A High Proportion of Novel ACAN Mutations and Their Prevalence in a Large Cohort of Chinese Short Stature Children.

CONTEXT: Aggrecan, encoded by the ACAN gene, is the main proteoglycan component in the extracellular cartilage matrix. Heterozygous mutations in ACAN have been reported to cause idiopathic short stature. However, the prevalence of ACAN pathogenic variants in Chinese short stature patients and clinical phenotypes remain to be evaluated. OBJECTIVE: We sought to determine the prevalence of ACAN pathogenic variants among Chinese short stature children and characterize the phenotypic spectrum and their responses to growth hormone therapies. PATIENTS AND METHODS: Over 1000 unrelated short stature patients ascertained across China were genetically evaluated by next-generation sequencing-based test. RESULT: We identified 10 novel likely pathogenic variants and 2 recurrent pathogenic variants in this cohort. None of ACAN mutation carriers exhibited significant dysmorphic features or skeletal abnormities. The prevalence of ACAN defect is estimated to be 1.2% in the whole cohort; it increased to 14.3% among those with advanced bone age and to 35.7% among those with both advanced bone age and family history of short stature. Nonetheless, 5 of 11 ACAN mutation carries had no advanced bone age. Two individuals received growth hormone therapy with variable levels of height SD score improvement. CONCLUSION: Our data suggest that ACAN mutation is 1 of the common causes of Chinese pediatric short stature. Although it has a higher detection rate among short stature patients with advanced bone age and family history, part of affected probands presented with delayed bone age in Chinese short stature population. The growth hormone treatment was moderately effective for both individuals.

EPIDEMIOLOGIC CHARACTERISTICS AND RISK FACTORS FOR CONGENITAL HYPOTHYROIDISM FROM 2009 TO 2018 IN XIAMEN, CHINA.

Objective: Early diagnosis and treatment of children with congenital hypothyroidism (CH) through newborn screening can effectively prevent delayed development. This study was designed to investigate the pathogenesis and factors that influence CH in urban areas of China between 2009 and 2018. Methods: A retrospective analysis of newborn screening data and diagnosis and treatment information for CH diagnosed in the information database of the neonatal disease screening center in one of China's five special economic zones from 2009 to 2018. Results: Of the 947,258 newborns screened between 2009 and 2018, 829 (406 girls) were diagnosed with CH at birth (1 diagnosis/1,136 births). Among the 608 cases of CH diagnosed at birth and re-evaluated at the age of 3 years, 487 were permanent congenital hypothyroidism (PCH, 1/1,429), and 121 were transient congenital hypothyroidism (TCH, 1/5,882). A total of 83.2% of infants with PCH (405/487) underwent thyroid imaging in the neonatal period, of which thyroid dysgenesis accounted for 28.64% (116/405) and functional defects accounted for 71.36% (289/405). The incidence of CH changed significantly in infants with initial serum thyroid-stimulating hormone concentrations of 41 to 100 mIU/L and ≥100 mIU/L, whereas the incidence of mild CH showed a slight increase. The incidence of CH was significantly higher in postterm infants (1/63) and low-birth-weight infants (1/370). Conclusion: In the past decade, the incidence of CH has increased, mainly due to the increase in the incidence of PCH and TCH. The incidence of mild CH has increased slightly. Postterm birth and low birth weight are important factors affecting the incidence of CH. Abbreviations: CH = congenital hypothyroidism; FT4 = free thyroxine; L-T4 = levothyroxine sodium; PCH = permanent congenital hypothyroidism; TCH = transient congenital hypothyroidism; TSH = thyroid-stimulating hormone; TT4 = total thyroxine.

Trends and Prevalence of Overweight and Obesity among Children Aged 2-7 Years from 2011 to 2017 in Xiamen, China.

BACKGROUND: Childhood overweight and obesity have become some of the most serious public health problems in the 21st century and have a significant impact on affected children as they grow into adulthood. OBJECTIVE: The purpose of this study was to evaluate the overweight and obesity status and their main influencing factors in preschool children aged 2-7 years in urban areas of China between 2011 and 2017. METHODS: A stratified cluster random sampling method was used to conduct a sample survey of children aged 2-7 years in Xiamen, one of China's five special economic zones. The 56,738 participants (29,444 boys, 27,294 girls) were examined at three time points (15,757 in 2011, 19,098 in 2014, and 21,883 in 2017), and were analyzed for factors influencing obesity. RESULTS: Between 2011 and 2017, the prevalence of overweight and obesity in preschool children between 2 and 7 years old was 10.91 and 5.66%, respectively. The overweight and obesity rates were higher in boys (11.85 and 7.11%) than in girls (9.90 and 4.09%), and the difference was statistically significant (p < 0.01). In the past 7 years, the overweight and obesity rates showed a downward trend in both boys and girls (p < 0.01). The peak ages for overweight were 6 years in boys and 2 years in girls, while the obesity rate peaked at 6 years. In those children with obesity, the proportion of those with moderate to severe obesity decreased from 40.70% in 2011 to 32.80% in 2017. Multiple stepwise regression analysis showed that children who were averse to sports activities preferred greasy foods and had earlier introduction of solid foods as infants, as well as those who were born at a high birth weight, ate fast, and those with parents with obesity were more likely to have obesity themselves (p < 0.05). CONCLUSIONS: Although preventative and control measures for childhood obesity have achieved initial results, Chinese preschool children remain to have high levels of overweight and obesity. It is therefore necessary to strengthen monitoring of overweight and obesity in preschool-aged children and implement appropriate interventions when necessary.

Secular Trends in Growth and Nutritional Outcomes of Children under Five Years Old in Xiamen, China.

The purpose of this study was to examine secular changes in growth and nutritional outcomes of Chinese urban children under five years old, in 2009, 2012, and 2015. Cluster random sampling methods were used to select children under five years old in Xiamen, one of five special economic zones in China. Subjects (N = 71,229) under five years old (39,413 boys, 31,816 girls) were examined at three different times (22,576 in 2009, 24,816 in 2012, and 23,837 in 2015). Significant differences in the boys' height and weight (p < 0.05) were found across the three time points; subjects in the 2015 sample were the heaviest and tallest, and they had the highest BMI (2009 < 2015; 2012 < 2015). Among the girls, those in the 2015 sample were similar to the boys (2009 < 2012; 2012 < 2015). In general, similar patterns were observed when mean values were analyzed by age. An increasing trend was found in the prevalence of overweight and obesity and a decreasing trend for stunting, underweight, and wasting. The results revealed that the burden of childhood under- and over-nutrition might constitute a public health concern in modern China.

[Further Exploration on the Essence of Yin Deficiency Caused Fire Hyperactivity Syndrome in Precocious Puberty Children Patients].

In this paper 200 girls with precocious puberty or advanced puberty were clinically sur- veyed, and the literatures of traditional Chinese medicine (TCM) for treating precocious puberty in previ- ous 33 years were retrospectively analyzed. By conjecturing syndromes from symptoms and identifying syndrome types from efficacies of TCM drugs, authors proved that Gan yin deficiency syndrome occupies the same important position as Shen yin deficiency syndrome, or even more important position in syn- drome based treatment of precocious puberty children patients with yin deficiency caused fire hyperactivity syndrome. Therefore, Gan yin deficiency syndrome cannot be neglected in treating precocious puberty pa- tients. Authors further suggested that yin deficiency caused fire hyperactivity syndrome in precocious pu- berty should be exactly described as Gan-Shen yin deficiency caused fire hyperactivity syndrome.

Surveying mercury levels in hair, blood and urine of under 7-year old children from a coastal city in China.

AIM: The average mercury load in children under 7-years old was determined in a populated but not overly industrial coastal area in China. METHODS: 395 blood samples, 1072 urine samples, and 581 hair samples were collected from 1076 children, aged 0 to 6 years, from eight representative communities of Xiamen, China. Mercury levels in the samples were surveyed. RESULTS: The 95% upper limits of mercury in blood, urine, and hair for the children were 2.30, 1.50 and 2100.00 µg/kg, respectively. Levels tended to increase with age. Correlation analyses showed that mercury levels in blood and urine correlated with those in hair (n = 132), r = 0.49, p < 0.0001 and r = 0.20, p = 0.0008; however, blood mercury levels did not correlate with urine levels (n = 284), r = 0.07, p = 0.35. CONCLUSIONS: Surveying the average mercury load in children 0 to 6 years, and the 95% upper limit value of mercury in their blood, urine, and hair should help guide risk assessment and health management for children.

[Correlations of blood lead levels in infant, in maternal blood and in breast milk].

OBJECTIVE: To understand the correlation of blood lead levels in infant, in maternal blood and in breast milk as to providing evidence for prevention of potential infant hazard from lead. METHODS: Lead levels were measured by using graphite stove atom absorption spectrographic methods in maternal breast milk, maternal blood and infant blood in infants aged 0 to 11 months and their mothers between November and December 2002 in Xiamen City. Blood samples were collected from both mother and infant's fingertips. Questionnaires were also used to collect information about childbirth, mothers, families and other related environmental factors. RESULTS: All 177 infants and their mothers were enrolled in the study. Infant blood lead levels reached a range from 0.12 micromol/L to 1.36 micromol/L, with a geometric mean (GM) of 0.37 micromol/L. There were 46 infants (21.64%) having blood lead levels over 0.48 micromol/L. And the maternal blood lead levels ranged from 0.21 micromol/L to 2.38 micromol/L (GM = 0.50 micromol/L). Among the 177 infants, 160 (93.8%) were breastfed; breast milk was collected from 105 (63.3%) of these mothers. Infant blood lead level was significantly correlated with the levels of maternal blood lead and breast milk lead, which indicated that maternal blood lead level might influence the infant blood lead levels through the breast milk. Blood lead levels in infants living in old business district and the breast milk lead levels of their mothers were higher than those in any other areas (P < 0.01); partial correlation analysis showed that infant blood lead levels were positively associated with the maternal blood lead level, infant's age and mother's work, and negatively associated with mother's height. CONCLUSION: The infant blood lead levels should not only relate to the maternal blood lead and the breast milk lead levels, so regards should be had to the other environmental factors, when selecting the feeding pattern and family rearing behaviors.