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Category 1

21st Jun 2019

Introduction: Life-course approaches to determine risk factor exposure are increasingly favoured over traditional ‘once-only’ epidemiological determination. One is latent class trajectory modelling (LCTM), which clusters individuals’ changes in exposure over time and can be used as a tool for identifying early divergent adverse trajectories. There is increasing use of LCTMs in mainstream epidemiology, but often with poor model description, and an over-reliance on BIC for model selection. Here, we aimed to explore methods in deriving and validating LCTMs from multiple cohorts to ensure that they properly represent observed patterns across different populations.
Methods: We interrogated three cohorts, AARP (N: 321,827), PLCO (N: 147,488) and WHI (N: 151,363), with longitudinal BMI as the exposure and cancer incidence as the endpoint of interest. We extended our previous work (https://bmjopen.bmj.com/content/8/7/e020683) to (i) testing multiple start points to obtain the global maximums; (ii) facilitating model choice with alternative metrics to BIC; (iii) developing visual model assessment tools.
Results: We illustrate a number of examples where deviation from model assumptions yield very different classifications. After arriving at preferred models, we show that LCTM improve the performance characteristics of BMI exposure, compared with once only BMI measures, however, this improvement is clinically modest. LCTM might best identify specific sub-populations that have very high risk for cancer incidence.
Conclusions: The study highlights that model selection needs to be undertaken with care and not based solely determined by lowest BIC. We emphasise that multiple start points should be tested when using these models.


06th Jun 2019

INTRODUCTION: Clinical tooth eruption is defined as the first evidence of tooth emergence of the crown through the gingiva into the mouth. Studies report it to be earlier in African groups to others with different ethnic background or origin. Assessing eruption from radiographs presents clearer and more detailed reference points, such as the alveolar crest and roots, and is thought to be less variable compared to clinical emergence. No studies describe alveolar eruption from Africa.
AIM: To describe alveolar ridge attainment for children from Sudan and compare them to other groups with different ancestry.
METHODS Alveolar ridge attainment, of all mandibular and maxillary teeth on the left side, was assessed from dental radiographs, in teeth and 782 children (452 males, 330 females), from a dental practice in Khartoum. The children were equally distributed across age (3-23 years). The left maxillary and mandibular permanent teeth scored in relation to alveolar ridge bone. Mean age was calculated using probit regression analysis. Males and females were compared using student t-test.
RESULTS: Mean ages at entry of alveolar eruption were similar males and females (p>0.05). Only males were compared in this study. Alveolar eruption was similar between males from Sudan and children from London. Mean alveolar times are presented for all teeth.
Discussion AND CONCLUSIONS: This is the first study to present data from African groups and shows that eruption is similar in 2 geographically distinct regions. No studies on alveolar eruption exist from African to enable comparison. Further studies are required to investigate why Africans are advanced in clinical emergence but not radiographic alveolar crest attainment.


21st May 2019

Second Abstract Proposal
Human Genetics code(Unmasked).
My Research works consist of these: 1) Y chromosomes confirmation both found and exist inside the human female egg cells and male sperm cells with X chromosome inside. 2) early detection of infertility and fertility, menopause and stress (Male/Female). 3) Detection of DNA’s Child links – connected to his/her original parents (Father/Mother). 4) Early detection of gender fetus/embryos either first Baby, 2nd Baby, 3rd Baby…etc.. within 24 hours – 3 days after the sperm cells enter into the egg cells of female mammals. 5) Early detection’s of future Gender of embryos twins, triplets, quadruplets …etc.. 6) Early detection to all future gender of embryos or next baby gender of embryos even if the mother is not yet pregnant. 7) Single male/ married/single father will have a chance an opportunity to know all his future sons and daughter’s 1st future baby gender, 2nd, 3rd…etc.. All Human Male mammals will have the opportunity to know if he has a future twin gender, triplets, and quadruplets baby gender..etc… these are detectable and real. 8) X and Y chromosomes natural cycles using helix function inside the sperm cells of male mammals and egg cells of female mammals – It can detect and divulge the exact time of cycles, month and exact year of cycles. 9) Early detection of Human clone Personnel or Person by tracing and detecting his/her Unseen Genetic engineering codes that my technology only can detect it. 10) Unseen Individual Identity of person – aside from the thumb mark example identical twin, triplets, quadruplets identity. 11) Pro-Life manufacture and producing correct future gender selection or sex selection is real and possible


20th May 2019

2001, I started my human codes experiment research alone after I accidentally discovered new combined elements that can interpret the messages using teleportation subatomic wave particles an applied into the human DNA’s. Using Quantum biology theory to detect 100% function of the human genome unseen codes, like quantum computer codes is a new interesting discovery that I discovered since 2001. I develop and invented a new super advanced technology and it’s called ‘Stellar Technology’ fit to validate the owner’s DNA’s from the human Male mammals or Female mammal’s chromosomes like the identification of chromosomes inside the human female mammal’s egg cells and also in male mammal’s sperm cells. Stellar Technology is the one responsible to separate the formation of the chromosomes inside the egg cells of female mammals and sperm cells of male mammals. It can detect and confirmed the existence of Y chromosomes inside the human female mamma’s egg cells with X chromosomes inside by translating the unseen codes into Y and X chromosomes using the slope and pi formulas. Stellar Technology can validate also the surrogacy, human cloning, sperm donation, DNA testing in an external approach, early detection of the human clone, infertility and stress, menopause, helix role, and natural function cycle in terms of gender selection, early detection of future baby gender either girl or boy gender, early of twin gender, triplets gender, quadruplets gender even before pregnancy occurs. and identification of identical twin, triplets, quadruplets identity.


2001, I started my human codes experiment research alone after I accidentally discovered new combined elements that can interpret the messages using teleportation subatomic wave particles an applied into the human DNA’s. Using Quantum biology theory to detect 100% function of the human genome unseen codes, like quantum computer codes is a new interesting discovery that I discovered since 2001. I develop and invented a new super advanced technology and it’s called ‘Stellar Technology’ fit to validate the owner’s DNA’s from the human Male mammals or Female mammal’s chromosomes like the identification of chromosomes inside the human female mammal’s egg cells and also in male mammal’s sperm cells. Stellar Technology is the one responsible to separate the formation of the chromosomes inside the egg cells of female mammals and sperm cells of male mammals. It can detect and confirmed the existence of Y chromosomes inside the human female mamma’s egg cells with X chromosomes inside by translating the unseen codes into Y and X chromosomes using the slope and pi formulas. Stellar Technology can validate also the surrogacy, human cloning, sperm donation, DNA testing in an external approach, early detection of the human clone, infertility and stress, menopause, helix role, and natural function cycle in terms of gender selection, early detection of future baby gender either girl or boy gender, early of twin gender, triplets gender, quadruplets gender even before pregnancy occurs. and identification of identical twin, triplets, quadruplets identity.

I’m looking forward to your reply.

Ranel


15th May 2019

The CRoatian Islands Birth Cohort Study (CRIBS) was the first Croatian birth cohort study and the first birth cohort study ever conducted in Southeastern Europe, designed to prospectively follow a sample of 500 pregnant women and their children up to two years of age. The aim was to assess the prevalence of risk factors (biological, environmental and behavioural) for the development of metabolic syndrome (MetS) and other NCDs, in two Croatian islands (islands Hvar and Brač) and one mainland subpopulation (city of Split). Although birth cohorts and life course designs offer a wealth of opportunities, their implementation is uniquely challenging. Being the first birth cohort in Croatia, CRIBS faced certain methodological, logistical, and sociocultural challenges – including small sample size, incomplete data, problems with participant retention and lack of logistic support on the national level. The presentation will discuss such methodological shortcomings and highlight efforts of the CRIBS researchers to address them. Although limited in sample size, the success of the study lies in the wealth of collected data generating a great potential for cross-cohort collaborations and inclusion into larger consortia. However, this would not have been possible without a personal contact with the participants, making it a challenge and opportunity at the same time.


03rd May 2019

The Developmental Origins of Health and Disease hypothesis purports that early life factors determine long-term risks of death and disease. Prospective birth cohorts and more recently genetic studies consistently indicate that the rapid weight gain trajectory to later obesity starts in the first months of life, even from birth. Rapid infant weight gain and childhood overweight lead to earlier pubertal maturation in boys and girls, and in turn these adolescent traits are predictive for obesity, diabetes, hypertension and cardiovascular disease events in later life. Understanding of the nutritional, parental and wider determinants of rapid infant weight gain are informing the development of obesity prevention strategies starting in early life. These are important efforts in light the observed high levels of nutrition and weight in UK infants. However, many questions remain. Does rapid growth in infancy length ameliorate effects of rapid infancy weight gain on obesity risk? Conversely, do rapid gains in infancy adiposity exacerbate such effects and predict even worse metabolic health? As more accurate markers of infancy body composition and metabolism emerge and are incorporated into new cohort studies, do we have to wait for follow-up time to elapse before inferring their relevance to later obesity and disease risks? This paper will review what is currently known and consider how genetic epidemiological approaches might be used more widely to infer long-term relationships between early life growth and later outcomes.


01st May 2019

Introduction: Most tooth formation reference data are based on radiographs taken in the course of diagnosis and dental treatment; however, re-analysis of a historical longitudinal radiographic study allows a more reliable description of the timing, variation in timing and the duration of consecutive tooth stages. One of the early longitudinal dental studies was by Carmen Nolla, who detailed permanent tooth formation in 25 boys and 25 girls from annual dental radiographs. The aim of our study was to reconstruct Nolla’s longitudinal data and calculate the timing of permanent tooth stages.
Methods: The material for this study was data reconstructed from plots showing individual tooth stage curves from dental radiographs of 25 boys and 25 girls in Nolla’s thesis (1952). These were assessed from annual radiographs taken from the ages of 2 to 18. We transcribed the data and calculated mean age of attainment of mandibular tooth stages in two ways. Firstly, data were treated as cross sectional and mean age calculated by probit regression. Secondly, data were analysed longitudinally by transition analysis using auglag in R. First results were compared to results from 946 dental radiographs of contemporary children aged 3-16.
Results: Our results show the timing of most tooth stages was similar to contemporary children. Some results of the longitudinal analyses could be compared to recently published reanalysis of longitudinal radiographic data and similarities were noted.
Conclusion: These findings suggest that the timing of permanent teeth is broadly similar between groups with little evidence of a secular trend.


29th Apr 2019

Introduction:Completion of the full series of childhood vaccines on-time is crucial to ensuring protection against vaccine-preventable diseases. Health effects of the potential “non-specific effects” of vaccines are linked to vaccines timeliness. We examines determinants of complete and on-time vaccination and evaluates the relationship between vaccination patterns and severe morbidity outcomes
Methods:The paper uses data from maternal and child health survey which recruited and followed up a cohort of children born in the Nairobi Urban Health and Demographic Surveillance System between 2007 and 2014. Vaccination information were collected from child health cards. Logistic regression was used to identify determinants of vaccination completion and timeliness. Cox regression model was used to evaluate the relationship between vaccination statuses and subsequent severe morbidity. Several children reported more than one hospitalization episodes – a typical recurrent survival outcome. A frailty parametric cox model was fitted to account for the heterogeneity
Results:Maternal age, post-natal care, parity, ethnicity and residence place were identified as determinants of vaccination completion. Institutional deliveries and residence place were identified as the determinant of on-time vaccination. A significant 58% (CI: 15-79%) (p=0.017) lower mortality was observed among fully immunized children compared with not fully immunized. Lower mortality observed among on-time immunized children, 64% (CI: 20-84%) compared to those with delays
Conclusions:Improving vaccination timeliness and completion schedule is critical for protection against vaccines preventable diseases, and may potentially provide protection beyond these targets


Introduction: The DOHaD hypothesis contends that exposures early in life can impact on lifelong health, especially in contexts where there is a ‘mismatch’ between the early and later life environment. Much of the evidence in support of DOHaD comes from studies in high-income countries using retrospective records, with less data from low-income countries. Here, I describe how we have used longitudinal data from rural sub-Saharan Africa to contribute to explore nutrition and human health interactions.
Methods: Using demographic records initiated in 1947 in rural Gambia, coupled with records on maternal and child health, we have explored; (i) the impact of the early-life nutritional environment on later health in a rural African population, and (ii) secular trends in childhood growth, with a focus on factors contributing to growth faltering.
Results: Firstly, building on epidemiological associations between season of birth and infection-related mortality, we have shown that the human immune system is sensitive to nutritional exposures early in life, adding a novel dimension to the DOHaD field. Secondly, using routine data on childhood anthropometry, we observe that, despite a significant decline in child undernutrition, rates remain unacceptably high, likely reflecting the very high socio-economic threshold required to eliminate undernutrition.
Conclusions: The foresight to establish demographic data collection over 7 decades ago, has provided longitudinal data enabling novel research within a traditional African context. The addition of detailed clinical records on maternal and child health is helping us to understand the factors driving child undernutrition in rural Africa, and to identify targets for intervention.


Introduction
Long-term effects of exposures in early life on outcomes in adulthood are well-recognised but ‎hard to evaluate in randomised controlled trials (RCT) because of attrition. We demonstrate ‎unconsented record-level linkage between 9 dormant RCTs of infant nutrition and the ‎English National Pupil Database (NPD). Educational achievement was used as an indicator of ‎cognitive ability. The RCTs had assigned 3507 babies between 1982 and 2001. Infants were ‎randomised to different types of enriched milk formula or standard formula.

Methods
Our objective was to investigate linkage accuracy. Longitudinal RCT data containing name, date of ‎birth, sex and changes of postcode over time were captured through follow up contacts, and ‎linked to data contained in each yearly school census for children attending state ‎school in England. Deterministic rules and manual review were used by the external linkage ‎service, to generate a rank score of linkage ‎certainty for each candidate pair. Trial participants could have multiple candidate pairs. ‎

Results
‎3350 participants were linked to 1-3 candidate pupils. Only 1044/3544 (29.5%) pairs matched on ‎all linkage identifiers. We will present results comparing linked and unlinked characteristics in RCT ‎participants according to varying thresholds for linkage certainty. We will also illustrate the impact ‎of the threshold used for determining a link on effect measures for school outcomes, using ‎sensitivity analyses. ‎

Conclusion
Unconsented linkage between extant RCTs and administrative data is a useful method to generate ‎evidence on the long-term efficacy and safety of ‎‎interventions, but errors due to linkage need to be measured and accounted for in analyses.


Evidence on secular trends in life course BMI trajectories is limited, especially in countries that are experiencing marked socio-economic and nutritional transitions. We investigated how life course BMI trajectories have changed across recent generations in China. We used the mixed longitudinal data from the China Health and Nutrition Survey (CHNS), which has so far had ten waves between 1989 and 2015 (N~30,000). We derived multiple cohorts born in five-year intervals between 1945 and 2004 and fitted fractional polynomial models with random effects to child-to-adult BMI, from 7y up to 70y.

Mean BMI trajectories increased over time, with later born cohorts having higher BMI and their mean BMI exceeded the normal BMI range (i.e. <25kg/m2) from early adulthood, compared to older cohorts. Comparing boys born 20 years apart in 1980-84 and 2004-04, mean BMI increased by 1.2kg/m2 at age 7y, increasing to 3.2kg/m2 at age 15y. The corresponding increases for girls were 2.1kg at both ages. The subsequent increases in adult BMI trajectories were greater for males than females until the old age. For example, mean BMI increased by 2.2kg/m2 at 45y in males and by ~1kg/m2 in females between cohorts born in 1950-54 and in 1970-74. At old age, the increase was similar for males and female (e.g. by ~1kg/m2 in 60s).


28th Apr 2019

Objectives: There are caste and ethnic groups in Nepal. Brhaman/Chhetri (B/C) is a major group of caste and Newar/Janajati (N/J) is a major adivasi (indigenous) group. Growth status of these groups has never been compared. Moreover, growth standard of Nepali children have not been presented to date. The purposes of this study were to compare their growth stats and integrate growth standard curve of B/C and N/J in Nepal.
Method: Height and weight of 2,787 boys and 2,936 girls, 5,723 children in total, which included 1,997 B/C children and 3,319 N/J children aged 5-19 years, were measured from 2014 to 2018 at both urban and rural area in Kathmandu Valley and Pokhara City in Nepal. LMS method was applied to draw the growth standard curves (3,10,25,50,75,90, and 97th percentile) height, weight and body mass index (BMI) by age.
Results and Discussion: Median of height was 111.4cm at 6-yr of age and 166.8cm at 18-yr of age for B/C boys and 108.9cm at 6-yr of age and 164.2cm at 18-yr of age for N/J boys, 110.8cm at 6-yr of age and 156.0cm at 18-yr of age for B/C girls and 107.8cm at 6-yr of age and 151.6cm at 18-yr of age for N/J boys. All height percentile curves of B/C were slightly higher (approx. 2-3cm) than N/J, though the shapes were similar to both groups for boys and girls till 16 years old. Weight percentile curves were identical between B/C and N/J for boys and girls, 55.1kg for boys and 48.6kg for girls at 18-yr of age. BMI of N/J was smaller than B/C. Their body size was similar to other Asian countries but smaller than European or WHO standard.
Conclusion: The growth standard curves of Nepali children were developed properly. The growth standard shall be developed separately in Asian countries.


Introduction: Quantifying relationships between time-appropriate components of the infant and young child feeding continuum and growth in early childhood presents an analytic challenge. We draw on counterfactual thinking to address this issue.
Methods: We used data from an epidemiologic birth cohort study in urban informal settlements (slums) in Mumbai, India to decompose the effect of feeding practices on length at 24 months into the direct effect of predominant breastfeeding (PBF) at 0-5 months and its indirect effect through consumption of animal source food (ASF) at 6-23 months. We estimated predicted length at 24 months from the SuperImposition by Translation and Rotation model fitted to longitudinal length measurements. We used the parametric g-computational formula to conduct causal mediation analysis with time-varying mediators and baseline-induced confounding by diarrhoea in late infancy (n=438).
Results: We found a negative total casual effect of PBF on length at 24 months (-1.1cm; 95%CI: -1.75, -0.46; p=0.001). This was partially (30%) mediated by the effect of ASF consumption between 6 and 23 months (-0.33 cm; 95%CI -0.55, -0.12; p= 0.003), with most of the effect (-0.77 cm, 95%CI -1.41, -0.13; p=0.018) being attributable to pathways from PBF to linear growth that did not involve ASF.
Conclusion: The negative effect of PBF on length was largely direct. Early success in adhering to recommended infant feeding practices does not form a protective chain of practices stretching into the second year of life in a deprived urban setting. We demonstrate the application of the counterfactual approach to study child nutrition, and recommend further integration of life course epidemiology and growth research.


Introduction
It is generally thought that inter-individual variation in ovarian steroid concentrations is correlated with variation in lifetime fertility (the number of live births). However, there have been no empirical tests of this assumption, largely because this would require collecting data over an extended time span. We have conducted such a study, following a cohort of rural women in the Bolivian altiplano for over 15 years.
Methods
In 1996 we began a community-based study (Project REPA) of health and ecology in rural Bolivian agropastoralists. This is a natural fertility population (no use of contraception). Participant’s reproductive histories and other data were collected during the 2-year study. Saliva and urine samples were collected for up to 8 sequential menstrual cycles, assayed for progesterone (P4) and tested for hCG (a biomarker of conception). Detected pregnancies were followed until loss (miscarriage) or live birth. Fifteen years later we updated these women’s reproductive histories and again collected samples for hormone assays.
Results
We previously found that successful conception and gestation were not adversely affected by relatively lower P4 in these women. Here we evaluate the extent to which P4 concentrations during the most fecund portion of the lifespan predict total lifetime fertility.
Conclusions
Our findings are consistent with the argument that there is no species-wide, or even population-wide, ideal hormone concentration for successful reproduction. Rather, the most salient signal for modulating an individual’s reproductive investment is a temporal change in ovarian steroid concentrations rather than the absolute concentration per se.
Funding: NSF 9506107, 1142201, & IU OVPR


Introduction
Alu elements are attractive markers for population genetics, diseases, forensics and paternity analysis due to their particular characteristics. Five polymorphic Alu insertions within the MHC class I region have been little examined in human populations.
In our study, we aimed to analyze the genetic diversity of autochthonous Comorians from the three major islands of the archipelago using polymorphic Alu insertions within the MHC calss I and to assess their relationships together and with other populations.
Subjects and Methods
257 unrelated participants from Comoros archipelago: Grande Comore (86), Anjouan (93) and Moheli (78), were examined for five MHC Alu insertions. The data were analyzed for intra and inter- population genetic variation.
Results
All MHC Alu were polymorphic in the three samples and only one significant differentiation was observed between Anjouan and Moheli.
According to the MDS and AMOVA results, the populations included in the inter-population analyses were grouped in three major clusters according to their genetic ancestry. The Comorians showed high haplotype diversity than other already studied African populations and occupied an intermediate position between African and Asian clusters.
Conclusion
MHC Alu insertions are useful markers to study micro-geographical genetic variations and interesting results about biological history and evolution of the Comoros have been obtained.


Introduction. The 2007/2008 economic crisis has had an unequal impact on the health of European populations, worse in those countries which adopted austerity measures and reduced social protection.Countries that implemented more severe austerity measures reported a worsening of birth outcome, analysis suggesting that the economic recession affected perinatal health both by an increase in psycho-social stress and by the deterioration of material conditions. The aim of this communication is to summarize evidences on trends in maternal profile and birth outcome associated with the economic crisis in Spain in a wide time frame, from 1996 to 2016. Methods. Using data from the National Vital Statistics, descriptive and multivariate analysis was performed in other to described and evaluate trends in maternal-foetal variables related to single live births born to Spanish mothers, including disparities in birth outcome by parity, maternal age and socioeconomic characteristics. Results. A general and immediate worsening in birth outcome is described following the outset of the crisis, as well as an increase in disparity among extreme socio-economic groups during the worst years of the recession. Simultaneously, during the economic crisis there was a significant increase in births to both primiparous and multiparous women from more privileged social backgrounds and a substantial reduction of births to housewives. Consequently, LBW stabilised at maximum temporal levels among primiparous mother, decreasing among multiparous ones. Conclusions. The crisis has determined a clear maternal socio-economic selection, determining the postponement of, or definite decision not to undergo, first-time motherhood among Spanish women.


Introduction: Common mental health problems (CMHP), such as symptoms of depression and anxiety, are often comorbid with dementia. It is estimated that 40% of people with dementia also experience CMHP. Research has also shown longitudinal associations between CMHP and cognitive function, however, the majority of research has focused on older samples (aged 60+) with short follow ups (<10 years). Less is known about how the association between CMHP and cognitive function operates over a longer period of time, and earlier in the life course.
Methods: The nature of this complex association across the life course is explored by utilising data from two national British birth cohorts: the National Survey of Health and Development, and the National Child Development Study.
Results: First, it was demonstrated that adolescent, but not adult CMHP significantly predicted poorer baseline memory and information processing speed scores, but not rate of decline over time. Second, CMHP significantly predicted subsequent level of memory and processing speed over a 16-year period, but that this association did not operate in the opposite direction. Third, accumulation of persistent CMHP, rather than sensitive periods, could better predict midlife cognitive function. Fourth, inflammation (as measured with C-reactive protein level) was shown to be an important mediator of the association between CMHP and cognitive function. Finally, a number of potential moderators of this association were found to contribute to risk and resilience pathways.
Conclusion: Taken together, our results suggest that accumulation of CMHP over the life course predicts later cognitive function, and reveal some important mediators and moderators of this link.


Introduction: With the continuing epidemic of obesity in childhood, gaining a better understanding of how body size and growth at these young ages, alone and in combination with later adult size, relate to non-communicable diseases is of great relevance for protecting the future health of children.
Methods: More than 50 studies investigating how childhood body size and growth relate to the later risks of disease based on data from the Copenhagen School Health Records Register (CSHRR) will be summarised. The CSHRR is a population-based cohort of 460,350 children born from 1930-1996 who had their heights and weights measured at school health exams. Outcomes were ascertained by linkages of personal identification numbers to national health registers. Adult body size came from linkages with studies, databases and national registers.
Results: Body mass index (BMI; kg/m2) at ages 7-13 years is positively associated with many diseases including cardiovascular disease, multiple sclerosis and type 2 diabetes. Childhood height is inversely associated with cardiovascular disease and type 2 diabetes. Childhood BMI, height and birth weight show a diverse pattern of associations with 15 forms of cancer. In studies on men, increasing in BMI from child to adult ages increased risks of type 2 diabetes and colon cancer.
Conclusions: Body size early in life and growth has a diverse pattern of associations with adult disease. These associations likely operate through many pathways, including tracking of body size. As body size in childhood can indicate later risks of disease, these studies highlight that this period of life may offer possibilities for intervention as to reduce the later burden of disease.


Introduction: The purposes of this study were to develop a standardized foot growth curve of Japanese children, and to compare the difference from JIS (Japanese Industrial Standard) S5037. Methods: The foot length(FL) and width (FW) of 5,765 children aged 18-78 months (1.5-6.5 years) were measured in 2013-2019. Measurements were made using a 2D foot scanner (Foot Look). The LMS method (Cole and Green(1992)) was applied to the standardized growth curves (FL, FW, and FW/FL ratio by age, FW by FL) of the 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentiles. The results were compared with the JIS S5037. Results and discussion: The median of FL was 127.0mm (ranged 115.9 (3%ile)-137.2mm (97%ile), the same hereinafter) at 18-month-old. It increased quickly until 36-month-old; the median is 147.0mm (134.0-159.4mm) at 42-month-old. After that, the increment ratio became slow and the distribution range became larger; the median was 179.6mm (163.6-197.4mm) at 78-month-old. The median of FW was 55.3mm (50.0-62.3mm) at 18-month-old. It increased until 42-month-old; the median is 62.7mm (56.3-70.0mm) at 42-month-old. After that, the increment ratio became slow slightly, but the distribution range was almost same during the early childhood. The median was 72.0mm (64.9-79.9mm) at 78-month-old. Children’s shoes sizes were regulated based on JIS. The growth curve of foot width on foot length was linear and the distribution ratio was almost same during the period. Conclusions : JIS might not have been based on experimental data for under 36-month-old: they were determined by extrapolation from the data of 3 to 6-year-old. It means that the children’s shoes were produced in Japan is not appropriate Japanese children’s foot shape.



Introduction: The Ola Tuputupua’e “Growing Up” in Samoa study is the first cohort established among the Pacific Island countries. We aim to document the growth of these children between 2-7 years of age and examine variations by urbanicity and diet.
Methods: Data were from 456 Samoan children with measurements taken in 2015 (at 2-4 years) and 2017-2018 (at 3.5-7 years) across three census regions with varying urbanicity: Apia urban area, Northwestern Upolu (peri-urban), and Rest of Upolu (rural). Adherence to a modern dietary pattern with energy-dense, high-fat foods was identified using factor analysis. Z-scores were calculated based on WHO growth standards and references. Multilevel models were used to examine the relationships of urbanicity and diet with weight, height, and body mass index (BMI) z-score trajectories between 2 and 7 years of age.
Results: Compared to the WHO standard, children had a greater weight (median:0.20 SD, IQR: 1.39) and BMI (median:0.99, IQR:1.18), but lower height (median:-0.66 SD, IQR: 1.70) at 2-4 years of age. Weight and BMI remained above the reference median (0.40 and 0.65 SD, respectively), while height was 0.12 SD below the median at 5-7 years of age. On average, children gained 0.07 SD in weight (95%CL: 0.04,0.10) and 0.29 SD in height (95%CL: 0.25,0.34), but decreased by 0.16 SD in BMI (,95%CL: -0.21,-0.12) for every 1-year increase in age and this did not vary by urbanicity and modern dietary pattern adherence.
Conclusions: Samoan children show higher weight and BMI for age, but slower height gain compared to the WHO standard and reference population. Despite differential exposure to urbanicity and diet modernization, children experience similar growth between 2-7 years of age



27th Apr 2019

Introduction: The use of wearable technology is becoming increasingly popular in cohort studies to overcome biases of self-reported physical activity. However, numerous brands of device are available that employ different wear protocols. A combined physical activity and postural allocation technique is increasingly considered to be the gold standard approach to obtain accurate, free-living data across the whole physical activity spectrum. This methodology is, however, rare in large scale population studies.
Methods: The mid-life biomedical assessment of the 1970 British Cohort Study (BCS70) utilised a novel physical activity and postural allocation sensor (activPAL-3 micro device) to collect data on free-living physical activity, standing, sitting, and sleep across the 24 hr cycle. The device was placed (n=6,187 participants – 86% of those visited by a nurse) on the thigh using a waterproof dressing for a 7 day wear period.
Results: A total of 5,252 devices were returned via post (~900 lost) with data successfully downloaded. The device was largely well tolerated with high wear compliance, although complaints relating to skin irritation were the main source of objection. We examine associations between various socio-economic and demographic factors with different domains of physical behaviour (sitting, standing, stepping). We further explore the extent to which socio-economic / demographic factors drive non-consent, incomplete wear, and/or non-return of reliable data.
Conclusion: This study demonstrates the feasibility of using novel wearable technology at large scale. The ability to collect accurate data on physical behaviours in large cohort studies will help inform future policy on disease prevention.


Background: With the success of treatment for HIV, mother-to-child transmission of the disease is decreasing. Increasingly, efforts are being focused to support the health and wellbeing of the HIV-exposed and -uninfected (HEU) infants born to HIV-positive women.
Methods: We pooled data from two studies of HEU infants: the BAN study in Malawi (n=530) and the Kabeho study in Rwanda (n=563). We then use SITAR and latent class growth mixture modeling to determine if infants from the two countries experience similar patterns in linear and ponderal growth.
Results: Infants from the Malawi cohort had, on average, smaller size than Rwandan infants; however, growth velocity was similar. Each latent class was composed of 40-60% infants from each cohort, except for the largest class, which was predominantly infants from Rwanda. Increasing maternal height was related to increased odds of being in the heaviest and tallest classes of infants. Among Rwandan infants, maternal height was also related to increased size in length and weight. Increasing neonatal WAZ was associated with increased odds of being in the largest growth classes as well. Neonatal WAZ was also positively related to size in length and weight and accelerated ponderal growth. These effects were most pronounced among Malawian infants.
Conclusion: Although there are some similarities in the growth patterns of the HEU infants in these two settings, the effects of risk factors for poor growth, such as short maternal stature and low neonatal WAZ, are not the same across settings. These finding highlight the importance of contextual considerations when designing interventions in new contexts.


26th Apr 2019

Introduction
Adrenarche has been an enigmatic part of human growth and development. Despite its association with middle childhood, the functional significance of increasing levels of DHEA is largely uncharted. Findings from the NIH normal brain development study provide strong evidence for an impact of DHEA on the brain including both cortical maturation and functional connectivity of the amygdala to the prefrontal cortex. Yet, the impact of undernutrition on adrenarche and its implications for cognitive development remain unexplored.

We hypothesize that undernutrition, specifically low protein intake, before the age of 6 will lead to lower levels of IGF-1, with reduced development of the adrenal zona reticularis and lower DHEA levels. We expect to see lower DHEA levels associated with changes in cognitive function after the age of 6.

Methods
We propose to follow 300 (150 female) Ju’Hoansi children from villages in the Nyae Nyae Conservancy, Namibia starting at age 3. Yearly data collection will include standard anthropometrics. Protein intake will be determined using food frequency questionnaires. DHEA, DHEA-S and cortisol will be assayed in saliva and IGF-1 using dried blood spots. Cognitive development will be assessed using the dimensional change card sort (DCCS) and Raven’s progressive matrix. Regression analysis will be used to test a path model in which protein intake before the age of 6 has both direct and indirect effects through IGF-1 and DHEA on cognitive status.

Results
We have no results at present.

Conclusions
This study will help to determine if changes in DHEA represent one potential mechanism by which stunting leads to changes in cognitive development


INTRODUCTION
Youth sports excellence is the result of complex interactions of genetic material and environmental factors. Although such interactions are accepted as determinants of players´ development, apparently no coherent research agenda has integrated young players’ skills and aptitudes within their family support systems, coaches´ levels of expertise or clubs´ contexts. To address these issues longitudinal data is required to tweeze out the independent effects of each variable. This study presents the overall design of the project In search of excellence in sport – a mixed-longitudinal study in young athletes (INEX), its methodology, and reports baseline results of the basketball cohort.
METHODS
Two hundred and thirty-eight male basketball players, aged 11-15 years, were recruited from the INEX project, coming from 19 clubs of the Porto Basketball Association. Players were assigned to five age-cohorts (C1=11y, n=41; C2=12y, n=56; C3=13y, n=47; C4=14y, n=53; C5=15y, n=41). Data were clustered into three domains: (i) biological (anthropometry, body composition, maturation, and performance), (ii) skill/game proficiency (technical and tactical skills), and (iii) contextual (clubs’ characterization and organization, infrastructures and equipment, human resources, and communication).
RESULTS
Baseline results by cohort of the INEX basketball sample from all variable domains will be presented.
CONCLUSION
It is expected that such extensive and integrated approach to youth basketballer’s development will provide and important body of knowledge and information for players, parents and coaches.
FUNDING
FCT (SFRH/BD/138740/2018), IPDJ (CP/594/DD/2018) and COP.


INTRODUCTION
Performance in young soccer players is multidimensional. Physiological development, technical, and tactical skills, training experience all play important roles in game performance. A longitudinal design and appropriate analytical approach will provide valuable insights into the roles of growth, maturation and the environments on soccer performance. This study aims to present the design and methodology of the INEX project in a young soccer player’s cohort.
METHODS
Players were recruited from the In search of excellence in sport – a mixed-longitudinal study in young athletes (INEX), from 6 clubs of the Oporto Soccer Association. At baseline, a sample of 200 players was divided into four age-cohorts (11, 12, 13, and 14 yrs) with 50 players in each and followed annually for four years. Variables cluster around 5 domains (1) biological (anthropometry, body composition, maturation), (2) performance (physical and technical), (3) game knowledge (tactical skills), (4) training history and (5) clubs´ infrastructures, equipment, human resources and development. The intention is to have ~800 observations across the entire sample across the 4 years, and an overall mass of data of ~40.000 data points. Ecological systems linked to multilevel models will be the joint templates for this project.
RESULTS
Baseline results from all domains of the different cohorts will be presented.
CONCLUSION
This study will provide relevant information to coaches and clubs when conceiving solid and coherent developmental trajectories of young players´ careers. Further, parents will also profit from the study when preparing themselves to support their sons´ interests in training and competition.


Continuous and normally distributed measures of body structure and function, measured repeatedly over time, provide dynamic tools for investigating development, health and ageing across the life course, and for studying the biological imprint of exposures. It is of importance to understand normal life course age-related trajectories of such measures, and the factors that influence deviations from the norm. Signs of impaired function may act as intermediate markers of underlying disease processes, failure to reach developmental potential, or accelerated ageing, and offer opportunities for early intervention. Comparing trajectories across cohorts born at different times and in different places may offer additional insight into the effects of social context.

There are a number of key challenges in maximising the use of life course biological trajectories across cohorts. Harmonisation of measures, both within a cohort over long periods of time and at different ages, as well as between cohorts, is required. The frequency with which repeated measures are collected within cohorts must balance costs and the burden on participants against the scientific rationale where the timing of measurement should reflect the velocity of change in the phenomena under study. As most cohort studies currently have measures at widely spaced intervals across life, research has tended to focus on study of smooth average long-term changes, with less attention paid to shorter-term changes and fluctuations. Innovations in technology could allow data to be collected on more frequent schedules of assessment.


Background/Aims: Evidence linking early-life adversity with an adverse cardiometabolic profile in adulthood is equivocal. The current study investigates early-life adversity in relation to weight and cardio-metabolic health status at age 60-64 years.
Methods: The study includes 1,059 individuals in the 1946 National Survey of Health and Development (NSHD). Data on adversity between ages 0-16 years were used to create a cumulative childhood psychosocial adversity score and a socioeconomic adversity score. Cardiometabolic, weight, height, and body composition data collected at ages 60-64 years were used to create four groups: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obese (MHO), and metabolically unhealthy overweight/obese (MUO). Associations between the two exposure scores and weight/health status were examined using multinomial logistic regression, with adjustment for sex and age at the outcome visit.
Results: 62% of normal weight individuals were metabolically healthy, whereas only 34% of overweight/obese individuals were metabolically healthy. In a mutually adjusted model including both exposure scores, a psychosocial score of ≥ 3 (compared to 0) was associated with increased risk of being metabolically unhealthy (compared to healthy) in both normal weight adults (RR 2.49; 95% CI 0.87, 7.13), and overweight/obese adults (1.87; 0.96, 3.61). However, the socioeconomic adversity score was more strongly related to metabolic health status in overweight/obese adults (1.60; 0.98, 2.60) than normal weight adults (0.95; 0.46, 1.96).
Conclusions: Independently of socioeconomic position, psychosocial adversity in childhood may be associated with


Introduction
The Swedish Adoption/Twin Study of Aging (SATSA) is a population-based cohort of same-sex twins (n=859) established in 1984 by recruiting twins who were reared apart from the Swedish Twin Registry, and an age-matched sample of twins reared together. At baseline, the heritability estimate for fasting insulin-like growth factor-binding protein (IGFBP)-1, a marker of insulin sensitivity, was 36% and for IGF-I, a nutritional marker, 63%. SATSA is longitudinal, with nine waves of extensive in-person testing over a 30-year period. The aim of this study was to determine the relationship between baseline IGFBP-1 and IGF-I levels, and lifetime trajectories of weight and waist measurements.

Methods
Latent growth curve modelling with age centred at 73 y was used to determine whether BMI (weight(kg)/height(m)2) and WHtR (waist(cm)-to-height(m) ratio), and their change, differed as a function of baseline fasting IGFBP-1 and IGF-I. Sex and birth cohort (1900-17, 1918-25, 1926-48) were included as covariates. Between- and within-twin pair effects, rearing status and zygosity were included in the models.

Results
BMI, and to some extent WHtR, changed curvilinearly with age. Lower IGFBP-1 was significantly associated with higher BMI and WHtR (1.8kg/m2 and 3 cm/m, respectively, per unit decrease in log-IGFBP-1) at age 73 y, but not with rate of change. The associations were weakened, but remained, after adjustment for insulin. Twin models indicate part of the association is explained by genetic factors. There was no relationship between IGF-I and BMI or WHtR levels or rate of change.

Conclusion
Lower fasting IGFBP-1 levels are associated with increased adiposity, but not change in adiposity, across the lifespan.


Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age affecting 5-20% of women worldwide. It is multifactorial in aetiology and associated with adverse reproductive and metabolic complications. Adult body size is potentially linked with PCOS risk. However, as PCOS already appears in the teenage years, we prospectively investigated if childhood body mass index (BMI [kg/m2]) and height are associated with subsequent risks of PCOS.
Methods: A cohort of 171,213 girls from the Copenhagen School Health Records Register, born 1930-1996 with measured weights and heights at ages 7-13 years were included. Women were prospectively followed in the Danish National Patient Register for PCOS diagnoses from ages 15-50 years. Cox regressions were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
Results: During a 40-year period of follow-up, 630 women were diagnosed with PCOS (age range: 15.2-49.8 years). Girls with a BMI above average (z-score > 0) had a significantly increased risk of PCOS, whereas BMIs below average (z-score ≤ 0) were not associated with PCOS risks. At age 7 years, the HR was 1.73 (95% CI: 1.57-1.90) per BMI z-score among girls with above-average BMI. The associations were positive and significant at all childhood ages. Childhood height was linearly and positively associated with risks of PCOS at all childhood ages. At age 7 years, the HR was 1.19 (95% CI: 1.09-1.29) per height z-score.
Conclusions: Girls who are heavier than average or tall at school ages have increased risks of PCOS. These findings suggest that childhood body size at ages before PCOS typically emerges indicates a risk for the development of this disease.


Cohort studies are special forms of longitudinal studies that have long been accepted as the primary designs to acquire information on the process of human growth and development. Whilst a number of longitudinal studies of individuals and small groups of children, usually attending educational or military institutions, were conducted in the 18th and 19th centuries in Europe, it was not until the first half of the 20th century that longitudinal study designs of child development became common in the USA. The UK, by contrast, was a late developer in this regard and could not boast of the organisation of a longitudinal growth study of British children until James Tanner’s initiation of the Harpenden Growth Study in 1949. Tanner was prompted to undertake a such a study design after visiting the American longitudinal studies in 1947 and appreciating their power to model the process of human growth and its variation within and between the sexes.
The further development of longitudinal studies in Europe owed a great deal to the emergence of ‘social paediatrics’, a post-WWII movement that recognised the importance of the child’s environment to their growth, development, health and wellbeing. Longitudinal study research groups, primarily from Europe and the USA, met biennially in the 1960s and 1970s, at the Centre Internationale de l’Enfance in Paris, to discuss their studies and to compare and contrast their logistical methods, analysis procedures, and results. In those days of limited access to computing power, the exchange of experiences and information disseminated at those meetings was fundamental to the development and design of subsequent longitudinal and cohort studies that are being discussed at this meeting.


In bioarchaeological sciences, skeletal remains are often the only still preserved part of the decomposed body. Human nutrition and health can thus only be studied through bones and teeth, commonly with the isotopic analyses of their collagen. As teeth do not remodel, the collagen of primary dentine contains the isotopic data from the time of formation. On the other hand, bones remodel throughout life and their isotopic values represent an average of several years. One exception to the bone remodelling rule are human auditory ossicles. They develop in utero and finish forming in the first two years of life. In theory, their collagen should represent the isotopic values of these two periods. However, as isotopic profiles of human auditory ossicles were never studied before, it is not clear if this is true. As a step towards resolving the issue, we compared δ13C and δ15N of collagen from ossicles with collagen from teeth that form at approximately the same time.
12 individuals aged 0.5 ± 0.4 years to 13 ± 1 years from the 19th century St. Peter`s burial ground in Blackburn were included in the study. An ossicle and a tooth were collected from each individual and their collagen analysed for δ13C and δ15N. Results obtained from the ossicle were then compared with the results from tooth increments.
A significant and systematic offset between ossicles and dentine formed at the approximately same time was noticed. Based on the comparisons, it seems that the second, post-natal phase of the ossicle development does not influence the isotopic values of collagen significantly. Results indicate that data stored in the collagen of human auditory ossicles mostly reflects the in-utero period.


Introduction:
High adult blood pressure (BP) is an important risk factor for cardiovascular disease (CVD) and mortality. Childhood BP tracks into adulthood. Little is known whether BP trajectories in children have changed over time, as BP is strongly associated with body-size, especially in countries with rapid economic growth. We investigated whether BP trajectories have changed among Chinese children and whether changes can be explained by BMI and height trends.
Methods:
China Health and Nutrition Survey (eight waves 1991-2011) was used to create four cohorts (7-17y, born in 1981-85, 1986-90, 1991-95, 1996-2000, N=~16000). Multilevel cubic functions were applied to estimate child-to-adolescent trajectories for systolic and diastolic BP (SBP and DBP) with and without adjustment for BMI and height (age-/gender standardised z-scores). Between-cohort differences were examined by testing the interactions of each cohort with age terms.
Results:
Trajectories for SBP increased across cohorts: those for later-born cohorts tended to lay above early-born cohorts in both sexes. After the adjustment differences mean SBP reduced. The reduction was more evident in adolescence (vs childhood) and with adjustment for height (vs for BMI) trajectories.
For example, the difference between the last (born 1996-2000) and first (1981-85) cohorts was 1.90mmHg (95% CI: 0.54-3.26) for boys and 2.58 mmHg (95% CI: 1.18-3.98) for girls at 7y, and there was no difference at 16y after adjustments. Similar patterns were seen for DBP.
Conclusions:
Trends for BP in recent decades among Chinese children and adolescents were partly explained by more rapid growth in height and BMI in later-born children.


25th Apr 2019

Introduction: Obesity is a major cause of cardiometabolic disease but there is significant variability in risk factors between people with the same body mass index (BMI). The aim of this ongoing MRC-funded work is to understand how the well-known relationships of adulthood BMI and obesity with cardiometabolic disease risk factors might be modified by childhood growth and life course obesity patterns.
Methods: We have pooled weight and height (and thus BMI) data across the National Survey of Health and Development (NSHD, N=5,362, visits at ages 11, 15, 20, 26, 36, 43, and 53 years), the National Child Development Study (NCDS, N=18,558, visits at ages 11, 16, 23, 33, 42, and 44 years), and the British Cohort Study (BCS, N=19,101, visits at ages 10, 16, 26, 30, 34, 42, and 46 years). At the most recent sweep in each study, bloods were taken and used to define hypertension, low high-density lipoprotein cholesterol (HDL-C), high triglycerides, and high glycated haemoglobin (HbA1c). Childhood weight and height been summarised using age- and sex- specific Z-scores. Life course obesity patterns have been summarised from individual BMI trajectories as the following traits: age of onset, duration of exposure, number of periods, and AUC but above the cut-off. Poisson regression models are being developed to explore how the relationships of adulthood BMI and obesity with the number of risk factors (0-4) might be modified by these traits.
Results:
Conclusion: This work will quantify heterogeneity in cardiometabolic disease risk among people with the same BMI or weight status, due to different childhood growth and life course obesity patterns.


Introduction: Adult obesity may increase the risks of systemic lupus erythematosus (SLE), and there are genetic links between adult height and SLE. Thus, it is plausible that body size earlier in life may be important as well. Therefore, we investigated whether childhood body mass index (BMI [kg/m2]), height and growth are associated with adult SLE risks.
Methods: A cohort of 346,627 children (171,141 girls) from the Copenhagen School Health Records Register, born 1930-1996 with measured weights and heights from 7-13 years were included. Linkages were made to the Danish National Patient Register for information on adult SLE registrations. During 40 years of follow-up, 435 individuals (366 women) were registered with SLE. Cox proportional hazard regressions were performed to estimate hazard ratios (HR) and 95% confidence intervals (CI).
Results: No differences in any associations were detected between men and women. Childhood BMI and height were positively and linearly associated with SLE risks and the estimates were similar in magnitude across all childhood ages. For BMI at age 7, the HR was 1.11 (95% CI: 1.01-1.23) per z-score. For height at age 7, the HR was 1.13 (95% CI: 1.02-1.24) per z-score. Children who were heavier or taller at 7 and 13 years than average-sized children had a tendency for increased risks of SLE, with a HR of 1.06 (95% CI: 1.00-1.12) and 1.06 (95% CI: 1.00-1.12) per 0.5 z-score change in BMI and height, respectively.
Conclusion: Heavy and tall children have increased risks of adult SLE. These findings reinforce the hypothesis that early life factors are important in SLE aetiology.


Background: Health in childhood is patterned by socioeconomic background, but also influences later socioeconomic outcomes. This suggests a role for childhood health in intergenerational transmission of (dis)advantage, but presents challenges for identifying causal processes. Using genetic instrumental variables for health (Mendelian Randomization) can circumvent these difficulties.
Methods: In 7898 children born in the Bristol area in 1991-1992, we investigate impact on educational attainment of 6 aspects of childhood health (depressive symptoms, attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), asthma, body mass index (BMI), migraines) using polygenic risk scores (PGSs). With linked educational records, we explore associations of health in late primary school (age 10-11) and mid-secondary school (age 13-14) with GCSEs at 16. We investigate mediation by absenteeism, and complement analyses with summary-level two-sample MR. Objectives were 1) to determine which aspects of childhood health causally impact attainment, and 2) whether absenteeism mediates associations, offering a point for intervention.
Results: Genetic liability for higher BMI and ADHD were associated with lower GCSE results. Two-stage least-squares models of measured BMI and ADHD symptoms also support negative effects. There was little evidence for impact of depressive symptoms, ASD, asthma or migraine, but weaker instruments, especially for ASD, may have affected results. The polygenic scores did not predict absenteeism. Results of summary-level MR were largely consistent with main results.
Conclusions: Results support a causal impact of some aspects of childhood health (BMI and ADHD symptoms) on educational attainment.


Introduction
Measuring The isotope ratios of carbon and nitrogen from bone collagen, hair and nails have been a well-established method for investigating diet and physiological status in modern and ancient populations
Novel methods of analysis have allowed researchers to investigate childhood diet and physiology by applying this method to incremental sections of dentine. These have revealed short-term changes in diet, evidence for famine, breastfeeding and weaning behaviour, and the potential to identify in-uterine stress in Archaeological populations. Here we present initial results from modern deciduous teeth coupled with dietary and health data.
Methods
Teeth have been donated by children undergoing dental extractions in Bradford along with health and dietary information, which have then been demineralised, sectioned and isotope ratios measured using mass spectrometry at the University if Bradford. They are compared to 2 other modern populations and archaeological data.
Results
This is the first study to reveal the patterns associated with the shift in dietary markers from in-utero through breastfeeding and weaning in a modern British population. As such it has the benefits of both a cohort and longitudinal study of the changes in diet and physiology in this critical period of life.
Conclusions
The patterns seen in this extant tissue from the first 1000 days of life may help to identify infants who have experienced in-utero stress previously invisible to health professionals. This window on the womb could be critical in our approach to the long-term effects on an individual life course.


24th Apr 2019

Introduction
James M. Tanner’s career spanned the latter half of the 20th century, dramatically advancing our understanding of growth and development. His favourite research topic was growth at adolescence, the title of his first book. He emphasised the “tempo” of growth, where the pubertal growth spurt is summarised by peak velocity (PV) and age at peak velocity (APV). The talk will explore the fit of the SITAR growth curve model (2010) to the wide-ranging pubertal anthropometry data collected by Tanner and Whitehouse in the Harpenden Growth Study. It will also clarify the pattern of growth for early, average and late developers in puberty using data from the ALSPAC study.

Methods
SITAR models pubertal growth as a smooth mean curve with APV and PV fitted as subject-specific random effects on the age scale, and a random intercept on the measurement scale. Data on ten distinct anthropometric measurements in 371 boys and 248 girls aged 7-20 years from the Harpenden Growth Study were analysed, along with height and weight in 4975 boys and 4985 girls aged 8-20 years from the ALSPAC study.

Results
Mean APV for Harpenden boys ranged from 13.2 to 14.3 (mean 13.9) years for ten measurements, and for girls from 10.7 to 12.6 (mean 11.9) years. Peak velocity expressed as % per year lay in the narrow range of 5-8% (mean 6.0%/5.5% for boys/girls). Splitting the ALSPAC subjects into nine groups by APV, and each into five groups by PV, led to 45 groups each with ~100 subjects. The patterns of mean height and weight growth by group varied much more than predicted by the SITAR model.

Conclusions
SITAR works well to clarify pubertal growth. The disappointment is that Tanner did not live to see it in action.


Background: Early menarche (EM) (<12 years) is associated with height growth, higher adiposity, and body fatness but the relative contribution of each is not known. The present study was part of a growth and nutrition project; data were collected twice with a gap of one year in 2008-2009 (Baseline 1 and 2). Objectives: To compare height growth in adolescence, adult height, adiposity and body fatness between EM and not early menarche (NEM) peers during their adolescence (13-15 years) and adulthood (21-23 years). Methods: A cohort-based prospective study was done in 2016, selecting 25 participants (convenience sample) aged 21-23 years from the same cohort of Baseline 1 (13-15 years; n = 164). Height, weight, waist circumference (WC) were measured. Body fat (BF, % and kg) was estimated using bioelectrical impedance analysis. Body mass index (BMI), waist-to-height ratio (WHtR), fat mass index (FMI) were calculated. Recalled age at menarche (AAM) was recorded at Baseline 1. Blood glucose (BG) level and lipid profile were estimated among women. Results: Mean values of age were 14.35 years (Baseline 1) and 22.00 years (Follow-up) (n= 25). Mean AAM: 10.56 and 12.33 years among EM and NEM groups. EM participants (36%) had higher mean values of BMI, WC, WHtR, FMI, and BF compared to NEM peers. EM girls were taller in adolescence, but they were shorter in adulthood. EM girls had higher annual height increase (2%) at 13 years but lower at 14 years (0.4%) and 15 years (0.18%) compared to the values 1.5%, 0.5%, and 0.43% respectively among NEM peers. EM women had higher BG and low HDL levels. Conclusion: EM was observed to be associated with low final height, higher BF and a tendency towards having metabolic syndrome in adulthood.


Introduction: Attending childcare is related to greater childhood obesity risk, but there are few long-term follow-up studies. We aimed to examine the associations of childcare type, duration, and intensity with BMI trajectories from ages 10-42 years.
Methods: The sample comprised 8234 individuals in the 1970 British Cohort Study, who had data on childcare attendance (no, yes), type (formal, informal), duration (4-5, 3-3.99, 0-2.99 years old when started), and intensity (1, 2, 3, 4-5 days/week) reported at age five years and 32563 BMI observations. Multilevel linear spline models were used to estimate the association of each exposure with the sample-average BMI trajectory, with adjustment for sex, father’s occupational class, and mother’s age of leaving full time education. A combined duration and intensity exposure was also examined.
Results: Childcare attendance and type were not strongly related to BMI trajectories. Results for the combined exposure revealed additive effects of childcare duration and intensity. Among participants who attended childcare 1-2 days a week, those who started when 3-3.99 years old had a 0.197 (-0.004, 0.399) kg/m2 higher BMI at age 10 years than those who started when 4-5 years old, and those who started when 0-2.99 years old had a 0.289 (0.049, 0.529) kg/m2 higher BMI. A similar dose-response pattern for intensity was observed when holding duration constant. By age 42 years, individuals who started childcare at age 0-2.99 years and attended 3-5 days/week had a 1.356 kg/m2 (0.637, 2.075) higher BMI than individuals who started at age 4-5 years and attended 1-2 days/week.
Conclusions: Children who start childcare earlier and/ or attend more frequently have greater long-term obesity risk


Introduction: We aimed to investigate how the weight-height relationship, captured by the Benn parameter (kg/m^B), changes across age (10-65 years) and time (1956 to 2012) and differs between sexes and individual children.

Methods: The samples comprised 4,724 participants in the 1946 National Survey of Health and Development (NSHD), 16,307 in the 1958 National Child Development Study (NCDS), and 15,437 in the 1970 British Cohort Study (BCS). For each sex and cohort, we modelled log weight against log height in a multilevel framework, allowing the log height (i.e., Benn) parameter to change flexibly over age. In models restricted to childhood data in the NSHD and NCDS, we also allowed the Benn parameter to vary between individuals.

Results: The Benn parameter was closest to two in childhood but was consistently lower across adulthood, particularly in females and the most recently born cohort (e.g., ~1.2 in adult females in the BCS). In the childhood models, in which a Benn parameter is estimated for each child based on the relationship between their serial weight and height data, heavier children tended to need a lower height scaling power. This correlation was weaker in the NCDS than the NSHD (e.g., -0.902 vs -0.199 in males), reflecting a decline in the weight-height correlation over time.

Conclusions: The BMI may not properly capture the weight-height relationship at the population- or individual-level. Groups of individuals with high levels of adiposity may have BMI values that are systematically too low because the correct height scaling power is closer to one than two.


22nd Apr 2019

Longitudinal cohort studies provide unprecedented opportunities to address questions about growth and aging, including the links between early life experiences and health across the lifecourse. Life history theory (LHT) is a branch of evolutionary biology that studies the relationships between growth, reproduction, and aging and is thus a useful organizing framework, and source of testable hypotheses, for cohort studies. Several assumptions of LHT are particularly relevant to human studies. First, the body’s ability to harvest and distribute metabolic resources is finite, leading unavoidably to trade-offs between functions. One example is the trade-off between reproductive effort and somatic maintenance that slows senescence. Because repairing and maintaining the body’s tissues to extend late life function only makes sense if that individual is likely to live into the future, organisms are predicted to adjust patterns of allocation in response to cues reflecting unavoidable mortality. Another assumption of LHT is that metabolic resources in excess of maintenance needs are available for “productivity”, which manifests first in growth, and later in adulthood as offspring growth (females) or in costly, sexually dimorphic traits and behaviors (males). This paper will review the application of these and other principles of LHT to analysis of data from the Cebu Longitudinal Health and Nutrition Survey, a large prospective cohort study in the Philippines that spans more than 3 decades. At Cebu, LHT-inspired work has illuminated issues like the connections between growth and reproduction, the early life experiences that motivate adult reproductive behavior, and the links between reproduction and aging.


18th Apr 2019

The Children with HIV early antiretroviral trial (CHER) was aimed at investigating ART initiation strategies in infants and children in a resource limited setting in South Africa. The resulting cohort of infants followed up for a 36 months provided data on growth in anthropometric measurements, including head circumference that serves as a proxy measurement for brain size, especially before the age of two which is the period when almost all brain growth occurs. The aim of this analysis was to look at the impact of HIV infection and ART treatment on head circumference measurements, as a proxy for brain development, to assess the appropriateness of the WHO reference ranges for our cohort of healthy children, and to derive South African specific reference ranges using this cohort.

We adopted a broken-stick growth model for the head circumference profiles by including piecewise linear splines in a mixed effect model for the impact of the ART strategies on head circumference profiles over age. The LMS method was used to calculate z-scores using the WHO references ranges and the groups were compared with reference to these z-scores. Cohort specific percentiles and z-scores were calculated based on the Box-Cox Power distribution.

The model illustrated the positive effect of ART treatment with children on early ART catching up faster to the HIV- children than children on delayed ART. The latter group started catching up as the children start using ART at later ages.

Head circumference measurements for children included in the HIV-uninfected control groups were larger than expected based on WHO standards. Cohort specific derived reference ranges thus illustrated an upward adjustment of the percentile bands.


Introduction: Lower childhood cognitive ability, commonly measured by the Intelligence Quotient (IQ), is associated with worse later life social, economic, and health outcomes. This study aimed to assess inequalities in childhood IQ trajectories in a large sample of Guatemalan school children, according to birth year, school, and height-for-age Z-scores (HAZ).
Methods: A multilevel model was developed to describe 57 244 IQ observations (level 1) in 22 646 children (level 2), aged 6-15 years born between 1955 and 1993, in five schools (level 3) from Guatemala City, Guatemala. Briefly, IQ trajectories were modelled as a quadratic polynomial age function (with random effects at level 2 & 3), birth year was added as a linear term and interacted with age, and HAZ was included as a two-term linear spline (with a random effect at level 3 for the first term).
Results: IQ trajectories differed across schools across ages, the inequality in average IQ at age 11 between the students of a high fee private institution and a no-fee public school was 28.5 points. Later born individuals had higher IQ compared to earlier born individuals (B=0.16, 95% CI 0.15 – 0.18), although this inequality narrowed in adolescence. A higher HAZ score was associated with higher IQ only in individuals with HAZ scores below 0 (1.4, 0.8 – 2.05), this effect was stronger in public compared to private school students.
Conclusions: We found large inequalities in the IQ of Guatemalan children. Lower HAZ was associated with lower IQ more strongly in children who attended disadvantaged schools, possibly reflecting the damaging effects of poor early life environments both for linear growth and cognitive development.


17th Apr 2019

Introduction: Gestational diabetes mellitus (GDM) management consists of advice on diet and exercise, followed by pharmacotherapy if hyperglycaemia persists. Previous studies have highlighted maternal differences between treatment groups however only a few of them involved metformin-treated patients, in a UK clinical setting. This UK-based study aimed to identify relationships between maternal characteristics and GDM treatment modalities. Methods: Maternal records from Born in Bradford cohort participants receiving treatment for GDM during their singleton pregnancies were studied (N=727). Treatment groups consisted of lifestyle modifications (diet and/or exercise), pharmacotherapy (insulin and/or metformin) and combined treatment (lifestyle modifications and pharmacotherapy). Differences between groups were evaluated using Pearson’s χ2 and Fisher’s exact tests for categorical variables and Kruskal-Wallis test for continuous variables. Multinomial logistic regression examined maternal predictors of GDM treatment. Results: Mothers receiving lifestyle modifications (N=196) and combined therapy (N=209) were younger than mothers receiving pharmacotherapy (N=322). 57.4% of women treated with pharmacotherapy were obese compared to 17.7% and 24.9% of women in lifestyle modifications and combined therapy groups, respectively. Pakistani women were less likely to be treated with pharmacotherapy than lifestyle modifications (RRR 0.6(0.3-1.3)). Higher fasting glucose levels at diagnosis increased the risk of combined treatment compared to lifestyle modifications (RRR 1.9(1.3-2.6)). Conclusions: Being older and having a less healthy clinical profile increased the risk of treatment involving insulin and/or metformin for women with GDM.


15th Apr 2019

Introduction: The Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS) was initiated in 1991, when 248 boys and girls, aged 8-15 years, were recruited. Using serial measures (1991-1997, 2002-2007, 2009-2011 and 2016-2017) the study aimed to identify the development of body composition and its relationship to risk of adult disease. Previously, a relationship between adolescent trunk fat mass (TFM) and cardiometabolic risk at 26 years was identified. The present study examines developmental trajectories of TFM, during both adolescence and emerging adulthood (EA), of individuals categorized as either low or high metabolic risk (MRS) at 36 years of age. Methods: Fifty-five individuals were assessed from adolescence (11.5 ± 1.8 years), through EA (26.2 ± 2.2) into young adulthood (35.6 ± 2.2 years) (median of 11 visits) for anthropometrics, blood pressure, blood metabolites, DXA, diet and physical activity. MRS groups were created using sex-specific median splits of continuous standardized risk scores (blood pressure and serum markers) at 36 years of age. TFM trajectories were analyzed using multilevel random effects models. Results: The high MRS group had significantly steeper trajectories of TFM development in both adolescence and EA, 0.65±0.11 and 0.44±0.11 log g (p0.05) to TFM accrual, however physical activity was (−0.04±0.02; p<0.05). Conclusions: Young adults with high cardiometabolic risk at 36 years of age had greater trunk fat mass accrual during both adolescence and emerging adulthood. These results support the need for intervention at both these critical periods of fat accrual.


12th Apr 2019

Data linkage is an important tool for increasing the value of existing longitudinal studies. Linkage to multiple data sources can provide a low-cost, efficient means of collecting extensive and detailed data on cross-sectoral services, society, and the environment, as well as augmenting direct data collection through linkage with biological samples, social media and other digital sources. These data can be used to supplement traditional cohort studies, or to create population-level electronic cohorts generated from administrative data. Such administrative data cohorts offer the ability to answer questions that require large sample sizes or detailed data on heard-to-reach populations, and to generate evidence with a high level of external validity and applicability for policy-making. There is increasing interest in using these two models of data collection in conjunction, combining population-level administrative data with detailed attribute data collected directly from participants, in order to provide a deeper insight into what determines our health.

Lack of access to unique or accurate identifiers means that linkage is not always straightforward. Errors occurring during linkage (false-matches and missed-matches) can lead to substantial bias in results based on linked data. This issue is compounded by difficulties in evaluating linkage quality or determining the potential impact of errors on results due to the separation of linkage from analyses of inked data. This talk will give an overview of the opportunities, challenges and methods for using data linkage in cohort studies.


02nd Apr 2019

Introduction
Diverse tooth development staging techniques use a prediction of the mature tooth root length as a reference to classify the observed tooth development. Proportions of the predicted mature root length are used as tresholds between the root stages. Longitudinal data permit to collect information of a specific tooth position while in development and while mature. This information allows to establish the exact tooth development stage thresholds for the considered subjects and can be used to validate observers’ stage allocation performances.
Methods
Longitudinal tooth development data were extracted from 119 series of retrospectively collected digital dental panoramic radiographs. Each series included at least two radiographs from the same subject registered at different moments. The youngest radiograph contained mature and the older maturing second molars. All second molars were staged by six observers according to the technique of Köhler et al.. The ratio between the second molar root length measured in the last and each previously recorded radiograph was calculated for each subject. The calculated range of second molar root length ratios that confirmed correct Köhler staging were as follows: range=0.25 to <0.50, Stage 5; range=0.5 to <0.75, Stage 6; range=0.75 to <1, Stage 7; ratio=1 (i.e., no range), Stage 8-10. The registered Köhler stages and the calculated ratios were independently verified for each second molar position and for each of the six observers.
Results
Verification of the calculated ratios and registered Köhler stages revealed that all observers generally classified the developing tooth in a more advanced stage than the correct stage, except for Stage 5.
Conclusion
Significant discrepa


01st Apr 2019

Despite the ubiquity of the modern ‘obesogenic’ environment, we have not uniformly developed obesity. On the contrary, there is considerable variation in weight gain, which is observable from early infancy. In fact, it is not uncommon for siblings to vary considerably in their weight, even when they live in the same household. Obesity risk is about far more than just the environment we are exposed to. Genetic susceptibility to the environment is thought to explain some of the variation in adiposity. Nearly 100 twin studies have established that weight is a highly heritable trait (50-90%), and ~1000 common genetic variants (single nucleotide polymorphisms) have been discovered. Individual differences in appetite have been implicated as one of the mechanisms through which genes influence adiposity, so-called ‘Behavioural Susceptibility Theory’ (BST). BST hypothesises that individuals who inherit a set of genes that confer greater responsiveness to food cues (wanting to eat in response to the sight, smell or taste of palatable food), and lower sensitivity to satiety (fullness), are more vulnerable to overeating in response to the modern food environment, and therefore to developing obesity. At the same time, our environment is not simply an ‘exposure’ – we select and shape our environment to suit our preferences, many of which have some genetic basis (called gene-environment correlation). This talk summarises the interplay between genes, appetite and the home family environment in early weight gain, using data from Gemini and TEDS – two large, population-based British twin birth cohorts set up to study genetic and environmental influence on health and development.



06th Feb 2019

There has been interest in finding separate effects of age, year and birth cohort for decades, in both the biological and social sciences. However, the exact collinearity between these three (Age = Year – Birth Year) lead to difficulty in estimating these effects. Because of this, it is impossible to estimate near-linear effects (or linear components of these effects) without making strong assumptions about at least one of these. This is a problem for anyone interested in any of age, period and/or cohort patterns in a particular outcome.

There have been many attempts to ‘solve’ this identification problem without having to make strong assumptions – however in each case, it turns out such models are, in fact, making hidden assumptions that were not intended by the user, as I show with simulations. I then consider what researchers should do, drawing on literature from across the social, biological and health sciences. This includes consideration of non-linearities around linear APC effects (with both statistical and graphical techniques), strong and explicit assumptions based on theory (for example assuming there are no linear period effects), including constraints on certain parameters to estimate ranges within which other parameters must fall. I provide an example focusing on mortality in the twentieth century. In each case, these methods acknowledge that there is a ‘line of solutions’ of possible combinations of APC effects, and not a single answer that can be estimated empirically. None of these methods represent a solution to the identification problem – rather they are an honest acknowledgement of the problem, with an awareness that the methods are limited by their assumptions.



03rd Feb 2019

Objective: Attending childcare is related to greater childhood obesity risk, but there are few long-term follow-up studies. We aimed to examine the associations of childcare type, duration, and intensity with BMI trajectories from ages 10-42 years.

Research Design and Methods: The sample comprised 8234 individuals in the 1970 British Cohort Study, who had data on childcare attendance (no, yes), type (formal, informal), duration (4-5, 3-3.99, 0-2.99 years old when started), and intensity (1, 2, 3, 4-5 days/week) reported at age five years and 32563 BMI observations. Multilevel linear spline models were used to estimate the association of each exposure with the sample-average BMI trajectory, with adjustment for sex, father’s occupational class, and mother’s age of leaving full time education. A combined duration and intensity exposure was also examined.

Results: Childcare attendance and type were not strongly related to BMI trajectories. Results for the combined exposure revealed additive effects of childcare duration and intensity. Among participants who attended childcare 1-2 days a week, those who started when 3-3.99 years old had a 0.197 (-0.004, 0.399) kg/m2 higher BMI at age 10 years than those who started when 4-5 years old, and those who started when 0-2.99 years old had a 0.289 (0.049, 0.529) kg/m2 higher BMI. A similar dose-response pattern for intensity was observed when holding duration constant.




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