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1.  Associations between infant feeding and the size, tempo and velocity of infant weight gain: SITAR analysis of the Gemini twin birth cohort 
Infant growth trajectories, in terms of size, tempo and velocity, may program lifelong obesity risk. Timing of breastfeeding cessation and weaning are both implicated in rapid infant growth; we examined the association of both simultaneously with a range of growth parameters.
Longitudinal population-based twin birth cohort
The Gemini cohort provided data on 4680 UK infants with a median of 10 (IQR 8-15) weight measurements between birth and a median of 6.5 months. Age at breastfeeding cessation and weaning were reported by parents at mean age 8.2 months (SD 2.2, range 4-20). Growth trajectories were modelled using SITAR to generate three descriptors of individual growth relative to the average trajectory: size (grams), tempo (weeks, indicating the timing of the peak growth rate), and velocity (% difference from average, reflecting mean growth rate). Complex-samples general linear models adjusting for family clustering and confounders examined associations between infant feeding and SITAR parameters.
Longer breastfeeding (> 4 months vs. never) was independently associated with lower growth velocity by 6.8% (SE 1.3%), and delayed growth tempo by 1.0 (SE 0.2 weeks), but not with smaller size. Later weaning (≥ 6 months vs. < 4 months) was independently associated with lower growth velocity by 4.9% (SE 1.1%) and smaller size by 102g (SE 25g).
Infants breastfed for longer grew slower for longer after birth (later peak growth rate) but were no different in size, while infants weaned later grew slower overall and were smaller but the timing of peak growth did not differ. Slower trajectories with a delayed peak in growth may have beneficial implications for programming later obesity risk. Replication in cohorts with longer follow-up, alternative confounding structures or randomised controlled trials are required to confirm the long-term effects and directionality, and to rule out residual confounding.
PMCID: PMC4088337  PMID: 24722545
weight gain; growth; infancy; feeding; weaning; breastfeeding; SITAR; Gemini
2.  Prenatal Influences on Size, Velocity and Tempo of Infant Growth: Findings from Three Contemporary Cohorts 
PLoS ONE  2014;9(2):e90291.
Studying prenatal influences of early life growth is relevant to life-course epidemiology as some of its features have been linked to the onset of later diseases.
We studied the association between prenatal maternal characteristics (height, age, parity, education, pre-pregnancy body mass index (BMI), smoking, gestational diabetes and hypertension) and offspring weight trajectories in infancy using SuperImposition by Translation And Rotation (SITAR) models, which parameterize growth in terms of three biologically interpretable parameters: size, velocity and tempo. We used data from three contemporary cohorts based in Portugal (GXXI, n = 738), Italy (NINFEA, n = 2,925), and Chile (GOCS, n = 959).
Estimates were generally consistent across the cohorts for maternal height, age, parity and pre-pregnancy overweight/obesity. Some exposures only affected one growth parameter (e.g. maternal height (per cm): 0.4% increase in size (95% confidence interval (CI):0.3; 0.5)), others were either found to affect size and velocity (e.g. pre-pregnancy underweight vs normal weight: smaller size (−4.9%, 95% CI:−6.5; −3.3), greater velocity (5.9%, 95% CI:1.9;10.0)), or to additionally influence tempo (e.g. pre-pregnancy overweight/obesity vs normal weight: increased size (7.9%, 95% CI:4.9;10.8), delayed tempo (0.26 months, 95% CI:0.11;0.41), decreased velocity (−4.9%, 95% CI: −10.8;0.9)).
By disentangling the growth parameters of size, velocity and tempo, we found that prenatal maternal characteristics, especially maternal smoking, pre-pregnancy overweight and underweight, parity and gestational hypertension, are associated with different aspects of infant weight growth. These results may offer insights into the mechanisms governing infant growth.
PMCID: PMC3937389  PMID: 24587314
3.  Childhood obesity and overweight prevalence trends in England: evidence for growing socio-economic disparities 
International journal of obesity (2005)  2009;34(1):10.1038/ijo.2009.217.
Previous data indicate a rapidly increasing prevalence of obesity and overweight among English children and an emerging socioeconomic gradient in prevalence. The main aim of this study was to update prevalence trends among school-age children and assess the changing socioeconomic gradient.
A series of nationally representative household-based health surveys conducted between 1997 and 2007 in England.
15,271 white children (7880 boys) aged 5 to 10 years with measured height and weight.
Height and weight were directly measured by trained fieldworkers. Overweight (including obesity) and obesity prevalence were calculated using the international body mass index cut-offs. Socioeconomic position (SEP) score was a composite score based on income and social class. Multiple linear regression assessed the prevalence odds with time point (1997/8, 2000/1, 2002/3, 2004/5, 2006/7) as the main exposure. Linear interaction terms of time by SEP were also tested for.
There are signs that the overweight and obesity trend has levelled off from 2002/3 to 2006/7. The odds ratio (OR) for overweight in 2006/7 compared to 2002/3 was 0.99 (95% CI 0.88 to 1.11) and for obesity OR = 1.06 (0.86 to 1.29). The socioeconomic gradient has increased in recent years, particularly 2006/7. Compared to 1997/8, the 2006/7 age and sex-adjusted OR for overweight was 1.88 (1.52 to 2.33) in low SEP, 1.25 (1.04 to 1.50) in middle SEP, and 1.13 (0.86 to 1.48) in high SEP children.
Childhood obesity and overweight prevalence among school-age children in England has stabilised in recent years, but children from lower socio-economic strata have not benefited from this trend. There is an urgent need to reduce socio-economic disparities in childhood overweight and obesity.
PMCID: PMC3865596  PMID: 19884892
Obesity; overweight; children; trends; England; socioeconomic status; socioeconomic position; income
4.  The effect of prepubertal calcium carbonate supplementation on the age of peak height velocity in Gambian adolescents1234 
Background: Limited evidence suggests that calcium intake before puberty influences adolescent height growth and the timing of puberty. Such an effect might be particularly marked in populations in whom low calcium intake, stunting, and delayed puberty are common.
Objective: The objective was to test whether 12 mo of calcium supplementation at age 8–12 y to increase intakes toward international recommendations had long-term effects on adolescent growth and pubertal development in rural Gambian children.
Design: This was a longitudinal study of 160 Gambian boys (n = 80) and girls (n = 80) who had participated in a 12-mo, randomized, double-blind, placebo-controlled, calcium carbonate supplementation trial (1000 mg Ca/d, 5 d/wk) at age 8–12 y. Anthropometric measures were made every 1–2 y until age 21–25 y; pubertal status and menarche data were collected. Repeated-measures ANCOVA and Superimposition by Translation and Rotation Method (SITAR) growth models were used to assess the effects of treatment.
Results: In boys, midadolescent height growth was advanced in the calcium group, which resulted in greater stature at a mean age of 15.5 y (mean ± SEM: 2.0 ± 0.8 cm; P = 0.01) and an earlier age of peak height velocity by 7.4 ± 2.9 mo. Subsequently, the calcium group stopped growing earlier (P = 0.02) and was 3.5 ± 1.1 cm shorter (P = 0.002) at a mean age of 23.5 y. Weight and midupper arm circumference paralleled height. No significant effects were observed in girls, but a sex-by-supplement interaction on height growth could not be confirmed.
Conclusion: Calcium supplementation of boys in late childhood advanced the age of peak height velocity and resulted in shorter adult stature in a population in whom low calcium intakes and delayed puberty are common. This trial was registered at as ISRCTN28836000.
PMCID: PMC3642996  PMID: 22990031
The European respiratory journal  2012;40(6):1324-1343.
Derive continuous prediction equations and their lower limits of normal for spirometric indices, which are applicable globally.
Over 160,000 data points from 72 centres in 33 countries were shared with the European Respiratory Society Global Lung Function Initiative. Eliminating data that could not be used (mostly missing ethnic group, some outliers) left 97,759 records of healthy nonsmokers (55.3% females) aged 2.5–95 years.
Lung function data were collated, and prediction equations derived using the LMS (λ, µ, σ) method, which allows simultaneous modelling of the mean (mu), the coefficient of variation (sigma) and skewness (lambda) of a distribution family.
After discarding 23,572 records, mostly because they could not be combined with other ethnic or geographic groups, reference equations were derived for healthy individuals from 3–95 years for Caucasians (N=57,395), African Americans (N=3,545), and North (N=4,992) and South East Asians (N=8,255). FEV1 and FVC between ethnic groups differed proportionally from that in Caucasians, such that FEV1/FVC remained virtually independent of ethnic group. For individuals not represented by these four groups, or of mixed ethnic origins, a composite equation taken as the average of the above equations is provided to facilitate interpretation until a more appropriate solution is developed.
Spirometric prediction equations for the 3–95 age range are now available that include appropriate age-dependent lower limits of normal. They can be applied globally to different ethnic groups. Additional data from the Indian subcontinent, Arab, Polynesian, Latin American countries, and Africa will further improve these equations in the future.
PMCID: PMC3786581  PMID: 22743675
6.  Randomized, placebo-controlled, calcium supplementation trial in pregnant Gambian women accustomed to a low calcium intake: effects on maternal blood pressure and infant growth1234 
Background: Dietary calcium intake in rural Gambian women is very low (∼350 mg/d) compared with international recommendations. Studies have suggested that calcium supplementation of women receiving low-calcium diets significantly reduces risk of pregnancy hypertension.
Objective: We tested the effects on blood pressure (BP) of calcium carbonate supplementation (1500 mg Ca/d) in pregnant, rural Gambian women.
Design: The study was a randomized, double-blind, parallel, placebo-controlled supplementation trial from 20 wk of gestation (P20) until delivery (calcium: n = 330; placebo; n = 332). BP and anthropometric measures were taken at P20 and then 4 weekly until 36 wk of gestation (P36), and infant anthropometric measures were taken at 2, 13, and 52 wk postdelivery.
Results: A total of 525 (calcium: n = 260; placebo: n = 265) women had BP measured at P36 and subsequently delivered a healthy term singleton infant. Mean compliance was 97%, and urinary calcium measures confirmed the group allocation. At P20, the mean (±SD) systolic blood pressure (SBP) was 101.2 ± 9.0 and 102.1 ± 9.3 mm Hg, and diastolic blood pressure (DBP) was 54.5 ± 7.3 and 55.8 ± 7.8 mm Hg, in the calcium and placebo groups, respectively. The intention-to-treat analysis that was adjusted for confounders showed no significant effect of calcium supplementation on the change between P20 and P36 (calcium compared with placebo; mean ± SEM) in SBP (−0.64 ± 0.65%; P = 0.3) or DBP (−0.22 ± 1.15%; P = 0.8). There was no significant effect of supplementation on BP, pregnancy weight gain, weight postpartum, or infant weight, length, and other measures of growth. However, the comparability of the original randomly assigned groups may have been compromised by the exclusion of 20.7% of women from the final analysis.
Conclusions: Calcium supplementation did not affect BP in pregnancy. This result may have been because the Gambian women were adapted to a low dietary calcium intake, and/or obesity, high gestational weight gain, high underlying BP, tobacco use, alcohol consumption, and sedentary lifestyles were rare. This trial was registered at the International Standard Randomized Controlled Trial Register ( as ISRCTN96502494.
PMCID: PMC3778867  PMID: 24004887
7.  Unexpected long-term effects of calcium supplementation in pregnancy on maternal bone outcomes in women with a low calcium intake: a follow-up study123 
Background: Calcium supplementation of pregnant Gambian women with a low calcium intake results in lower maternal bone mineral content in the subsequent lactation.
Objective: The objective was to investigate whether the lower bone mineral content persists long term.
Design: All women in the calcium supplementation trial (International Trial Registry ISRCTN96502494) who had been scanned with dual-energy X-ray absorptiometry at 52 wk of lactation (L52; n = 79) were invited for follow-up when neither pregnant nor lactating for ≥3 mo (NPNL) or at 52 wk postpartum in a future lactation (F52). Bone scans and anthropometric and dietary assessments were conducted.
Results: Sixty-eight women participated (35 at both NPNL and F52 and 33 at only one time point): n = 59 NPNL (n = 31 calcium, n = 28 placebo) and n = 44 F52 (n = 24 calcium, n = 20 placebo). The mean (±SD) time from L52 was 4.9 ± 1.9 y for NPNL and 5.0 ± 1.3 y for F52. Size-adjusted bone mineral content (SA-BMC) was greater at NPNL than at L52 in the placebo group (P ≤ 0.001) but not in the calcium group (P for time-by-group interaction: lumbar spine, 0.002; total hip, 0.03; whole body, 0.03). No significant changes in SA-BMC from L52 to F52 were observed in either group. Consequently, the lower SA-BMC in the calcium group at L52 persisted at NPNL and F52 (P ≤ 0.001): NPNL (lumbar spine, −7.5 ± 0.7%; total hip, −10.5 ± 1.0%; whole body, −3.6 ± 0.5%) and F52 (lumbar spine, −6.2 ± 0.9%; total hip, −10.3 ± 1.4%; whole body, −3.2 ± 0.6%).
Conclusion: In rural Gambian women with a low-calcium diet, a calcium supplement of 1500 mg/d during pregnancy resulted in lower maternal bone mineral content in the subsequent lactation that persisted long term. This trial was registered at www/ as ISRCTN96502494.
PMCID: PMC3743734  PMID: 23902782
8.  How active are our children? Findings from the Millennium Cohort Study 
BMJ Open  2013;3(8):e002893.
To describe levels of physical activity, sedentary time and adherence to Chief Medical Officers (CMO) physical activity guidelines among primary school-aged children across the UK using objective accelerometer-based measurements.
Nationally representative prospective cohort study.
Children born across the UK, between 2000 and 2002.
6497 7-year-old to 8-year-old singleton children for whom reliable accelerometer data were available for at least 10 h a day for at least 2 days.
Main outcome measures
Physical activity in counts per minute (cpm); time spent in sedentary and moderate-to-vigorous intensity physical activity (MVPA); proportion of children meeting CMO guidelines (≥60 min/day MVPA); average daily steps.
Explanatory measures
Gender, ethnicity, maternal current/most recent occupation, lone parenthood status, number of children in the household and country/region of residence.
The median daily physical activity level was 595 cpm (IQR 507, 697). Children spent a median of 60 min (IQR 47–76) in MVPA/day and were sedentary for a median of 6.4 h/day (IQR 6–7). Only 51% met CMO guidelines, with girls (38%) less active than boys (63%). Children took an average of 10 229 (95% CI (8777 to 11 775)) steps each day. Children of Indian ethnicity were significantly less active overall than all other ethnic groups. Children of Bangladeshi origin and those living in Northern Ireland were least likely to meet CMO guidelines.
Only half of 7-year-old children in the UK achieve recommended levels of physical activity, with significant gender, ethnic and geographic variations. Longitudinal studies are needed to better understand the relevance of these (in)activity patterns for long-term health and well-being. In the meantime population-wide efforts to boost physical activity among young people are needed which are likely to require a broad range of policy interventions.
PMCID: PMC3752053  PMID: 23965931
Public Health; Sports Medicine; Paediatrics
9.  Blood pressure centiles for Great Britain 
Archives of Disease in Childhood  2006;92(4):298-303.
To produce representative cross‐sectional blood pressure reference centiles for children and young people living in Great Britain.
Analysis of blood pressure data from seven nationally representative surveys: Health Surveys for England 1995–8, Scottish Health Surveys 1995 and 1998, and National Diet & Nutrition Survey 1997.
Blood pressure was measured using the Dinamap 8100 with the same protocol throughout. Weight and height were also measured. Data for 11 364 males and 11 537 females aged 4–23 years were included in the analysis, after excluding 0.3% missing or outlying data. Centiles were derived for systolic, diastolic, mean arterial and pulse pressure using the latent moderated structural (LMS) equations method.
Blood pressure in the two sexes was similar in childhood, rising progressively with age and more rapidly during puberty. Systolic pressure rose faster and was appreciably higher in adult men than in adult women. After adjustment for age, blood pressure was related more to weight than height, the effect being stronger for systolic blood pressure. Pulse pressure peaked at 18 years in males and 16 years in females.
These centiles increase our knowledge of blood pressure norms in contemporary British children and young people. High blood pressure for age should be defined as blood pressure above the 98th centile, and high‐normal blood pressure for age as blood pressure between the 91st and 98th centiles. The centiles identify children and young people with increased blood pressure, and will be of benefit to both clinical practice and research.
PMCID: PMC2083671  PMID: 16905566
10.  Designing the new UK-WHO growth charts to enhance assessment of growth around birth 
The decision to adopt the new WHO standard in the UK necessitated substantial changes to the neonatal section of the chart, including separation of the preterm UK birthweight reference from the WHO standard. The evidence-based design process has led to several novel features that could be generally applied in other chart designs, and revealed uncertainties leading to inconsistencies in charting. Failing to plot birthweight of term infants at age 0 can lead to spurious centile crossing in the early weeks of life, particularly among infants at the extreme of gestation. Users will need training to use the charts, but this should improve overall understanding and use of charts.
PMCID: PMC3546314  PMID: 21398325
11.  Human Life History Evolution Explains Dissociation between the Timing of Tooth Eruption and Peak Rates of Root Growth 
PLoS ONE  2013;8(1):e54534.
We explored the relationship between growth in tooth root length and the modern human extended period of childhood. Tooth roots provide support to counter chewing forces and so it is advantageous to grow roots quickly to allow teeth to erupt into function as early as possible. Growth in tooth root length occurs with a characteristic spurt or peak in rate sometime between tooth crown completion and root apex closure. Here we show that in Pan troglodytes the peak in root growth rate coincides with the period of time teeth are erupting into function. However, the timing of peak root velocity in modern humans occurs earlier than expected and coincides better with estimates for tooth eruption times in Homo erectus. With more time to grow longer roots prior to eruption and smaller teeth that now require less support at the time they come into function, the root growth spurt no longer confers any advantage in modern humans. We suggest that a prolonged life history schedule eventually neutralised this adaptation some time after the appearance of Homo erectus. The root spurt persists in modern humans as an intrinsic marker event that shows selection operated, not primarily on tooth tissue growth, but on the process of tooth eruption. This demonstrates the overarching influence of life history evolution on several aspects of dental development. These new insights into tooth root growth now provide an additional line of enquiry that may contribute to future studies of more recent life history and dietary adaptations within the genus Homo.
PMCID: PMC3544739  PMID: 23342167
12.  Trade-Offs in Relative Limb Length among Peruvian Children: Extending the Thrifty Phenotype Hypothesis to Limb Proportions 
PLoS ONE  2012;7(12):e51795.
Background and Methods
Both the concept of ‘brain-sparing’ growth and associations between relative lower limb length, childhood environment and adult disease risk are well established. Furthermore, tibia length is suggested to be particularly plastic under conditions of environmental stress. The mechanisms responsible are uncertain, but three hypotheses may be relevant. The ‘thrifty phenotype’ assumes that some components of growth are selectively sacrificed to preserve more critical outcomes, like the brain. The ‘distal blood flow’ hypothesis assumes that blood nutrients decline with distance from the heart, and hence may affect limbs in relation to basic body geometry. Temperature adaptation predicts a gradient of decreased size along the limbs reflecting decreasing tissue temperature/blood flow. We examined these questions by comparing the size of body segments among Peruvian children born and raised in differentially stressful environments. In a cross-sectional sample of children aged 6 months to 14 years (n = 447) we measured head circumference, head-trunk height, total upper and lower limb lengths, and zeugopod (ulna and tibia) and autopod (hand and foot) lengths.
Highland children (exposed to greater stress) had significantly shorter limbs and zeugopod and autopod elements than lowland children, while differences in head-trunk height were smaller. Zeugopod elements appeared most sensitive to environmental conditions, as they were relatively shorter among highland children than their respective autopod elements.
The results suggest that functional traits (hand, foot, and head) may be partially protected at the expense of the tibia and ulna. The results do not fit the predictions of the distal blood flow and temperature adaptation models as explanations for relative limb segment growth under stress conditions. Rather, our data support the extension of the thrifty phenotype hypothesis to limb growth, and suggest that certain elements of limb growth may be sacrificed under tough conditions to buffer more functional traits.
PMCID: PMC3521697  PMID: 23272169
13.  Assessing the efficacy of the healthy eating and lifestyle programme (HELP) compared with enhanced standard care of the obese adolescent in the community: study protocol for a randomized controlled trial 
Trials  2011;12:242.
The childhood obesity epidemic is one of the foremost UK health priorities. Childhood obesity tracks into adult life and places individuals at considerable risk for diabetes, cardiovascular disease, liver disease and other morbidities. There is widespread need for paediatric lifestyle programmes as change may be easier to accomplish in childhood than later in life.
Study Design/Method
The study will evaluate the management of adolescent obesity by conducting a Medical Research Council complex intervention phase III efficacy randomised clinical trial of the Healthy Eating Lifestyle Programme within primary care. The study tests a community delivered multi-component intervention designed for adolescents developed from best practice as identified by National Institute for Health and Clinical Excellence. The hospital based pilot reduced body mass index and improved health-related quality of life.
Subjects will be individually randomised to receiving either the Healthy Eating Lifestyle Programme (12 fortnightly family sessions) or enhanced standard care. Baseline and follow up assessments will be undertaken blind to allocation status. A health economic evaluation is also being conducted.
200 obese young people (13-17 years, body mass index > 98th centile for age and sex) will be recruited from primary care within the greater London area.
The primary hypothesis is that a motivational and solution-focused family-based weight management programme delivered over 6 months is more efficacious in reducing body mass index in obese adolescents identified in the community than enhanced standard care.
The primary outcome will be body mass index at the end of the intervention, adjusted for baseline body mass index, age and sex.
The secondary hypothesis is that the Healthy Eating Lifestyle Programme is more efficacious in improving quality of life and psychological function and reducing waist circumference and cardiovascular risk factors in obese adolescents than enhanced standard care assessed at 6 and 12 months post baseline assessment.
Improvement in quality of life predicts on-going lifestyle change and maximises the chances of long-term weight reduction. We will explore whether improvement in QOL may be intermediate on the pathway between the intervention and body mass index change.
Trial registration
PMCID: PMC3267689  PMID: 22088133
14.  Effect of oxandrolone and timing of pubertal induction on final height in Turner’s syndrome: randomised, double blind, placebo controlled trial 
Objective To examine the effect of oxandrolone and the timing of pubertal induction on final height in girls with Turner’s syndrome receiving a standard dose of growth hormone.
Design Randomised, double blind, placebo controlled trial.
Setting 36 paediatric endocrinology departments in UK hospitals.
Participants Girls with Turner’s syndrome aged 7-13 years at recruitment, receiving recombinant growth hormone therapy (10 mg/m2/week).
Interventions Participants were randomised to oxandrolone (0.05 mg/kg/day, maximum 2.5 mg/day) or placebo from 9 years of age. Those with evidence of ovarian failure at 12 years were further randomised to oral ethinylestradiol (year 1, 2 µg daily; year 2, 4 μg daily; year 3, 4 months each of 6, 8, and 10 μg daily) or placebo; participants who received placebo and those recruited after the age of 12.25 years started ethinylestradiol at age 14.
Main outcome measure Final height.
Results 106 participants were recruited, of whom 14 withdrew and 82/92 reached final height. Both oxandrolone and late pubertal induction increased final height: by 4.6 (95% confidence interval 1.9 to 7.2) cm (P=0.001, n=82) for oxandrolone and 3.8 (0.0 to 7.5) cm (P=0.05, n=48) for late pubertal induction with ethinylestradiol. In the 48 children who were randomised twice, the effects on final height (compared with placebo and early induction of puberty) of oxandrolone alone, late induction alone, and oxandrolone plus late induction were similar, averaging 7.1 (3.4 to 10.8) cm (P<0.001). No cases of virilisation were reported.
Conclusion Oxandrolone had a positive effect on final height in girls with Turner’s syndrome treated with growth hormone, as did late pubertal induction with ethinylestradiol at age 14 years. However, these effects were not additive, so using both had no advantage. Oxandrolone could, therefore, be offered as an alternative to late pubertal induction for increasing final height in Turner’s syndrome.
Trial registration Current Controlled Trials ISRCTN50343149.
PMCID: PMC3076731  PMID: 21493672
15.  SITAR—a useful instrument for growth curve analysis 
Background Growth curve analysis is a statistical issue in life course epidemiology. Height in puberty involves a growth spurt, the timing and intensity of which varies between individuals. Such data can be summarized with individual Preece–Baines (PB) curves, and their five parameters then related to earlier exposures or later outcomes. But it involves fitting many curves.
Methods We present an alternative SuperImposition by Translation And Rotation (SITAR) model, a shape invariant model with a single fitted curve. Curves for individuals are matched to the mean curve by shifting their curve up–down (representing differences in mean size) and left–right (for differences in growth tempo), and the age scale is also shrunk or stretched to indicate how fast time passes in the individual (i.e. velocity). These three parameters per individual are estimated as random effects while fitting the curve. The outcome is a mean curve plus triplets of parameters per individual (size, tempo and velocity) that summarize the individual growth patterns. The data are heights for Christ’s Hospital School (CHS) boys aged 9–19 years (N = 3245, n = 129 508), and girls with Turner syndrome (TS) aged 9–18 years from the UK Turner Study (N = 105, n = 1321).
Results The SITAR model explained 99% of the variance in both datasets [residual standard deviation (RSD) 6–7 mm], matching the fit of individually-fitted PB curves. In CHS, growth tempo was associated with insulin-like growth factor-1 measured 50 years later (P = 0.01, N = 1009). For the girls with TS randomized to receive oxandrolone from 9 years, velocity was substantially increased compared with placebo (P = 10−8).
Conclusions The SITAR growth curve model is a useful epidemiological instrument for the analysis of height in puberty.
PMCID: PMC2992626  PMID: 20647267
Height; puberty; Turner syndrome; growth curve; random effects
16.  An ecological systems approach to examining risk factors for early childhood overweight: findings from the UK Millennium Cohort Study 
To use an ecological systems approach to examine individual-, family-, community-, and area-level risk factors for overweight (including obesity) in 3-year-old children.
Prospective nationally representative cohort study
England, Wales, Scotland, Northern Ireland
13 188 singleton children age three in the Millennium Cohort Study, born between 2000 and 2002, who had complete height/weight data
Main outcome measure
Childhood overweight (including obesity) defined by the International Obesity TaskForce cut-offs for body mass index
23.0% of 3-year-old children were overweight or obese. In the fully adjusted model, primarily individual- and family-level factors were associated with early childhood overweight: birthweight z-score (adjusted odds ratio, 1.36, 95% CI 1.30 to 1.42), Black ethnicity (1.41, 1.11 to 1.80) (compared to white), introduction to solid foods <4 months (1.12, 1.02 to 1.23), lone motherhood (1.32, 1.15 to 1.51), smoking during pregnancy (1-9 cigarettes daily: 1.34, 1.17 to 1.54; 10-19: 1.49, 1.26 to 1.75; 20+: 1.34, 1.05 to 1.70), parental overweight (both: 1.89, 1.63 to 2.19; father only: 1.45, 1.28 to 1.63; mother only: 1.37, 1.18 to 1.58), prepregnancy overweight (1.28, 1.14 to 1.45), and maternal employment ≥21 hours/week (1.23, 1.10 to 1.37) (compared to never worked). Breastfeeding ≥4 months (0.86, 0.76 to 0.97) (compared to none) and Indian ethnicity (0.63, 0.42 to 0.94) were associated with a decreased risk of early childhood overweight. Children from Wales were also more likely to be overweight than children from England.
Most risk factors for early childhood overweight are modifiable or would allow at-risk groups to be identified. Policies and interventions should focus on parents and providing them with an environment to support healthy behaviours for themselves and their children.
PMCID: PMC2678539  PMID: 18801795
obesity; preschool children; parents
17.  Regional differences in overweight: an effect of people or place? 
Archives of disease in childhood  2007;93(5):407-413.
To examine UK country and regional differences, within England only, in childhood overweight (including obesity) at three years and determine whether any differences persist after adjustment for individual risk factors.
Nationally representative prospective study
England, Wales, Scotland, and Northern Ireland
13 194 singleton children from the UK Millennium Cohort Study with height and weight data at age three years.
Main outcome measure:
Overweight (including obesity) was defined by the International Obesity TaskForce cut-offs for body mass index, which are age and sex specific.
At three years, 23.0% (3102) of children were overweight or obese. In univariable analyses, children from Northern Ireland (odds ratio 1.30, 95% Confidence Interval 1.14 to 1.48) and Wales (1.26, 1.11 to 1.44) were more likely to be overweight than children from England. There were no differences in overweight between children from Scotland and England. Within England, children from the East (0.71, 0.57 to 0.88) and South East regions (0.82, 0.68 to 0.99) were less likely to be overweight than children from London. There were no differences in overweight between children from other English regions and children from London. These differences were maintained after adjustment for individual socio-demographic characteristics and other risk factors for overweight.
UK country and English regional differences in early childhood overweight are independent of individual risk factors. This suggests a role for policies to support environmental changes that remove barriers to physical activity or healthy eating for young children.
PMCID: PMC2679152  PMID: 18089633
obesity; preschool children; public policy
18.  Maternal employment and early childhood overweight: findings from the UK Millennium Cohort Study 
In most developed countries, maternal employment has increased rapidly. Changing patterns of family life have been suggested to be contributing to the rising prevalence of childhood obesity.
Our primary objective was to examine the relationship between maternal and partner employment and overweight in children aged three years. Our secondary objective was to investigate factors related to early childhood overweight only among mothers in employment.
Cohort study
13113 singleton children aged three years in the Millennium Cohort Study, born between 2000 and 2002 in the United Kingdom, who had complete height/weight data and parental employment histories.
Parents were interviewed when the child was aged 9 months and 3 years and the child's height and weight were measured at 3 years. Overweight (including obesity) was defined by the International Obesity Task Force cut-offs.
23% (3085) of children were overweight at 3 years. Any maternal employment after the child's birth was associated with early childhood overweight (OR [95% CI]; 1.14 [1.00, 1.29]), after adjustment for potential confounding and mediating factors. Children were more likely to be overweight for every 10 hours a mother worked per week (OR [95% CI]; 1.10 [1.04, 1.17]), after adjustment. An interaction with household income revealed that this relationship was only significant for children from households with an annual income of £33,000 ($57,750) or higher. There was no evidence for an association between early childhood overweight and whether or for how many hours the partner worked or with mothers' or partners' duration of employment. These relationships were found to be stronger among mothers in employment. Independent risk factors for early childhood overweight were consistent with the published literature.
Long hours of maternal employment rather than lack of money may impede young children's access to healthy foods and physical activity. Policies supporting work-life balance may help parents reduce potential barriers.
PMCID: PMC2679151  PMID: 17637703
obesity; preschool children; employment; mothers; fathers
19.  Child body mass index in four cities of East China compared to Western references 
Annals of Human Biology  2008;36(1):98-109.
The rising trends in child obesity worldwide are poorly documented in China.
The present study compared the distribution of body mass index (BMI) by age in children from four cities in East China with Western references.
Subjects and methods
94 370 boys and 90 048 girls aged 0–19 years from Shanghai, Jinan, Xuzhou and Hefei were measured in 1999–2004 for length/height and weight. The LMS method was used to construct BMI centiles for each city. Shanghai children aged 0–6 years in 1986 and US and UK BMI references were used for comparison.
The median BMI curves for the four cities differed in shape from those for the USA and UK. Chinese boys were fatter than US boys in early to mid-childhood but less so in adolescence, and US boys were fatter at age 18. Within China the adiposity rebound was earlier in boys than girls. Shanghai children were appreciably fatter in 2000 than in 1986, and boys more so than girls.
The roots of child obesity lie in early life, particularly in boys, and are linked to economic development, which has important implications for both the aetiology of child obesity and the health of current and future Chinese children.
PMCID: PMC2645134  PMID: 19085513
Child; overweight; obesity; body mass index; China
20.  Reference Ranges for Spirometry Across All Ages 
Rationale: The Third National Health and Nutrition Examination Survey (NHANES III) reference is currently recommended for interpreting spirometry results, but it is limited by the lack of subjects younger than 8 years and does not continuously model spirometry across all ages.
Objectives: By collating pediatric data from other large-population surveys, we have investigated ways of developing reference ranges that more accurately describe the relationship between spirometric lung function and height and age within the pediatric age range, and allow a seamless transition to adulthood.
Methods: Data were obtained from four surveys and included 3,598 subjects aged 4–80 years. The original analyses were sex specific and limited to non-Hispanic white subjects. An extension of the LMS (lambda, mu, sigma) method, widely used to construct growth reference charts, was applied.
Measurements and Main Results: The extended models have four important advantages over the original NHANES III analysis as follows: (1) they extend the reference data down to 4 years of age, (2) they incorporate the relationship between height and age in a way that is biologically plausible, (3) they provide smoothly changing curves to describe the transition between childhood and adulthood, and (4) they highlight the fact that the range of normal values is highly dependent on age.
Conclusions: The modeling technique provides an elegant solution to a complex and longstanding problem. Furthermore, it provides a biologically plausible and statistically robust means of developing continuous reference ranges from early childhood to old age. These dynamic models provide a platform from which future studies can be developed to continue to improve the accuracy of reference data for pulmonary function tests.
PMCID: PMC2643211  PMID: 18006882
spirometry; pulmonary function; reference values
21.  Influence of moving to the UK on maternal health behaviours: prospective cohort study 
BMJ : British Medical Journal  2008;336(7652):1052-1055.
Objective To compare health behaviours during pregnancy (smoking and alcohol consumption) and after birth (initiation and duration of breast feeding) between British/Irish white mothers and mothers from ethnic minority groups; and, in mothers from ethnic minority groups, to examine whether indicators of acculturation (generational status, language spoken at home, length of residency in the United Kingdom) were associated with these health behaviours.
Design Prospective nationally representative cohort study.
Setting England.
Participants 6478 British/Irish white mothers and 2110 mothers from ethnic minority groups.
Main outcome measures Any smoking during pregnancy; any alcohol consumption during pregnancy; initiation of breast feeding; breast feeding for at least four months.
Results Compared with British/Irish white mothers, mothers from ethnic minority groups were less likely to smoke (15% v 37%) or consume alcohol (14% v 37%) during pregnancy but more likely to initiate breast feeding (86% v 69%) and breast feed for at least four months (40% v 27%). Among mothers from ethnic minority groups, first and second generation mothers were more likely to smoke during pregnancy (odds ratio 3.85, 95% confidence interval 2.50 to 5.93, and 4.70, 2.49 to 8.90, respectively), less likely to initiate breast feeding (0.92, 0.88 to 0.97, and 0.86, 0.75 to 0.99), and less likely to breast feed for at least four months (0.72, 0.62 to 0.83, and 0.52, 0.30 to 0.89) than immigrants, after adjustment for sociodemographic characteristics. There were no consistent differences in alcohol consumption. Among immigrants, for every additional five years spent in the UK the likelihood of mothers smoking during pregnancy increased by 31% (4% to 66%) and they were 5% (0% to 10%) less likely to breast feed for at least four months.
Conclusions After immigration, maternal health behaviours worsen with length of residency in the UK. Health professionals should not underestimate women’s likelihood of engaging in risky health behaviours because of their ethnicity.
PMCID: PMC2375984  PMID: 18403500
22.  Factors associated with uptake of measles, mumps, and rubella vaccine (MMR) and use of single antigen vaccines in a contemporary UK cohort: prospective cohort study 
BMJ : British Medical Journal  2008;336(7647):754-757.
Objectives To estimate uptake of the combined measles, mumps, and rubella vaccine (MMR) and single antigen vaccines and explore factors associated with uptake and reasons for not using MMR.
Design Nationally representative cohort study.
Setting Children born in the UK, 2000-2.
Participants 14 578 children for whom data on immunisation were available.
Main outcome measures Immunisation status at 3 years defined as “immunised with MMR,” “immunised with at least one single antigen vaccine,” and “unimmunised.”
Results 88.6% (13 013) were immunised with MMR and 5.2% (634) had received at least one single antigen vaccine. Children were more likely to be unimmunised if they lived in a household with other children (risk ratio 1.74, 95% confidence interval 1.35 to 2.25, for those living with three or more) or a lone parent (1.31, 1.07 to 1.60) or if their mother was under 20 (1.41, 1.08 to 1.85) or over 34 at cohort child’s birth (reaching 2.34, 1.20 to 3.23, for ≥40), more highly educated (1.41, 1.05 to 1.89, for a degree), not employed (1.43, 1.12 to 1.82), or self employed (1.71, 1.18 to 2.47). Use of single vaccines increased with household income (reaching 2.98, 2.05 to 4.32, for incomes of ≥£52 000 (€69 750, $102 190)), maternal age (reaching 3.04, 2.05 to 4.50, for ≥40), and education (reaching 3.15, 1.78 to 5.58, for a degree). Children were less likely to have received single vaccines if they lived with other children (reaching 0.14, 0.07 to 0.29, for three or more), had mothers who were Indian (0.50, 0.25 to 0.99), Pakistani or Bangladeshi (0.13, 0.04 to 0.39), or black (0.31, 0.14 to 0.64), or aged under 25 (reaching 0.14, 0.05 to 0.36, for 14-19). Nearly three quarters (74.4%, 1110) of parents who did not immunise with MMR made a “conscious decision” not to immunise.
Conclusions Although MMR uptake in this cohort is high, a substantial proportion of children remain susceptible to avoidable infection, largely because parents consciously decide not to immunise. Social differentials in uptake could be used to inform targeted interventions to promote uptake.
PMCID: PMC2287222  PMID: 18309964
23.  Body mass index cut offs to define thinness in children and adolescents: international survey 
BMJ : British Medical Journal  2007;335(7612):194.
Objective To determine cut offs to define thinness in children and adolescents, based on body mass index at age 18 years.
Design International survey of six large nationally representative cross sectional studies on growth.
Setting Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States.
Subjects 97 876 males and 94 851 females from birth to 25 years.
Main outcome measure Body mass index (BMI, weight/height2).
Results The World Health Organization defines grade 2 thinness in adults as BMI <17. This same cut off, applied to the six datasets at age 18 years, gave mean BMI close to a z score of −2 and 80% of the median. Thus it matches existing criteria for wasting in children based on weight for height. For each dataset, centile curves were drawn to pass through the cut off of BMI 17 at 18 years. The resulting curves were averaged to provide age and sex specific cut-off points from 2-18 years. Similar cut offs were derived based on BMI 16 and 18.5 at 18 years, together providing definitions of thinness grades 1, 2, and 3 in children and adolescents consistent with the WHO adult definitions.
Conclusions The proposed cut-off points should help to provide internationally comparable prevalence rates of thinness in children and adolescents.
PMCID: PMC1934447  PMID: 17591624
24.  Blood pressure centiles for Great Britain 
Archives of Disease in Childhood  2006;92(4):298-303.
To produce representative cross-sectional blood pressure reference centiles for children and young people living in Great Britain.
Analysis of blood pressure data from seven nationally representative surveys: Health Surveys for England 1995–8, Scottish Health Surveys 1995 and 1998, and National Diet & Nutrition Survey 1997.
Blood pressure was measured using the Dinamap 8100 with the same protocol throughout. Weight and height were also measured. Data for 11 364 males and 11 537 females aged 4–23 years were included in the analysis, after excluding 0.3% missing or outlying data. Centiles were derived for systolic, diastolic, mean arterial and pulse pressure using the lambda-mu-sigma (LMS) equations method.
Blood pressure in the two sexes was similar in childhood, rising progressively with age and more rapidly during puberty. Systolic pressure rose faster and was appreciably higher in adult men than in adult women. After adjustment for age, blood pressure was related more to weight than height, the effect being stronger for systolic blood pressure. Pulse pressure peaked at 18 years in males and 16 years in females.
These centiles increase our knowledge of blood pressure norms in contemporary British children and young people. High blood pressure for age should be defined as blood pressure above the 98th centile, and high-normal blood pressure for age as blood pressure between the 91st and 98th centiles. The centiles identify children and young people with increased blood pressure, and will be of benefit to both clinical practice and research.
PMCID: PMC2083671  PMID: 16905566
25.  Development of adiposity in adolescence: five year longitudinal study of an ethnically and socioeconomically diverse sample of young people in Britain 
BMJ : British Medical Journal  2006;332(7550):1130-1135.
Objective To examine the developmental trajectory of obesity in adolescence in relation to sex, ethnicity, and socioeconomic status.
Design Five year longitudinal cohort study of a socioeconomically and ethnically diverse sample of school students aged 11-12 years at baseline.
Setting 36 London schools recruited to the study in 1999 by a stratified random sampling procedure.
Participants 5863 students participated in one or more years.
Main outcome measures Weight, height, and waist circumference measured annually by trained researchers; overweight and obesity defined according to International Obesity Task Force criteria; adiposity and central adiposity indexed by body mass index (BMI) and waist standard deviation scores relative to 1990 British reference values.
Results In school year 7 (age 11-12), the prevalence of overweight and obesity combined was almost 25%, with higher rates in girls (29%) and students from lower socioeconomic backgrounds (31%) and the highest rates in black girls (38%). Prevalence of obesity increased over the five years of the study at the expense of overweight, but no reduction occurred in the proportion of students with BMIs in the healthy range. Waist circumferences were high compared with 1990 norms at age 11 (by 0.79 SD in boys and by 1.15 SD in girls) and increased further over time. Both BMI and waist circumference tracked strongly over the five years.
Conclusions Prevalence of overweight and obesity was high in London school students, with significant socioeconomic and ethnic inequalities. Little evidence was found of new cases of overweight or obesity emerging over adolescence, but few obese or overweight adolescents reduced to a healthy weight. The results indicate that persistent obesity is established before age 11 and highlight the need to target efforts to prevent obesity in the early years.
PMCID: PMC1459611  PMID: 16679329

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