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1.
Invest Ophthalmol Vis Sci ; 61(6): 18, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32516404

RESUMO

Purpose: Rare genetic variants in complement factor I (CFI) that cause low systemic levels of the protein (FI) have been reported as a strong risk factor for advanced age-related macular degeneration (AMD). This study set out to replicate these findings. Methods: FI levels were measured by sandwich ELISA in an independent cohort of 276 patients with AMD and 205 elderly controls. Single-nucleotide polymorphism genotyping and Sanger sequencing were used to assess genetic variability. Results: The median FI level was significantly lower in those individuals with AMD and a rare CFI variant (28.3 µg/mL) compared to those with AMD without a rare CFI variant (38.8 µg/mL, P = 0.004) or the control population with (41.7 µg/mL, P = 0.0085) or without (41.5 µg/mL, P < 0.0001) a rare CFI variant. Thirty-six percent of patients with AMD with a rare CFI variant had levels below the fifth percentile, compared to 6% in controls with CFI variants. Multiple regression analyses revealed a decreased FI level associated with a rare CFI variant was a risk factor for AMD (early or late AMD: odds ratio [OR] 12.05, P = 0.03; early AMD: OR 30.3, P = 0.02; late AMD: OR 10.64, P < 0.01). Additionally, measurement of FI in aqueous humor revealed a large FI concentration gradient between systemic circulation and the eye (∼286-fold). Conclusions: Rare genetic variants in CFI causing low systemic FI levels are strongly associated with AMD. The impermeability of the Bruch's membrane to FI will have implications for therapeutic replacement of FI in individuals with CFI variants and low FI levels at risk of AMD.

2.
PLoS One ; 15(5): e0231989, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369488

RESUMO

BACKGROUND AND OBJECTIVE: Birth weight and post-natal growth are important predictors of adult health. Preeclampsia (PE) is associated with low birth weight and may have long term effects on the health of the children. The current study aims to compare anthropometry and blood pressure between children of mothers with and without PE in an Indian cohort. METHODS: We studied children born to women with (PE; n = 211) and without preeclampsia (non-PE; n = 470) at Bharati Hospital, Pune, India. Anthropometry and blood pressure were measured in children at 3-7 years of age. Weight and height Z-scores were calculated using the WHO 2006 growth reference. Independent t-tests were used to compare means between the two groups, and associations between preeclampsia and child outcomes were analyzed using multiple linear regression, adjusting for potential confounders. RESULTS: Weight and height Z-scores (p = 0.04 and 0.008), and subscapular skinfold thickness (p = 0.03) were higher among children of PE compared with children of non-PE mothers. Systolic blood pressure was also higher in children of PE mothers (1.70 mmHg [95% CI 0.05, 2.90] p = 0.006). BMI and diastolic blood pressure did not differ between groups. In regression models adjusted for newborn weight and gestational age, current age and sex, and maternal height, BMI and socio-economic status, children of PE mothers had higher weight Z-score (0.27 SD [95%CI 0.06, 0.48] p = 0.01), height Z-score (0.28 SD [95%CI 0.09, 0.47] p = 0.005), and subscapular skinfold thickness (0.38 mm [95%CI 0.00, 0.76] p = 0.049). A trend for higher systolic blood pressure (1.59 mmHg [95%CI -0.02, 3.20] p = 0.053) in the children was also observed in the adjusted model. The difference in systolic blood pressure was attenuated after adjusting further for the child's weight and height (1.09 mmHg [95%CI -0.48, 2.67] p = 0.17). There was no evidence of differences in effects between boys and girls. CONCLUSION: Children of PE mothers were taller and heavier, and had higher systolic blood pressure, partly explained by their increased body size, than children of non-PE mothers. In utero exposure to preeclampsia may increase the risk of future cardiovascular disease.


Assuntos
Peso ao Nascer , Pressão Sanguínea , Estatura , Pré-Eclâmpsia/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Determinação da Pressão Arterial , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Índia , Masculino , Idade Materna , Gravidez , Medição de Risco
3.
J Endocrinol ; 244(2): 249-259, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31661671

RESUMO

Low weight in early infancy is a known risk factor for cardio-metabolic syndrome in adult life. However, little is known either about developmental programming in subjects of normal birthweight or about events between the ages which separate early programming and the occurrence of disease at late adulthood. We tested the hypothesis that circulating concentrations of leptin, adiponectin and insulin in young, healthy adults, born with a birth size within the normal range, are influenced by early life growth patterns. In an observational study of 188 healthy volunteers aged 18-25 years (97 males, 91 females) we investigated the association of metabolic function with their birth size, their growth during childhood and their body composition. High plasma leptin in early adulthood, a risk factor for cardio-metabolic syndrome, was associated with low weight at age 2 years (correlation coefficient controlled for adult weight = -0.21, P < 0.01). It was also positively associated with pre-prandial insulin and with HOMA (Homeostasis Model Assessment) insulin resistance. Leptin, leptin-adiponectin ratio and insulin correlated with lean mass, fat mass and percent fat (P < 0.0001). In conclusion, high leptin in early adulthood was associated with both low weight at age 2 years and insulin resistance. We speculate that high leptin is developmentally programmed and can contribute to the association between low weight in early infancy and increased cardio-metabolic risk in adulthood in healthy subjects.

4.
Fertil Steril ; 113(2): 260-269, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31870562

RESUMO

OBJECTIVE: To study the impact of increased dietary intake of omega-3 fatty acids, vitamin D, and olive oil for 6 weeks before in vitro fertilization (IVF) or IVF-intracytoplasmic sperm injection (ICSI) on morphokinetic markers of early embryo development. DESIGN: A double-blinded randomized controlled trial. SETTING: Academic IVF unit. PATIENT(S): A total of 111 couples undergoing IVF or IVF-ICSI were recruited. INTERVENTIONS(S): Fifty-five couples received the 6-week study intervention of a daily supplement drink enriched with omega-3 fatty acids and vitamin D plus additional olive oil and olive oil-based spread, and 56 couples received the control intervention. MAIN OUTCOME MEASURE(S): The primary end point for the study was the time taken for completion of the second cell cycle after fertilization (CC2). Secondary end points included time to complete the third and fourth cell cycles (CC3 and CC4), the synchrony of the second and third cell cycles (S2 and S3), and the day 3 and day 5 Known Implantation Data Scores (KIDScores). RESULT(S): There was no difference in CC2 between the two groups. However, CC4 was accelerated in the study group compared with the control group, and a significantly shortened S3 as well as an increase in KIDScore on day 3 were observed, indicating improved embryo quality in the study group. CONCLUSION(S): This study demonstrates that a short period of dietary supplementation alters the rate of embryo cleavage. Further research is required to investigate the mechanisms that regulate this effect, and whether the impact on embryo development translates into improved clinical outcomes. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN50956936.


Assuntos
Suplementos Nutricionais , Desenvolvimento Embrionário/fisiologia , Ácidos Graxos Ômega-3/administração & dosagem , Fertilização In Vitro , Azeite de Oliva/administração & dosagem , Vitamina D/administração & dosagem , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Cooperação do Paciente , Gravidez , Taxa de Gravidez , Vitamina D/sangue
5.
J Endocr Soc ; 3(11): 2051-2063, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31637346

RESUMO

Background: Nonobese nonalcoholic fatty liver disease is reported in several populations. However, because persons of African origin display unique fat accumulation, insulin resistance, and lipid profiles, we investigated fatty liver in nonobese persons of African origin. Method: We recruited 78 urban Jamaican volunteers. CT was used to estimate liver and abdominal fat and dual-energy X-ray absorptiometry to measure body composition. Fasting blood was collected for lipids, alanine aminotransferase (ALT), adiponectin, and fetuin-A. Homeostatic model assessment of insulin resistance (HOMA-IR), whole-body insulin sensitivity index (WBISI), insulinogenic index (IGI), and oral disposition index (oDI) were calculated after a 75-g oral glucose tolerance test. Results: Fifty-two percent of participants were male; mean (±SD) age was 28.5 ± 7.8 years, and body mass index was 22.4 ± 3.0 kg/m2. Mean liver attenuation (MLA) and liver/spleen (LS) ratio, both inversely correlated to liver fat, were 62.8 ± 4.3 HU and 1.2 ± 0.1, respectively; 3.8% of participants had liver fat >30% (LS ratio < 1). In age, sex, and BMI-adjusted correlations, MLA was negatively associated with weight (r = -0.30; P = 0.009) and height (r = -0.28; P = 0.017) and was associated with fasting glucose (r = 0.23; P = 0.05), fasting insulin (r = 0.42; P ≤ 0.001) and HOMA-IR (r = 0.35; P = 0.004). Serum lipids, ALT, adiponectin, fetuin-A, WBISI, IGI, and oDI were not associated with liver fat. Conclusions: In nonobese Afro-Caribbean participants, greater liver fat was associated with weight and height and lower fasting insulin and hyperinsulinemia appears to be influential in the reduction of NAFLD. These findings may be influenced by ethnicity, body size, and method of estimating liver fat.

6.
Age Ageing ; 48(1): 80-86, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30272114

RESUMO

Objective: childhood adversities have been linked with adverse health outcomes, but less is known about the long-term consequences of childhood home atmosphere. We investigated whether childhood adversities and home atmosphere were associated with physical and mental functioning in older age. Methods: in the Helsinki Birth Cohort Study 2003, participants born in the year 1934-44 had data available on nine childhood home atmosphere items, e.g. whether it was supportive and warm (sum score ranged between 0 and 36, higher score indicating better atmosphere), and nine childhood adversities, e.g. unemployment and divorce (sum score 0-9, coded into no; one; and two or more adversities) assessed in 2001-04. Of those, 835 had data on physical and mental functioning assessed using the Short Form 36 questionnaire in 2011-13. Results: those who had experienced two or more childhood adversities were more likely to have poorer physical and mental functioning in older age compared to those with no adversities. A better home atmosphere score was associated with better mental functioning (per one unit higher score ß 0.24, 95% CI 0.16-0.32, P < 0.001). In models including both childhood adversities and home atmosphere, a more favourable home atmosphere was associated with better mental functioning while the association for childhood adversities attenuated. There were no associations between childhood adversities or home atmosphere and physical functioning in the models that included both childhood exposures. Conclusions: childhood adversities and home atmosphere have long-term associations with physical and mental functioning in older age.


Assuntos
Atividades Cotidianas , Experiências Adversas da Infância/estatística & dados numéricos , Idoso , Feminino , Finlândia , Avaliação Geriátrica , Nível de Saúde , Humanos , Masculino , Saúde Mental/estatística & dados numéricos , Pessoa de Meia-Idade , Relações Pais-Filho , Psicologia , Fatores Socioeconômicos , Inquéritos e Questionários
8.
Wellcome Open Res ; 3: 56, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30027123

RESUMO

Background: Early life nutrition may affect individuals' susceptibility to adult non-communicable diseases (NCD). Psychological stress is a well-recognised NCD risk factor. Recent evidence suggests that impaired foetal nutrition alters neuro-endocrine pathways, and hypothalamic-pituitary-adrenal axis feedback systems, resulting in abnormal stress responses, and NCD risk. This study aims to examine adolescent cortisol and cardiovascular stress responses in relation to maternal nutrition and contemporaneous NCD risk markers. Methods: The study sample will be drawn from three well-established birth cohorts in India; the Parthenon cohort, Mysore (N=550, age~20y), the SARAS KIDS prenatal intervention cohort, Mumbai (N=300, age~10-12y) and the Pune Rural Intervention in Young Adults/ PRIYA cohort, Pune (N=100, age~22y). We will perform the 'Trier Social Stress Test (TSST)', a well-accepted stress-test module which involves participants performing 5-minutes each of public speaking and mental arithmetic tasks in front of unfamiliar 'judges' (stressor). Repeated measures of salivary cortisol and autonomic cardiovascular outcomes relative to the stressor will be assessed. Measures of psychological stress, cognitive function, blood pressure, glucose-insulin metabolism and depression will be carried out. Mechanistic studies including DNA methylation in gluco-corticoid receptor ( NR3C1) and 11ß-HSD2 gene loci and neuroimaging will be carried out in a subsample. Qualitative interviews and focus group discussions in a subsample of the Parthenon cohort will explore the perception of stress and stressors among the youth. We will convert repeated measures into time-weighted averages before analysis. We will carry out multivariable regression analysis to test the associations. We will further refine the analyses using the mixed-model regression and conditional analyses for the association with repeated measures.   Ethics and dissemination: This study has been approved by the research ethics committee of CSI Holdsworth Memorial Hospital, Mysore. The findings will be disseminated locally and at international meetings, and reports will be submitted to open access peer reviewed journals.

9.
Acta Diabetol ; 55(10): 1051-1058, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30032324

RESUMO

AIMS: To assess whether disturbances in glucose regulation are associated with impairment in physical performance during a 10-year follow-up. METHODS: 475 Men and 603 women from the Helsinki Birth Cohort Study were studied. Glucose regulation was evaluated with a 2-h 75-g oral glucose tolerance test (OGTT) in 2001-2004. Subjects were categorised as having either impaired fasting glucose (IFG), impaired glucose tolerance (IGT), newly diagnosed diabetes or previously known diabetes. Physical performance was assessed approximately 10 years later using the validated senior fitness test (SFT). The relationship between glucose regulation and the overall SFT score was estimated using multiple linear regression models. RESULTS: The mean age was 70.8 years for men and 71.0 years for women when physical performance was assessed. The mean SFT score for the whole population was 45.0 (SD 17.5) points. The SFT score decreased gradually with increased impairment in glucose regulation. Individuals with previously known diabetes had the lowest overall SFT score in the fully adjusted model (mean difference compared to normoglycaemic individuals - 11.56 points, 95% CI - 16.15 to - 6.98, p < 0.001). Both individuals with newly diagnosed diabetes and individuals with IGT had significantly poorer physical performance compared to those with normoglycaemia. No significant difference in physical performance was found between those with IFG and those with normoglycaemia. CONCLUSIONS: Among older people, impaired glucose regulation is strongly related with poor physical performance. More severe disturbances in glucose regulation are associated with a greater decrease in physical function, indicating the importance of diagnosing these disturbances at an early stage.


Assuntos
Envelhecimento/fisiologia , Glicemia/metabolismo , Aptidão Física/fisiologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Glicemia/análise , Estudos de Coortes , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/fisiopatologia , Feminino , Finlândia/epidemiologia , Seguimentos , Intolerância à Glucose/sangue , Intolerância à Glucose/epidemiologia , Intolerância à Glucose/fisiopatologia , Teste de Tolerância a Glucose , Humanos , Masculino , Estado Pré-Diabético/sangue , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/fisiopatologia
10.
J Epidemiol Community Health ; 72(10): 888-895, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29907704

RESUMO

BACKGROUND: Women's groups interventions in Bangladesh reduced neonatal deaths by 38% and improved hygienic delivery, newborn care practices and breast feeding. We explore the longer-term impact of exposure to women's groups during pregnancy on child growth at 2-4 years. METHODS: We performed a cross-sectional survey of child anthropometric measures (analysed as z-scores) among children born to women who had participated in the women's groups interventions while pregnant, compared with an age-matched and sex-matched sample of children born to control mothers. Results were stratified by maternal body mass index (BMI) and adjusted for possible confounding effects of maternal education, household asset ownership and, in a separate model, mother-child height difference, a proxy for improved survival of small babies in intervention groups. RESULTS: Data were obtained from 2587 mother-child pairs (91% response). After adjustment for asset ownership, maternal education and potential survival effects, children whose mothers were exposed to the women's group intervention had higher head (0.16 (0.04 to 0.28)), mid-upper arm (0.11 (0.04 to 0.19)), abdominal (0.13 (0.00 to 0.26)) and chest (0.18 (0.08 to 0.29)) circumferences than their control counterparts. No significant differences in subcutaneous fat (subscapular and triceps skinfold thickness) were observed. When stratified by maternal BMI, intervention children had higher weight, BMI and circumferences, and these effects decreased with increasing maternal BMI category. CONCLUSIONS: Women's groups appear to have had a lasting, positive impact on child anthropometric outcomes, with most significant results clustering in children of underweight mothers. Observed differences are likely to be of public health significance in terms of the nutritional and metabolic development of children.


Assuntos
Composição Corporal , Desenvolvimento Infantil/fisiologia , Mães/educação , Antropometria , Bangladesh , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino
11.
Arch Gerontol Geriatr ; 77: 163-168, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29783137

RESUMO

BACKGROUND: This study assessed how different measures of body composition predict physical performance ten years later among older adults. METHODS: The participants were 1076 men and women aged 57 to 70 years. Body mass index (BMI), waist circumference, and body composition (bioelectrical impedance analysis) were measured at baseline and physical performance (Senior Fitness Test) ten years later. Linear regression analyses were adjusted for age, education, smoking, duration of the follow-up and physical activity. RESULTS: Greater BMI, waist circumference, fat mass, and percent body fat were associated with poorer physical performance in both sexes (standardized regression coefficient [ß] from -0.32 to -0.40, p < 0.001). Lean mass to BMI ratio was positively associated with later physical performance (ß = 0.31 in men, ß = 0.30 in women, p < 0.001). Fat-free mass index (lean mass/height2) in both sexes and lean mass in women were negatively associated with later physical performance. Lean mass residual after accounting for the effect of height and fat mass was not associated with physical performance. CONCLUSIONS: Among older adults, higher measures of adiposity predicted poorer physical performance ten years later whereas lean mass was associated with physical performance in a counterintuitive manner. The results can be used when appraising usefulness of body composition indicators for definition of sarcopenic obesity.


Assuntos
Adiposidade/fisiologia , Composição Corporal/fisiologia , Exercício Físico/fisiologia , Previsões , Obesidade/epidemiologia , Desempenho Físico Funcional , Sarcopenia/epidemiologia , Idoso , Criança , Estudos de Coortes , Feminino , Finlândia/epidemiologia , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Sarcopenia/fisiopatologia
13.
BMJ Open ; 8(4): e019675, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29643156

RESUMO

INTRODUCTION: South Asians have high rates of cardiovascular disease (CVD) and its risk factors (hypertension, diabetes, dyslipidaemia and central obesity). Left ventricular (LV) hypertrophy and dysfunction are features of these disorders and important predictors of CVD mortality. Lower birth and infant weight and greater childhood weight gain are associated with increased adult CVD mortality, but there are few data on their relationship to LV function. The IndEcho study will examine associations of birth size, growth during infancy, childhood and adolescence and CVD risk factors in young adulthood with midlife cardiac structure and function in South Asian Indians. METHODS AND ANALYSIS: We propose to study approximately 3000 men and women aged 43-50 years from two birth cohorts established in 1969-1973: the New Delhi Birth Cohort (n=1508) and Vellore Birth Cohort (n=2156). They had serial measurements of weight and height from birth to early adulthood. CVD risk markers (body composition, blood pressure, glucose tolerance and lipids) and lifestyle characteristics (tobacco and alcohol consumption, physical activity, socioeconomic status) were assessed at age ~30 years. Clinical measurements in IndEcho will include anthropometry, blood pressure, biochemistry (glucose, fasting insulin and lipids, urinary albumin/creatinine ratio) and body composition by dual energy X-ray absorptiometry and bioelectrical impedance. Outcomes are LV mass and indices of LV systolic and diastolic function assessed by two-dimensional and Doppler echocardiography, carotid intimal-media thickness and ECG indicators of ischaemia. Regression and conditional growth models, adjusted for potential confounders, will be used to study associations of childhood and young adult exposures with these cardiovascular outcomes. ETHICS AND DISSEMINATION: The study has been approved by the Health Ministry Steering Committee, Government of India and institutional ethics committees of participating centres in India and the University of Southampton, UK. Results will be disseminated through scientific meetings and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN13432279; Pre-results.


Assuntos
Peso ao Nascer , Desenvolvimento Infantil , Infarto do Miocárdio , Adolescente , Adulto , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Criança , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Gravidez , Estudos Prospectivos , Fatores de Risco
14.
BMJ Open ; 8(4): e018231, 2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29703847

RESUMO

OBJECTIVE: To evaluate associations between early life air pollution and subsequent mortality. DESIGN: Geographical study. SETTING: Local government districts within England and Wales. EXPOSURE: Routinely collected geographical data on the use of coal and related solid fuels in 1951-1952 were used as an index of air pollution. MAIN OUTCOME MEASURES: We evaluated the relationship between these data and both all-cause and disease-specific mortality among men and women aged 35-74 years in local government districts between 1993 and 2012. RESULTS: Domestic (household) coal consumption had the most powerful associations with mortality. There were strong correlations between domestic coal use and all-cause mortality (relative risk per SD increase in fuel use 1.124, 95% CI 1.123 to 1.126), and respiratory (1.238, 95% CI 1.234 to 1.242), cardiovascular (1.138, 95% CI 1.136 to 1.140) and cancer mortality (1.073, 95% CI 1.071 to 1.075). These effects persisted after adjustment for socioeconomic indicators in 1951, current socioeconomic indicators and current pollution levels. CONCLUSION: Coal was the major cause of pollution in the UK until the Clean Air Act of 1956 led to a rapid decline in consumption. These data suggest that coal-based pollution, experienced over 60 years ago in early life, affects human health now by increasing mortality from a wide variety of diseases.


Assuntos
Poluição do Ar , Carvão Mineral , Mortalidade , Adulto , Idoso , Poluentes Atmosféricos , Poluição do Ar/efeitos adversos , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Reino Unido , País de Gales
15.
Am J Kidney Dis ; 71(1): 20-26, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28838764

RESUMO

BACKGROUND: According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, several noncommunicable diseases, including hypertension, type 2 diabetes, and coronary heart disease, have their origins in early life. Chronic kidney disease (CKD) has traditionally been assumed to develop as the result of an interaction between genetic and environmental factors, although more recently, the importance of factors present early in life has been recognized. STUDY DESIGN: Longitudinal birth cohort study. SETTING & PARTICIPANTS: 20,431 people born in 1924 to 1944 in Helsinki, Finland, who were part of the Helsinki Birth Cohort Study were followed up through their life course from birth until death or age 86 years. PREDICTOR: Prenatal growth and socioeconomic factors. OUTCOMES: Death or hospitalization for CKD. RESULTS: Smaller body size at birth was associated with increased risk for developing CKD. Each standard deviation higher birth weight was associated with an HR for CKD of 0.82 (95% CI, 0.74-0.91; P<0.001). Associations with ponderal index at birth, placental weight, and birth length were also statistically significant (P<0.001, P<0.001, and P=0.002, respectively), but only among men. Prematurity also predicted increased risk for CKD. LIMITATIONS: The study was restricted to people who were born in Helsinki in 1924 to 1944. CONCLUSIONS: Smaller body size at birth was associated with increased risk for developing CKD in men. Prematurity was also associated with increased risk for CKD in women. These findings in the Helsinki Birth Cohort Study support the importance of early life factors in the development of CKD.


Assuntos
Recém-Nascido de Baixo Peso/fisiologia , Recém-Nascido Prematuro/fisiologia , Insuficiência Renal Crônica , Adulto , Idoso de 80 Anos ou mais , Criança , Desenvolvimento Infantil , Estudos de Coortes , Finlândia/epidemiologia , Humanos , Recém-Nascido , Estudos Longitudinais , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Fatores Sexuais
16.
Am J Epidemiol ; 187(6): 1165-1173, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29087442

RESUMO

While previous studies have shown intergenerational transmission of birth weight from mother to child, whether the continuity persists across 3 generations has rarely been assessed. We used the Aberdeen Maternity and Neonatal Databank (United Kingdom) to examine the intergenerational correlations of birth weight, birth weight adjusted for gestational age and sex, and small- and large-for-gestational-age births across 3 generations among 1,457 grandmother-mother-child triads. All participants were born between 1950 and 2015. The intergenerational transmission was examined with linear regression analyses. We found that grandmaternal birth weight was associated with grandchild birth weight, independently of prenatal and sociodemographic covariates and maternal birth weight (B = 0.12 standard deviation units, 95% confidence interval: 0.07, 0.18). Similar intergenerational continuity was found for birth weight adjusted for sex and gestational age as well as for small-for-gestational-age births. In conclusion, birth weight and fetal growth showed intergenerational continuity across 3 generations. This supports the hypothesis that the developmental origins of birth weight and hence later health and disease are already present in earlier generations.


Assuntos
Peso ao Nascer/genética , Desenvolvimento Fetal/genética , Avós , Mães/estatística & dados numéricos , Linhagem , Bases de Dados Factuais , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Análise de Regressão , Reino Unido
17.
Biochim Biophys Acta Mol Basis Dis ; 1864(2): 590-600, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29196239

RESUMO

Mouse maternal low protein diet exclusively during preimplantation development (Emb-LPD) is sufficient to programme altered growth and cardiovascular dysfunction in offspring. Here, we use an in vitro model comprising preimplantation culture in medium depleted in insulin and branched-chain amino acids (BCAA), two proposed embryo programming inductive factors from Emb-LPD studies, to examine the consequences for blastocyst organisation and, after embryo transfer (ET), postnatal disease origin. Two-cell embryos were cultured to blastocyst stage in defined KSOM medium supplemented with four combinations of insulin and BCAA concentrations. Control medium contained serum insulin and uterine luminal fluid amino acid concentrations (including BCAA) found in control mothers from the maternal diet model (N-insulin+N-bcaa). Experimental medium (three groups) contained 50% reduction in insulin and/or BCAA (L-insulin+N-bcaa, N-insulin+L-bcaa, and L-insulin+N-bcaa). Lineage-specific cell numbers of resultant blastocysts were not affected by treatment. Following ET, a combined depletion of insulin and BCAA during embryo culture induced a non sex-specific increase in birth weight and weight gain during early postnatal life. Furthermore, male offspring displayed relative hypertension and female offspring reduced heart/body weight, both characteristics of Emb-LPD offspring. Combined depletion of metabolites also resulted in a strong positive correlation between body weight and glucose metabolism that was absent in the control group. Our results support the notion that composition of preimplantation culture medium can programme development and associate with disease origin affecting postnatal growth and cardiovascular phenotypes and implicate two important nutritional mediators in the inductive mechanism. Our data also have implications for human assisted reproductive treatment (ART) practice.


Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Blastocisto/metabolismo , Pressão Sanguínea , Técnicas de Cultura Embrionária , Insulina/metabolismo , Ganho de Peso , Animais , Animais Recém-Nascidos , Determinação da Pressão Arterial , Peso Corporal , Dieta com Restrição de Proteínas , Desenvolvimento Embrionário , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Hipertensão , Camundongos , Fenótipo , Distribuição Tecidual
18.
J Am Heart Assoc ; 6(6)2017 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-28649086

RESUMO

BACKGROUND: Early life risk factors are associated with cardiometabolic disease, but have not been fully studied in atrial fibrillation (AF). There are discordant results from existing studies of birth weight and AF, and the impact of maternal body size, gestational age, placental size, and birth length is unknown. METHODS AND RESULTS: The Helsinki Birth Cohort Study includes 13 345 people born as singletons in Helsinki in the years 1934-1944. Follow-up was through national registries, and ended on December 31, 2013, with 907 incident cases. Cox regression analyses stratified on year of birth were constructed for perinatal variables and incident AF, adjusting for offspring sex, gestational age, and socioeconomic status at birth. There was a significant U-shaped association between birth weight and AF (P for quadratic term=0.01). The lowest risk of AF was found among those with a birth weight of 3.4 kg (3.8 kg for women [85th percentile] and 3.0 kg for men [17th percentile]). High maternal body mass index (≥30 kg/m2) predicted offspring AF; hazard ratio 1.36 (95% CI 1.07-1.74, P=0.01) compared with normal body mass index (<25 kg/m2). Maternal height was associated with early-onset AF (<65.3 years), hazard ratio 1.47 (95% CI 1.24-1.74, P<0.0001), but not with later onset AF. Results were independent of incident coronary artery disease, hypertension, or diabetes mellitus. CONCLUSIONS: High maternal body mass index during pregnancy and maternal height are previously undescribed predictors of offspring AF. Efforts to prevent maternal obesity might reduce later AF in offspring. Birth weight has a U-shaped relation to incident AF independent of other perinatal variables.


Assuntos
Fibrilação Atrial/epidemiologia , Mães , Obesidade/epidemiologia , Efeitos Tardios da Exposição Pré-Natal , Fatores Etários , Idoso , Fibrilação Atrial/diagnóstico , Estatura , Índice de Massa Corporal , Peso Corporal , Feminino , Finlândia/epidemiologia , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Gravidez , Medição de Risco , Fatores de Risco , Fatores de Tempo
19.
J Cyst Fibros ; 16(5): 585-591, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28462874

RESUMO

BACKGROUND: Outcome data for UK cystic fibrosis centres are publicly available in an annual report, which ranks centres by median FEV1% predicted. We wished to assess whether there are differences in lung function outcomes between adult centres that might imply differing standards of care. METHODS: UK Registry data from 4761 subjects at 34 anonymised adult centres were used to calculate mean FEV1% and rate of change of lung function for 2007-13. These measures were used to rank centres and compare outcomes. RESULTS: There are minor differences between centres for mean FEV1% for some years of the study and for rate of change of lung function over the study period. However, rankings are critically dependent on the outcome measure chosen and centre variation becomes negligible once patient population characteristics are taken into account. CONCLUSIONS: We have demonstrated that the ranking of centres is biased and any apparent difference in respiratory outcomes is unlikely to be related to differing standards of care between centres.


Assuntos
Fibrose Cística , Sistema de Registros , Testes de Função Respiratória , Centros de Atenção Terciária , Adolescente , Adulto , Idoso , Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Fibrose Cística/fisiopatologia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/normas , Administração dos Cuidados ao Paciente/organização & administração , Administração dos Cuidados ao Paciente/normas , Sistema de Registros/normas , Sistema de Registros/estatística & dados numéricos , Testes de Função Respiratória/métodos , Testes de Função Respiratória/normas , Testes de Função Respiratória/estatística & dados numéricos , Centros de Atenção Terciária/normas , Centros de Atenção Terciária/estatística & dados numéricos , Reino Unido/epidemiologia
20.
Br J Nutr ; 117(6): 872-881, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28393739

RESUMO

Prenatal low vitamin D may have consequences for bone health. By means of a nationwide mandatory vitamin D fortification programme, we examined the risk of fractures among 10-18-year-old children from proximate birth cohorts born around the date of the termination of the programme. For all subjects born in Denmark during 1983-1988, civil registration numbers were linked to the Danish National Patient Registry for incident and recurrent fractures occurring at ages 10-18 years. Multiplicative Poisson models were used to examine the association between birth cohort and fracture rates. The variation in fracture rates across birth cohorts was analysed by fitting an age-cohort model to the data. We addressed the potential modification of the effect of vitamin D availability by season of birth. The risk of fractures was increased among both girls and boys who were born before the vitamin D fortification terminated in 1985 (rate ratio (RR) exposed v. non-exposed girls: 1·15 (95 % CI 1·11, 1·20); RR exposed v. non-exposed boys: 1·11 (95 % CI 1·07, 1·14). However, these associations no longer persisted after including the period effects. There was no interaction between season of birth and vitamin D availability in relation to fracture risk. The study did not provide evidence that prenatal exposure to extra vitamin D from a mandatory fortification programme of 1·25 µg vitamin D/100 g margarine was sufficient to influence the risk of fractures in late childhood, regardless of season of birth. Replication studies are needed.


Assuntos
Alimentos Fortificados , Fraturas Ósseas , Efeitos Tardios da Exposição Pré-Natal , Fenômenos Fisiológicos da Nutrição Pré-Natal , Deficiência de Vitamina D/dietoterapia , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Adolescente , Criança , Estudos de Coortes , Dinamarca , Feminino , Fraturas Ósseas/prevenção & controle , Humanos , Masculino , Margarina , Gravidez , Complicações na Gravidez/dietoterapia , Risco , Estações do Ano , Deficiência de Vitamina D/complicações
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