Social and Biological Determinants of Blood Pressure in Afro-Caribbean Youth Trevor S Ferguson, MBBS, DM, MSc, FACP Senior Lecturer (Epidemiology), Caribbean Institute for Health Research, UWI Honorary Consultant (General Internal Medicine), UHWI Caribbean Institute of Nephrology 10th Annual International Conference on Nephrology and Hypertension January 19 & 20, 2018

GLOBAL BURDEN OF HYPERTENSION Hypertension is a global public problem causing ≈ 9.4 million deaths worldwide every year Causes at least 45% of deaths from heart disease and 51% of stroke deaths Globally, the overall prevalence of HTN in adults aged ≥18 yrs was around 22% in 2014 Prevalence was highest in Africa - 30% and lowest prevalence was in the Americas - 18% Prevalence is higher in low income countries Hypertension causes 9.4 million deaths worldwide every year and was responsible for at least 45% of deaths from heart disease and 51% of stroke deaths. Worldwide prevalence is approximately 40% for adults 25 years and older. Prevalence of HTN is highest in the African Region (46%); lowest in the Americas (35%). Additionally High-income countries have a lower prevalence 35% vs. 40%. Source: A Global Brief on Hypertension. WHO/DCO/WHD/2013.2 WHO Global Health Observatory (Blood Pressure) http://www.who.int/gho/ncd/risk_factors/blood_pressure_text/en/

Source: Global Status Report On Noncommunicable Diseases 2014 MALES Jamaica = 24.5% Source: Global Status Report On Noncommunicable Diseases 2014

Source: Global Status Report On Noncommunicable Diseases 2014 FEMALES Jamaica = 19.2% Source: Global Status Report On Noncommunicable Diseases 2014

Prevalence of hypertension by world regions in 1975-2015 Overall prevalence of HTN decreasing But # of adults with HTN  from 594 M in 1975 – 1.13 B in 2015  seen in high income and some middle income countries but unchanged in other regions Some evidence for  prevalence in Sub-Saharan Africa and Southeast Asia Source: NCD Risk Factor Collaboration. Worldwide trends in blood pressure from 1975 to 2015; The Lancet; 2016. http://dx.doi.org/10.1016/S0140-6736(16)31919-5  

Hypertension is the leading risk factor for global disease burden Figure shows the burden of disease attributable to 20 leading risk factors in 2010, expressed as percent of global DALYs Hypertension accounted for 7% of global DALYs Data form the 2010 Global Burden of Diseases study showed that hypertension is the leading risk factor for global disease burden accounting for 7% of global DALYs (disability adjusted life years). Tobacco smoking and household air pollution were the other two leading risk factors. Figure: Burden of disease attributable to 20 leading risk factors in 2010, expressed as a percentage of global disability-adjusted life-years. For men (A), women (B), and both sexes (C). Source: The Lancet 2012; 380:2224-2260 (DOI:10.1016/S0140-6736(12)61766-8)

Hypertension is a major cause of mortality in the Caribbean Leading causes of death in Jamaica and CAREC member countries in 2004 Data from CAREC and the RGD in Jamaica showed that in 2004 hypertension was the 4th leading cause of death in the Caribbean. It should be noted that in addition to the deaths directly linked to hypertension, hypertension would also be responsible for about a half the deaths from stroke and IHD. Hypertensive diseases - 4th leading cause of death Also major contributor to stroke & IHD deaths Ferguson & Tulloch-Reid. Curr Cardio Risk Rep (2010) 4:76–82

Definition & Classification of High BP JNC 7 (2003) ACC/AHA 2017 BP Category BP Values Normal SBP <120 mmHg & DBP <80 mmHg Prehypertension SBP 120-139 mmHg or DBP 80-89 mmHg Hypertension Stage 1 SBP 140-159 mmHg or DBP 90-99 mmHg Stage 2 SBP ≥ 160 mmHg or DBP ≥ 100 mmHg BP Category BP Values Normal SBP <120 mmHg & DBP <80 mmHg Elevated BP SBP 120-129 mmHg or DBP <80 mmHg Hypertension Stage 1 SBP 130-139 mmHg or DBP 80-89 mmHg Stage 2 SBP ≥ 140 mmHg or DBP ≥ 90 mmHg

Hypertension Prevalence in Jamaica Year of Study Lead Investigator Sample Sample Size Age Range Prevalence Estimate 1993 Figueroa1 National 958 15-49 yrs. 13.4%* 2000 - 2001 Wilks2 2012 15-74 yrs. 20.9% 2007 - 2008 2848 25.2% *Self-reports Figueroa et al. West Indian Med J 1999; 48 (I): 9 -15 Ferguson et al. West Indian Med J. 2011 Jul;60(4):422-8.

Prehypertension in Jamaica 30% in JHLS-1 35% in JHLS-2 29% among youth 15-19 years old in JYRRBS 20% among young adults 18-20 years on in 1986 Birth Cohort Prevalence higher in men compared to women Ferguson et al. BMC Cardiovascular Disorders 2008, 8:20 Ferguson et al. West Indian Med J 2011; 60 (4): 429

Consequences of hypertension Mortality – acute myocardial infarction, heart failure, ischaemic and haemorrhagic stroke, end stage renal disease Morbidity – ischaemic heart disease, hypertensive heart disease, non-fatal stroke, chronic kidney disease Social and economic – high health care costs, especially for treating complications; lost of income; increased dependency

Aetiology of Hypertension

Risk / Causal Factors in Hypertension Multifactorial Life Course Model Parental SES, Neighbourhood SES, Own SES, Environmental exposures Social factors across the life course Adult Blood Pressure Genetic & non-modifiable risk factors Intrauterine growth & early life factors Childhood growth Adult characteristics & behaviours Single gene mutations Familial genetic factors Sex Age Race/Ethnicity Maternal nutrition Fetal nutrition Fetal growth Birth size Prematurity Rapid catch up growth Childhood obesity and weight gain Body size & adiposity Insulin resistance Salt intake Nutrition Physical Inactivity Alcohol consumption Smoking Stress

Early life influences on Hypertension

Early life origins of chronic disease Early life factors are now recognised as important predictors of hypertension and other NCDs in adults Barker et al demonstrated an inverse relationship between measures of intra-uterine growth (chiefly birth weight) CVD, type 2 diabetes and dyslipidemia Initial studies focused on middle age and older adults in developed countries, but similar findings have now been replicated in several counties A large body of evidence has accumulated over the past two decades showing that early life factors play an important role in the development of adult diseases. Early life factors are now recognised as important predictors of hypertension, other NCDs, and their risk factors, in adults. Barker and colleagues were the first to demonstrate an inverse relationship between birth weight and other measures of intra-uterine growth and cardiovascular disease, type 2 diabetes and dyslipidemia in middle aged adults. Similar findings have now been seen in several counties.

Early life origins of hypertension Early life influences identified include: Intrauterine growth Placental size Infant and postnatal growth Perinatal socioeconomic factors

Birth weight and hypertension Data from Helsinki Birth Cohort – included 2003 persons examined at 62 years This slide shows the relationship between birth weight and previously diagnosed hypertension among 2003 persons from the Helsinki Birth Cohort at age 62 years. Low birth weight was associated with an almost four-fold increase in the risk of previously diagnosed hypertension, with a statistically significant trend. While there was an increase in the risk of newly diagnosed hypertension this was not statistically significant, Eriksson et al. Childhood Growth and Hypertension in Later Life. Hypertension. 2007;49:1415-1421

Parental social class and hypertension Data from Helsinki Birth Cohort – included 2003 persons examined at 62 years An important addition to the literature on the early life origins of adult disease was the work looking at the role of socioeconomic factors. Initial critique of the original studies suggested that the birth weight effect was really a due to confounding by socioeconomic status. Further studies however demonstrated that birth weight effect was still significant after adjusting for socioeconomic status and that SES itself had an independent effect. This table shows data from Barker and colleagues which demonstrated that the odds of hypertension was two-fold higher among persons whose fathers were laborers compared to those whose fathers were in the upper middle income social class. Barker et al. Maternal and Social Origins of Hypertension Hypertension. 2007;50:565-571

Low Birth weight and subsequent blood pressure: a meta-analysis (OR for HTN for LBW vs. NBW) Since the work of Barker and his team a large number of studies have looked at this relationship. Most have shown a clear inverse association between birth weight and measured SBP and DBP, but some have shown conflicting results. This slide shows the results from a recent meta-analysis. Among 20 studies included in the analysis odds of hypertension was increased by 21% for persons with low birth weight compared to persons with normal birth weight. Mean SBP was on average 2.3 mmHg higher among persons with low birth weight compared to those with normal birth weight. Odds of hypertension was increased by 21% for persons with LBW compared to persons with NBW Mean SBP was on average 2.3 mmHg higher among persons with LBW compared to those with NBW Mu et al. Archives of Cardiovascular Disease (2012) 105, 99—113

Early life origins of hypertension: Studies from Jamaica Previous studies examined associations between blood pressure and birth weight and other early life factors Fetal growth and cardiovascular risk in Jamaican school children 6-16 years – Forrester et al BMJ 1996 Birth weight and postnatal linear growth retardation on blood pressure at 11-12 years – Walker et al JECH 2001 Limited data on the effect of early life or life-course factors in older adolescents or adults

Social Determinants of Hypertension

Socioeconomic status and hypertension Several studies have documented associations between HTN and SES or other social factors, including neighbourhood characteristics Recent meta-analysis of 51 studies published in 2015 Overall increased risk of HTN with lower SES Income - pooled OR 1.19, 95% CI 0.96–1.48 Occupation - pooled OR 1.31, 95% CI 1.04–1.64 Education - pooled OR 2.02, 95% CI 1.55–2.63 Associations were significant in high-income countries Association more consistent among women Source: Leng et al. Socioeconomic status and hypertension: a meta-analysis; J Hypertens 33:221–229. DOI:10.1097/HJH.0000000000000428

Knowledge Gaps Most studies done in developed countries Limited data for developing countries and for African origin populations Limited data for young adults

Manuscript Series by ERU team Early life predictors of blood pressure in Afro-Caribbean young adults: the Jamaica 1986 Birth Cohort Study Effect of growth velocity and change in adiposity in childhood and adolescence on blood pressure in Afro- Caribbean youth: the Vulnerable Windows Cohort Study Factors associated with elevated blood pressure or hypertension in Afro-Caribbean youth

Paper - 1: Early Life Social and Biological Determinants of Blood Pressure at 18-20 years old: The Jamaica 1986 Birth Cohort Study We turn now to the most recent analysis from the 1986 Birth Cohort where we looked at early life early life social and biological determinants of blood pressure at 18-20 years old.

The 1986 Jamaica Birth Cohort Assembled from a subgroup of participants in the 1986 Jamaica Perinatal Mortality Survey Original survey enrolled consecutive births in all fourteen parishes in Jamaica during Sept – Oct 1986 Birth Cohort - sub-sample of participants from the parishes of Kingston and St. Andrew, and St. Catherine Last follow up - 902 participants enrolled; 794 participants included in analyses on birth weight and blood pressure

Paper 1 - Objective To investigate how birth weight, parental socioeconomic circumstances (SEC), current SEC, and current body size, influence blood pressure in young adults at 18-20 years old

Proportion (%) of male and female infants in 500 g birth weight categories

Relationship between systolic blood pressure, birth weight and other characteristics in multi-level regression models2 Variable Males Females    (95% CI) Birth weight Z-score -1.16 (-2.15, -0.17)* -1.34 (-2.21, -0.47)** Current Age (years) 1.39 (-0.24, 3.03) 1.73 (0.42, 3.05)* BMI (kg/m2) 0.83 (0.60, 1.07)*** 0.39 (0.25, 0.54)*** Current Height (cm) 0.08 (-0.07, 0.24) 0.17 (0.04, 0.31)* Maternal age at child’s birth 0.21 (0.04, 0.39)* 0.00 (-0.14, 0.14) Maternal occupation Highly Skilled/Skilled Reference Semi-skilled/Unskilled 3.67 (0.49, 6.85)* 1.81 (-0.65, 4.29) Unemployed 4.81 (1.99, 7.64)** 2.10 (-0.37, 4.39) Housewife 3.37 (0.64, 6.11)* 1.85 (-0.57, 4.26) In the fully adjusted model, one standard deviation increase in BWT was associated with 1.16 mmHg reduction in SBP among men (95%CI 2.15 to 0.17; p=0.021) and 1.34 mmHg reduction in SBP among women (95%CI 2.21 to 0.47; p=0.003). Participants whose mothers had lower SEC had higher SBP compared to those with mothers of high SEC (β, 3.4-4.8 mmHg for men, p<0.05 for all SEC categories, and 1.8-2.1 for women, p>0.05) 1Coefficients represent change in systolic or diastolic blood pressure (mmHg) for each unit change in the various characteristics. 2Cluster variable for multilevel model was place of birth (29 clusters, usually a hospital or maternity centre) * p<0.05; ** p<0.01; *** p<0.001; BMI = body mass index Ferguson et al. (2015) Birth weight and maternal socioeconomic circumstances were inversely related to systolic blood pressure among Afro-Caribbean young adults. J Clin Epidemiol. 2015 Feb 12. doi: 10.1016/j.jclinepi.2015.01.026.

Predicted systolic blood pressure by birth weight and mothers occupation category Male Female These figures show predicted SBP by maternal occupation at birth and birth weight z-scores, based on the final SBP model. Among men, there was a consistent gradient in SBP by maternal occupation and birth weight SD distribution, with SBP consistently highest for those whose mothers were unemployed and lowest for those whose mothers were in a highly skilled/skilled occupation. Among women, the trend was less delineated by maternal occupation. SBP was lowest among whose mothers were in a highly skilled/skilled occupation category but there was little difference in SBP between the other groups. skilled/highly skilled semi-skilled/unskilled unemployed housewife Ferguson et al. (2015) Birth weight and maternal socioeconomic circumstances were inversely related to systolic blood pressure among Afro-Caribbean young adults. J Clin Epidemiol. 2015 Feb 12. doi: 10.1016/j.jclinepi.2015.01.026.

CONCLUSIONS FROM PAPER 1 Intrauterine growth and early life SEC are important predictors of blood pressure in young adults Early life factors should be considered in the development of policies and interventions to reduce the burden of HTN and other NCDs

DOHAD Conference October 17, 2017 Paper 2 Effect of linear growth rate and change in adiposity in childhood and adolescence on blood pressure in Afro-Caribbean youth Trevor Ferguson, Tamika Royal-Thomas, Lisa Chin-Harty, Minerva Thame, Terrence Forrester, Michael Boyne, Rainford Wilks Caribbean Institute for Health Research, The University of the West Indies, Jamaica Department of Medicine, The University of the West Indies, Jamaica Department of Child and Adolescent Health, The University of the West Indies, Jamaica UWI Solutions for Developing Countries, The University of the West Indies, Jamaica DOHAD Conference October 17, 2017 Good afternoon everyone, Let me thank the conference organisers for providing this opportunity to present our research.

Objectives To evaluate the effect of postnatal linear growth and change in body mass index from birth to adolescence on systolic and diastolic blood pressure in Afro-Caribbean youth We therefore undertook this study in order to evaluate the effect of postnatal linear growth and change in body mass index from birth to adolescence on systolic and diastolic blood pressure in Afro-Caribbean youth.

Methods Participants from Vulnerable Windows Cohort Study in Jamaica Mothers recruited during 1st trimester of pregnancy in 1992 and 1993; children (singleton only) followed from birth at regular intervals (6 wks; 3mths; q3mths – 2yrs; then q6mths) This analysis included 366 persons age 15 years or older Growth and adiposity measurements calculated for four growth periods: early infancy (0-6 months), late infancy (6 months - 2 years), early childhood (2-8 years), and late childhood (8-15 years) The study was conducted using data from participants in the Vulnerable Windows Cohort Study In Jamaica. In this study, mothers of participants were recruited during the first trimester of pregnancy in 1992 and 1993 and then followed from birth at six month to 1 year intervals. Data for analysis for this paper includes 366 persons age 15 years or older. Growth and adiposity measurements were calculated for four growth periods. These were: early infancy (0-6 months), late infancy (6 months - 2 years), early childhood (2-8 years), and later childhood (8-15 years).

Methods Growth rates were computed using conditional models which calculated how much body size at the end of a growth period differed from that predicted by the body size at the beginning of the period Calculated growth rates were standardized by converting them to z-scores Linear mixed models were used to estimate the effect of growth rates on SBP and DBP Growth rates were computed by calculating how much body size at the end of a growth period differed from that predicted by the body size at the beginning of the period. Calculated growth rates were standardized by converting them to z-scores. We then used linear mixed models to estimate the effect of growth rates on SBP and DBP. Models accounted for repeated measures within individuals with random intercepts and random slopes. Multiple imputation was used to fill in missing values.

Participants and measurements Analyses included 162 males and 204 females Mean age 16.7 years (range 15.0, 21.2 years).  Each individual had on average 5.2 BP measurements (range 1-10) The analysed sample included 162 males and 204 females., with mean age of 16.7 years and range. Each individual had an average 5.2 BP measurements (range 1-10). In total, there were 1910 SBP measurements and 1908 DBP measurements included in the analyses.

Regression Coefficient Final multivariable model with regression coefficients for the effect of linear growth on systolic BP at age ≥15 years Variable Regression Coefficient 95% Confidence Interval P-value Birth length z-score 0.72 -0.25, 1.68 0.145 Linear growth rate 0-6 month 1.00 0.14, 1.88 0.024 Linear growth rate 6 mths – 2 yrs -0.17, 1.61 0.113 Linear growth rate 2 yrs – 8 yrs 0.62 -0.22, 1.46 0.144 Linear growth rate 8 years – 15 yrs 0.07 -1.12, 1.27 0.907 Gestational age at birth (days) -0.07 -0.15, 0.01 0.069 Age (years) -1.08 -1.37, -0.78 <0.001 Sex (male vs. female) 7.21 5.01, 9.40 BMI at age 15 (kg/m2) 0.34 0.16, 0.52 This slide shows the final multivariable model for the effect of linear growth on systolic blood pressure. Statistically significant association was found only for the 0-6 months growth period. Age at the time of BP measurement, sex and BMI at age 15 were also significant. Contrary to expectation, the coefficients for age was negative, indicate lower SBP with age between 15-21.

Regression Coefficient Final multivariable model with regression coefficients for the effect of change in BMI on systolic BP at age ≥15 years Variable Regression Coefficient 95% Confidence Interval P-value BMI at birth z-score 0.28 -0.60, 1.16 0.527 Change in BMI 0-6 month 0.59 -0.18, 1.36 0.131 Change in BMI 6 mths – 2 yrs 1.52 0.72, 2.32 <0.001 Change in BMI 2 yrs – 8 yrs 1.17 0.45, 1.88 0.002 Change in BMI 8 yrs – 15 yrs 0.66 0.01, 1.32 0.048 Gestational age at birth (days) -0.06 -0.13, 0.01 0.095 Socioeconomic status score at birth -0.02 -0.20, 0.17 0.866 Age (years) -1.08 -1.38, -0.78 Sex (male vs. female) 7.34 5.63, 9.05 Height at age 15 0.05 -0.01, 0.11 0.134 We now turn to the results for change in BMI and SBP. After adjusting for covariates, faster gain in BMI the 6 months to 2 years, 2-8 years and 8-15 years growth periods were significantly associated with SBP, with the largest effect being in the 6 month – 2 years growth period.

Results for Diastolic BP Findings were generally similar for diastolic blood pressure, but were smaller in magnitude

Conclusion Both faster linear growth and greater rate of increase in BMI were associated with higher BP Associations were stronger and more consistent for increase in BMI Findings suggest that postnatal growth trajectories should be closely monitored and faster than expected gain in adiposity should be discouraged In summary therefore, both faster linear growth and greater rate of increase in BMI were associated with higher SBP and DBP, however the associations were stronger and more consistent for increase in BMI. These findings suggest that that postnatal growth trajectories should be closely monitored during childhood and faster than expected gain in adiposity should be discouraged

Paper 3 Factors associated with elevated blood pressure or hypertension in Afro-Caribbean youth: a cross-sectional study Under review at PeerJ

Paper 3 - Objectives To evaluate the association between putative risk factors and elevated BP or hypertension (EBP/HTN), defined as BP ≥120/80 mmHg, among Afro-Caribbean youth. To estimate the relative risk for having EBP/HTN among participants with putative CVD risk factors To evaluate whether there were significant sex differences in risk factors for EBP/HTN

Paper 3 - Methods Cross-sectional analysis from Jamaica 1986 Birth Cohort 898 young adults, 18-20 years old BP was measured with a mercury sphygmomanometer after participants had been seated for 5 min. Anthropometric measurements were done and venous blood obtained to measure fasting glucose, lipids and insulin.

Paper 3 - Methods Data on socioeconomic status (SES) were obtained via questionnaire. CVD risk factor status was defined using standard cut-points or the upper quintile of the distribution. Relative risks were computed using odds ratios (OR) from logistic regression models. Multiple imputation by chained equations used to fill in missing values

Distribution of BP Categories by 2017 ACC/AHA Criteria Prevalence HTN: Males 17% males; 8% females P<0.001 for male: female difference

Prevalence of Elevated BP or Hypertension SBP ≥120 mmHg or DBP ≥80 mmHg

Factors associated with elevated BP or HTN among MALES in multivariable logistic regression models Odds Ratio 95% CI P-Value Age (years) 1.74 1.16 - 2.61 0.007 BMI Category   Normal weight (18.5 -24.9 kg/m2) 1.0 - Underweight (<18.5 kg/m2) 0.64 0.20 – 2.00 0.441 Overweight (25-29.9 kg/m2) 1.76 0.90 – 3.43 0.096 Obese (≥30kg/m2) 8.48 2.64 – 27.2 <0.001 High Glucose (upper quintile) 2.01 1.20– 3.37 0.008 HOMA-IR (log transformed, upper quintile) 2.08 0.94 – 4.58 0.069 High hsCRP 0.45 0.17 – 1.17 0.101 Household possessions High (15-17 items) Moderate (10-14 items) 0.62 0.33 – 1.18 0.147 Low (0-9 items) 1.21 0.59 – 2.45 0.604 Physical Activity Level High Physical Activity Level Moderate Physical Activity Level 0.55 0.33 – 0.93 0.026 Low Physical Activity Level 0.49 0.24 – 0.97 0.042 Estimates derived from sex-specific models which included all variables in the table. N=409. Multiple imputation used to fill in missing values

Factors associated with elevated BP or HTN among FEMALES in multivariable logistic regression models Odds Ratio 95% CI P-Value Age (years) 2.55 1.60 – 4.08 <0.001 Height (cm) 1.07 1.02 - 1.12 0.003 BMI Category (vs. Normal weight)   Underweight 1.70 0.74 – 3.91 0.211 Overweight 1.31 0.63 – 2.72 0.461 Obese 1.44 0.58 – 3.56 0.436 High Triglycerides (upper quintile) 1.98 1.03– 3.81 0.040 HOMA-IR (log transformed, upper quintile) 2.07 1.03 – 4.12 0.039 White blood cell count 1.14 0.99 – 1.31 0.076 Household possessions [vs. high (15-17 items)] Moderate (10-14 items) 4.63 1.31 – 16.4 0.017 Low (0-9 items) 2.61 0.70 – 9.77 0.154 Physical Activity Level [vs High PAL] Moderate Physical Activity Level 0.71 0.31 – 1.65 0.429 Low Physical Activity Level 0.42 0.18 – 0.97 0.043 Alcohol Consumption [vs Never Drank Alcohol] Rarely Drinks Alcohol (<once/week) 0.41 0.18 – 0.90 0.026 Drinks Alcohol 1-2 times/week 0.46 0.19– 1.15 0.099 Drinks Alcohol ≥3 times/week 0.28 0.11 – 0.76 0.012 Estimates derived from sex-specific models which included all variables in the table. N=489. Multiple imputation used to fill in missing values Estimates derived from sex-specific models which included all variables in the table. N=489. Multiple imputation used to fill in missing values

PAPER 3 - CONCLUSION Factors associated with elevated BP among Jamaican young adults include measures of obesity and insulin resistance, with some significant differences by sex Lower SES was associated with elevated BP among females only Reducing obesity and improving insulin sensitivity may reduce hypertension risk in Afro-Caribbean populations

SUMMARY Hypertension remains a global public health problem Understanding the determinants of hypertension in youth can help in developing interventions to reduce the impact of hypertension on public health Early life factors including birth weight, postnatal growth and maternal SEC contribute to the risk of elevated blood pressure or hypertension in youth Obesity, measures of insulin resistance (glucose, triglycerides, HOMA-IR) and SES are associated with elevated BP in youth These factors should be considered in efforts to prevent hypertension

Acknowledgements Prof Rainford Wilks Dr Novie Younger-Coleman, Prof Michael Boyne, Prof Seeromanie Harding, Prof Clive Osmond Dr Tamika Royal-Thomas Other investigators (1986 Birth Cohort, VWS, JHLS-I & III, YRRBS), collaborators and co- authors

QUESTIONS / DISCUSSION