Early-life exposure to ambient air pollutants and kidney function in adolescents: a cohort study based on the 'Children of 1997' Hong Kong birth cohort.

OBJECTIVES: Air pollution is increasingly linked to impaired kidney function in adults. However, little is known about how early-life exposure to air pollutants affects kidney function in adolescents. STUDY DESIGN: Cohort study. METHODS: We leveraged data from the 'Children of 1997' Hong Kong population-representative birth cohort (N = 8327). Residential exposure to average ambient levels of four air pollutants, including inhalable particle (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and nitrogen monoxide (NO), during in utero, infancy, and childhood periods was estimated using the inverse distance weighting. Kidney function was assessed using estimated glomerular filtration rate (eGFR) calculated from age-adjusted equations for adolescents. Generalized linear regression was used to examine the association of air pollutant exposure in each period with kidney function at 17.6 years. Two-pollutant models tested the robustness of the association. RESULTS: Of the 3350 participants included, 51.4% were boys. Exposure to PM10 was associated with poorer kidney function. Each interquartile range increment in PM10 was inversely associated with eGFR (ß: -2.933, 95% confidence interval -4.677 to -1.189) in utero, -2.362 (-3.992 to -0.732) infancy, -2.708 (-4.370 to -1.047) childhood, and -2.828 (-4.409 to -1.247) overall. Exposure to PM10 and SO2in utero had a stronger inverse association with kidney function in males. The associations were robust to PM10 exposure in two-pollutant models. CONCLUSIONS: Our findings suggest that early-life exposure to ambient PM10 and SO2 is associated with reduced kidney function in adolescents, especially exposure in utero.

Correction to: In utero exposure to gestational diabetes and adiposity: does breastfeeding make a difference?

In the original version of this article, the Publisher incorrectly listed the affiliation of the author, G.M. Leung. The correct affiliation for this author should be: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

In utero exposure to gestational diabetes and adiposity: does breastfeeding make a difference?

BACKGROUND/OBJECTIVES: Short-term breastfeeding from mothers with gestational diabetes (GDM) may programme metabolism and increase offspring diabetes risk. We examined the association of in utero GDM exposure with adiposity from infancy to adolescence, and whether any association was modified by breastfeeding during early infancy. METHODS: In the prospective Chinese birth cohort "Children of 1997" (n = 7342, 88% follow-up rate), generalised estimate equations with multiple imputation were used to assess associations of in utero GDM exposure with age- and sex-specific body mass index (BMI) z-score during infancy (3 and 9 months), childhood (2- < 8 years) and adolescence (8-16 years), adjusted for sex, parity, maternal age, birth place, preeclampisa, smoking, and family socio-economic position. We also tested whether the associations differed by mode of infant feeding (always formula-fed, mixed, always breastfed) during the first three months of life. RESULTS: In utero GDM exposure (7.5%) was associated with a lower BMI z-score during infancy (-0.13, 95% confidence interval (CI) -0.22, -0.05) but higher BMI z-scores during childhood (0.14, 95% CI 0.03, 0.25) and adolescence (0.25 95% CI 0.11, 0.38). Breastfeeding for the first three months did not modify the association of in utero GDM status with subsequent BMI (all p values for interaction >0.4). CONCLUSIONS: In utero GDM exposure was associated with greater adiposity during childhood and adolescence. Breastfeeding in early infancy from mothers with GDM was not associated with greater adiposity in children and thus should still be encouraged.

Migrant status and childhood hospitalizations for asthma and other wheezing disorders.

BACKGROUND: In developed Western settings, asthma is more prevalent among second-generation compared to first-generation migrants. However, these studies are difficult to interpret as they include migrants of various ethnicities and countries of origin. OBJECTIVE: We assessed the association of parental migrant status with wheezing disorders among children born in Hong Kong, a developed non-Western setting, where many children have migrant parents from mainland China of the same ethnicity. METHODS: We used Cox regression to examine the adjusted associations of parental migrant status with time to first public hospital admission for asthma, bronchitis and bronchiolitis (International Classification of Diseases, Ninth Version Clinical Modification 466, 490 and 493) from 9 days to 12 years in a population-representative birth cohort of 8327 Chinese children in Hong Kong. RESULTS: Having both parents as migrants was associated with higher risk of hospitalization for asthma and other wheezing disorders, compared to both parents being Hong Kong born (hazard ratio 1.30, 95% confidence interval 1.05-1.60 from 9 days to 6 years), adjusted for type of hospital at birth, parental history of allergies, mother's age at birth, father's age at birth and highest parental education. CONCLUSIONS AND CLINICAL RELEVANCE: In the unique, non-Western context of Hong Kong, second-generation migrants had higher risk of hospitalization for childhood wheezing disorders compared to the native population, particularly before 6 years of age. Further study is required to clarify the underlying mechanisms involved.

Diabetes incidence and prevalence in Hong Kong, China during 2006-2014.

AIMS: To estimate recent secular changes in the incidence and prevalence of diabetes and pre-diabetes among Hong Kong Chinese adults, and thus show possible future trends for developing mainland China. METHODS: Based on a complete census of the public sector health records of 6.4 million people from 2006 to 2014, diabetes cases were ascertained using different methods including the World Health Organization (WHO) 2011 guidelines (HbA1c , fasting plasma glucose and glucose tolerance test), American Diabetes Association (ADA) 2015 guidelines (plus random plasma glucose), and additionally recorded diagnosis codes and medication dispensation. Pre-diabetes was defined using ADA 2015 guidelines. RESULTS: We identified 697 201 people with diabetes (54.2% were incident cases); and 1 229 731 people with diabetes or pre-diabetes. In 2014, the overall incidence of diabetes was 9.46 per 1000 person-years [95% confidence interval (CI): 9.38 to 9.54], and overall prevalence was 10.29% (95% CI: 10.27% to 10.32%). Incidence of diabetes decreased significantly from 2007 to 2014 (quadratic trend, P < 0.001). From 2006 to 2014, the prevalence of diabetes increased significantly in both sexes and across all age groups (quadratic trend, P < 0.001). The overall incidence of pre-diabetes in 2014 was 18.88 per 1000 person-years (95% CI: 18.76 to 18.99), and the overall prevalence of pre-diabetes was 8.90% (95% CI: 8.87% to 8.92%). CONCLUSIONS: Similar to other developed western and Asian populations, diabetes (and pre-diabetes) incidence in Hong Kong Chinese appeared to have stabilized and there have been small declines during the period of observation. Ageing and survivorship will likely drive a continued increase in the prevalence of diabetes and pre-diabetes, albeit with a decelerating growth rate if past trends persist.

Duration of puberty in preterm girls.

OBJECTIVES: Preterm birth is associated with altered pubertal timing, but the effect on pubertal duration has rarely been assessed. Here, we tested the hypothesis that preterm birth is associated with shorter duration of puberty among girls in Hong Kong where preterm birth has little social patterning. METHODS: In the population-representative Chinese birth cohort "Children of 1997", we used multivariable linear regression to assess the association of preterm status (≤36 completed gestational weeks, n = 170; term birth 37-42 gestational weeks, n = 3476) with duration of puberty, adjusted for parent's highest education, mother's place of birth, maternal smoking during pregnancy, gestational diabetes, preeclampsia, and mother's age of menarche. RESULTS: The mean duration from thelarche to menarche was 2.53 years. Preterm girls had a shorter duration from thelarche to menarche by 2.6 months, 95% confidence interval 0.5-4.7 months. Age of menarche did not differ by preterm status but preterm girls had later thelarche. Preterm birth was not associated with a shorter duration from pubarche to menarche. CONCLUSIONS: Preterm births may be associated with shorter duration of puberty from thelarche to menarche, possibly through effects of in utero estrogen exposure, the drivers of thelarche, or the drivers of pubertal duration/progression, with potential implications for subsequent risk of cardiovascular disease and hormonal cancers.

Breast cancer incidence and mortality in a transitioning Chinese population: current and future trends.

BACKGROUND: Projections of future trends in cancer incidence and mortality are important for public health planning. METHODS: By using 1976-2010 data in Hong Kong, we fitted Poisson age-period-cohort models and made projections for future breast cancer incidence and mortality to 2025. RESULTS: Age-standardised breast cancer incidence (/mortality) is projected to increase (/decline) from 56.7 (/9.3) in 2011-2015 to 62.5 (/8.6) per 100,000 women in 2021-2025. CONCLUSIONS: The incidence pattern may relate to Hong Kong's socio-economic developmental history, while falling mortality trends are, most likely, due to improvements in survival from treatment advancement and improved health service delivery.

Mode of delivery and childhood hospitalizations for asthma and other wheezing disorders.

BACKGROUND: Observationally, delivery by Caesarean section is associated with higher risk of childhood asthma and wheeze in developed Western settings, but associations are less consistent in other settings. OBJECTIVE: To examine the association of mode of delivery with hospitalizations for asthma and other wheezing disorders in a developed non-Western setting with high rates of Caesarean section. METHODS: Using Cox regression, we examined the adjusted association of mode of delivery with public hospital admissions for asthma, bronchitis, and bronchiolitis (International Classification of Diseases, Ninth Version Clinical Modification 466, 490 and 493) from 9 days to 12 years of age in a population-representative prospective birth cohort of 8327 Chinese children in Hong Kong. Confounders included sex, birth and parental characteristics, and socio-economic position (SEP). RESULTS: Delivery by Caesarean section accounted for 27% of all births and was not clearly associated with hospitalizations for asthma and other wheezing disorders to 12 years [hazard ratio (HR) 1.11, 95% confidence interval (CI) 0.91 to 1.36] compared to vaginal delivery. Similarly, there were no clear associations to 2 years (HR 1.07, 95% CI 0.83 to 1.38) or 6 years (HR 1.12, 95% CI 0.91 to 1.37), although we cannot rule out residual confounding by SEP. CONCLUSIONS AND CLINICAL RELEVANCE: We cannot rule out an association, but our findings suggest that the observed associations of delivery by Caesarean section with childhood wheezing disorders may vary with setting and may not be biologically mediated. Further studies with different designs are needed to clarify the role of the microbiome and mode of delivery in the aetiology of asthma and other childhood wheezing disorders.

Adolescent testosterone, muscle mass and glucose metabolism: evidence from the 'Children of 1997' birth cohort in Hong Kong.

AIMS: Diabetes rates are high in Asia despite relatively low rates of obesity, which might be related to lower muscle mass. Muscle mass plays an important role in glucose metabolism. Peak muscle mass is obtained in late adolescence. We tested the hypothesis that pubertal testosterone is negatively associated with glucose metabolism mediated by muscle mass. METHODS: Participants aged 15 years (278 boys and 223 girls) were recruited from the Hong Kong's 'Children of 1997' birth cohort in 2012. Multivariable linear regression with multiple imputation and inverse probability weighting was used to examine the adjusted associations of pubertal testosterone with skeletal muscle index, body fat percentage, fasting glucose, insulin and homeostasis model of assessment - insulin resistance. RESULTS: Total testosterone was negatively associated with fasting glucose (-0.008, 95% confidence interval -0.015 to -0.002), insulin (-0.43, 95% confidence interval -0.56 to -0.30) and insulin and homeostasis model of assessment - insulin resistance (-0.09, 95% confidence interval -0.12 to -0.06) adjusted for sex, birth weight, highest parental education, mother's place of birth and physical activity. These associations were attenuated by additional adjustment for skeletal mass index or body fat percentage. CONCLUSIONS: Adolescent glucose metabolism may be influenced by testosterone, perhaps partially via skeletal muscle mass.

The Association of Infant Growth Patterns with Adiposity in Adolescence: Prospective Observations from Hong Kong's 'Children of 1997' Birth Cohort.

BACKGROUND: The role of infant growth in adiposity remains unclear. METHODS: We used multivariable linear regression, with inverse probability weighting and multiple imputation to account for loss to follow-up, in a population-representative Chinese birth cohort, 'Children of 1997' in Hong Kong, to examine, in terms births, the adjusted association of infant (birth to 12 months) weight growth trajectories with body mass index (BMI) (n = 6861, 88% follow-up), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR) (n = 5398, 69% follow-up) at ∼ 14 years. RESULTS: Infant weight growth trajectories had graded associations with adolescent BMI and WHtR but not with WHR, such that compared with adolescents born light with slow infant growth, adolescents born heavy with fast infant growth had higher BMI z-score [0.60, 95% confidence interval (CI) 0.49, 0.70], higher WHtR z-score (0.17, 95% CI 0.08, 0.26) but similar WHR z-score (-0.02, 95% CI -0.11, 0.08), adjusted for sex, gestational age, parental education, parental BMI, parental height, and parental place of birth. CONCLUSIONS: Varying associations of infant growth with different adiposity measures suggest a complex role of infant growth in long-term health, perhaps because infant growth, or its underlying drivers, influences build and body composition as well as adiposity.

Multivariate analysis of factors affecting the immunogenicity of trivalent inactivated influenza vaccine in school-age children.

We examined factors affecting the immunogenicity of trivalent inactivated influenza vaccination (TIV) in children using the antibody titres of children participating in a Hong Kong community-based study. Antibody titres of strains included in the 2009-2010 northern hemisphere TIV [seasonal A(H1N1), seasonal A(H3N2) and B (Victoria lineage)] and those not included in the TIV [2009 pandemic A(H1N1) and B (Yamagata lineage)] were measured by haemagglutination inhibition immediately before and 1 month after vaccination. Multivariate regression models were fitted in a Bayesian framework to characterize the distribution of changes in antibody titres following vaccination. Statistically significant rises in geometric mean antibody titres were observed against all strains, with a wide variety of standard deviations and correlations in rises observed, with the influenza type B antibodies showing more variability than the type A antibodies. The dynamics of antibody titres after vaccination can be used in more complex models of antibody dynamics in populations.

Preliminary epidemiological assessment of MERS-CoV outbreak in South Korea, May to June 2015.

South Korea is experiencing the largest outbreak of Middle East respiratory syndrome coronavirus infections outside the Arabian Peninsula, with 166 laboratory-confirmed cases, including 24 deaths up to 19 June 2015. We estimated that the mean incubation period was 6.7 days and the mean serial interval 12.6 days. We found it unlikely that infectiousness precedes symptom onset. Based on currently available data, we predict an overall case fatality risk of 21% (95% credible interval: 14­31).

Optimal design of studies of influenza transmission in households. II: comparison between cohort and case-ascertained studies.

Both case-ascertained household studies, in which households are recruited after an 'index case' is identified, and household cohort studies, where a household is enrolled before the start of the epidemic, may be used to test and estimate the protective effect of interventions used to prevent influenza transmission. A simulation approach parameterized with empirical data from household studies was used to evaluate and compare the statistical power of four study designs: a cohort study with routine virological testing of household contacts of infected index case, a cohort study where only household contacts with acute respiratory illness (ARI) are sampled for virological testing, a case-ascertained study with routine virological testing of household contacts, and a case-ascertained study where only household contacts with ARI are sampled for virological testing. We found that a case-ascertained study with ARI-triggered testing would be the most powerful design while a cohort design only testing household contacts with ARI was the least powerful. Sensitivity analysis demonstrated that these conclusions varied by model parameters including the serial interval and the risk of influenza virus infection from outside the household.

Testosterone concentrations in young healthy US versus Chinese men.

BACKGROUND: Previous small studies examining differences in testosterone concentrations by ethnicity found mixed results for Caucasians and Chinese men, which might be confounded by age differences and living standards. The aim of the present study is to examine the differences in total, free, and bioavailable testosterone concentrations between healthy young men from the United States (US) and from the most economically developed part of China, i.e., Hong Kong (HK). METHODS: Cross-sectional analysis based on 365 young men from the Third National Health and Nutrition examination Survey (NHANES III) in the US and 299 Chinese men recruited from university students. All participants were aged from 18 to 29 years. Main outcome measures were total testosterone (TT) and calculated bioavailable testosterone (Bio T) and free testosterone (FT). RESULTS: In both US and Chinese men, TT, FT, and Bio T concentration peaked at 20-24 years of age, at 23.19, 0.49, and 12.23 nmol/l in US men, and 20.72, 0.48 and 12.59 nmol/l in Chinese men, respectively. Among those aged 18-24 years, after adjusting for age, US men had higher TT (mean, 95% confidence interval: 21.64, 21.31-21.99 versus 20.20, 20.12-20.28 nmol/l), but not FT (0.47, 0.47-0.48 versus 0.47, 0.47-0.47 nmol/l) or Bio T (11.90, 11.83-11.97 versus 12.39, 12.35-12.42 nmol/l) than Chinese men. CONCLUSIONS: TT, but not FT or Bio T concentrations are lower in young healthy Chinese men than US men. These differences apparent in young men may be important in understanding different patterns of diseases between Western and Asian populations.

Height, its components, and coagulability among older Chinese: the Guangzhou biobank cohort study.

OBJECTIVES: The causal role of some cardiovascular risk factors, such as HDL cholesterol, has been increasingly challenged and attention is returning to all elements of Virchow's triad, i.e., hypercoagulability (including viscosity) as well as endothelial function and blood flow. We examined the life course origins of coagulability. METHODS: We used multivariable linear regression to assess whether childhood influences, proxied by height and its components, were associated with hematocrit (Hct), hemoglobin (HGB), and other hematological parameters in 28,595 older Chinese adults (mean age = 61.8 years) from the Guangzhou Biobank Cohort Study. RESULTS: Adjusted for age, sex, and recruitment phase, leg length was negatively associated with platelets (PLT) (-0.83 × 10(9) /l per centimeter (cm), 95% confidence interval (CI) -1.01 to -0.65). Sitting height and height were positively associated with Hct (0.05% per cm, 95% CI 0.04-0.07 for sitting height; 0.02% per cm, 95% CI 0.01-0.02 for height), HGB (0.21 g/l per cm, 95% CI 0.17-0.25; 0.07 g/l per cm, 95% CI 0.04-0.09) and negatively associated with PLT (-1.2 × 10(9) /l per cm, 95% CI -1.4 to -1.0; -0.83 × 10(9) /l per cm, 95% CI -0.95 to -0.70). Further adjustment for potential confounders did little to change the estimates. CONCLUSIONS: For the first time we provide anthropometric evidence for the different roles of prepubertal and pubertal influences in relation to Hct and HGB. Whether factors that promote leg growth but reduce growth of sitting height may help to prevent cardiovascular events, via effects on hypercoagulability or viscosity, overall or in specific subgroups, remains to be determined.