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1.  Prenatal Influences on Size, Velocity and Tempo of Infant Growth: Findings from Three Contemporary Cohorts 
PLoS ONE  2014;9(2):e90291.
Background
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.
Methods
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).
Results
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)).
Conclusions
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.
doi:10.1371/journal.pone.0090291
PMCID: PMC3937389  PMID: 24587314
2.  Rich micronutrient fortification of locally produced infant food does not improve mental and motor development of Zambian infants: a randomised controlled trial 
The British journal of nutrition  2011;107(4):556-566.
It is uncertain whether multiple micronutrients benefit the mental and psychomotor development of young children in developing countries. We conducted a randomised double-blind controlled trial to evaluate the effect of a richly micronutrient-fortified v. a basal fortified porridge on mental and psychomotor development in Zambian infants. Infants (n 743) were randomised at age 6 months to receive either the richly fortified or the basal fortified infant food and were followed up until 18 months of age. All the infants were evaluated monthly for achievement of a series of developmental milestones. The Bayley scales of infant development II were administered to a subsample of 502 infants at 6, 12 and 18 months. Rich micronutrient fortification had no significant benefit on the following: (a) number of developmental milestones achieved (rate ratio at 12 months = 1·00; 95 % CI 0·96, 1·05; P=0·81, adjusted for sex, socio-economic status and maternal education, with similar results at 15 and 18 months); (b) ages of walking unsupported (hazard ratio (HR) 1·04; 95 % CI 0·88, 1·24; P=0·63, adjusted for the above covariates) and of speaking three or four clear words (HR 1·01; 95 % CI 0·84, 1·20; P=0·94, adjusted for the above covariates); (c) mental development index (MDI) and psychomotor development index (PDI) of the Bayley scales (scores difference adjusted for baseline scores, age at the assessment, sex, socio-economic status, maternal education, language, age and HIV status: MDI 0·3 (95 % CI −0·5, 1·1), P=0·43; PDI −0·1 (95 % CI −0·9, 0·7), P=0·78). In conclusion, the results do not support the hypothesis that rich micronutrient fortification improves Zambian infants’ mental and motor development.
doi:10.1017/S0007114511003217
PMCID: PMC3787297  PMID: 21733297
Micronutrient-fortified food; Mental and psychomotor development; Bayley scales of infant development; Developmental milestones
3.  Effect of the Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA) on Malnutrition of Infants in Rajasthan, India: A Mixed Methods Study 
PLoS ONE  2013;8(9):e75089.
Objectives
Analyse the effect of the Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA), a wage-for-employment policy of the Indian Government, on infant malnutrition and delineate the pathways through which MGNREGA affects infant malnutrition. Hypothesis: MGNREGA could reduce infant malnutrition through positive effects on household food security and infant feeding.
Method
Mixed methods using cross-sectional study and focus group discussions conducted in Dungarpur district, Rajasthan, India. Participants: Infants aged 1 to <12 months and their mothers/caregivers. Final sample 528 households with 1056 participants, response rate 89.6%. Selected households were divided into MGNREGA-households and non-MGNREGA-households based on participation in MGNREGA between August-2010 and September-2011. Outcomes: Infant malnutrition measured using anthropometric indicators - underweight, stunting, and wasting (WHO criteria).
Results
We included 528 households with 1,056 participants. Out of 528, 281 households took part in MGNREGA between August’10, and September’11. Prevalence of wasting was 39%, stunting 24%, and underweight 50%. Households participating in MGNREGA were less likely to have wasted infants (OR 0·57, 95% CI 0·37–0·89, p = 0·014) and less likely to have underweight infants (OR 0·48, 95% CI 0·30–0·76, p = 0·002) than non-participating households. Stunting did not differ significantly between groups. We did 11 focus group discussions with 62 mothers. Although MGNREGA reduced starvation, it did not provide the desired benefits because of lower than standard wages and delayed payments. Results from path analysis did not support existence of an effect through household food security and infant feeding, but suggested a pathway of effect through low birth-weight.
Conclusion
Participation in MGNREGA was associated with reduced infant malnutrition possibly mediated indirectly via improved birth-weight rather than by improved infant feeding. Addressing factors such as lack of mothers’ knowledge and inappropriate feeding practices, over and above the social and economic policies, is key in efforts to reduce infant malnutrition.
doi:10.1371/journal.pone.0075089
PMCID: PMC3783470  PMID: 24086447
4.  Social origin, schooling and individual change in intelligence during childhood influence long-term mortality: a 68-year follow-up study 
Background Intelligence at a single time-point has been linked to health outcomes. An individual's IQ increases with longer schooling, but the validity of such increase is unclear. In this study, we assess the hypothesis that individual change in the performance on IQ tests between ages 10 and 20 years is associated with mortality later in life.
Methods The analyses are based on a cohort of Swedish boys born in 1928 (n = 610) for whom social background data were collected in 1937, IQ tests were carried out in 1938 and 1948 and own education and mortality were recorded up to 2006. Structural equation models were used to estimate the extent to which two latent intelligence scores, at ages 10 and 20 years, manifested by results on the IQ tests, are related to paternal and own education, and how all these variables are linked to all-cause mortality.
Results Intelligence at the age of 20 years was associated with lower mortality in adulthood, after controlling for intelligence at the age of 10 years. The increases in intelligence partly mediated the link between longer schooling and lower mortality. Social background differences in adult intelligence (and consequently in mortality) were partly explained by the tendency for sons of more educated fathers to receive longer schooling, even when initial intelligence levels had been accounted for.
Conclusions The results are consistent with a causal link from change in intelligence to mortality, and further, that schooling-induced changes in IQ scores are true and bring about lasting changes in intelligence. In addition, if both these interpretations are correct, social differences in access to longer schooling have consequences for social differences in both adult intelligence and adult health.
doi:10.1093/ije/dyr139
PMCID: PMC3324451  PMID: 22493324
Intelligence; socioeconomic factors; public health; mortality; child; adolescent; child development; parents
5.  Socio-demographic Predictors of Dimensions of the AUDIT Score in A Population Sample of Working-age Men in Izhevsk, Russia 
Aims: To investigate the relationship between socio-demographic factors and alcohol drinking patterns identified through a formal analysis of the factor structure of the Alcohol Use Disorders Identification Test (AUDIT) score in a population sample of working-age men in Russia. Methods: In 2008–2009, a sample of 1005 men aged 25–59 years living in Izhevsk, Russia were interviewed and information collected about socio-demographic circumstances. Responses to the AUDIT questions were obtained through a self-completed questionnaire. Latent dimensions of the AUDIT score were determined using confirmatory factor analysis and expressed as standard deviation (SD) units. Structural equation modelling was used to estimate the strength of association of these dimensions with socio-demographic variables. Results: The AUDIT was found to have a two-factor structure: alcohol consumption and alcohol-related problems. Both dimensions were higher in men who were unemployed seeking work compared with those in regular paid employment. For consumption, there was a difference of 0.59 SDs, (95% confidence interval (CI): 0.23, 0.88) and for alcohol-related problems one of 0.66 SD (95% CI: 0.31, 1.00). Alcohol-related problems were greater among less educated compared with more educated men (P-value for trend = 0.05), while consumption was not related to education. Similar results were found for associations with an amenity index based on car ownership and central heating. Neither dimension was associated with marital status. While we found evidence that the consumption component of AUDIT was underestimated, this did not appear to explain the associations of this dimension with socio-demographic factors. Conclusions: Education and amenity index, both measures of socio-economic position, were inversely associated with alcohol-related problems but not with consumption. This discordance suggests that self-reported questions on frequency and volume may be less sensitive markers of socio-economic variation in drinking than are questions about dependence and harm. Further investigation of the validity of the consumption component of AUDIT in Russia is warranted as it appears that the concept of a standard ‘drink’ as used in the instrument is not understood.
doi:10.1093/alcalc/agr076
PMCID: PMC3196365  PMID: 21727097
6.  Dietary Intake and Rural-Urban Migration in India: A Cross-Sectional Study 
PLoS ONE  2011;6(6):e14822.
Background
Migration from rural areas of India contributes to urbanisation and lifestyle change, and dietary changes may increase the risk of obesity and chronic diseases. We tested the hypothesis that rural-to-urban migrants have different macronutrient and food group intake to rural non-migrants, and that migrants have a diet more similar to urban non-migrants.
Methods and findings
The diets of migrants of rural origin, their rural dwelling sibs, and those of urban origin together with their urban dwelling sibs were assessed by an interviewer-administered semi-quantitative food frequency questionnaire. A total of 6,509 participants were included. Median energy intake in the rural, migrant and urban groups was 2731, 3078, and 3224 kcal respectively for men, and 2153, 2504, and 2644 kcal for women (p<0.001). A similar trend was seen for overall intake of fat, protein and carbohydrates (p<0.001), though differences in the proportion of energy from these nutrients were <2%. Migrant and urban participants reported up to 80% higher fruit and vegetable intake than rural participants (p<0.001), and up to 35% higher sugar intake (p<0.001). Meat and dairy intake were higher in migrant and urban participants than rural participants (p<0.001), but varied by region. Sibling-pair analyses confirmed these results. There was no evidence of associations with time in urban area.
Conclusions
Rural to urban migration appears to be associated with both positive (higher fruit and vegetables intake) and negative (higher energy and fat intake) dietary changes. These changes may be of relevance to cardiovascular health and warrant public health interventions.
doi:10.1371/journal.pone.0014822
PMCID: PMC3120774  PMID: 21731604
7.  The Association between Household Socioeconomic Position and Prevalent Tuberculosis in Zambia: A Case-Control Study 
PLoS ONE  2011;6(6):e20824.
Background
Although historically tuberculosis (TB) has been associated with poverty, few analytical studies from developing countries have tried to: 1. assess the relative impact of poverty on TB after the emergence of HIV; 2. explore the causal mechanism underlying this association; and 3. estimate how many cases of TB could be prevented by improving household socioeconomic position (SEP).
Methods and Findings
We undertook a case-control study nested within a population-based TB and HIV prevalence survey conducted in 2005–2006 in two Zambian communities. Cases were defined as persons (15+ years of age) culture positive for M. tuberculosis. Controls were randomly drawn from the TB-free participants enrolled in the prevalence survey. We developed a composite index of household SEP combining variables accounting for four different domains of household SEP. The analysis of the mediation pathway between household SEP and TB was driven by a pre-defined conceptual framework. Adjusted Population Attributable Fractions (aPAF) were estimated.
Prevalent TB was significantly associated with lower household SEP [aOR = 6.2, 95%CI: 2.0–19.2 and aOR = 3.4, 95%CI: 1.8–7.6 respectively for low and medium household SEP compared to high]. Other risk factors for prevalent TB included having a diet poor in proteins [aOR = 3.1, 95%CI: 1.1–8.7], being HIV positive [aOR = 3.1, 95%CI: 1.7–5.8], not BCG vaccinated [aOR = 7.7, 95%CI: 2.8–20.8], and having a history of migration [aOR = 5.2, 95%CI: 2.7–10.2]. These associations were not confounded by household SEP. The association between household SEP and TB appeared to be mediated by inadequate consumption of protein food. Approximately the same proportion of cases could be attributed to this variable and HIV infection (aPAF = 42% and 36%, respectively).
Conclusions
While the fight against HIV remains central for TB control, interventions addressing low household SEP and, especially food availability, may contribute to strengthen our control efforts.
doi:10.1371/journal.pone.0020824
PMCID: PMC3117783  PMID: 21698146
8.  Life-Course Analysis of a Fat Mass and Obesity-Associated (FTO) Gene Variant and Body Mass Index in the Northern Finland Birth Cohort 1966 Using Structural Equation Modeling 
American Journal of Epidemiology  2010;172(6):653-665.
The association between variation in the fat mass and obesity-associated (FTO) gene and adulthood body mass index (BMI; weight (kg)/height (m)2) is well-replicated. More thorough analyses utilizing phenotypic data over the life course may deepen our understanding of the development of BMI and thus help in the prevention of obesity. The authors used a structural equation modeling approach to explore the network of variables associated with BMI from the prenatal period to age 31 years (1965–1997) in 4,435 subjects from the Northern Finland Birth Cohort 1966. The use of structural equation modeling permitted the easy inclusion of variables with missing values in the analyses without separate imputation steps, as well as differentiation between direct and indirect effects. There was an association between the FTO single nucleotide polymorphism rs9939609 and BMI at age 31 years that persisted after controlling for several relevant factors during the life course. The total effect of the FTO variant on adult BMI was mostly composed of the direct effect, but a notable part was also arising indirectly via its effects on earlier BMI development. In addition to well-established genetic determinants, many life-course factors such as physical activity, in spite of not showing mediation or interaction, had a strong independent effect on BMI.
doi:10.1093/aje/kwq178
PMCID: PMC2938267  PMID: 20702506
body mass index; molecular epidemiology; structural equation model
9.  A structured approach to modelling the effects of binary exposure variables over the life course 
Background There is growing interest in the relationship between time spent in adverse circumstances across life course and increased risk of chronic disease and early mortality. This accumulation hypothesis is usually tested by summing indicators of binary variables across the life span to form an overall score that is then used as the exposure in regression models for health outcomes. This article highlights potential issues in the interpretation of results obtained from such an approach.
Methods We propose a model-building framework that can be used to formally compare alternative hypotheses on the effect of multiple binary exposure measurements collected across the life course. The saturated model where the order and value of the binary variable at each time point influence the outcome of interest is compared with nested alternative specifications corresponding to the critical period, cumulative risk or hypotheses about the effect of changes in environment. This framework is illustrated with data on adult body mass index and socioeconomic position measured once in childhood and twice in adulthood from the Medical Research Council National Survey of Health and Development, using a series of liner regression models.
Results We demonstrate how analyses that only consider the association of a cumulative score with a later outcome may produce misleading results.
Conclusion We recommend comparing a set of nested models—each corresponding to the accumulation, critical period and effect modification hypotheses—to an all-inclusive (saturated) model. This approach can provide a formal and clearer understanding of the relative merits of these alternative hypotheses.
doi:10.1093/ije/dyn229
PMCID: PMC2663717  PMID: 19028777
Longitudinal studies; social class; body mass index; critical period; social mobility; regression analysis
10.  Years of sunlight exposure and cataract: a case-control study in a Mediterranean population 
BMC Ophthalmology  2007;7:18.
Background
We aimed to investigate the relation between sunlight exposure and risk of cataract.
Methods
We carried out a frequency-matched case-control study of 343 cases and 334 controls attending an ophthalmology outpatient clinic at a primary health-care center in a small town near Valencia, Spain.
All cases were diagnosed as having a cataract in at least one eye based on the Lens Opacification Classification system (LOCS II). Controls had no opacities in either eye. All cases and controls were interviewed for information on outdoor exposure, "usual" diet, history of severe episodes of diarrhea illness, life-style factors and medical and socio-demographic variables. Blood antioxidant vitamin levels were also analyzed. We used logistic regression models to estimate sex and age-adjusted odds ratios (ORs) by quintiles of years of occupational outdoor exposure, adjusting for potential confounders such as smoking, alcohol consumption, serum antioxidants and education.
Results
No association was found between years of outdoor exposure and risk of cataract. However, exploratory analyses suggested a positive association between years of outdoor exposure at younger ages and risk of nuclear cataract later in life.
Conclusion
Our study does not support an association with cataract and sunlight exposure over adult life.
doi:10.1186/1471-2415-7-18
PMCID: PMC2234085  PMID: 18039367
11.  Predicting prognosis in stable angina—results from the Euro heart survey of stable angina: prospective observational study 
BMJ : British Medical Journal  2006;332(7536):262-267.
Objectives To investigate the prognosis associated with stable angina in a contemporary population as seen in clinical practice, to identify the key prognostic features, and from this to construct a simple score to assist risk prediction.
Design Prospective observational cohort study.
Setting Pan-European survey in 156 outpatient cardiology clinics.
Participants 3031 patients were included on the basis of a new clinical diagnosis by a cardiologist of stable angina with follow-up at one year.
Main outcome measure Death or non-fatal myocardial infarction.
Results The rate of death and non-fatal myocardial infarction in the first year was 2.3 per 100 patient years; the rate was 3.9 per 100 patient years in the subgroup (n = 994) with angiographic confirmation of coronary disease. The clinical and investigative factors most predictive of adverse outcome were comorbidity, diabetes, shorter duration of symptoms, increasing severity of symptoms, abnormal ventricular function, resting electrocardiogaphic changes, or not having any stress test done. Results of non-invasive stress tests did not significantly predict outcome in the population who had tests done. A score was constructed using the parameters predictive of outcome to estimate the probability of death or myocardial infarction within one year of presentation with stable angina.
Conclusions A score based on the presence of simple, objective clinical and investigative variables makes it possible to discriminate effectively between very low risk and very high risk patients and to estimate the probability of death or non-fatal myocardial infarction over one year.
doi:10.1136/bmj.38695.605440.AE
PMCID: PMC1360391  PMID: 16415069
12.  The cognitive cost of being a twin: evidence from comparisons within families in the Aberdeen children of the 1950s cohort study 
BMJ : British Medical Journal  2005;331(7528):1306.
Objectives To determine whether twins have lower IQ scores in childhood than singletons in the same family and, if so, whether differences in fetal growth explain this deficit.
Design Cohort study.
Setting Scotland.
Participants 9832 singletons and 236 twins born in Aberdeen between 1950 and 1956.
Results At age 7, the mean IQ score of twins was 5.3 points lower (95% confidence interval 1.5 to 9.1) and at age 9, 6.0 points lower (1.7 to 10.2) than that of singletons in the same family. Adjustment for sex, mother's age, and number of older siblings had little effect on these differences. Further adjustment for birth weight and gestational age attenuated the IQ difference between twins and singletons: the difference in mean IQ was 2.6 points (-1.5 to 6.7) at age 7 and 4.1 points (-0.5 to 8.8) at age 9.
Conclusions Twins have substantially lower IQ in childhood than singletons in the same family. This effect cannot be explained by confounding due to socioeconomic, maternal, or other family characteristics, or by recruitment bias. The reduced prenatal growth and shorter gestations of twins may explain an important part of their lower IQ in childhood.
doi:10.1136/bmj.38633.594387.3A
PMCID: PMC1298851  PMID: 16299014
13.  Issues in the reporting of epidemiological studies: a survey of recent practice 
BMJ : British Medical Journal  2004;329(7471):883.
Objectives To review current practice in the analysis and reporting of epidemiological research and to identify limitations.
Design Examination of articles published in January 2001 that investigated associations between risk factors/exposure variables and disease events/measures in individuals.
Setting Eligible English language journals including all major epidemiological journals, all major general medical journals, and the two leading journals in cardiovascular disease and cancer.
Main outcome measure Each article was evaluated with a standard proforma.
Results We found 73 articles in observational epidemiology; most were either cohort or case-control studies. Most studies looked at cancer and cardiovascular disease, even after we excluded specialty journals. Quantitative exposure variables predominated, which were mostly analysed as ordered categories but with little consistency or explanation regarding choice of categories. Sample selection, participant refusal, and data quality received insufficient attention in many articles. Statistical analyses commonly used odds ratios (38 articles) and hazard/rate ratios (23), with some inconsistent use of terminology. Confidence intervals were reported in most studies (68), though use of P values was less common (38). Few articles explained their choice of confounding variables; many performed subgroup analyses claiming an effect modifier, though interaction tests were rare. Several investigated multiple associations between exposure and outcome, increasing the likelihood of false positive claims. There was evidence of publication bias.
Conclusions This survey raises concerns regarding inadequacies in the analysis and reporting of epidemiological publications in mainstream journals.
doi:10.1136/bmj.38250.571088.55
PMCID: PMC523109  PMID: 15469946
15.  Alcohol-Related Dysfunction in Working-Age Men in Izhevsk, Russia: An Application of Structural Equation Models to Study the Association with Education 
PLoS ONE  2013;8(5):e63792.
Background
Acute alcohol-related dysfunctional behaviours, such as hangover, are predictive of poor health and mortality. Although much is known about the association of education with alcohol consumption, little is known about its association with these dysfunctional behaviours.
Methods
The study population was 1,705 male drinkers aged 25–54 years resident in the city of Izhevsk, Russia who participated in a cross-sectional survey (2003–6). Structural equation modelling was used to examine the relationships between education, beverage and non-beverage alcohol intake, drinking patterns, and acute alcohol-related dysfunction score among these drinkers.
Results
Dysfunction was related to all other drinking variables, with the strongest predictors being spirit intake, non-beverage alcohol consumption and drinking patterns. There was a strong relationship between education and acute dysfunction which was not explained by adjusting for alcohol intake and drinking patterns (mean adjusted dysfunction score 0.35 SD (95% CI 0.10, 0.61) lower in men with higher versus secondary education).
Conclusions
Although by definition one or more aspects of alcohol consumption should explain the educational differences in alcohol-related dysfunction, detailed information on drinking only partly accounted for the observed patterns. Thus beyond their intrinsic interest, these results illustrate the challenges in constructing statistical models that convincingly identify the pathways that link educational differences to health-related outcomes.
doi:10.1371/journal.pone.0063792
PMCID: PMC3648513  PMID: 23667673

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