Epidemiologic Changes of Neonatal Early-onset Sepsis After the Implementation of Universal Maternal Screening for Group B Streptococcus in Hong Kong.

BACKGROUND: The epidemiology of neonatal early-onset sepsis (EOS) has changed with time and with changes in prevention strategy. Population-representative contemporary data provide insights on how to further improve EOS prevention and triage strategies. METHODS: Neonates born in public hospitals in Hong Kong from January 1, 2006, to December 31, 2017 were included. The epidemiological characteristics of EOS and the use of intrapartum antibiotic prophylaxis (IAP) were compared between the 2 epochs before (January 1, 2006 to December 31, 2011) and after (January 1, 2012 to December 31, 2017) the territory-wide implementation of universal maternal group B Streptococcus (GBS) screening. RESULTS: EOS developed in 1.07‰ of live births (522/490,034). After the implementation of universal GBS screening, the EOS rate decreased in neonates born ≥34 weeks (1.17‰-0.56‰, P < 0.001) and remained similar in those born <34 weeks (7.8‰-10.9‰, P = 0.15), whereas the proportions of IAP coverage increased in both groups [7.6%-23.3% ( P < 0.001) and 28.5%-52.0% ( P < 0.001), respectively]. The major pathogen for EOS shifted from GBS to Escherichia coli , and for early-onset meningitis from GBS to Streptococcus bovis . IAP was associated with subsequent isolation of pathogens resistant to ampicillin [adjusted odds ratio (aOR) 2.3; 95% confidence interval (CI): 1.3-4.2], and second-generation [aOR 2.0; 95% CI: 1.02-4.3] and third-generation [aOR 2.2; 95% CI: 1.1-5.0] cephalosporins. CONCLUSIONS: Pathogen profile of EOS changed with the implementation of universal GBS screening. S. bovis has emerged as a more common pathogen associated with the risk of meningitis. IAP may not be as effective in reducing EOS rate among infants born <34 weeks as compared with those ≥34 weeks, and newer strategies may be needed.

Secular trends of sleep-wake patterns in Hong Kong preschoolers.

OBJECTIVE: To evaluate the secular trends of sleep-wake patterns of Hong Kong preschool children. METHODS: Kindergartens from the four geographical regions of Hong Kong were randomly invited to take part in a sleep survey in 2012 and again in 2018. The parent-completed questionnaire provided information on socioeconomic status (SES), children's, and parental sleep-wake patterns. Secular trends and risk factors associated with short sleep duration in preschoolers were explored. RESULTS: A sample of 5048 preschool children was included in the secular comparison, with 2306 and 2742 from the 2012 and 2018 surveys, respectively. A higher percentage of children in 2018 (41.1% vs 26.7%, p < 0.001) did not achieve the recommended sleep duration. During the survey years, sleep duration decreased by 13 ([95%CI: 18.5 to -8.1]) and 18 min ([95%CI: 23.6 to -12.2]) on weekdays and weekends, respectively. The overall trend of nap decrease was not significant. Sleep onset latency significantly increased on both weekdays (6 min [95%CI: 3.5 to 8.5]) and weekends (7 min [95%CI: 4.7 to 9.9]). Children's sleep duration was positively correlated with parental sleep duration with a correlation coefficient ranging from 0.16 to 0.27 (p < 0.001). CONCLUSIONS: A significant proportion of Hong Kong preschool children did not achieve the recommended amount of sleep. A downward secular trend in sleep duration was observed during the survey period. Public health measures to improve sleep duration in preschool children should be a high priority.

Prenatal methylmercury exposure is associated with decrease heart rate variability in children.

BACKGROUND: Although several epidemiological studies have suggested mercury (Hg) might be associated with cardiotoxicity, the impact of Hg exposure on cardiac autonomic activity and blood pressure in children has not been investigated at Hg exposure levels equivalent to the Environmental Protection Agency (EPA) reference dose. OBJECTIVE: To investigate the association between low dose prenatal and recent methylmercury (MeHg) exposures and cardiac autonomic function and blood pressure with adjustment for factors such as fish consumption among children from a high fish consumption coastal city. METHODS: Children aged 7-8 years were recruited from the birth cohort of our previous study. Heart rate variability (HRV), resting heart rate (RHR) and blood pressure were measured as surrogate markers of cardiac autonomic function. Cord blood and current whole blood Hg concentration were used as biomarkers of prenatal and recent MeHg exposure, respectively. Recent fish consumption information was estimated with a food frequency questionnaire. RESULTS: Among 604 children, median cord blood and whole blood Hg concentrations were 45.9 nmol/L (IQR: 32.8-65.03 nmol/L) and 13.57 nmol/L (IQR: 9.29-19.72 nmol/L), respectively. Our results demonstrated that prenatal MeHg exposure was associated with decreased HRV (i.e. low CVRR, SDRR, and RMSSD), reflecting reduced parasympathetic activity (i.e. low CCVHF and HF), and a sympathovagal balance shift toward sympathetic predominance (i.e. high %LF and LF/HF ratio). Adjustment of recent fish consumption further increased the significance and magnitude of the adverse associations of MeHg. CONCLUSION: The results of this study suggest that prenatal MeHg exposure is associated with decreased parasympathetic modulation of cardiac autonomic function in children.

Association between genetic variations in GSH-related and MT genes and low-dose methylmercury exposure in children and women of childbearing age: a pilot study.

BACKGROUND: Genetic variations in glutathione (GSH)-related and metallothionein (MT) genes, which are involved in producing enzymes in the methylmercury (MeHg) metabolism pathway, have been proposed as one of the reasons for the individual variability in MeHg toxicokinetics. OBJECTIVE: To investigate the impact of genetic variations in MT and GSH-related genes on the association of fish consumption with body burden of MeHg, as measured by hair Hg concentrations among young children and women of childbearing age. METHODS: A total of 179 unrelated children and 165 mothers with either high or low fish consumption were recruited from the community. Their hair total Hg (tHg) and MeHg levels and genotypes for SNPs located on the GCLC, GCLM, GPX1, GSTA1, GSTP1, MT1A, MT2A, and MT4 genes were determined. Based on their 14-day food records, the amounts of fish consumed and their MeHg intakes were estimated. The impact of genetic variations on hair Hg concentrations was examined by using Mann-Whitney tests and multivariable linear regression analyses. RESULTS: The presence of minor alleles of GCLC-129 (rs17883901), GPX1-198 (rs1050450) and MT1M (rs9936741) were associated with significantly lower hair tHg levels in mothers whereas mothers with minor alleles of GSTP1-105(rs1695) and MT1M (rs2270836) have significantly higher hair tHg levels. After adjustment for fish consumption and other confounding factors, apart from MT1M (rs2270836), all of the above SNPs remain significant in the multivariable linear regression models. CONCLUSIONS: Our results in a group of children and women show that genetic variants of GSH-related and MT genes are associated with hair Hg concentrations. These genetic variations are likely to significantly affect MeHg metabolism and thus influence the accumulation of Hg in the human body.

Methylmercury levels in commonly consumed fish and methylmercury exposure of children and women of childbearing age in Hong Kong, a high fish consumption community.

BACKGROUND: Despite high fish consumption levels of Hong Kong residents, little is known about the MeHg exposure levels of Hong Kong high-risk populations (i.e. young children and women of childbearing age). OBJECTIVES: To investigate the MeHg levels in fish commonly consumed in Hong Kong and assess the exposure levels of local kindergarten children and women of childbearing age. METHODS: A community-based survey was conducted in randomly recruited local kindergartens. The MeHg concentrations of the most commonly consumed fish items were measured. Based on their fish consumption data, subjects' MeHg exposure levels were estimated and compared with the reference dose (RfD) set by U.S. Environmental Protection Agency. RESULTS: A total of 2917 mother-child pairs were recruited. The MeHg levels of the fish samples ranged from < 2-1498.7 ng/g. Six frozen cod fish samples contained MeHg levels exceeding the local legal limit of 500 ng/g. The median estimated MeHg intake for children and mothers were 0.29 and 0.22 µg/kg bw/wk, respectively. Approximately 16% children and 9% mothers exceeded the RfD. CONCLUSIONS: Apart from frozen cod fish, most fish species commonly consumed in Hong Kong had low MeHg content. Although the majority of our subjects were exposed to low MeHg levels, high fish consumers could still exceed the RfD and are potentially at risk of MeHg toxicity. To avoid excessive MeHg exposure, we suggest that young children and their mothers may consume a variety of locally available fish, but avoid consumption of frozen cod fish.

Impact of fetal and childhood mercury exposure on immune status in children.

BACKGROUND: Mercury exposure have been shown to affect immune status in animals as reflected by cytokine expression. It is unclear whether low levels of exposure during fetal and/or childhood periods could impact on immune status in humans. OBJECTIVES: To test the hypothesis that fetal and childhood mercury exposure is associated with childhood cytokine profiles and to investigate whether childhood selenium levels interact with any of the associations found. METHODS: Children were recruited from a previously established birth cohort between the ages of 6-9 years for assessment and measurement of blood mercury, selenium and cytokine profile (interleukin (IL)-4, IL-6, IL-8, IL-10, IL-13 and TNF-alpha). Multivariable linear regression models were used to assess the adjusted association of cord blood mercury concentration and current mercury concentrations with levels of the cytokine levels. We tested whether the association with current mercury level varied by current selenium level and cord blood mercury level. RESULTS: IL-10 was negatively associated with current blood mercury concentration. The effect was greatest in cases with low cord blood mercury and low current selenium concentrations. None of the other cytokine levels were associated with either cord blood or current blood mercury concentrations, except that cord blood mercury was negatively associated with IL-6. CONCLUSIONS: Childhood mercury exposure was negatively associated with childhood IL-10 levels. It is postulated that while selenium is protective, low levels of fetal mercury exposure may increase the degree of this negative association during childhood. Further studies into the clinical significance of these findings are required.

Long term neurocognitive impact of low dose prenatal methylmercury exposure in Hong Kong.

BACKGROUND: International studies suggest that low dose prenatal methylmercury exposure (>29 nmol/L) has long-term adverse neurocognitive effects. There is evidence that the majority of children in Hong Kong exceed this level as a result of high fish consumption of mothers during pregnancy. OBJECTIVE: To study whether there are any associations between low-dose prenatal methylmercury exposure and neurocognitive outcomes in Hong Kong children. MATERIALS AND METHODS: All 1057 children from the original birth cohort were eligible for entry into the study, except children with conditions that would affect neurocognitive development, but were unrelated to methylmercury exposure. Subjects were assessed by a wide panel of tests covering a broad range of neurocognitive functions: Hong Kong Wechsler Intelligence Scale for Children (HK-WISC), Hong Kong List Learning Test (HKLLT), Tests of Everyday Attention for Children (TEACH), Boston Naming Test, and Grooved Pegboard Test. RESULTS: 608 subjects were recruited (median age 8.2 years, IQR 7.3, 8.8; 53.9% boys). After correction by confounders including child age and sex, multivariate analysis showed that cord blood mercury concentration was significantly associated with three subtests: Picture Arrangement of HK-WISC (coefficient -0.944, P=0.049) and Short and Long Delay Recall Difference of the HKLLT (coefficient -1.087, P=0.007 and coefficient -1.161, P=0.005, respectively), i.e., performance worsened with increasing prenatal methylmercury exposure in these subtests. CONCLUSIONS: Small, but statistically significant adverse associations between prenatal methylmercury exposure and long-term neurocognitive effects (a visual sequencing task and retention ability of verbal memory) were found in our study. These effects are compatible with findings of studies with higher prenatal methylmercury exposure levels and suggest that safe strategies to further reduce exposure levels in Hong Kong are desirable.