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ABSTRACT: OBJECTIVE: To identify correlates and longitudinal changes in circulating antimüllerian hormone (AMH) levels as a marker of ovarian primordial follicle recruitment in normal peripubertal girls. DESIGN: Observational study using mixed longitudinal and cross-sectional analyses. SETTING: Not applicable. PATIENT(S): Unselected girls assessed at ages 7-11 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): AMH, inhibin B, and FSH levels were analyzed in blood samples collected at ages 7, 9, and 11 years for longitudinal analyses and at age 8 years for cross-sectional analyses. RESULT(S): In the cross-sectional analysis, AMH levels at age 8 years were lower in pubertal girls (median 25.0 pmol/L, interquartile range [IQR] 16.0-33.9; n = 39) than in prepubertal girls (33.5 pmol/L, IQR 22.3-49.1; n = 342). In prepubertal girls, higher AMH levels were associated with higher inhibin B levels, lower FSH levels, and larger body mass index at age 8 years and subsequently with later age at menarche. AMH levels were unrelated to birth weight or birth length. In the longitudinal analysis, AMH levels increased between ages 7 (median 27.0 pmol/L, IQR 19.2-34) and 9 years (32.0 pmol/L, IQR 26.5-42.7), then declined between 9 and 11 years (26.5 pmol/L, IQR 19-42.25) with high intraindividual correlation in AMH levels between ages 7 and 9 years and 7 and 11 years. CONCLUSION(S): Measurement of circulating AMH and inhibin B levels suggests that the rate of ovarian primordial follicle recruitment increases in the prepubertal years then declines again following the onset of puberty as follicular activity pattern changes.
Fertility and sterility 02/2013; · 3.97 Impact Factor
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Abigail Fraser,
Corrie Macdonald-Wallis,
Kate Tilling,
Andy Boyd,
Jean Golding,
George Davey Smith,
John Henderson,
John Macleod,
Lynn Molloy, Andy Ness,
Susan Ring,
Scott M Nelson,
Debbie A Lawlor
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ABSTRACT: Summary The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13 761 women (contributing 13 867 pregnancies) were recruited. These women have been followed over the last 19-22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17-18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on >10 000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile.
International Journal of Epidemiology 04/2012; · 6.41 Impact Factor
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ABSTRACT: The Avon Longitudinal Study of Parents and Children (ALSPAC) is a transgenerational prospective observational study investigating influences on health and development across the life course. It considers multiple genetic, epigenetic, biological, psychological, social and other environmental exposures in relation to a similarly diverse range of health, social and developmental outcomes. Recruitment sought to enrol pregnant women in the Bristol area of the UK during 1990-92; this was extended to include additional children eligible using the original enrolment definition up to the age of 18 years. The children from 14 541 pregnancies were recruited in 1990-92, increasing to 15 247 pregnancies by the age of 18 years. This cohort profile describes the index children of these pregnancies. Follow-up includes 59 questionnaires (4 weeks-18 years of age) and 9 clinical assessment visits (7-17 years of age). The resource comprises a wide range of phenotypic and environmental measures in addition to biological samples, genetic (DNA on 11 343 children, genome-wide data on 8365 children, complete genome sequencing on 2000 children) and epigenetic (methylation sampling on 1000 children) information and linkage to health and administrative records. Data access is described in this article and is currently set up as a supported access resource. To date, over 700 peer-reviewed articles have been published using ALSPAC data.
International Journal of Epidemiology 04/2012; · 6.41 Impact Factor
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ABSTRACT: There are reasons why survival may have improved in people with head and neck cancer, but few studies have reported on trends in the UK, and results are not consistent. We examined recent trends in survival for people diagnosed with head and neck cancer in the south west of England. Patients were identified over four one-year audits in a population (roughly 6.5 million) served by five cancer networks, and the work was collated by the South West Public Health Observatory (SWPHO) tumour panel. The SWPHO cancer registry provided data on death. Prognostic data, including stage, time to treatment, and deprivation index were extracted or derived from clinical records. A total of 2164 cases of oral, laryngeal, and pharyngeal squamous cell carcinomas (SCC) were diagnosed. Crude total 5-year mortality decreased from 55% (95% CI 50.3-59.4) in people diagnosed in 1996 to 44% (95% CI 37.9-46.4) in those diagnosed in 2003 (p<0.001). Adjusted hazard ratios (HRs) for death within five years of diagnosis for surveys 2, 3, and 4 (compared with survey 1), respectively, were reduced in subsequent groups: HR 0.79 (95% CI 0.64-0.98), HR 0.70 (95% CI 0.56-0.87), and HR 0.72 (95% CI 0.58-0.90) (chi square for trend, p<0.001). Improvements over time were most pronounced among those with late-stage disease and with pharyngeal tumours. We have shown that survival has improved for people with head and neck cancer. Further large prospective studies are required to understand how quality of care, treatment, aetiology of tumour, individual risk, and behaviour contribute to survival.
British Journal of Oral and Maxillofacial Surgery 03/2012; · 1.95 Impact Factor
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Tuomas O Kilpeläinen,
Lu Qi,
Soren Brage,
Stephen J Sharp,
Emily Sonestedt,
Ellen Demerath,
Tariq Ahmad,
Samia Mora,
Marika Kaakinen,
Camilla Helene Sandholt, [......],
Keri L Monda,
Thomas Illig,
Marjo-Riitta Järvelin,
Nicholas J Wareham,
Frank B Hu,
Leif C Groop,
Marju Orho-Melander,
Ulf Ekelund,
Paul W Franks,
Ruth J F Loos
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ABSTRACT: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268).
All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents.
The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.
PLoS Medicine 11/2011; 8(11):e1001116. · 16.27 Impact Factor
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ABSTRACT: Few studies have examined the association between physical activity (PA), measured objectively, and adolescent depressive symptoms. The aim of this study was to determine whether there is an association between objective measures of PA (total PA and time spent in moderate and vigorous PA (MVPA)) and adolescent depressive symptoms.
Data on 2,951 adolescents participating in ALSPAC were used. Depressive symptoms were measured using the self-report Mood and Feelings Questionnaire (MFQ) (short version). Measures of PA were based on accelerometry. The association between PA and MFQ scores was modelled using ordinal regression.
Adolescents who were more physically active (total PA or minutes of MVPA) had a reduced odds of depressive symptoms [OR(adj) total PA (tertiles): medium 0.82 (95% CI: 0.69, 0.97); high 0.69 (95% CI: 0.57, 0.83)]; OR(adj) per 15 min MVPA: 0.92 (95% CI: 0.86, 0.98). In a multivariable model including both total PA and the percentage of time spent in MVPA, total PA was associated with depressive symptoms (OR(adj) total PA (tertiles): medium 0.82 (95% CI: 0.70, 0.98); high 0.70 (95% CI: 0.58, 0.85) but the percentage of time spent in MVPA was not independently associated with depressive symptoms [OR(adj) MVPA (tertiles) medium 1.05 (95% CI: 0.88, 1.24), high 0.91 (95% CI: 0.77, 1.09)].
The total amount of PA undertaken was associated with adolescent depressive symptoms, but the amount of time spent in MVPA, once total PA was accounted for, was not. If confirmed in longitudinal studies and randomised controlled trials, this would have important implications for public health messages.
Social Psychiatry 08/2011; 47(7):1023-33. · 2.05 Impact Factor
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ABSTRACT: The aim of the current study was to test the hypothesis that children with probable Developmental Coordination Disorder have an increased risk of reduced moderate to vigorous physical activity (MVPA), using data from a large population based study. Prospectively collected data from 4331 children (boys=2065, girls=2266) who had completed motor coordination testing at 7 years and accelerometry at 12 years were analysed from the Avon Longitudinal Study of Parents and Children (ALSPAC). Probable DCD (p-DCD) was defined, using criteria based on the DSM IV classification, as those children below the 15th centile of the ALSPAC Coordination Test at seven years who had a functional impairment in activities of daily living or handwriting, excluding children with a known neurological diagnosis or IQ<70. Secondary exposure variables consisted of subtests from the ALSPAC Coordination test (manual dexterity, ball skills and balance). Objective measurement of the average daily minutes of MVPA was recorded as ≥3600 counts per minute (cpm) using actigraph accelerometry. Boys with p-DCD were less physically active than boys without DCD (mean difference in MVPA 4.36 cpm, t=2.69; p=0.007). For boys, targeting skill (bean bag toss) was related to increased MVPA, after adjustment for confounding factors including neonatal, family and environmental factors as well as Body Mass Index at age seven and 12 years (β=0.76, t=3.37, p<0.001, CI 0.32-1.20). There was no difference in level of MVPA in girls with and without p-DCD (mean difference 1.35 min, t=0.97, p=0.31), which may reflect the low levels of MVPA of girls in this cohort. Our findings suggest that the presence of movement difficulties, particularly poor targeting (bean bag toss/ball skills), at a young age is a potential risk factor for reduced MVPA in boys.
Research in developmental disabilities 02/2011; 32(4):1332-42. · 4.41 Impact Factor
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ABSTRACT: Little is known about the effects of overall diet in childhood and intelligence later in life.
The current study, based on the Avon Longitudinal Study of Parents and Children, uses data on children's diet reported by parents in food-frequency questionnaires at 3, 4, 7 and 8.5 years of age. Dietary patterns were identified using principal-components analysis and scores computed at each age. IQ was assessed using the Wechsler Intelligence Scale for Children at 8.5 years. Data on a number of confounders were collected, and complete data were available for 3966 children.
After adjustment, the 'processed' (high fat and sugar content) pattern of diet at 3 years of age was negatively associated with IQ assessed at 8.5 years of age-a 1 SD increase in dietary pattern score was associated with a 1.67 point decrease in IQ (95% CI -2.34 to -1.00; p<0.0001). The 'health-conscious' (salad, rice, pasta, fish, fruit) pattern at 8.5 years was positively associated with IQ: a 1 SD increase in pattern score led to a 1.20 point increase in IQ (95% CI 0.52 to 1.88; p=0.001).
There is evidence that a poor diet associated with high fat, sugar and processed food content in early childhood may be associated with small reductions in IQ in later childhood, while a healthy diet, associated with high intakes of nutrient rich foods described at about the time of IQ assessment may be associated with small increases in IQ.
Journal of epidemiology and community health 02/2011; 66(7):624-8. · 3.04 Impact Factor
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ABSTRACT: To examine the associations between childhood growth and the presence of dental caries at age 5.
Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) a population-based, prospective cohort study were used. We enrolled 14,541 pregnancies, and a 10% sample of these were dentally examined and measured at 61 months of age. Birthweight was obtained from medical records, and birth length and birthweight were assessed by trained ALSPAC measurers. A number of social and lifestyle factors were treated as potential confounding factors.
Of 985, children, 242 (24.6%) had caries at 61 months of age. After adjustment, increased weight at birth was associated with a small increased risk of caries at 61 months (OR: 1.08 (95% CI: 1.03, 1.13) per 100 g increase, P = 0.002). A similar association was noted with respect to increased length at birth. Current weight and height did not appear to be associated with caries risk. Children who had caries at 61 months had slower increases in weight and height between birth and 61 months than those without decay at 61 months.
The weak associations we have demonstrated between weight and length at birth and risk of caries at age 61 months cannot be considered causal, however, the relationship between the two variables warrants further investigation.
Community Dentistry And Oral Epidemiology 10/2010; 38(5):408-14. · 1.89 Impact Factor
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ABSTRACT: Differences in sex-typed behaviour, including physical activity, are already apparent among preschool children.
To examine the associations between early sex-typed behaviour and later physical activity.
Children from the Avon Longitudinal Study of Parents and Children were asked to wear an accelerometer for 7 days at age 12. Physical activity outcomes were counts per minute (counts/min) and minutes of moderate to vigorous physical activity (MVPA). Sex-typed behaviour was assessed using the Pre-School Activities Inventory (PSAI) at age 3(1/2). Multivariable regression was used to examine the association between PSAI and physical activity, separately for boys and girls.
Accelerometer data were collected from 2593 boys and 2858 girls, mean (SD) age 11.8 (0.23) years. A one point higher PSAI score (mean (SD) 61.7 (8.7) and 37.0 (9.1) for boys and girls, respectively) was associated with a higher level of physical activity (counts/min) of 2.3 (95% CI 0.9 to 3.7) in boys and 0.7 (95% CI -0.1 to 1.4) in girls. This is equivalent to a higher counts/min of 56.7 (95% CI 23.1 to 90.3) and 16.6 (95% CI -2.4 to 35.5) for boys and girls, respectively, for a higher PSAI score equivalent to the difference between boys and girls (24.7). Results for MVPA were similar.
Higher male-typical behaviour in early childhood is associated with higher physical activity in early adolescence, particularly in boys.
Archives of Disease in Childhood 07/2010; 95(7):509-12. · 2.88 Impact Factor
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Abigail Fraser,
Kate Tilling,
Corrie Macdonald-Wallis,
Naveed Sattar,
Marie-Jo Brion,
Li Benfield, Andy Ness,
John Deanfield,
Aroon Hingorani,
Scott M Nelson,
George Davey Smith,
Debbie A Lawlor
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ABSTRACT: We sought to examine the association of gestational weight gain (GWG) and prepregnancy weight with offspring adiposity and cardiovascular risk factors.
Data from 5154 (for adiposity and blood pressure) and 3457 (for blood assays) mother-offspring pairs from a UK prospective pregnancy cohort were used. Random-effects multilevel models were used to assess incremental GWG (median and range of repeat weight measures per woman: 10 [1, 17]). Women who exceeded the 2009 Institute of Medicine-recommended GWG were more likely to have offspring with greater body mass index, waist, fat mass, leptin, systolic blood pressure, C-reactive protein, and interleukin-6 levels and lower high-density lipoprotein cholesterol and apolipoprotein A1 levels. Children of women who gained less than the recommended amounts had lower levels of adiposity, but other cardiovascular risk factors tended to be similar in this group to those of offspring of women gaining recommended amounts. When examined in more detail, greater prepregnancy weight was associated with greater offspring adiposity and more adverse cardiovascular risk factors at age 9 years. GWG in early pregnancy (0 to 14 weeks) was positively associated with offspring adiposity across the entire distribution but strengthened in women gaining >500 g/wk. By contrast, between 14 and 36 weeks, GWG was only associated with offspring adiposity in women gaining >500 g/wk. GWG between 14 and 36 weeks was positively and linearly associated with adverse lipid and inflammatory profiles, with these associations largely mediated by the associations with offspring adiposity.
Greater maternal prepregnancy weight and GWG up to 36 weeks of gestation are associated with greater offspring adiposity and adverse cardiovascular risk factors. Before any GWG recommendations are implemented, the balance of risks and benefits of attempts to control GWG for short- and long-term outcomes in mother and child should be ascertained.
Circulation 06/2010; 121(23):2557-64. · 14.74 Impact Factor
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ABSTRACT: Nutrition during pregnancy and in early life may influence developmental plasticity and alter susceptibility to obesity and adult disease. One mechanism by which this could occur is through epigenetic changes, such as changes in methylation levels, which modify gene expression patterns. Folate intake during pregnancy, as well as maternal methyltetrahydrofolate reductase (MTHFR) C677T genotype, influences the availability of methyl donors for methylation during gestation and therefore may be associated with offspring body composition in childhood. We looked at associations between maternal folic acid supplementation at 18 and 32 weeks of pregnancy, folate intake in the diet (from self-reported FFQ) at 32 weeks of pregnancy and offspring body composition at age 9 years among 5783 children from a population-based birth cohort study in the UK. We also looked at maternal and offspring's MTHFR C677T genotype in relation to offspring body composition. We found no evidence to support the hypothesis that intra-uterine exposure to folate influences childhood body composition.
The British journal of nutrition 09/2009; 102(4):493-6. · 3.45 Impact Factor
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Rebecca Gilbert,
Chris Metcalfe,
Steven E Oliver,
David C Whiteman,
Chris Bain, Andy Ness,
Jenny Donovan,
Freddie Hamdy,
David E Neal,
J Athene Lane,
Richard M Martin
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ABSTRACT: There is currently no means of primary prevention for prostate cancer. Increased exposure to ultraviolet-radiation may be protective, but the literature is inconclusive. We investigated associations of life course exposure to sunlight with prostate cancer. The study design was a UK-wide nested case-control study, based on 1,020 prostate specific antigen-detected cases and 5,044 matched population controls and a systematic review with meta-analysis. Men with olive/brown skin (OR = 1.47; 95% CI: 1.00 to 2.17), men who burnt rarely/never (OR = 1.11; 0.95 to 1.29) and men with the lowest levels of intense sun exposure in the 2 years prior to diagnosis (OR = 1.24; 1.03 to 1.50) had an increased prostate cancer risk. However, amongst men with prostate cancer, spending less time outside was associated with a reduced risk of advanced cancer (OR = 0.49; 0.27 to 0.89) and high Gleason grade (OR = 0.62; 0.43 to 0.91), and men who burnt rarely/never had a reduced risk of advanced cancer (OR = 0.71; 0.47 to 1.08). The meta-analysis provided weak evidence that men with the lowest (versus highest) sunlight exposure had an increased prostate cancer risk (4 studies, random-effects pooled relative risk = 1.13; 0.98 to 1.29) and higher advanced or fatal prostate cancer risk (6 studies, random-effects pooled relative risk = 1.14; 0.98 to 1.33). Our data and meta-analyses provide limited support for the hypothesis that increased exposure to sunlight may reduce prostate cancer risk. The findings warrant further investigation because of their implications for vitamin D chemoprevention trials.
International Journal of Cancer 04/2009; 125(6):1414-23. · 5.44 Impact Factor
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ABSTRACT: To assess the association between active travel to school and physical activity (PA) in a large population-based sample of 11-year old children.
Cross-sectional analyses using data from the Avon Longitudinal Study of Parents and Children (Bristol, UK), collected in 2002-2004. The analyses include all children providing valid data on objectively measured PA (Actigraph accelerometer), and having parent-proxy reported data on travel mode (walk, cycle, public transport, car) and distance to school (N=4688).
43.5% of children regularly walked or cycled to school (i.e. on every or most days). Compared with car travelers, walking to school was associated with 5.98 (95%CI: 3.82-8.14) more minutes of moderate-to-vigorous PA (MVPA) on weekdays in those living 0.5-1 miles from school, and with 9.77 (95%CI: 7.47-12.06) more minutes in those living at 1-5 miles. This equates to 24.6 to 40.2% of the average daily minutes of MVPA. Only modest differences were observed in those living <0.5 mile from school.
Children who regularly walk to school are more active during the week than those travelling by car, especially if the distance is >0.5 mile. Increasing participation in active travel might be a useful part of an overall strategy to increase population PA.
Preventive Medicine 03/2009; 48(6):519-24. · 3.22 Impact Factor
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ABSTRACT: Indices for lean and fat mass adjusted for height derived from bioelectrical impedance for children aged 7 years have been published previously and their usefulness in the clinical assessment of undernutrition has been demonstrated. However, there is a need for norms that cover a wider age range and to explore their functional significance. The aim of the present study is to derive lean and fat indices for children aged 7-11 years and investigate associations with objective measures of cardio-respiratory fitness and grip strength. Subjects were 9574 children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Bioelectrical impedance analysis (BIA) data collected longitudinally between ages 7 and 11 were used to derive lean and fat indices using the method of standardised residuals. Cardio-respiratory fitness (CRF) (9 years) and grip strength (11 years) were also measured. Correlation coefficients and 95 % CI were calculated to assess the strength of association between lean index, fat index and CRF and grip strength. Equations for calculating lean and fat indices in children aged 7-11 years relative to the ALSPAC population are presented. Lean index was linearly associated with CRF (rboys 0.20 (95 % CI 0.15, 0.25), rgirls 0.26 (95 % CI 0.22, 0.30)) and grip strength (rboys 0.29 (95 % CI 0.26, 0.32), rgirls 0.26 (95 % CI 0.23, 0.29)). BMI showed slightly weaker associations, while fat index was unrelated to either CRF or grip strength. Lean indices relate to muscle function and fitness while fat index does not.
The British journal of nutrition 12/2008; 101(12):1753-60. · 3.45 Impact Factor
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ABSTRACT: To examine factors in early life (up to age 5 years) that are associated with objectively measured physical activity in 11-12 year olds.
Prospective cohort study.
Avon longitudinal study of parents and children, United Kingdom.
Children aged 11-12 years from the Avon longitudinal study of parents and children.
Physical activity levels in counts per minute (cpm) and minutes of moderate to vigorous physical activity for seven days measured with a uniaxial actigraph accelerometer.
Valid actigraph data, defined as at least three days of physical activity for at least 10 hours a day, were collected from 5451 children. Several factors were associated with physical activity at ages 11-12 years. Regression coefficients are compared with the baseline of "none" for categorical variables: maternal brisk walking during pregnancy (regression coefficient 5.0, 95% confidence interval -8.5 to 18.5; cpm for < 1 h/wk and > or = 2 h/wk of physical activity 17.7, 5.3 to 30.1), maternal swimming during pregnancy (21.5, 10.9 to 32.1 and cpm for < 1 h/wk and > or = 2 h/wk of physical activity 24.2, 7.8 to 40.7), parents' physical activity when the child was aged 21 months (28.5, 15.2 to 41.8 and cpm of physical activity for either parent active and both parents active 33.5, 17.8 to 49.3), and parity assessed during pregnancy (2.9, -7.6 to 13.4 and cpm of physical activity for 1 and > or = 2 parity 21.2, 7.1 to 35.3).
Few factors in early life predicted later physical activity in 11-12 year olds. Parents' physical activity during pregnancy and early in the child's life showed a modest association with physical activity of the child at age 11-12 years, suggesting that active parents tend to raise active children. Helping parents to increase their physical activity therefore may promote children's activity.
British journal of sports medicine 10/2008; 42(9):721-4. · 2.55 Impact Factor
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ABSTRACT: Epidemiological studies have shown that low folate levels are associated with a high body mass index (BMI). These findings have potentially important health implications and warrant further investigation to determine whether a causal relationship exists and the direction of this relationship. The methylenetetrahydrofolate reductase (MTHFR) C677T TT genotype is associated with reduced folate availability and may be a surrogate for measuring folate levels. We sought to determine whether MTHFR C677T genotype was associated with obesity.
We carried out our study on four populations from three longitudinal studies based in the UK and Denmark in which DNA for genotyping was obtained along with measures of obesity.
Our subjects were taken from the British Women's Heart and Health Study (BWHHS), the Avon Longitudinal Study of Parents and Children (two populations: mothers and children) and the Copenhagen City Heart Study. We performed analyses separately by population, and then carried out a meta-analysis, combining similar populations.
Initial findings in the BWHHS suggested that the TT genotype may be associated with an increased risk of obesity BMI > or =30, however, no association was found with BMI or central adiposity in this cohort. This genotype was not associated with obesity in our other cohorts.
Our results suggest that the initial positive finding with obesity in the BWHHS was a chance finding. Our findings do not support a causal effect of low folate on obesity.
European Journal of Endocrinology 07/2008; 159(1):35-40. · 3.42 Impact Factor
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ABSTRACT: The developmental overnutrition hypothesis suggests that greater maternal obesity during pregnancy results in increased offspring adiposity in later life. If true, this would result in the obesity epidemic progressing across generations irrespective of environmental or genetic changes. It is therefore important to robustly test this hypothesis.
We explored this hypothesis by comparing the associations of maternal and paternal pre-pregnancy body mass index (BMI) with offspring dual energy X-ray absorptiometry (DXA)-determined fat mass measured at 9 to 11 y (4,091 parent-offspring trios) and by using maternal FTO genotype, controlling for offspring FTO genotype, as an instrument for maternal adiposity. Both maternal and paternal BMI were positively associated with offspring fat mass, but the maternal association effect size was larger than that in the paternal association in all models: mean difference in offspring sex- and age-standardised fat mass z-score per 1 standard deviation BMI 0.24 (95% confidence interval [CI]: 0.22 to 0.26) for maternal BMI versus 0.13 (95% CI: 0.11, 0.15) for paternal BMI; p-value for difference in effect < 0.001. The stronger maternal association was robust to sensitivity analyses assuming levels of non-paternity up to 20%. When maternal FTO, controlling for offspring FTO, was used as an instrument for the effect of maternal adiposity, the mean difference in offspring fat mass z-score per 1 standard deviation maternal BMI was -0.08 (95% CI: -0.56 to 0.41), with no strong statistical evidence that this differed from the observational ordinary least squares analyses (p = 0.17).
Neither our parental comparisons nor the use of FTO genotype as an instrumental variable, suggest that greater maternal BMI during offspring development has a marked effect on offspring fat mass at age 9-11 y. Developmental overnutrition related to greater maternal BMI is unlikely to have driven the recent obesity epidemic.
PLoS Medicine 03/2008; 5(3):e33. · 16.27 Impact Factor
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ABSTRACT: To explore the developmental origins of cardiorespiratory fitness.
We examined the associations of birth size and duration of breast feeding with cardiorespiratory fitness assessed at the 9 year follow-up examination in 3612 participants of the Avon Longitudinal Study of Parents and Children (ALSPAC). We used physical work capacity at a heart rate of 170 beats per minute (PWC(170)) as our assessment of cardiorespiratory fitness. This was estimated using standard regression methods from parameters measured using an electronically braked cycle ergometer.
Birth weight, length and ponderal index were all positively associated with cardiorespiratory fitness in both sexes, with no strong evidence of a difference in effect between girls and boys. Work capacity increased by 1.12 W (95% CI: 0.83, 1.40) on average per 1 standard deviation (SD) greater birth weight. This association was not affected by adjustment for socioeconomic position and maternal smoking during pregnancy; there was some attenuation with adjustment for both maternal and paternal height and body mass index and more marked attenuation with adjustment for the child's height and body mass index. In the fully adjusted model work capacity increased by 0.51 W (95% CI: 0.21, 0.81) per SD birth weight. Whether an individual had been breastfed and duration of breastfeeding were not associated with cardiorespiratory fitness in any models.
Our results provide some support for a role of intrauterine factors in determining cardiorespiratory fitness in childhood.
European Journal of Epidemiology 02/2008; 23(6):411-22. · 4.71 Impact Factor
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ABSTRACT: The purpose of this study was to compare the accuracy of physical activity energy expenditure (PAEE)-prediction models using accelerometry alone (ACC) and accelerometry combined with heart rate monitoring (HR+ACC) to estimate PAEE during six common activities in children (lying, sitting, slow and brisk walking, hop-scotch, running). Three PAEE-prediction models derived using the current data, and five previously published prediction models were cross-validated to estimate PAEE in this sample.
PAEE was assessed using ACC, HR+ACC, and indirect calorimetry during six activities in 145 children (12.4 +/- 0.2 yr). One ACC and two HR+ACC PAEE-prediction models were derived using linear regression on data from the current study. These three new models were cross-validated using a jackknife approach, and a modified Bland-Altman method was used to assess the validity of all eight models.
PAEE predictions using the one ACC and two HR+ACC models derived in the current study correlated strongly with measured values (RMSE = 97.3-118.0 J.min.kg). All five previously published models agreed well overall (RMSE = 115.6-245.3 J.min.kg), but systematic error was present for most of these, to a greater extent for ACC.
ACC and HR+ACC can both be used to predict overall PAEE during these six activities in children; however, systematic error was present in all predictions. Although both ACC and HR+ACC provide accurate predictions of overall PAEE, according to the activities in this study, PAEE-prediction models using HR+ACC may be more accurate and widely applicable than those based on accelerometry alone.
Medicine & Science in Sports & Exercise 01/2008; 39(12):2180-8. · 4.43 Impact Factor
