Reference intervals of 14 biochemical markers for children and adolescence in China: the PRINCE study.

OBJECTIVES: The Pediatric Reference Intervals in China (PRINCE) was initiated to establish the reference intervals (RIs) of Chinese children, as well as to make it possible to compare the variability of biochemical markers among countries internationally. METHODS: Healthy participants, aged up to 20 years, from 11 provinces across China, were enrolled in PRINCE and according to a standard screening procedure, that included a questionnaire survey, physical examinations and laboratory tests. Fasting venous blood specimens were collected. All serum specimens were analyzed with Cobas C702 in the center laboratory, i.e. clinical laboratory of Beijing Children's Hospital, with certified qualification (ISO15189). The nonparametric method recommended by Clinical Laboratory Standards Institute guidelines, was used to calculate the age- and sex-specified RIs. RESULTS: Among the 15,150 participants enrolled, 12,352 children (6,093 males and 6,259 females) were included to calculate RIs. The RIs for total protein, albumin, globulin, calcium, phosphate, potassium, sodium, chlorine, alkaline phosphatase, γ-glutamyl transpeptadase, alanine aminotransferase, aspartate aminotransferase, creatinine and urea were established by age- or sex-partitions. Most biochemical markers displayed larger variability and higher dispersion during the periods between 28 days and 1 year old, and included 4-6 age partitions commonly during 1 to <20 years old. In addition, differences of RIs between sexes usually occurs around the initiation of puberty at 12-13 years old. CONCLUSIONS: The age- and sex-specified RIs of 14 biochemical markers in PRINCE study can provide a solid reference, which will be transferred into relevant RIs for other clinical laboratory's platforms according to the CLSI guidelines.

Clinical features and outcomes of 31 children with congenital hypothyroidism missed by neonatal screening.

OBJECTIVE: To investigate the clinical features and outcomes of children with congenital hypothyroidism (CH) missed by neonatal screening. METHODS: The clinical and laboratory date of 31 children with CH missed by neonatal screening from February 2015 to February 2022 in Guangzhou Women and Children's Medical Center were retrospectively analyzed. Whole-exome high-throughput sequencing analysis was performed in 17 patients. RESULTS: Among the 31 patients, 19 cases (61.3%) were preterm, 12 cases (38.7%) were term neonates. The median value of gestation age was 36 (26-40) weeks, birth weight was 2.35 (0.75-3.70) kg, diagnosed age was 20 d (7 d-4 years), dry blood spot thyrotropin was 4.18 (0.34-8.97) mU/L. Nine cases (29.0%) were same-sex twins and 4 cases (12.9%) had a family history of hypothyroidism. The initial clinical symptoms were growth retardation in 11 cases (35.5%), prolonged jaundice in 7 cases (22.6%), short stature, abdominal distension, fetal edema and goiter in 1 case (3.2%), respectively. Genetic analysis of the 17 children showed that DUOX2 gene mutations were detected in 10 cases (6 cases with biallelic mutations and 4 cases with monoallelic mutations), of whom 3 had a family history of hypothyroidism. A total of 22 patients were reevaluated at the age of 2-3 years, of whom 17 cases (77.3%) were transient CH and 5 cases (22.7%) were permanent CH. Among the 10 cases with DUOX2 gene mutations, 6 cases were transient CH, 1 case was permanent CH, and 3 cases (< 3 years old) were still under treatment with L-thyroxine. CONCLUSIONS: False negative results on neonatal screening for CH often occurs in preterm birth, low birth weight, same-sex twins, family history of hypothyroidism, and DUOX2 defects are the common molecular pathogenesis, most of whom are transient CH. Thyroid function should be evaluated in time for children with unexplained slow growth and delayed jaundice regression.

The Role of Serum Calcium Levels in Pediatric Dyslipidemia: Are There Any?

Background: No previous study explored the association between serum calcium levels and dyslipidemia in children. This study aimed to explore this relationship in children, based on a multicenter cross-sectional study population in China. Methods: Cross-sectional data was derived from the Pediatric Reference Intervals in China (PRINCE) study conducted between 2017 and 2018 involving 5,252 males and 5,427 females with a mean age of 10.0 ± 4.6 years. Multivariable logistic regression models were applied to calculate odds ratios (ORs), with 95% confidence intervals (CIs), for dyslipidemia of each serum calcium level and albumin-corrected calcium levels, which were sorted into quartiles. The restricted cubic spline model was fitted for the dose-response analysis. An L-shaped dose-response relation between calcium levels and the probability of dyslipidemia was found after the adjustment for multiple potential confounding factors, p for non-linear < 0.001. Results: Using the middle category of calcium level as the reference, multivariable-adjusted ORs and 95% CIs of the lowest and the highest quartile categories were 0.96 (0.82-1.12) and 1.29 (1.12-1.48), respectively, for total serum calcium levels and 1.06 (0.91-1.23) and 1.39 (1.21-1.60) for albumin-corrected calcium levels. Conclusions: Individuals with higher levels of serum calcium were associated with increased risk of dyslipidemia in a sample of a healthy Chinese pediatric population. The association between serum calcium levels and dyslipidemia needs to be examined prospectively in future studies.

Pediatric reference intervals in China (PRINCE): design and rationale for a large, multicenter collaborative cross-sectional study.

There is a lack of accurate pediatric reference intervals (RIs) in China, with most commonly used RIs established without consideration of the effect of age and gender. The Pediatric Reference Intervals in China (PRINCE) project aims to establish and verify pediatric RIs for 31 common laboratory measurands. The project will be a large, multicenter cross-sectional study: 14,490 healthy children and adolescents aged up to 19 years will be surveyed by 10 children's hospitals and one pediatric department of a university hospital. To evaluate the feasibility and efficiency of the study methods, 602 children were surveyed in the pilot phase of the PRINCE study in April 2017: it found that some measurands were distinctly age dependent and that there were differences between values for males and females. The results of the pilot study affirmed the necessity of the PRINCE project for Chinese pediatrics. The pilot also indicated potential difficulties in the full survey, e.g., difficulties in recruiting children aged under 3 years and insufficient collection of blood samples from infants. The operation of the PRINCE project has been modified based on the findings in the pilot study toward improving the validity of the PRINCE project and promoting its openness and transparency.

[Study on the distribution and correlation of trace elements in whole blood of children in Beijing].

OBJECTIVE: To study the distribution and correlation of trace elements in peripheral blood of children in Beijing so as to offer scientific evidence for the supplementation of trace elements and to prevent lead intoxication. METHODS: Contents of trace elements in whole blood of 13 929 children in Beijing region were detected by Atomic Absorption Spectrometer. According to developmental condition, children were divided into young infancy group, infancy group, toddler's age group, preschool age group, school age group and adolescence group. Every group was divided into males and females. Distribution and correlation of trace elements in different age groups and in different sex sets were then analyzed and compared. RESULTS: The level of copper, calcium and magnesium were stable in different age groups and in different sex sets. There were no obvious significant differences in age groups and sex sets and there were no deficiency of copper, calcium and magnesium discovered. The level of zinc increased gradually following the growth of age and the level of zinc was (81.71 +/- 15.91) micromol/L. There were significant differences in different age groups noticed as well in sex sets of infancy group, toddler's age group and preschool age group. The rate of deficiency of zinc decreased gradually following the growth of age. The rate of zinc deficiency was 13.7% and there were obvious differences noticed in sex sets of toddler, preschool and school age groups. The level of iron increased gradually following the growth of age with the level of iron as (8.28 +/- 0.78) mmol/L. There were significant differences noticed in different age groups, after infancy stage. There was significant difference noticed also in sex sets after school age group. The rate of iron deficiency decreased obviously following the growth of age. The iron deficiency rate was 12.9%, and significantly different in sex sets of young infancy, school age and adolescence groups. The level of lead increased gradually following the growth of age, with the overall level as (59.97 +/- 26.52) microg/L; There was an obvious significant differences noticed in different age groups with significant differences noticed in sex sets after toddler's age group. The rate of lead intoxication increased gradually following the growth of age. The rate of lead intoxication was 8.2%. There were significant differences noticed in sex sets after toddler's age group. However, there were negative correlations noticed among the levels of lead and copper, zinc, calcium, magnesium and iron. There were no correlations between the level of calcium and iron found but showed positive correlation among other trace elements. CONCLUSION: The deficiency of calcium was basically corrected but the deficiency of zinc and iron were still obvious. There was a high level of lead noticed in these children. It is important to advocate on healthy feeding program, on culture good hygienic habit and on away from the lead pollution sites.