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.

Investigating pleiotropic effects of statins on ischemic heart disease in the UK Biobank using Mendelian randomisation.

We examined whether specifically statins, of the major lipid modifiers (statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe) have pleiotropic effects on ischemic heart disease (IHD) via testosterone in men or women. As a validation, we similarly assessed whether a drug that unexpectedly likely increases IHD also operates via testosterone. Using previously published genetic instruments we conducted a sex-specific univariable and multivariable Mendelian randomization study in the UK Biobank, including 179918 men with 25410 IHD cases and 212080 women with 12511 IHD cases. Of these three lipid modifiers, only genetically mimicking the effects of statins in men affected testosterone, which partly mediated effects on IHD. Correspondingly, genetically mimicking effects of anakinra on testosterone and IHD presented a reverse pattern to that for statins. These insights may facilitate the development of new interventions for cardiovascular diseases as well as highlighting the importance of sex-specific explanations, investigations, prevention and treatment.

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.

Genetically predicted milk consumption and bone health, ischemic heart disease and type 2 diabetes: a Mendelian randomization study.

BACKGROUND/OBJECTIVES: Milk provides protein and micronutrients, and is recommended by some dietary guidelines, particularly for bone health. Meta-analysis of small randomized controlled trials suggests that milk may increase bone mineral density, but they are very heterogeneous. No randomized controlled trial has assessed the effects of milk on major chronic diseases. Previous Mendelian randomization studies of milk did not consider bone health, found no effects on ischemic heart disease (IHD) or type 2 diabetes (T2D) but higher body mass index. Using larger genetic studies, we estimated the effects of milk on osteoporosis, IHD, T2D, adiposity, lipids and glycemic traits. SUBJECTS/METHODS: Instrumental variable analysis based on a genetic variant endowing lactase persistence (rs4988235 (MCM6)) was used to obtain estimates for osteoporosis (GEFOS), IHD (CARDIoGRAMplusC4D), T2D (DIAGRAM), adiposity (GIANT), lipids (GLGC) and glycaemic traits (MAGIC). Eye color was a negative control for IHD, as it mirrors the distribution of lactase persistence and IHD in Western Europe. RESULTS: Genetically predicted adult milk consumption was not clearly associated with bone mineral density, IHD (odds ratio (OR): 1.03 per s.d., 95% confidence interval (CI): 0.95-1.12) and or T2D (OR: 0.92, 95% CI: 0.83-1.02) but was associated with higher log-transformed fasting insulin (0.05, 95% CI: 0.02-0.07) and body mass index (0.06, 95% CI: 0.03-0.09). Genetically predicted eye color was not associated with IHD. CONCLUSIONS: The lack of association of genetically predicted milk consumption with bone health, IHD or T2D suggests few beneficial effects but is more consistent with milk promoting adiposity.

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.

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.

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.

Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome.

Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.

Cohort Profile: Hong Kong Department of Health Elderly Health Service Cohort.

The Department of Health Elderly Health Service Cohort in Hong Kong was set up to promote understanding of ageing in a global context, to exploit the role of Hong Kong as a sentinel for populations currently experiencing very rapid economic development, to provide a developed non-Western 'social laboratory' where empirically derived hypotheses can be tested and to leverage the different patterns of common chronic diseases between East and West to generate novel hypotheses about their determinants. The initial cohort enrolled from July 1998 to the end of December 2001 includes 66 820 people aged 65 years or older, forming about 9% of the population of this age. A comprehensive health assessment was made at enrollment and then repeated regularly on an ongoing basis. The health assessment included a comprehensive assessment of lifestyle, social circumstances, physical health and mental health, including an assessment of cognition and depressive symptoms. Health services use and deaths have been obtained by record linkage and confirmed, where necessary, by telephone interview. Currently, the data are not publicly available; we would welcome collaborations and research proposals.

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).

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.

Burden, seasonal pattern and symptomatology of acute respiratory illnesses with different viral aetiologies in children presenting at outpatient clinics in Hong Kong.

Respiratory viruses cause acute respiratory diseases with a broad and overlapping spectrum of symptoms. We examined the clinical symptoms and explored the patterns of various respiratory viral infections in children in Hong Kong. Among 2090 specimens collected from outpatient care (2007-2010), 1343 (64.3%) were positive for any virus by the xTAG assay, and 81 (3.9%) were positive for co-infection. The most frequently detected viruses among children aged 6-15 years were enterovirus/rhinovirus and influenza virus A, whereas most non-influenza viruses were more frequently detected in younger children. Higher body temperature was more common for illnesses associated with influenza viruses than for those associated with non-influenza viruses, but other symptoms were largely similar across all infections. The seasonality pattern varied among different viruses, with influenza virus A being the predominant virus detected in winter, and enterovirus/rhinovirus being more commonly detected than influenza virus A in the other three seasons, except for 2009.