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BACKGROUND: Adiposity has been characterised as a modifiable risk factor of prostate cancer. Its association with outcomes after prostate cancer diagnosis, however, needs to be better understood and obtain more evidence to assist the development of lifestyle guidance for prostate cancer patients. METHODS: We investigated the associations between adiposity indices close to prostate cancer diagnosis (up to two years pre- or up to five years post-diagnosis) and mortality in 1,968 men of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Men were followed for a median of 9.5 years. Cox proportional-hazards models were adjusted for age and year of diagnosis, stage, grade, smoking and stratified by country. RESULTS: Each 5-unit increment in pre- or post-diagnosis body mass index (BMI) combined was associated with a 30% higher rate of all-cause and a 49% higher rate of prostate cancer-specific mortality. Similarly, each 5-unit increment in pre-diagnosis BMI was associated with a 35% higher rate of all-cause and a 51% higher rate of prostate cancer-specific mortality. The associations were less strong for post-diagnosis BMI with a lower number of men in analyses. Less clear positive associations were shown for waist circumference, hip circumference, and waist-to-hip ratio but data was limited. CONCLUSIONS: Elevated levels of adiposity close to prostate cancer diagnosis could lead to higher risk of mortality; therefore, men are encouraged to maintain a healthy weight. Additional research is needed to confirm if excessive adiposity after prostate cancer diagnosis could worsen prognosis.
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Based on the World Cancer Research Fund Global Cancer Update Programme, we performed systematic reviews and meta-analyses to investigate the association of post-diagnosis adiposity, physical activity, sedentary behaviour, and dietary factors with colorectal cancer prognosis. We searched PubMed and Embase until 28th February, 2022. An independent expert committee and expert panel graded the quality of evidence. A total of 167 unique publications were reviewed, and all but five were observational studies. The quality of the evidence was graded conservatively due to the high risk of several biases. There was evidence of non-linearity in the associations between body mass index and colorectal cancer prognosis. The associations appeared reverse J-shaped, and the quality of this evidence was graded as limited (likelihood of causality: limited-no conclusion). The evidence on recreational physical activity and lower risk of all-cause mortality (relative risk [RR] highest vs. lowest: 0.69, 95% confidence interval [CI]: 0.62-0.77) and recurrence/disease-free survival (RR: 0.80, 95% CI: 0.70-0.92) was graded as limited-suggestive. There was limited-suggestive evidence for the associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), intake of whole grains and coffee with lower risk of all-cause mortality, and between unhealthy dietary patterns and intake of sugary drinks with higher risk of all-cause mortality. The evidence for other exposures on colorectal cancer outcomes was sparse and graded as limited-no conclusion. Analyses were conducted excluding cancer patients with metastases without substantial changes in the findings. Well-designed intervention and cohort studies are needed to support the development of lifestyle recommendations for colorectal cancer patients.
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Adiposidade , Neoplasias Colorretais , Dieta , Exercício Físico , Comportamento Sedentário , Humanos , Prognóstico , Suplementos Nutricionais , Fatores de RiscoRESUMO
Low physical activity and high sedentary behaviour have been clearly linked with colorectal cancer development, yet data on their potential role in colorectal cancer survival is limited. Better characterisation of these relationships is needed for the development of post-diagnosis physical activity and sedentary behaviour guidance for colorectal cancer survivors. We searched PubMed and Embase through 28 February 2022 for studies assessing post-diagnosis physical activity, and/or sedentary behaviour in relation to all-cause and cause-specific mortality and recurrence after colorectal cancer diagnosis. Total and recreational physical activity were assessed overall and by frequency, duration, intensity, and volume using categorical, linear, and non-linear dose-response random-effects meta-analyses. The Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel interpreted and graded the likelihood of causality. We identified 16 observational studies on 82,220 non-overlapping patients from six countries. Physical activity was consistently inversely associated with colorectal cancer morbidity and mortality outcomes, with 13%-60% estimated reductions in risk. Sedentary behaviour was positively associated with all-cause mortality. The evidence had methodological limitations including potential confounding, selection bias and reverse causation, coupled with a limited number of studies for most associations. The CUP Global Expert panel concluded limited-suggestive evidence for recreational physical activity with all-cause mortality and cancer recurrence. Total physical activity and its specific domains and dimensions, and sedentary behaviour were all graded as limited-no conclusion for all outcomes. Future research should focus on randomised trials, while observational studies should obtain objective and repeated physical activity measures and better adjustment for confounders.
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Neoplasias Colorretais , Exercício Físico , Comportamento Sedentário , Humanos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/diagnóstico , Prognóstico , Estudos Observacionais como AssuntoRESUMO
The role of diet in colorectal cancer prognosis is not well understood and specific lifestyle recommendations are lacking. We searched for randomised controlled trials (RCTs) and longitudinal observational studies on post-diagnosis dietary factors, supplement use and colorectal cancer survival outcomes in PubMed and Embase from inception until 28th February 2022. Random-effects dose-response meta-analyses were conducted when at least three studies had sufficient information. The evidence was interpreted and graded by the CUP Global independent Expert Committee on Cancer Survivorship and Expert Panel. Five RCTs and 35 observational studies were included (30,242 cases, over 8700 all-cause and 2100 colorectal cancer deaths, 3700 progression, recurrence, or disease-free events). Meta-analyses, including 3-10 observational studies each, were conducted for: whole grains, nuts/peanuts, red and processed meat, dairy products, sugary drinks, artificially sweetened beverages, coffee, alcohol, dietary glycaemic load/index, insulin load/index, marine omega-3 polyunsaturated fatty acids, supplemental calcium, circulating 25-hydroxyvitamin D (25[OH]D) and all-cause mortality; for alcohol, supplemental calcium, circulating 25(OH)D and colorectal cancer-specific mortality; and for circulating 25(OH)D and recurrence/disease-free survival. The overall evidence was graded as 'limited'. The inverse associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), whole grains, total, caffeinated, or decaffeinated coffee and all-cause mortality and the positive associations between unhealthy dietary patterns, sugary drinks and all-cause mortality provided 'limited-suggestive' evidence. All other exposure-outcome associations provided 'limited-no conclusion' evidence. Additional, well-conducted cohort studies and carefully designed RCTs are needed to develop specific lifestyle recommendations for colorectal cancer survivors.
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Neoplasias Colorretais , Suplementos Nutricionais , Humanos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/epidemiologia , Prognóstico , Dieta , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Observacionais como AssuntoRESUMO
The adiposity influence on colorectal cancer prognosis remains poorly characterised. We performed a systematic review and meta-analysis on post-diagnosis adiposity measures (body mass index [BMI], waist circumference, waist-to-hip ratio, weight) or their changes and colorectal cancer outcomes. PubMed and Embase were searched through 28 February 2022. Random-effects meta-analyses were conducted when at least three studies had sufficient information. The quality of evidence was interpreted and graded by the Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel. We reviewed 124 observational studies (85 publications). Meta-analyses were possible for BMI and all-cause mortality, colorectal cancer-specific mortality, and cancer recurrence/disease-free survival. Non-linear meta-analysis indicated a reverse J-shaped association between BMI and colorectal cancer outcomes (nadir at BMI 28 kg/m2). The highest risk, relative to the nadir, was observed at both ends of the BMI distribution (18 and 38 kg/m2), namely 60% and 23% higher risk for all-cause mortality; 95% and 26% for colorectal cancer-specific mortality; and 37% and 24% for cancer recurrence/disease-free survival, respectively. The higher risk with low BMI was attenuated in secondary analyses of RCTs (compared to cohort studies), among studies with longer follow-up, and in women suggesting potential methodological limitations and/or altered physiological state. Descriptively synthesised studies on other adiposity-outcome associations of interest were limited in number and methodological quality. All the associations were graded as limited (likelihood of causality: no conclusion) due to potential methodological limitations (reverse causation, confounding, selection bias). Additional well-designed observational studies and interventional trials are needed to provide further clarification.
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Adiposidade , Índice de Massa Corporal , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/diagnóstico , Prognóstico , Circunferência da Cintura , Relação Cintura-Quadril , Feminino , Obesidade/complicaçõesRESUMO
Objective: To explore the associations between adiposity indices, assessed at or after a diagnosis of prostate cancer, and mortality. Design: Systematic review and meta-analysis. Data sources: PubMed and Embase, from inception to 16 November 2022. Eligibility criteria for selecting studies: Cohort studies or randomised controlled trials of men with a diagnosis of prostate cancer that investigated the associations between adiposity (body mass index, waist and hip circumference, waist-to-hip ratio, and subcutaneous and visceral adipose tissue) after diagnosis and mortality outcomes. A modified version of the risk of bias for nutrition observational studies tool was used to assess risk of bias. Results: 79 studies were identified that investigated adiposity indices after a diagnosis of prostate cancer in relation to mortality. No randomised controlled trials were found. A non-linear dose-response meta-analysis indicated a J shaped association between body mass index and all cause mortality (33 910 men, 11 095 deaths, 17 studies). The highest rate of all cause mortality was found at the lowest and upper range of the distribution: 11-23% higher rate for a body mass index of 17-21 and 4-43% higher rate for a body mass index of 30-40. The association between body mass index and mortality specific to prostate cancer was flat until body mass index reached 26-27, and then increased linearly by 8-66% for a body mass index of 30-40 (33 137 men, 2947 deaths, 13 studies), but the 95% confidence intervals were wide. These associations did not differ in most predefined subgroups by study design, number of deaths, anthropometric assessment, follow-up time, geographical location, prostate cancer risk group, and adjustment variables. No associations were found in meta-analyses between 10 cm increases in waist circumference and all cause mortality or mortality specific to prostate cancer, but only three studies were available. The few studies with data on change in weight, waist-to-hip ratio, and subcutaneous and visceral adipose tissue reported conflicting results. Conclusions: This review suggests that patients with prostate cancer might benefit from maintaining a healthy weight and avoiding obesity. Future studies should investigate adiposity across different stages of cancer survivorship and use various parameters for distribution of adipose tissue. Systematic review registration: Open Science Framework https://osf.io/qp3c4.
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Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta-analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random-effects meta-analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all-cause mortality (RR per 5 kg/m2 in body mass index: 1.07, 95% CI: 1.05-1.10), breast cancer-specific mortality (RR: 1.10, 95% CI: 1.06-1.14) and second primary breast cancer (RR: 1.14, 95% CI: 1.04-1.26) was graded as strong (likelihood of causality: probable). The evidence for body fatness and breast cancer recurrence and other nonbreast cancer-related mortality was graded as limited (likelihood of causality: limited-suggestive). The evidence on recreational physical activity and lower risk of all-cause (RR per 10 metabolic equivalent of task-hour/week: 0.85, 95% CI: 0.78-0.92) and breast cancer-specific mortality (RR: 0.86, 95% CI: 0.77-0.96) was judged as limited-suggestive. Data on dietary factors was limited, and no conclusions could be reached except for healthy dietary patterns, isoflavone and dietary fibre intake and serum 25(OH)D concentrations that were graded with limited-suggestive evidence for lower risk of the examined outcomes. Our results encourage the development of lifestyle recommendations for breast cancer patients to avoid obesity and be physically active.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Recidiva Local de Neoplasia , Índice de Massa Corporal , Mama , Exercício FísicoRESUMO
Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited-suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist-hip-ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random-effects meta-analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre-defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all-cause mortality (64 studies, 32 507 deaths), breast cancer-specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m2 BMI were 1.07 (1.05-1.10), 1.10 (1.06-1.14) and 1.14 (1.04-1.26), with high between-study heterogeneity (I2 = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist-hip-ratio and all-cause and breast cancer-specific mortality. There was limited-suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited-no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease-free-survival, but more intervention trials and well-designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Índice de Massa Corporal , Tecido Adiposo , Circunferência da Cintura , Relação Cintura-QuadrilRESUMO
It is important to clarify the associations between modifiable lifestyle factors such as physical activity and breast cancer prognosis to enable the development of evidence-based survivorship recommendations. We performed a systematic review and meta-analyses to summarise the evidence on the relationship between postbreast cancer diagnosis physical activity and mortality, recurrence and second primary cancers. We searched PubMed and Embase through 31st October 2021 and included 20 observational studies and three follow-up observational analyses of patients enrolled in clinical trials. In linear dose-response meta-analysis of the observational studies, each 10-unit increase in metabolic equivalent of task (MET)-h/week higher recreational physical activity was associated with 15% and 14% lower risk of all-cause (95% confidence interval [CI]: 8%-22%, studies = 12, deaths = 3670) and breast cancer-specific mortality (95% CI: 4%-23%, studies = 11, deaths = 1632), respectively. Recreational physical activity was not associated with breast cancer recurrence (HR = 0.97, 95% CI: 0.91-1.05, studies = 6, deaths = 1705). Nonlinear dose-response meta-analyses indicated 48% lower all-cause and 38% lower breast cancer-specific mortality with increasing recreational physical activity up to 20 MET-h/week, but little further reduction in risk at higher levels. Predefined subgroup analyses across strata of body mass index, hormone receptors, adjustment for confounders, number of deaths, menopause and physical activity intensities were consistent in direction and magnitude to the main analyses. Considering the methodological limitations of the included studies, the independent Expert Panel concluded 'limited-suggestive' likelihood of causality for an association between recreational physical activity and lower risk of all-cause and breast cancer-specific mortality.
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Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Risco , Prognóstico , Estilo de VidaRESUMO
Little is known about how diet might influence breast cancer prognosis. The current systematic reviews and meta-analyses summarise the evidence on postdiagnosis dietary factors and breast cancer outcomes from randomised controlled trials and longitudinal observational studies. PubMed and Embase were searched through 31st October 2021. Random-effects linear dose-response meta-analysis was conducted when at least three studies with sufficient information were available. The quality of the evidence was evaluated by an independent Expert Panel. We identified 108 publications. No meta-analysis was conducted for dietary patterns, vegetables, wholegrains, fish, meat, and supplements due to few studies, often with insufficient data. Meta-analysis was only possible for all-cause mortality with dairy, isoflavone, carbohydrate, dietary fibre, alcohol intake and serum 25-hydroxyvitamin D (25(OH)D), and for breast cancer-specific mortality with fruit, dairy, carbohydrate, protein, dietary fat, fibre, alcohol intake and serum 25(OH)D. The results, with few exceptions, were generally null. There was limited-suggestive evidence that predefined dietary patterns may reduce the risk of all-cause and other causes of death; that isoflavone intake reduces the risk of all-cause mortality (relative risk (RR) per 2 mg/day: 0.96, 95% confidence interval (CI): 0.92-1.02), breast cancer-specific mortality (RR for high vs low: 0.83, 95% CI: 0.64-1.07), and recurrence (RR for high vs low: 0.75, 95% CI: 0.61-0.92); that dietary fibre intake decreases all-cause mortality (RR per 10 g/day: 0.87, 95% CI: 0.80-0.94); and that serum 25(OH)D is inversely associated with all-cause and breast cancer-specific mortality (RR per 10 nmol/L: 0.93, 95% CI: 0.89-0.97 and 0.94, 95% CI: 0.90-0.99, respectively). The remaining associations were graded as limited-no conclusion.
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Suplementos Nutricionais , Neoplasias , Animais , Dieta , Gorduras na Dieta , VerdurasRESUMO
BACKGROUND: Physical activity (PA) is associated with improved health-related quality of life (HRQoL) among women with breast cancer; however, uncertainty remains regarding PA types and dose (frequency, duration, intensity) and various HRQoL measures. A systematic review and meta-analysis of randomized controlled trials was conducted to clarify whether specific types and doses of physical activity was related to global and specific domains of HRQoL, as part of the Global Cancer Update Programme, formerly known as the World Cancer Research Fund-American Institute for Cancer Research Continuous Update Project. METHODS: PubMed and CENTRAL databases were searched up to August 31, 2019. Weighted mean differences (WMDs) in HRQoL scores were estimated using random effects models. An independent expert panel graded the evidence. RESULTS: A total of 79 randomized controlled trials (14â554 breast cancer patients) were included. PA interventions resulted in higher global HRQoL as measured by the Functional Assessment of Cancer Therapy-Breast (WMD = 5.94, 95% confidence intervals [CI] = 2.64 to 9.24; I2 = 59%, n = 12), Functional Assessment of Cancer Therapy-General (WMD = 4.53, 95% CI = 1.94 to 7.13; I2 = 72%, n = 18), and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (WMD = 6.78, 95% CI = 2.61 to 10.95; I2 = 76.3%, n = 17). The likelihood of causality was considered probable that PA improves HRQoL in breast cancer survivors. Effects were weaker for physical function and mental and emotional health. Evidence regarding dose and type of PA remains insufficient for firm conclusions. CONCLUSION: PA results in improved global HRQoL in breast cancer survivors with weaker effects observed for physical function and mental and emotional health. Additional research is needed to define the impact of types and doses of activity on various domains of HRQoL.
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Neoplasias da Mama , Qualidade de Vida , Humanos , Feminino , Neoplasias da Mama/terapia , Exercício FísicoRESUMO
BACKGROUND: Although neutrophils have been linked to the progression of cancer, uncertainty exists around their association with cancer outcomes, depending on the site, outcome and treatments considered. We aimed to evaluate the strength and validity of evidence on the association between either the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis. METHODS: We searched MEDLINE, Embase and Cochrane Database of Systematic Reviews from inception to 29 May 2020 for systematic reviews and meta-analyses of observational studies on neutrophil counts (here NLR or TAN) and specific cancer outcomes related to disease progression or survival. The available evidence was graded as strong, highly suggestive, suggestive, weak or uncertain through the application of pre-set GRADE criteria. RESULTS: A total of 204 meta-analyses from 86 studies investigating the association between either NLR or TAN and cancer outcomes met the criteria for inclusion. All but one meta-analyses found a hazard ratio (HR) which increased risk (HR > 1). We did not find sufficient meta-analyses to evaluate TAN and cancer outcomes (N = 9). When assessed for magnitude of effect, significance and bias related to heterogeneity and small study effects, 18 (9%) associations between NLR and outcomes in composite cancer endpoints (combined analysis), cancers treated with immunotherapy and some site specific cancers (urinary, nasopharyngeal, gastric, breast, endometrial, soft tissue sarcoma and hepatocellular cancers) were supported by strong evidence. CONCLUSION: In total, 60 (29%) meta-analyses presented strong or highly suggestive evidence. Although the NLR and TAN hold clinical promise in their association with poor cancer prognosis, further research is required to provide robust evidence, assess causality and test clinical utility. TRIAL REGISTRATION: PROSPERO CRD42017069131 .
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Linfócitos/metabolismo , Neoplasias/sangue , Neutrófilos/metabolismo , Feminino , Humanos , Masculino , Neoplasias/mortalidade , Prognóstico , Análise de SobrevidaRESUMO
PURPOSE: The purpose of the present study was to systematically review the complex associations between energy balance-related factors and breast cancer risk, for which previous evidence has suggested different associations in the life course of women and by hormone receptor (HR) status of the tumor. METHODS: Relevant publications on adulthood physical activity, sedentary behavior, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, and weight change and pre- and postmenopausal breast cancer risk were identified in PubMed up to 30 April 2017. Random-effects meta-analyses were conducted to summarize the relative risks across studies. RESULTS: One hundred and twenty-six observational cohort studies comprising over 22,900 premenopausal and 103,000 postmenopausal breast cancer cases were meta-analyzed. Higher physical activity was inversely associated with both pre- and postmenopausal breast cancers, whereas increased sitting time was positively associated with postmenopausal breast cancer. Although higher early adult BMI (ages 18-30 years) was inversely associated with pre- and postmenopausal breast cancers, adult weight gain and greater body adiposity increased breast cancer risk in postmenopausal women, and the increased risk was evident for HR+ but not HR- breast cancers, and among never but not current users of postmenopausal hormones. The evidence was less consistent in premenopausal women. There were no associations with adult weight gain, inverse associations with adult BMI (study baseline) and hip circumference, and non-significant associations with waist circumference and waist-to-hip ratio that were reverted to positive associations on average in studies accounting for BMI. No significant associations were observed for HR-defined premenopausal breast cancers. CONCLUSION: Better understanding on the impact of these factors on pre- and postmenopausal breast cancers and their subtypes along the life course is needed.
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Neoplasias da Mama/epidemiologia , Adiposidade , Peso Corporal , Estudos de Coortes , Exercício Físico , Humanos , Estudos Observacionais como Assunto , Fatores de Risco , Comportamento SedentárioRESUMO
OBJECTIVES: To estimate the prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency and investigate its association with mortality in children with acute or critical conditions. DESIGN: Systematic review and meta-analysis of observational studies. DATA SOURCES: PubMed, OVID, Google Scholar and the Cochrane Library searched until 21 December 2018. ELIGIBILITY CRITERIA: Studies of children hospitalised with acute or critical conditions who had blood 25(OH)D levels measured. DATA EXTRACTION AND SYNTHESIS: We obtained pooled prevalence estimates of 25(OH)D deficiency and ORs for mortality. We calculated 95% CI and prediction intervals and investigated heterogeneity and evidence of small-study effects. RESULTS: Fifty-two studies were included. Of 7434 children, 3473 (47.0%) were 25(OH)D deficient (<50 nmol/L). The pooled prevalence estimate of 25(OH)D deficiency was 54.6% (95% CI 48.5% to 60.6%, I2=95.3%, p<0.0001). Prevalence was similar after excluding smaller studies (51.5%). In children with sepsis (18 studies, 889 total individuals) prevalence was 64.0% (95% CI 52.0% to 74.4%, I2=89.3%, p<0.0001) and 48.7% (95% CI 38.2% to 59.3%; I2=94.3%, p<0.0001) in those with respiratory tract infections (RTI) (25 studies, 2699 total individuals). Overall, meta-analysis of mortality (18 cohort studies, 2463 total individuals) showed increased risk of death in 25(OH)D deficient children (OR 1.81, 95% CI 1.24 to 2.64, p=0.002, I2=25.7%, p=0.153). Four (22.0%) of the 18 studies statistically adjusted for confounders. There were insufficient studies to meta-analyse sepsis and RTI-related mortality. CONCLUSIONS: Our results suggest that 25(OH)D deficiency in acute and critically ill children is high and associated with increased mortality. Small-study effects, reverse causation and other biases may have confounded results. Larger, carefully designed studies in homogeneous populations with confounder adjustment are needed to clarify the association between 25(OH)D levels with mortality and other outcomes. PROSPERO REGISTRATION NUMBER: CRD42016050638.