STROBE and QUIPS checklists.
Results
After screening 7524 titles and abstracts, we included 38 articles, assessing 44,169 children and adolescents followed up for a median of 6 years. Eleven articles were of high quality. There was considerable heterogeneity in methodology, measurement of CRF, and outcomes, which hampered meta-analysis. In approximately half of the included articles higher CRF in childhood and adolescence was associated with lower body mass index (BMI), waist circumference, body fatness and lower prevalence of metabolic syndrome in later life. No associations between CRF in childhood and adolescence and future waist-to-hip ratio, blood pressure, lipid profile, and glucose homeostasis were observed.
Conclusion
Although about half of the included articles reported inverse associations between CRF in childhood and adolescence and future BMI, body fatness, and metabolic syndrome, evidence for other CVD risk factors was unconvincing. Many articles did not account for important confounding factors such as adiposity. Recommendations for future research include standardizing the measurement of CRF, i.e. by reporting
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, using standardized outcome assessments, and performing individual patient data meta-analyses.
The environment in which a person develops, from the very earliest stages of life, has a fundamental influence on their growth and development and affects their behaviour and susceptibility to ...disease.2 Domestic and family violence is widespread and often begins during pregnancy, or increases in severity if already present.3 Women who experience violence during pregnancy are more likely to deliver prematurely and have a baby with poorer neonatal outcomes.4 After birth, these children more often have internalising problems, and infants exposed to violence show insecure attachments, increased aggressive behaviour, reduced prosocial behaviour, and poorer health.56 Adverse childhood experiences such as child maltreatment or domestic violence increase the risk of mental and physical illness, substance abuse, and violence, perpetuating a vicious cycle of stress and adversity.7 Consequently, the current outbreak of violence not only harms the health and wellbeing of those affected now, but also affects their future health and wellbeing as well as that of their children. Maternal exposure to domestic violence and pregnancy and birth outcomes: a systematic review and meta-analyses. The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis.
Pregnant women with metabolic risk factors are at high risk of complications. We aimed to assess whether a Mediterranean-style diet reduces adverse pregnancy outcomes in high-risk women.
We conducted ...a multicentre randomised trial in 5 maternity units (4 in London and 1 in Birmingham) between 12 September 2014 and 29 February 2016. We randomised inner-city pregnant women with metabolic risk factors (obesity, chronic hypertension, or hypertriglyceridaemia) to a Mediterranean-style diet with high intake of nuts, extra virgin olive oil, fruits, vegetables, nonrefined grains, and legumes; moderate to high consumption of fish; low to moderate intake of poultry and dairy products; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat versus usual care. Participants received individualised dietary advice at 18, 20, and 28 weeks' gestation. The primary endpoints were composite maternal (gestational diabetes or preeclampsia) and composite offspring (stillbirth, small for gestational age, or admission to neonatal care unit) outcomes prioritised by a Delphi survey. We used an intention-to-treat (ITT) analysis with multivariable models and identified the stratification variables and prognostic factors a priori. We screened 7,950 and randomised 1,252 women. Baseline data were available for 593 women in the intervention (93.3% follow-up, 553/593) and 612 in the control (95.6% follow-up, 585/612) groups. Over a quarter of randomised women were primigravida (330/1,205; 27%), 60% (729/1,205) were of Black or Asian ethnicity, and 69% (836/1,205) were obese. Women in the intervention arm consumed more nuts (70.1% versus 22.9%; adjusted odds ratio aOR 6.8, 95% confidence interval CI 4.3-10.6, p ≤ 0.001) and extra virgin olive oil (93.2% versus 49.0%; aOR 32.2, 95% CI 16.0-64.6, p ≤ 0.001) than controls; increased their intake of fish (p < 0.001), white meat (p < 0.001), and pulses (p = 0.05); and reduced their intake of red meat (p < 0.001), butter, margarine, and cream (p < 0.001). There was no significant reduction in the composite maternal (22.8% versus 28.6%; aOR 0.76, 95% CI 0.56-1.03, p = 0.08) or composite offspring (17.3% versus 20.9%; aOR 0.79, 95% CI 0.58-1.08, p = 0.14) outcomes. There was an apparent reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47-0.91, p = 0.01) but not in other individual components of the composite outcomes. Mothers gained less gestational weight (mean 6.8 versus 8.3 kg; adjusted difference -1.2 Kg, 95% CI -2.2 to -0.2, p = 0.03) with intervention versus control. There was no difference in any of the other maternal and offspring complications between both groups. When we pooled findings from the Effect of Simple, Targeted Diet in Pregnant Women With Metabolic Risk Factors on Pregnancy Outcomes (ESTEEM) trial with similar trials using random effects meta-analysis, we observed a significant reduction in gestational diabetes (odds ratio OR 0.67, 95% CI 0.53-0.84, I2 = 0%), with no heterogeneity (2 trials, 2,397 women). The study's limitations include the use of participant reported tools for adherence to the intervention instead of objective biomarkers.
A simple, individualised, Mediterranean-style diet in pregnancy did not reduce the overall risk of adverse maternal and offspring complications but has the potential to reduce gestational weight gain and the risk of gestational diabetes.
ClinicalTrials.gov NCT02218931.
Sex differences occur in most non-communicable diseases, including metabolic diseases, hypertension, cardiovascular disease, psychiatric and neurological disorders and cancer. In many cases, the ...susceptibility to these diseases begins early in development. The observed differences between the sexes may result from genetic and hormonal differences and from differences in responses to and interactions with environmental factors, including infection, diet, drugs and stress. The placenta plays a key role in fetal growth and development and, as such, affects the fetal programming underlying subsequent adult health and accounts, in part for the developmental origin of health and disease (DOHaD). There is accumulating evidence to demonstrate the sex-specific relationships between diverse environmental influences on placental functions and the risk of disease later in life. As one of the few tissues easily collectable in humans, this organ may therefore be seen as an ideal system for studying how male and female placenta sense nutritional and other stresses, such as endocrine disruptors. Sex-specific regulatory pathways controlling sexually dimorphic characteristics in the various organs and the consequences of lifelong differences in sex hormone expression largely account for such responses. However, sex-specific changes in epigenetic marks are generated early after fertilization, thus before adrenal and gonad differentiation in the absence of sex hormones and in response to environmental conditions. Given the abundance of X-linked genes involved in placentogenesis, and the early unequal gene expression by the sex chromosomes between males and females, the role of X- and Y-chromosome-linked genes, and especially those involved in the peculiar placenta-specific epigenetics processes, giving rise to the unusual placenta epigenetic landscapes deserve particular attention. However, even with recent developments in this field, we still know little about the mechanisms underlying the early sex-specific epigenetic marks resulting in sex-biased gene expression of pathways and networks. As a critical messenger between the maternal environment and the fetus, the placenta may play a key role not only in buffering environmental effects transmitted by the mother but also in expressing and modulating effects due to preconceptional exposure of both the mother and the father to stressful conditions.
Prenatal exposure to undernutrition is widespread in both developing and industrialized countries, causing irreversible damage to the developing brain, resulting in altered brain structure and ...decreased cognitive function during adulthood. The Dutch famine in 1944/45 was a humanitarian disaster, now enabling studies of the effects of prenatal undernutrition during gestation on brain aging in late adulthood.
We hypothesized that study participants prenatally exposed to maternal nutrient restriction (MNR) would demonstrate altered brain structure resembling premature brain aging in late adulthood, expecting the effect being stronger in men. Utilizing the Dutch famine birth cohort (n = 118; mean age: 67.5 ± 0.9 years), this study implements an innovative biomarker for individual brain aging, using structural neuroimaging. BrainAGE was calculated using state-of-the-art pattern recognition methods, trained on an independent healthy reference sample, then applied to the Dutch famine MRI sample, to evaluate the effects of prenatal undernutrition during early gestation on individual brain aging in late adulthood.
Exposure to famine in early gestation was associated with BrainAGE scores indicative of an older-appearing brain in the male sample (mean difference to subjects born before famine: 4.3 years, p < 0.05). Furthermore, in explaining the observed variance in individual BrainAGE scores in the male sample, maternal age at birth, head circumference at birth, medical treatment of hypertension, history of cerebral incidences, actual heart rate, and current alcohol intake emerged to be the most influential variables (adjusted R2 = 0.63, p < 0.01).
The findings of our study on exposure to prenatal undernutrition being associated with a status of premature brain aging during late adulthood, as well as individual brain structure being shaped by birth- and late-life health characteristics, are strongly supporting the critical importance of sufficient nutrient supply during pregnancy. Interestingly, the status of premature brain aging in participants exposed to the Dutch famine during early gestation occurred in the absence of fetal growth restriction at birth as well as vascular pathology in late-life. Additionally, the neuroimaging brain aging biomarker presented in this study will further enable tracking effects of environmental influences or (preventive) treatments on individual brain maturation and aging in epidemiological and clinical studies.
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•Prenatal malnutrition is linked to older-appearing brains in males by 4.3y.•Variance in BrainAGE in males is explained by birth & health characteristics.•Increased BrainAGE occurred in absence of fetal growth.•Increased BrainAGE occurred in absence of vascular pathology in late-life.•BrainAGE biomarker enables tracking various effects on individual brain aging.
•Adverse environments early in life reprogram brain development with potentially lifelong consequences.•Foundation of successful aging is determined early in life or even in previous ...generations.•Descendants born to stress lineages may be at risk of accelerated aging and age-related disease.•Epigenetic mechanisms are central to impaired cellular function contributing to accelerated aging.•Adverse consequences of ancestral stress may be offset by beneficial experiences.
Adverse early life experiences are major influences on developmental trajectories with potentially life-long consequences. Prenatal or early postnatal exposure to stress, undernutrition or environmental toxicants may reprogram brain development and increase risk of behavioural and neurological disorders later in life. Not only experience within a single lifetime, but also ancestral experience affects health trajectories and chances of successful aging. The central mechanism in transgenerational programming of a disease may be the formation of epigenetic memory. This review explores transgenerational effects of early adverse experience on health and disease incidence in older age. First, we address mechanisms of developmental and transgenerational programming of disease and inheritance. Second, we discuss experimental and clinical findings linking early environmental determinants to adverse aging trajectories in association with possible parental contributions and sex-specific effects. Third, we outline the main mechanisms of age-related functional decline and suggest potential interventions to reverse negative effects of transgenerational programming. Thus, strategies that support healthy development and successful aging should take into account the potential influences of transgenerational inheritance.
Stable personality traits have long been presumed to have biological substrates, although the evidence relating personality to biological stress reactivity is inconclusive. The present study ...examined, in a large middle aged cohort (N=352), the relationship between key personality traits and both cortisol and cardiovascular reactions to acute psychological stress. Salivary cortisol and cardiovascular activity were measured at rest and in response to a psychological stress protocol comprising 5min each of a Stroop task, mirror tracing, and a speech task. Participants subsequently completed the Big Five Inventory to assess neuroticism, agreeableness, openness to experience, extraversion, and conscientiousness. Those with higher neuroticism scores exhibited smaller cortisol and cardiovascular stress reactions, whereas participants who were less agreeable and less open had smaller cortisol and cardiac reactions to stress. These associations remained statistically significant following adjustment for a range of potential confounding variables. Thus, a negative personality disposition would appear to be linked to diminished stress reactivity. These findings further support a growing body of evidence which suggests that blunted stress reactivity may be maladaptive.
► The relationship between personality and biological stress reactions was examined. ► Greater neuroticism was associated with diminished physiological stress reactions. ► Lower agreeableness was associated with attenuated biological stress reactivity. ► Lower openness was associated with smaller physiological stress reactions. ► Negative personality disposition appears to be linked to blunted stress reactivity.
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