Acute skin sun damage in children and its consequences in adults

Children spend more time outdoors than adults and there is compelling evidence that childhood is a particularly vulnerable time for the photocarcinogenic effects of the sun. The negative effects of solar radiation are accumulated during the entire lifetime; however 80% of total lifetime sun exposure is taking place before the age of 18 years. Child skin is more sensitive than adult skin because natural defense mechanisms are not fully developed. A short exposure to midday sun will result in sunburns. Epidemiologic studies show a higher incidence of malignant melanoma in persons with a history of sunburns during childhood and adolescence. Sun exposure among infants and pre-school children is largely dependent on the discretion of adult care providers. Sun protective habits of mothers may predict the level of sun exposure in children. It is very important to transfer the knowledge and positive habits of proper sun protection to children. The purpose of sun-safety behavior is not to avoid outdoor activities, but rather to protect the skin from detrimental sun effects. Proper sun protection of children includes protection from excessive sun exposure, sunburns and other forms of skin damage caused by sun, which may lead to the future development of skin cancers. This paper reviews acute skin reactivity to sun in childhood and adolescence that causes damage in skin structure and function and produces undesirable chronic changes in adults.     

Post-traumatic Stress Disorder in children and adolescents: from Sigmund Freud's "trauma" to psychopathology and the (Dys)metabolic syndrome.

Post-traumatic Stress Disorder (PTSD) is an anxiety syndrome that develops after exposure to traumatic life events. Symptoms include re-experience of the initial trauma, avoidance of stimuli associated with the trauma and symptoms of excessive arousal. Neuroendocrine studies in adults with PTSD have demonstrated that basal cerebrospinal fluid (CSF) CRH levels are elevated and urinary cortisol levels are variable--low in the majority of cases--whereas other studies demonstrate no differences in urinary and plasma cortisol concentrations. Urinary catecholamine excretion is higher in PTSD patients than those of control subjects and other psychiatric disorders. Children may differ from adults in their psychologic and physiologic responses to severe stressors. Also, exposure to stress during critical periods of development may have irreversible effects on behavioral maturation and may affect specific vulnerable brain areas, altering CNS development. Similar to findings in adult studies, PTSD in children is characterized by increased sympathetic nervous system (SNS) activity, as indicated by elevated norepinephrine levels in the periphery. High cortisol levels in urine or saliva have been reported in most studies of childhood PTSD, while prospective longitudinal studies concerning the natural history of neuroendocrine changes in pediatric PTSD after an acute stressor are limited. The identification of neurobiologic changes in response to early adverse experiences is of major importance for the prognosis, prevention, management, and treatment of children and adolescents at risk for or suffering from PTSD.     

Pharmaceutical Contaminants in Potable Water: Potential Concerns for Pregnant Women and Children

There has been increasing concern of late over measurable levels of pharmaceutical contaminants in drinking water. Because most data on water contaminants pertains to aquatic organisms, we wished to assess the risk of these contaminants to human health at currently reported levels. Unlike most other chemicals, there are large amounts of information for the effects of most pharmaceuticals to humans and the current model uses the clinical dose required to cause biological effects as an endpoint to assess risks for pregnant women, children, and the healthy adult population. Twenty-six drugs have been detected in water systems worldwide: 7 in drinking water, 16 in ground water and post-treatment effluent, and 3 in both. Current water treatment practices, clearly, do not always remove pharmaceutical residues. Although healthy adults are unlikely to be adversely affected at the levels of exposure reported, children were shown to have up to eightfold higher risk and may be exposed to several drugs that are contraindicated or not established for safe use in pediatric medicine. The time taken to ingest a single clinically used dose was 3.4–34,000 years. In addition, pregnant women may be exposed to several drugs that are teratogenic (range of % single doses ingested over 36 weeks was 0.0006–12.6%) and in the post-natal period to drugs that are not recommended during breastfeeding. Albeit at low levels, the exposure of pregnant women and children to contraindicated drugs through drinking water is of concern. Further research in this area should focus on integrated ecological and human health consequences of long-term, low-level exposure to pharmaceutical contaminants, particularly in pregnancy and childhood.     

The effects of prenatal exposure to Ramadan on stature during childhood and adolescence: Evidence from the Indonesian Family Life Survey

Many pregnant Muslim women fast during the Muslim holy month of Ramadan. A number of studies have reported negative life outcomes in adulthood for children who were prenatally exposed to Ramadan. However, other studies document minimal to no impact on neonatal indicators. Using data from the Indonesian Family Life Survey consisting of 45,246 observations of 21,723 children born to 9771 mothers, we contribute to the current discussion on prenatal exposure to Ramadan by examining the effects on stature (height-for-age Z-scores, weight-for-age Z-scores, and body-mass-index-for-age Z-scores: HAZ, WAZ, and BAZ, respectively) from early childhood to late adolescence (0–19 years of age). We introduce an objective mother’s religiosity indicator to improve the intention-to-treat estimations. Children were classified into three groups based on their mother’s religion-religiosity: religious Muslims, less-religious Muslims, and non-Muslims. Using cluster-robust mother fixed-effects, we found negative effects on stature for children born to religious Muslim mothers. The effects were age-dependent and timing-sensitive. For example, children born to religious Muslim mothers were shorter in late adolescence (15–19 years of age) compared to their unexposed siblings if they were prenatally exposed in the first trimester of pregnancy (HAZ difference = −0.105 SD; p-val. <0.05). Interestingly, we found positive effects on stature for exposed less-religious Muslim children that peak in early adolescence (10–14 years of age) and negative effects on stature for exposed non-Muslim children that occur only in early childhood (0–4 years of age). We nuance our discussion of health and socioeconomic factors to explain these surprising results.     

Acquired melanocytic nevi as risk factor for melanoma development. A comprehensive review of epidemiological data

Acquired melanocytic nevi (MN) in Caucasian populations are important markers for the risk of melanoma development. The total number of MN on the whole body is the most important independent risk factor for melanoma and the risk of melanoma development increases almost linearly with rising numbers of MN. Additionally, the presence of atypical MN and of actinic lentigines are likewise independent risk factors for melanoma. Atypical mole syndrome should be defined by the presence of many acquired MN and a threshold number of atypical MN. Acquired MN develops mainly during childhood and adolescence in the first two decades of life. The number of acquired nevi seems to be related to hereditary factors and nevus-prone families exist. The amount of sun exposure is the most important environmental risk factor for nevus development, particularly in early childhood. Interestingly, sunburns may play a role in nevus development, but seem not to be required, and even moderate sun exposure promotes the process. Therefore, preventive measures for nevus and melanoma development should target young children and adolescents.     

Long-Term Outcomes Associated with Traumatic Brain Injury in Childhood and Adolescence: A Nationwide Swedish Cohort Study of a Wide Range of Medical and Social Outcomes

BackgroundTraumatic brain injury (TBI) is the leading cause of disability and mortality in children and young adults worldwide. It remains unclear, however, how TBI in childhood and adolescence is associated with adult mortality, psychiatric morbidity, and social outcomes.ConclusionsGiven our findings, which indicate potentially causal effects between TBI exposure in childhood and later impairments across a range of health and social outcomes, age-sensitive clinical guidelines should be considered and preventive strategies should be targeted at children and adolescents.     

The long-term economic effects of polio: Evidence from the introduction of the polio vaccine to Sweden in 1957

This study explores the impact an exogenous improvement in childhood health has on later-life outcomes. Using extensive and detailed register data from the Swedish Interdisciplinary Panel covering up to 2011, we follow individuals exposed to the introduction of the first vaccine against polio in Sweden (birth cohorts 1937–1966) until adulthood in order to quantify the causal effect of polio vaccination on long-term economic outcomes. The results show that, contrary to what has been found in the literature for other health-related interventions, including other vaccines, exposure to the vaccine against polio did not seem to have any long-term effects on the studied adult economic outcomes. Upon closer inspection of how the disease affects children, this might be explained by the fact that no scarring effects from exposure to high incidence of polio were found on adult income, educational achievement, or hospitalizations, which seems to suggest that those who contracted the illness but suffered only the milder symptoms of the disease made a full recovery and had no lifelong sequels as a consequence of the condition. The absence of scarring effects is hypothesized to be related to the pathology and epidemiology of the disease itself, which infects many, but scars only those who suffer the most recognizable paralytic symptoms.     

Elevated C-Reactive Protein in Children from Risky Neighborhoods: Evidence for a Stress Pathway Linking Neighborhoods and Inflammation in Children

Background

Childhood socioeconomic status is linked to adult cardiovascular disease and disease risk. One proposed pathway involves inflammation due to exposure to a stress-inducing neighborhood environment. Whether CRP, a marker of systemic inflammation, is associated with stressful neighborhood conditions among children is unknown.

Methods and Results

The sample included 385 children 5–18 years of age from 255 households and 101 census tracts. Multilevel logistic regression analyses compared children and adolescents with CRP levels >3 mg/L to those with levels ≤3 mg/L across neighborhood environments. Among children living in neighborhoods (census tracts) in the upper tertile of poverty or crime, 18.6% had elevated CRP levels, in contrast to 7.9% of children living in neighborhoods with lower levels of poverty and crime. Children from neighborhoods with the highest levels of either crime or poverty had 2.7 (95% CI: 1.2–6.2) times the odds of having elevated CRP levels when compared to children from other neighborhoods, independent of adiposity, demographic and behavioral differences.

Conclusions

Children living in neighborhoods with high levels of poverty or crime had elevated CRP levels compared to children from other neighborhoods. This result is consistent with a psychosocial pathway favoring early development of cardiovascular risk that involves chronic stress from exposure to socially- and physically-disordered neighborhoods characteristic of poverty.     

Relationship between sunlight exposure, housing condition, and serum vitamin D and related physiologic biomarker levels in captive chimpanzees (Pan troglodytes)

In primates, the primary source of vitamin D is synthesis in the skin through sun exposure. Decreased sun exposure may lead to vitamin D deficiency and consequently other health issues. In laboratory, sanctuary, and zoo settings, chimpanzees (Pan troglodytes) may be housed indoors for prolonged periods of time without regular exposure to unfiltered sunlight. However, little research has examined the relationship between housing conditions and vitamin D serum levels in captive chimpanzees. In this study, we retrospectively compared serum levels of total vitamin D, calcium, ionic calcium, phosphorous, albumin, and alkaline phosphatase in 18 female and 12 male chimpanzees as they cycled between indoor-only and indoor-outdoor enclosures. Total vitamin D was significantly lower and alkaline phosphatase significantly higher when subjects were in the indoor-only enclosures compared with when they had regular access to outdoor enclosures. A vitamin D effect occurred only in young and prime-adult animals. Changes were significant in female but not in male chimpanzees. Calcium, ionic calcium, phosphorus, and albumin did not differ between indoor-only and indoor-outdoor enclosures. However, female chimpanzees exhibited significantly lower calcium and phosphorous levels while in the indoor-only enclosures. These results suggest that adult captive chimpanzees experience vitamin D deficiency when housed without regular access to unfiltered sunlight and that these effects may be more acute for adult female animals.     

Developmental and transplacental genotoxicology: fluconazole

Over the last 40 years mankind has been facing new types of radiochemical environmental settings with every decade. During the last decade, biomonitoring was additionally focused on assessing associations between environmental exposure(s) and both early and late biological effects in children. Despite efforts to control and avoid child exposure to genotoxic agents the incidence of childhood cancers is increasing. Some cancers in adulthood may be the consequence of a multi-step process which starts with intrauterine and childhood exposure. This highlights the importance of a comprehensive interpretation of multiple health effects, especially considering recent studies suggesting that most health disorders are related to DNA changes. When exposed to genotoxic agents, a developing organism (fetus or child) is constantly being forced to reorganize into new equilibriums in order to adjust to a xenobiotic environment. In addition, the influence of sex hormones on radiochemical sensitivity is still unknown. For this reason special attention should be paid to puberty. The results of recent studies on animal models and follow up studies on children after nuclear accidents show long-lasting cytogenetic damage even after low dose exposures and their transgenerational persistance. To evaluate age-related difference and transplacental genotoxic potency fluconazole (FC) was investigated by in vivo micronucleus (MN) assay in adult mice, young mice and in transplacentally exposed newborn pups. Compared to the baseline values, FC caused no detectable genome damage in adult animals, but there was a significant increase in MN frequency in young animals and in newborn pups. Our study thus exemplifies an age-related chemosensitivity, and argues that cancer-promoting disturbances of complex prenatal developmental mechanisms and maturation during childhood require a new approach using systems biology.     

Sucrose exposure in early life alters adult motivation and weight gain

The cause of the current increase in obesity in westernized nations is poorly understood but is frequently attributed to a 'thrifty genotype,' an evolutionary predisposition to store calories in times of plenty to protect against future scarcity. In modern, industrialized environments that provide a ready, uninterrupted supply of energy-rich foods at low cost, this genetic predisposition is hypothesized to lead to obesity. Children are also exposed to this 'obesogenic' environment; however, whether such early dietary experience has developmental effects and contributes to adult vulnerability to obesity is unknown. Using mice, we tested the hypothesis that dietary experience during childhood and adolescence affects adult obesity risk. We gave mice unlimited or no access to sucrose for a short period post-weaning and measured sucrose-seeking, food consumption, and weight gain in adulthood. Unlimited access to sucrose early in life reduced sucrose-seeking when work was required to obtain it. When high-sugar/high-fat dietary options were made freely-available, however, the sucrose-exposed mice gained more weight than mice without early sucrose exposure. These results suggest that early, unlimited exposure to sucrose reduces motivation to acquire sucrose but promotes weight gain in adulthood when the cost of acquiring palatable, energy dense foods is low. This study demonstrates that early post-weaning experience can modify the expression of a 'thrifty genotype' and alter an adult animal's response to its environment, a finding consistent with evidence of pre- and peri-natal programming of adult obesity risk by maternal nutritional status. Our findings suggest the window for developmental effects of diet may extend into childhood, an observation with potentially important implications for both research and public policy in addressing the rising incidence of obesity.     

Childhood Adversity Is Associated with Adult Theory of Mind and Social Affiliation,but Not Face Processing

People vary substantially in their ability to acquire and maintain social ties. Here, we use a combined epidemiological and individual differences approach to understand the childhood roots of adult social cognitive functioning. We assessed exposure to 25 forms of traumatic childhood experiences in over 5000 adults, along with measures of face discrimination, face memory, theory of mind, social motivation, and social support. Retrospectively-reported experiences of parental maltreatment in childhood (particularly physical abuse) were the most broadly and robustly associated with adult variations in theory of mind, social motivation, and social support. Adult variations in face discrimination and face memory, on the other hand, were not significantly associated with exposure to childhood adversity. Our findings indicate domains of social cognition that may be particularly vulnerable to the effects of adverse childhood environments, and suggest mechanisms whereby environmental factors might influence the development of social abilities.     

Non-cancer effects of chemical agents on children's health

This paper provides an overview about the non-cancer health effects for children from relevant chemical agents in our environment. In addition, a meta-analysis was conducted on the association between sudden infant death syndrome (SIDS) and maternal smoking during pregnancy as well as postnatal exposure to environmental tobacco smoke (ETS).In children, birth deformities, neurodevelopment, reproductive outcomes and respiratory system are mainly affected by chemical exposures. According to recent systematic reviews, evidence is sufficient for cognitive impairments caused by low lead exposure levels. Evidence for neurotoxicity from prenatal methylmercury exposure is sufficient for high exposure levels and limited for low levels. Prenatal exposure to polychlorinated biphenyls (PCB) and related toxicants results in cognitive and motor deficits.Maternal smoking during pregnancy is a risk factor for preterm birth, foetal growth deficit and SIDS. The meta-analytic pooled risk estimate for SIDS based on 15 studies is 2.94 (95% confidence interval: 2.43–3.57). Postnatal exposure to ETS was found to increase the SIDS risk by a factor of 1.72 (95% CI: 1.28–2.30) based on six studies which took into account maternal smoking during pregnancy. Additionally, postnatal ETS exposure causes acute respiratory infections, ear problems, respiratory symptoms, more severe asthma, and it slows lung growth. These health effects are also of concern for postnatal exposure to ambient and indoor air pollution.Children differ from adults with respect to several aspects which are relevant for assessing their health risk. Thus, independent evaluation of toxicity in childhood populations is essential.     

Genomic damage in children accidentally exposed to ionizing radiation: a review of the literature

During the last decade, our knowledge of the mechanisms by which children respond to exposures to physical and chemical agents present in the environment, has significantly increased. Results of recent projects and programmes focused on children's health underline a specific vulnerability of children to environmental genotoxicants. Environmental research on children predominantly investigates the health effects of air pollution while effects from radiation exposure deserve more attention. The main sources of knowledge on genome damage of children exposed to radiation are studies performed after the Chernobyl nuclear plant accident in 1986. The present review presents and discusses data collected from papers analyzing genome damage in children environmentally exposed to ionizing radiation. Overall, the evidence from the studies conducted following the Chernobyl accident, nuclear tests, environmental radiation pollution and indoor accidental contamination reveals consistently increased chromosome aberration and micronuclei frequency in exposed than in referent children. Future research in this area should be focused on studies providing information on: (a) effects on children caused by low doses of radiation; (b) effects on children from combined exposure to low doses of radiation and chemical agents from food, water and air; and (c) specific effects from exposure during early childhood (radioisotopes from water, radon in homes). Special consideration should also be given to a possible impact of a radiochemical environment to the development of an adaptive response for genomic damage. Interactive databases should be developed to provide integration of cytogenetic data, childhood cancer registry data and information on environmental contamination. The overall aim is to introduce timely and efficient preventive measures, by means of a better knowledge of the early and delayed health effects in children resulting from radiation exposure.     

Assessing Children's Exposures and Risks to Drinking Water Contaminants: A Manganese Case Study

Background: Compared to adults, children maybe more highly exposed to toxic substances in drinking water because they consume more water per unit of body weight. The U.S. Environmental Protection Agency (USEPA) has developed new guidance for selecting age groups and age-specific exposure factors for assessing children's exposures and risks to environmental contaminants. Research Aim: To demonstrate the application and importance of applying age-specific drinking water intake rates, health reference values, and exposure scenarios when assessing drinking water exposures because these approaches illustrate the potential for greater potential for adverse health effects among children. Methods: manganese, an essential nutrient and neurotoxicant, was selected as a case study and chemical of potential concern for children's health. A screening-level risk assessment was performed using age-specific drinking water intake rates and manganese concentrations from U.S. public drinking water systems. Results: When age-specific drinking water intake rates are used to calculate dose, formula-fed infants receive the highest dose of manganese from drinking water compared to all other age groups. Estimated hazard quotients suggest adverse health effects are possible. Use of USEPA's standardized childhood age groups and childhood exposure factors significantly improves the understanding of childhood exposure and risks.     

Familial hypercholesterolemia in children

PURPOSE OF THIS REVIEW: This review provides an update on recent advances in the diagnosis and management of children with familial hypercholesterolemia. RECENT FINDINGS: A large cross-sectional cohort study of paediatric familial hypercholesterolemia demonstrated that affected children had a 5-fold more rapid increase of carotid arterial wall intima-media thickness during childhood years than their affected siblings. This faster progression led to a significant deviation in terms of intima-media thickness from the age of 12 years and onwards. Low-density lipoprotein cholesterol was a strong and independent predictor of carotid artery intima-media thickness in these children, which confirms the pivotal role of low-density lipoprotein cholesterol for the development of atherosclerosis. In this condition lipid lowering by statin therapy is accompanied by carotid intima-media thickness regression in familial-hypercholesterolemic children, which suggests that initiation of low-density lipoprotein cholesterol-reducing medication in childhood already can inhibit or possibly reduce the faster progression of atherosclerosis. Furthermore, these trials demonstrated that statins are safe and do not impair growth or sexual development in these children. Conversely, products containing plant sterols reduced low-density lipoprotein cholesterol levels by 14%, but did not improve endothelial dysfunction as assessed by flow-mediated dilatation. SUMMARY: Children with familial hypercholesterolemia clearly benefit from lipid-lowering strategies. Statins are safe agents and have been proven to reduce elevated low-density lipoprotein cholesterol levels significantly. In addition, statins improve surrogate markers for atherosclerosis. Therefore these agents should become the pivotal therapy in children with familial hypercholesterolemia.     

A lifecourse mendelian randomization study highlights the long-term influence of childhood body size on later life heart structure

Children with obesity typically have larger left ventricular heart dimensions during adulthood. However, whether this is due to a persistent effect of adiposity extending into adulthood is challenging to disentangle due to confounding factors throughout the lifecourse. We conducted a multivariable mendelian randomization (MR) study to separate the independent effects of childhood and adult body size on 4 magnetic resonance imaging (MRI) measures of heart structure and function in the UK Biobank (UKB) study. Strong evidence of a genetically predicted effect of childhood body size on all measures of adulthood heart structure was identified, which remained robust upon accounting for adult body size using a multivariable MR framework (e.g., left ventricular end-diastolic volume (LVEDV), Beta = 0.33, 95% confidence interval (CI) = 0.23 to 0.43, P = 4.6 × 10⁻¹⁰). Sensitivity analyses did not suggest that other lifecourse measures of body composition were responsible for these effects. Conversely, evidence of a genetically predicted effect of childhood body size on various other MRI-based measures, such as fat percentage in the liver (Beta = 0.14, 95% CI = 0.05 to 0.23, P = 0.002) and pancreas (Beta = 0.21, 95% CI = 0.10 to 0.33, P = 3.9 × 10⁻⁴), attenuated upon accounting for adult body size. Our findings suggest that childhood body size has a long-term (and potentially immutable) influence on heart structure in later life. In contrast, effects of childhood body size on other measures of adulthood organ size and fat percentage evaluated in this study are likely explained by the long-term consequence of remaining overweight throughout the lifecourse.

Children with obesity typically have larger left ventricular heart dimensions during adulthood, but this is challenging to disentangle due to confounding factors throughout life. This study uses Mendelian randomization to provide evidence that being overweight in early life may indeed have a long-term influence on cardiac structure.     

Past exposure to sun,skin phenotype,and risk of multiple sclerosis: case-control study

Objective To examine whether past high sun exposure is associated with a reduced risk of multiple sclerosis.Design Population based case-control study.Setting Tasmania, latitudes 41-3°S.Participants 136 cases with multiple sclerosis and 272 controls randomly drawn from the community and matched on sex and year of birth.Main outcome measure Multiple sclerosis defined by both clinical and magnetic resonance imaging criteria.Results Higher sun exposure when aged 6-15 years (average 2-3 hours or more a day in summer during weekends and holidays) was associated with a decreased risk of multiple sclerosis (adjusted odds ratio 0.31, 95% confidence interval 0.16 to 0.59). Higher exposure in winter seemed more important than higher exposure in summer. Greater actinic damage was also independently associated with a decreased risk of multiple sclerosis (0.32, 0.11 to 0.88 for grades 4-6 disease). A dose-response relation was observed between multiple sclerosis and decreasing sun exposure when aged 6-15 years and with actinic damage.Conclusion Higher sun exposure during childhood and early adolescence is associated with a reduced risk of multiple sclerosis. Insufficient ultraviolet radiation may therefore influence the development of multiple sclerosis.     

Early life stress, MAOA, and gene-environment interactions predict behavioral disinhibition in children

Several, but not all, studies have shown that the monoamine oxidase A functional promoter polymorphism ( MAOA-LPR ) interacts with childhood adversity to predict adolescent and adult antisocial behavior. However, it is not known whether MAOA-LPR interacts with early life (pre-birth–3 years) stressors to influence behavior in prepubertal children.
The Avon Longitudinal Study of Parents and Children, UK, is a community-representative cohort study of children followed from pre-birth onwards. The impact of family adversity from pre-birth to age 3 years and stressful life events from 6 months to 7 years on behavioral disinhibition was determined in 7500 girls and boys. Behavioral disinhibition measures were: mother-reported hyperactivity and conduct disturbances (Strengths and Difficulties Questionnaire) at ages 4 and 7 years.
In both sexes, exposure to family adversity and stressful life events in the first 3 years of life predicted behavioral disinhibition at age 4, persisting until age 7. In girls, MAOA-LPR interacted with stressful life events experienced from 6 months to 3.5 years to influence hyperactivity at ages 4 and 7. In boys, the interaction of MAOA-LPR with stressful life events between 1.5 and 2.5 years predicted hyperactivity at age 7 years. The low activity MAOA-LPR variant was associated with increased hyperactivity in girls and boys exposed to high stress. In contrast, there was no MAOA-LPR interaction with family adversity.
In a general population sample of prepubertal children, exposure to common stressors from pre-birth to 3 years predicted behavioral disinhibition, and MAOA-LPR – stressful life event interactions specifically predicted hyperactivity.     

Estimation of causal effects of a time-varying exposure at multiple time points through multivariable mendelian randomization

Mendelian Randomisation (MR) is a powerful tool in epidemiology that can be used to estimate the causal effect of an exposure on an outcome in the presence of unobserved confounding, by utilising genetic variants as instrumental variables (IVs) for the exposure. The effect estimates obtained from MR studies are often interpreted as the lifetime effect of the exposure in question. However, the causal effects of some exposures are thought to vary throughout an individual’s lifetime with periods during which an exposure has a greater effect on a particular outcome. Multivariable MR (MVMR) is an extension of MR that allows for multiple, potentially highly related, exposures to be included in an MR estimation. MVMR estimates the direct effect of each exposure on the outcome conditional on all the other exposures included in the estimation. We explore the use of MVMR to estimate the direct effect of a single exposure at different time points in an individual’s lifetime on an outcome. We use simulations to illustrate the interpretation of the results from such analyses and the key assumptions required. We show that causal effects at different time periods can be estimated through MVMR when the association between the genetic variants used as instruments and the exposure measured at those time periods varies. However, this estimation will not necessarily identify exact time periods over which an exposure has the most effect on the outcome. Prior knowledge regarding the biological basis of exposure trajectories can help interpretation. We illustrate the method through estimation of the causal effects of childhood and adult BMI on C-Reactive protein and smoking behaviour.