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1.
J Am Heart Assoc ; : e016564, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030065

RESUMO

Background We aimed to quantify the role of the plasma metabolic profile in explaining the effect of adiposity on cardiac structure. Methods and Results Body mass index (BMI) was measured at age 11 in the Avon Longitudinal Study of Parents and Children. Left ventricular mass indexed to height2.7 (LVMI) was assessed by echocardiography at age 17. The metabolic profile was quantified via 1H-nuclear magnetic resonance spectroscopy at age 15. Multivariable confounder (maternal age, parity, highest qualification, maternal smoking, prepregnancy BMI, prepregnancy height, household social class, adolescent birthweight, adolescent smoking, fruit and vegetable consumption, and physical activity)-adjusted linear regression estimated the association of BMI with LVMI and mediation by metabolic traits. We considered 156 metabolomic traits individually and jointly as principal components explaining 95% of the variance in the nuclear magnetic resonance platform and assessed whether the principal components for the metabolic traits added to the proportion of the association explained by putative cardiovascular risk factors (systolic and diastolic blood pressures, insulin, triglycerides, low-density lipoprotein cholesterol, and glucose). A 1 kg/m2 higher BMI was associated with a 0.70 g/m2.7 (95% CI, 0.53-0.88 g/m2.7) and 0.66 g/m2.7 (95% CI, 0.53-0.79 g/m2.7) higher LVMI in males (n=437) and females (n=536), respectively. Putative risk factors explained 3% (95% CI, 2%-5%) of this association in males, increasing to 10% (95% CI, 8%-13%) when including metabolic principal components. In females, the standard risk factors explained 3% (95% CI, 2%-5%) of the association and did not increase when including the metabolic principal components. Conclusions The addition of the nuclear magnetic resonance-measured metabolic traits appears to mediate more of the association of BMI on LVMI than the putative risk factors alone in adolescent males, but not females.

2.
BMC Med ; 18(1): 247, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32862829

RESUMO

BACKGROUND: Women with diminished ovarian reserve are known to have increased cardiovascular risk, whether there is a continuous association between the ovarian reserve biomarkers; anti-Müllerian hormone (AMH), antral follicle count (AFC) and cardio-metabolic risk factors are unknown. METHODS: A cross-sectional study of 398 women intending to undergo IVF with pre-treatment early follicular AMH and AFC measurements. Serum lipids, lipoprotein subclasses and low-molecular-weight metabolites were quantified by NMR spectroscopy (155 metabolic measures). Associations were analysed using multivariable regression. RESULTS: Participants were mean 35.5 (SD 4.43) years old and had a median AMH of 16 pmol/l (IQR 8.8, 28.0 pmol/l) and a median AFC of 12 (IQR 7.16). AMH showed positive associations with HDL, omega-6 and polyunsaturated fatty acids and the amino acids isoleucine, leucine and tyrosine, with effects ranging from 0.11 (95%CI 0.004 to 0.21) for total lipids in small HDL to 0.16 (0.06 to 0.26) for isoleucine, for a mean difference of one SD of metabolite per one SD increment in AMH, and negatively with acetate: - 0.31(- 0.22, - 0.004) SD per 1 SD AMH. AFC was positively associated with alanine, glutamine and glycine. Results were consistent, though less precisely estimated, when restricted to those women who were preparing for treatment because of their partner's infertility. CONCLUSIONS: In women intending to have IVF, AMH and AFC were not associated with traditional lipid measured but were associated with a number of novel cardiovascular risk factors. Prospective studies will be required for replication, determination of causality and confirmation that ovarian reserve is impacting on metabolism rather than variation in metabolism is influencing ovarian reserve.

3.
Pediatr Obes ; : e12725, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32914569

RESUMO

BACKGROUND: Maternal obesity is associated with offspring cardiometabolic risk. UPBEAT was a randomised controlled trial of an antenatal diet and physical activity intervention in 1555 women with obesity. The intervention was associated with lower gestational weight gain, healthier diet and metabolic profile in pregnancy, and reduced infant adiposity at six months. OBJECTIVE: We have investigated whether the UPBEAT intervention influenced childhood cardiometabolic outcomes or was associated with sustained improvements in maternal lifestyle 3-years after delivery. METHODS: In UPBEAT mother-child dyads at the 3-year follow-up, we assessed childhood blood pressure, resting pulse rate, and adiposity (body mass index, skinfold thicknesses, body fat, waist and arm circumferences) and maternal diet, physical activity, and anthropometry. RESULTS: 514 three-year-old children attended the appointment (49% intervention, 51% standard care). There was no difference in the main outcome of interest, subscapular skinfold thickness, between the trial arms (-0.30 mm, 95% confidence interval: -0.92, 0.31). However, the intervention was associated with a lower resting pulse rate (-5 bpm [-8.41, -1.07]). There was also a non-significant lower odds of overweight/obesity (OR 0.73; 0.50, 1.08). Maternal dietary improvements observed in the UPBEAT trial, including glycaemic load and saturated fat were maintained 3-years postpartum. CONCLUSION: This study has demonstrated that an antenatal dietary and physical activity intervention in women with obesity is associated with lower offspring pulse rate and sustained improvement in maternal diet. Whilst larger than previous cohorts, there remains potential for bias from attrition and these findings require validation in future cohorts.

4.
J Musculoskelet Neuronal Interact ; 20(3): 301-313, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877967

RESUMO

OBJECTIVES: Hip development is influenced by mechanical loading, but associations between prenatal loading and hip shape in later life remain unexplored. METHODS: We examined associations between prenatal loading indicators (gestation length, oligohydramnios (OH) and breech) obtained from obstetric records and hip shape modes (HSMs) generated using dual-energy X-ray absorptiometry images taken at age 14- and 18-years in participants from the UK Avon Longitudinal Study of Parents and Children (ALSPAC). These associations were examined in 2453 (30 OH, 105 breech) and 2330 (27 OH, 95 breech) participants with complete data at age 14- and 18-years respectively using confounder-adjusted models. RESULTS: At 14 years HSM2 was 0.59SD lower in OH males, and HSM5 (-0.31SD) and HSM9 (-0.32SD) were lower in OH in both sexes. At 18 years HSM1 (-0.44SD) and HSM2 (-0.71SD) were lower and HSM6 (0.61SD) and HSM8 (1.06SD) were higher in OH males, whilst HSM5 was lower in OH in both sexes. OH appeared to be associated with a wider femoral neck and head, and larger lesser/greater trochanters. Only weak associations were observed between gestation length/breech and HSMs. CONCLUSIONS: These results suggest that prenatal skeletal loading, in particular oligohydramnios, may influence adolescent joint shape with associations generally stronger in males.

5.
BMC Womens Health ; 20(1): 177, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32795281

RESUMO

BACKGROUND: There may be changes in cognitive function in women going through the menopause. The current evidence remains unclear, however, whether these changes occur over and above those of general ageing. We aimed to evaluate the potential impact of the menopause (assessed by reproductive age and hormone levels) on cognitive function in women in mid-life accounting for the underlying effects of ageing. METHODS: The study was based on the follow up of women originally enrolled in pregnancy in a birth cohort when resident in the South West of England, UK between 1991 and 1992. Using up to three repeated measurements in 2411 women (mean age 51 at first assessment), we modelled changes in six cognitive function domains: immediate and delayed verbal episodic memory, working memory, processing speed, verbal intelligence and verbal fluency. The exposures of interest were reproductive age measured as years relative to the final menstrual period (FMP), chronological age and reproductive hormones (follicle-stimulating hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH)). RESULTS: Processing speed (- 0.21 (95% CI - 0.36 to - 0.06) standard deviation (SD) difference per 10 years since FMP), immediate verbal episodic memory (- 0.15 (95% CI - 0.35 to 0.06)) and delayed verbal episodic memory (- 0.17 (95% CI - 0.37 to 0.03)) declined with reproductive age. Reproductive hormones were not robustly associated with processing speed, but FSH and LH were both negatively associated with immediate (- 0.08 (95% CI - 0.13 to - 0.02) SD difference per SD difference in hormone level) and delayed verbal episodic memory (- 0.08 (95% CI - 0.13 to - 0.03)). There was little consistent evidence of cognitive function declining with menopause in other cognitive domains. CONCLUSIONS: Of the cognitive domains tested only verbal episodic memory declined both in relation to age since the menopause and in conjunction with the reproductive hormones that reflect the menopause. This decline was independent of normal ageing and suggests that the menopause is associated with a mild impact on this specific domain of cognitive function.

6.
JAMA Netw Open ; 3(8): e2013463, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32804215

RESUMO

Importance: Peak bone strength, which occurs in early adulthood, is an important marker of the future risk of osteoporosis. It is therefore important to identify modifiable early life factors that are associated with the attainment of peak hip strength. Objective: To investigate the association of time spent in moderate to vigorous-intensity and light-intensity physical activity throughout adolescence with peak hip strength in adulthood. Design, Setting, and Participants: The Avon Longitudinal Study of Parents and Children is a prospective birth cohort study that initially recruited all pregnant women residing within the catchment area of 3 health authorities in southwest England who had an expected delivery date between April 1, 1991, and December 31, 1992. In total, 15 454 eligible pregnant women were enrolled, and 15 589 infants were delivered. Of those, 14 901 infants were alive at age 1 year. The present analysis examined 2569 healthy offspring who had valid physical activity measurements obtained during a clinical assessment for at least 1 age (12, 14, 16, and/or 25 years), with up to 4 repeated accelerometer assessments performed (1 per age-associated clinical visit). Data were analyzed from June 2019 to June 2020. Exposures: Trajectories of accelerometer-assessed time spent in moderate to vigorous-intensity and light-intensity physical activity at ages 12, 14, 16, and 25 years (measured in minutes per day) were identified using latent trajectory modeling. Moderate to vigorous-intensity and light-intensity physical activity were determined using established thresholds of acceleration counts per minute. Main Outcomes and Measures: Femur neck bone mineral density (BMD; measured in g/cm2) at age 25 years assessed by dual-energy radiography absorptiometry scans of the hip. Results: A total of 2569 participants (1588 female participants [62%]) were included in the analysis. Male participants spent more time in moderate to vigorous-intensity activity at each age and had greater adult femur neck BMD than female participants. For each sex, 3 moderate to vigorous-intensity trajectory subgroups and 3 light-intensity trajectory subgroups were identified. With regard to the moderate to vigorous-intensity trajectories, most male participants (85%) were in the low adolescent subgroup, with only 6% and 9% in the high early-adolescent and high mid-adolescent subgroups, respectively. Moderate to vigorous-intensity trajectories in female participants were divided into low adolescent-low adult (73%), low adolescent-high adult (8%), and high adolescent (19%) subgroups. Light-intensity physical activity trajectories were classified into low nonlinear, moderate decreasing, and high decreasing subgroups for both sexes. Femur neck BMD in male participants was greater in the high early-adolescent subgroup (0.38 g/cm2; 95% CI, 0.11-0.66 g/cm2) and the high mid-adolescent subgroup (0.33 g/cm2; 95% CI, 0.07-0.60 g/cm2) compared with the low adolescent (reference) subgroup. Femur neck BMD in female participants was greater in the high adolescent subgroup (0.28 g/cm2; 95% CI, 0.15-0.41 g/cm2) but not in the low adolescent-high adult subgroup (-0.12 g/cm2; 95% CI, -0.44 to 0.20 g/cm2) compared with the low adolescent-low adult (reference) subgroup. A sensitivity analysis using a negative-outcome control variable to explore unmeasured confounding supported these findings. The light-intensity trajectories were not associated with femur neck BMD; for example, differences in femur neck BMD between the high decreasing and low nonlinear subgroups were 0.16 g/cm2 (95% CI, -0.08 to 0.40 g/cm2) in male participants and 0.20 g/cm2 (95% CI, -0.05 to 0.44 g/cm2) in female participants. Conclusions and Relevance: Supporting high-intensity physical activity throughout early life may help to maximize peak hip strength and prevent osteoporosis in later life. Replication of our findings in independent studies will be important.

7.
PLoS Med ; 17(8): e1003305, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32841251

RESUMO

BACKGROUND: Many maternal traits are associated with a neonate's gestational duration, birth weight, and birth length. These birth outcomes are subsequently associated with late-onset health conditions. The causal mechanisms and the relative contributions of maternal and fetal genetic effects behind these observed associations are unresolved. METHODS AND FINDINGS: Based on 10,734 mother-infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, we constructed haplotype genetic scores using single-nucleotide polymorphisms (SNPs) known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). Using these scores as genetic instruments, we estimated the maternal and fetal genetic effects underlying the observed associations between maternal phenotypes and pregnancy outcomes. We also used infant-specific birth weight genetic scores as instrument and examined the effects of fetal growth on pregnancy outcomes, maternal BP, and glucose levels during pregnancy. The maternal nontransmitted haplotype score for height was significantly associated with gestational duration (p = 2.2 × 10-4). Both maternal and paternal transmitted height haplotype scores were highly significantly associated with birth weight and length (p < 1 × 10-17). The maternal transmitted BMI scores were associated with birth weight with a significant maternal effect (p = 1.6 × 10-4). Both maternal and paternal transmitted BP scores were negatively associated with birth weight with a significant fetal effect (p = 9.4 × 10-3), whereas BP alleles were significantly associated with gestational duration and preterm birth through maternal effects (p = 3.3 × 10-2 and p = 4.5 × 10-3, respectively). The nontransmitted haplotype score for FPG was strongly associated with birth weight (p = 4.7 × 10-6); however, the glucose-increasing alleles in the fetus were associated with reduced birth weight through a fetal effect (p = 2.2 × 10-3). The haplotype scores for T2D were associated with birth weight in a similar way but with a weaker maternal effect (p = 6.4 × 10-3) and a stronger fetal effect (p = 1.3 × 10-5). The paternal transmitted birth weight score was significantly associated with reduced gestational duration (p = 1.8 × 10-4) and increased maternal systolic BP during pregnancy (p = 2.2 × 10-2). The major limitations of the study include missing and heterogenous phenotype data in some data sets and different instrumental strength of genetic scores for different phenotypic traits. CONCLUSIONS: We found that both maternal height and fetal growth are important factors in shaping the duration of gestation: genetically elevated maternal height is associated with longer gestational duration, whereas alleles that increase fetal growth are associated with shorter gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: taller maternal stature, higher maternal BMI, and higher maternal blood glucose are associated with larger birth size through maternal effects; in the fetus, the height- and metabolic-risk-increasing alleles are associated with increased and decreased birth size, respectively; alleles raising birth weight in the fetus are associated with shorter gestational duration and higher maternal BP. These maternal and fetal genetic effects may explain the observed associations between the studied maternal phenotypes and birth outcomes, as well as the life-course associations between these birth outcomes and adult phenotypes.


Assuntos
Peso ao Nascer/fisiologia , Estatura/fisiologia , Estudo de Associação Genômica Ampla/métodos , Haplótipos/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/fisiologia , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Testes Genéticos/métodos , Humanos , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos
8.
Reprod Biomed Online ; 41(3): 428-430, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32753362

RESUMO

RESEARCH QUESTION: Discontinuation of IVF cycles has been part of the radical transformation of healthcare provision to enable reallocation of staff and resources to deal with the COVID-19 pandemic. This study sought to estimate the impact of cessation of treatment on individual prognosis and US population live birth rates. DESIGN: Data from 271,438 ovarian stimulation UK IVF cycles was used to model the effect of age as a continuous, yet non-linear, function on cumulative live birth rate. This model was recalibrated to cumulative live birth rates reported for the 135,673 stimulation cycles undertaken in the USA in 2016, with live birth follow-up to October 2018. The effect of a 1-month, 3-month and 6-month shutdown in IVF treatment was calculated as the effect of the equivalent increase in a woman's age, stratified by age group. RESULTS: The average reduction in cumulative live birth rate would be 0.3% (95% confidence interval [CI] 0.3-0.3), 0.8% (95% CI 0.8-0.8) and 1.6% (95% CI 1.6-1.6) for 1-month, 3-month and 6-month shutdowns. This corresponds to a reduction of 369 (95% CI 360-378), 1098 (95% CI 1071-1123) and 2166 (95% CI 2116-2216) live births in the cohort, respectively. Th e greatest contribution to this reduction was from older mothers. CONCLUSIONS: The study demonstrated that the discontinuation of fertility treatment for even 1 month in the USA could result in 369 fewer women having a live birth, due to the increase in patients' age during the shutdown. As a result of reductions in cumulative live birth rate, more cycles may be required to overcome infertility at individual and population levels.


Assuntos
Betacoronavirus , Coeficiente de Natalidade , Infecções por Coronavirus/epidemiologia , Fertilização In Vitro/estatística & dados numéricos , Pandemias , Pneumonia Viral/epidemiologia , Adulto , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Nascimento Vivo/epidemiologia , Idade Materna , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Reino Unido/epidemiologia , Estados Unidos/epidemiologia
9.
Eur J Epidemiol ; 35(7): 709-724, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32705500

RESUMO

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.

11.
PLoS One ; 15(7): e0235385, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645067

RESUMO

The present study aims to: a) systematically map the of birth cohort studies from the South Asian region b) examine the major research foci and landmark contributions from these cohorts using reproducible scientometric techniques and c) offer recommendations on establishing new birth cohorts in Pakistan, building upon the strengths, weaknesses and gaps of previous cohorts. Bibliographic records for a total of 260 articles, published during through December 2018, were retrieved from the Web of Science (core database). All data were analysed using Microsoft Excel (2013), Web of Science platform and CiteSpace. A series of network analysis were then run for each time-period using the link reduction method and pathfinder network scaling. The co-cited articles were clustered into their homogeneous research clusters. The clusters were named using the Latent Semantic Indexing (LSI) method that utilized author keywords as source of names for these clusters. The scientometric analyses of original research output from these birth cohorts also paint a pessimistic landscape in Pakistan- where Pakistani sites for birth cohorts contributed only 31 publications; a majority of these utilized the MAL-ED birth cohort data. A majority of original studies were published from birth cohorts in India (156), Bangladesh (63), and Nepal (15). Out of these contributions, 31 studies reported data from multiple countries. The three major birth cohorts include prospective and multi-country MAL-ED birth cohort and The Pakistan Early Childhood Development Scale Up Trial, and a retrospective Maternal and infant nutrition intervention cohort. In addition to these, a few small-scale birth cohorts reported findings pertaining to neonatal sepsis, intrauterine growth retardation and its effects on linear growth of children and environmental enteropathy.


Assuntos
Parto , Ciência , Bibliometria , Estudos de Coortes , Comportamento Cooperativo , Geografia , Humanos , Estudos Longitudinais , Paquistão , Publicações , Pesquisa
12.
BMC Med ; 18(1): 181, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32669098

RESUMO

BACKGROUND: The prevalence of excess adiposity, as measured by elevated body mass index (BMI) and waist-hip ratio (WHR), is increasing in sub-Saharan African (SSA) populations. This could add a considerable burden of cardiovascular and metabolic diseases for which these populations are currently ill-prepared. Evidence from white, European origin populations shows that higher adiposity leads to an adverse lipid profile; whether these associations are similar in all SSA populations requires further exploration. This study compared the association of BMI and WHR with lipid profile in urban Malawi with a contemporary cohort with contrasting socioeconomic, demographic, and ethnic characteristics in the United Kingdom (UK). METHODS: We used data from 1248 adolescents (mean 18.7 years) and 2277 Malawian adults (mean 49.8 years), all urban-dwelling, and from 3201 adolescents (mean 17.8 years) and 6323 adults (mean 49.7 years) resident in the UK. Adiposity measures and fasting lipids were assessed in both settings, and the associations of BMI and WHR with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were assessed by sex and age groups in both studies. RESULTS: Malawian female adults were more adipose and had more adverse lipid profiles than their UK counterparts. In contrast, Malawian adolescent and adult males were leaner and had more favourable lipid profiles than in the UK. Higher BMI and WHR were associated with increased TC, LDL-C and TG and reduced HDL-C in both settings. The magnitude of the associations of BMI and WHR with lipids was mostly similar or slightly weaker in the Malawian compared with the UK cohort in both adolescents and adults. One exception was the stronger association between increasing adiposity and elevated TC and LDL-C in Malawian compared to UK men. CONCLUSIONS: Malawian adult women have greater adiposity and more adverse lipid profiles compared with their UK counterparts. Similar associations of adiposity with adverse lipid profiles were observed for Malawian and UK adults in most age and sex groups studied. Sustained efforts are urgently needed to address the excess adiposity and adverse lipid profiles in Malawi to mitigate a future epidemic of cardio-metabolic disease among the poorest populations.

13.
Ann Hum Biol ; 47(4): 391-399, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32380867

RESUMO

BACKGROUND: It is unclear if puberty timing influences future physical activity (PA). AIM: To investigate the association of puberty timing with PA across adolescence and adulthood. SUBJECTS AND METHODS: Data were from two British cohorts. Participants from an adolescent birth cohort (females = 2349, males = 1720) prospectively reported age at menarche and voice break and had PA recorded by Actigraph accelerometers at ages 14 years and 16 years. A cohort of middle-aged and older adults (40-70 years; females = 48,282; males = 36,112) recalled their age at puberty and had PA (mean acceleration; mg) measured by AxivityAX3 accelerometers. RESULTS: After adjustment for age, education, smoking and BMI, per 1-year older age at menarche was associated with higher mean counts/minute at age 14 years (0.07 SD counts/minute; 95% CI = 0.04-0.11) with associations attenuated at age 16 years (0.02; -0.03-0.07). Differences in mean acceleration per older year at menarche were close to the null in women aged 40-49 years (0.02 mg; 0.01-0.03), 50-59 years (0.01; 0.00-0.02) and 60-70 years (0.01; 0.00-0.01). Age at voice break and PA associations were close to the null in both cohorts. CONCLUSION: We found a positive association between puberty timing and PA in females which weakened at older ages and limited evidence of an association at any age in males.

14.
Syst Rev ; 9(1): 78, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32268905

RESUMO

BACKGROUND: Pre-eclampsia and being born small for gestational age are associated with significant maternal and neonatal morbidity and mortality. Placental dysfunction is a key pathological process underpinning these conditions; thus, markers of placental function have the potential to identify pregnancies ending in pre-eclampsia, fetal growth restriction, and the birth of a small for gestational age infant. PRIMARY OBJECTIVE: To assess the predictive ability of late pregnancy (after 24 weeks' gestation) tests in isolation or in combination for adverse pregnancy outcomes associated with placental dysfunction, including pre-eclampsia, fetal growth restriction, delivery of a SGA infant (more specifically neonatal growth restriction), and stillbirth. METHODS: Studies assessing the ability of biochemical tests of placental function and/or ultrasound parameters in pregnant women beyond 24 weeks' gestation to predict outcomes including pre-eclampsia, stillbirth, delivery of a SGA infant (including neonatal growth restriction), and/or fetal growth restriction will be identified by searching the following databases: EMBASE, MEDLINE, Cochrane CENTRAL, Web of Science, CINAHL, ISRCTN registry, UK Clinical Trials Gateway, and WHO International Clinical Trials Portal. Any study design in which the biomarker and ultrasound scan potential predictors have been assessed after 24 weeks' gestation but before diagnosis of outcomes (pre-eclampsia, fetal growth restriction, SGA (including neonatal growth restriction), and stillbirth) will be eligible (this would include randomized control trials and nested prospective case-control and cohort studies), and there will be no restriction on the background risk of the population. All eligible studies will be assessed for risk of bias using the modified QUADAS-2 tool. Meta-analyses will be undertaken using the ROC models to estimate and compare test discrimination and reclassification indices to test calibration. Validation will be explored by comparing consistency across studies. DISCUSSION: This review will assess whether current published data reporting either a single or combination of tests in late pregnancy can accurately predict adverse pregnancy outcome(s) associated with placental dysfunction. Accurate prediction could allow targeted management and possible intervention for high-risk pregnancies, ultimately avoiding adverse outcomes associated with placental disease. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018107049.

15.
PLoS One ; 15(4): e0232333, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348363

RESUMO

Elevated blood pressure in children is a significant risk factor for the development of cardiovascular disease in adulthood. We examined how children's body mass index (BMI), physical activity and sedentary time at ages 9 and 11 are associated with blood pressure at age 11. Data were from 1283 children from Bristol, UK, who participated in the study aged 11 years, 797 of whom also participated in the study aged 9 years. Child height, weight and blood pressure were measured, and children wore accelerometers for five days, from which moderate-to-vigorous-intensity physical activity and sedentary minutes per day were derived. Multiple imputation of missing data and adjusted linear and logistic regression models were used to examine associations. Child BMI at 11 years was cross-sectionally associated with higher systolic and diastolic blood pressure (mean difference [95% confidence interval]: 0.91 [0.32 to 1.50] mm Hg and 1.08 [0.54 to 1.62] mm Hg, respectively, per standard deviation (SD) of BMI). BMI at age 9 was also positively associated with diastolic blood pressure at age 11 (1.16 mmHg per two years [0.49 to 1.84], per SD of BMI). For girls, sedentary time at age 9 years was associated with increased odds of having high systolic blood pressure at age 11 (odds ratio: 1.08 [1.01 to 1.16], per 10 minutes per day). There was no evidence of associations between sedentary time and blood pressure among boys. Similarly, there was little evidence that physical activity was associated with blood pressure in either cross-sectional or prospective analyses. Effective strategies are needed to prevent excess bodyweight among children in order to reduce cardiovascular disease risk.


Assuntos
Pressão Sanguínea , Exercício Físico , Comportamento Sedentário , Índice de Massa Corporal , Criança , Estudos Transversais , Inglaterra , Feminino , Humanos , Masculino , Estudos Prospectivos , Instituições Acadêmicas
17.
Elife ; 92020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32207686

RESUMO

By sequencing autozygous human populations, we identified a healthy adult woman with lifelong complete knockout of HAO1 (expected ~1 in 30 million outbred people). HAO1 (glycolate oxidase) silencing is the mechanism of lumasiran, an investigational RNA interference therapeutic for primary hyperoxaluria type 1. Her plasma glycolate levels were 12 times, and urinary glycolate 6 times, the upper limit of normal observed in healthy reference individuals (n = 67). Plasma metabolomics and lipidomics (1871 biochemicals) revealed 18 markedly elevated biochemicals (>5 sd outliers versus n = 25 controls) suggesting additional HAO1 effects. Comparison with lumasiran preclinical and clinical trial data suggested she has <2% residual glycolate oxidase activity. Cell line p.Leu333SerfsTer4 expression showed markedly reduced HAO1 protein levels and cellular protein mis-localisation. In this woman, lifelong HAO1 knockout is safe and without clinical phenotype, de-risking a therapeutic approach and informing therapeutic mechanisms. Unlocking evidence from the diversity of human genetic variation can facilitate drug development.

18.
Int J Epidemiol ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31993631

RESUMO

BACKGROUND: Systematic reviews of prenatal alcohol exposure effects generally only include conventional observational studies. However, estimates from such studies are prone to confounding and other biases. OBJECTIVES: To systematically review the evidence on the effects of prenatal alcohol exposure from randomized controlled trials (RCTs) and observational designs using alternative analytical approaches to improve causal inference. SEARCH STRATEGY: Medline, Embase, Web of Science, PsychINFO from inception to 21 June 2018. Manual searches of reference lists of retrieved papers. SELECTION CRITERIA: RCTs of interventions to stop/reduce drinking in pregnancy and observational studies using alternative analytical methods (quasi-experimental studies e.g. Mendelian randomization and natural experiments, negative control comparisons) to determine the causal effects of prenatal alcohol exposure on pregnancy and longer-term offspring outcomes in human studies. DATA COLLECTION AND ANALYSIS: One reviewer extracted data and another checked extracted data. Risk of bias was assessed using customized risk of bias tools. A narrative synthesis of findings was carried out and a meta-analysis for one outcome. MAIN RESULTS: Twenty-three studies were included, representing five types of study design, including 1 RCT, 9 Mendelian randomization and 7 natural experiment studies, and reporting on over 30 outcomes. One study design-outcome combination included enough independent results to meta-analyse. Based on evidence from several studies, we found a likely causal detrimental role of prenatal alcohol exposure on cognitive outcomes, and weaker evidence for a role in low birthweight. CONCLUSION: None of the included studies was judged to be at low risk of bias in all domains, results should therefore be interpreted with caution. SYSTEMATIC REVIEW REGISTRATION: This study is registered with PROSPERO, registration number CRD42015015941.

19.
BMJ ; 368: l7057, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996343

RESUMO

OBJECTIVE: To study the impact of maternal smoking during pregnancy on fractures in offspring during different developmental stages of life. DESIGN: National register based birth cohort study with a sibling comparison design. SETTING: Sweden. PARTICIPANTS: 1 680 307 people born in Sweden between 1983 and 2000 to women who smoked (n=377 367, 22.5%) and did not smoke (n=1 302 940) in early pregnancy. Follow-up was until 31 December 2014. MAIN OUTCOME MEASURE: Fractures by attained age up to 32 years. RESULTS: During a median follow-up of 21.1 years, 377 970 fractures were observed (the overall incidence rate for fracture standardised by calendar year of birth was 11.8 per 1000 person years). The association between maternal smoking during pregnancy and risk of fracture in offspring differed by attained age. Maternal smoking was associated with a higher rate of fractures in offspring before 1 year of age in the entire cohort (birth year standardised fracture rates in those exposed and unexposed to maternal smoking were 1.59 and 1.28 per 1000 person years, respectively). After adjustment for potential confounders the hazard ratio for maternal smoking compared with no smoking was 1.27 (95% confidence interval 1.12 to 1.45). This association followed a dose dependent pattern (compared with no smoking, hazard ratios for 1-9 cigarettes/day and ≥10 cigarettes/day were 1.20 (95% confidence interval 1.03 to 1.39) and 1.41 (1.18 to 1.69), respectively) and persisted in within-sibship comparisons although with wider confidence intervals (compared with no smoking, 1.58 (1.01 to 2.46)). Maternal smoking during pregnancy was also associated with an increased fracture incidence in offspring from age 5 to 32 years in whole cohort analyses, but these associations did not follow a dose dependent gradient. In within-sibship analyses, which controls for confounding by measured and unmeasured shared familial factors, corresponding point estimates were all close to null. Maternal smoking was not associated with risk of fracture in offspring between the ages of 1 and 5 years in any of the models. CONCLUSION: Prenatal exposure to maternal smoking is associated with an increased rate of fracture during the first year of life but does not seem to have a long lasting biological influence on fractures later in childhood and up to early adulthood.


Assuntos
Fraturas Ósseas , Gestantes/psicologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar , Adulto , Fatores Etários , Criança , Correlação de Dados , Feminino , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/epidemiologia , Humanos , Lactente , Masculino , Gravidez , Sistema de Registros/estatística & dados numéricos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Suécia/epidemiologia
20.
Eur J Prev Cardiol ; 27(15): 1617-1626, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31996015

RESUMO

AIMS: Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. METHODS: Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. RESULTS: The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke. CONCLUSIONS: Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.

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