Biallelic and monoallelic pathogenic variants in CYP24A1 and SLC34A1 genes cause idiopathic infantile hypercalcemia.

OBJECTIVE: Idiopathic infantile hypercalcemia (IIH) is a rare disorder of PTH-independent hypercalcemia. CYP24A1 and SLC34A1 gene mutations cause two forms of hereditary IIH. In this study, the clinical manifestations and molecular aspects of six new Chinese patients were investigated. METHODS: The clinical manifestations and laboratory study of six patients with idiopathic infantile hypercalcemia were analyzed retrospectively. RESULTS: Five of the patients were diagnosed with hypercalcemia, hypercalciuria, and bilateral medullary nephrocalcinosis. Their clinical symptoms and biochemical abnormalities improved after treatment. One patient presented at age 11 years old with arterial hypertension, hypercalciuria and nephrocalcinosis, but normal serum calcium. Gene analysis showed that two patients had compound heterozygous mutations of CYP24A1, one patient had a monoallelic CYP24A1 variant, and three patients had a monoallelic SLC34A1 variant. Four novel CYP24A1 variants (c.116G > C, c.287T > A, c.476G > A and c.1349T > C) and three novel SLC34A1 variants (c.1322 A > G, c.1697_1698insT and c.1726T > C) were found in these patients. CONCLUSIONS: A monoallelic variant of CYP24A1 or SLC34A1 gene contributes to symptomatic hypercalcemia, hypercalciuria and nephrocalcinosis. Manifestations of IIH vary with onset age. Hypercalcemia may not necessarily present after infancy and IIH should be considered in patients with nephrolithiasis either in older children or adults.

Relationship of Glucagon-like Peptide 1 and Peptide YY with Catch-up Growth in Children Born Small for Gestational Age

Objective: Children born small for gestational age (SGA) are at a greater risk of developing insulin resistance, type 2 diabetes, and cardiovascular disease in adulthood. Gastrointestinal peptides, some secreted by intestinal L cells, regulate glucose and lipid metabolism and act on the hypothalamus to regulate energy homeostasis. The aim of this study was to explore whether gastrointestinal peptides are involved in metabolic disorders in SGA, which remains unclear. Methods: The secretion of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were investigated in prepubertal children born SGA, the differences between catch-up growth and persistent short stature were compared, and correlation with glucose and lipid metabolism was analyzed. GLP-1, PYY, insulin-like growth factor 1, glucose, insulin, and lipid concentrations were analyzed in prepubertal children aged 4-10 years, stratified into three groups: short-SGA (SGA-s), catch-up growth SGA, and normal growth appropriate for gestational age (AGA). Results: Fasting GLP-1 and PYY concentrations were significantly lower in the SGA group than in the AGA group (p<0.05), and the GLP-1 level in infants born SGA with catch-up growth was lower than that in the SGA-s group (p<0.05). In the SGA population, GLP-1 showed a weak negative correlation with catch-up growth (r=-0.326) and positive correlation with fasting insulin (r=0.331). Conclusion: Lower GLP-1 concentrations may be associated with abnormal glucose metabolism in prepubertal children born SGA with catch-up growth. This is indirect evidence that impaired intestinal L cell function may be involved in the development of metabolic complications in SGA children.

Genotype-phenotype correlations, surgical selections, and postoperative complications of 5α-reductase 2 deficiency in 69 children with hypospadias.

5α-reductase 2 deficiency prevents testosterone from being converted to dihydrotestosterone, which causes abnormal urogenital sinus development. The aim of this study was to analyze the relationship between genotype-phenotype, surgical selections, and postoperative complications of 5α-reductase 2-deficient patients with hypospadias. We retrospectively evaluated the medical records of patients who were diagnosed with 5α-reductase 2 deficiency after genetic testing in the Department of Endocrinology and underwent initial hypospadias surgery in the Department of Urology in Beijing Children's Hospital, Capital Medical University (Beijing, China), from April 2007 to December 2021. A total of 69 patients were included in this study; the mean age at surgery was 34.1 months, and the average follow-up time was 54.1 months. Sixty children were treated with preoperative hormone stimulation (PHS) to promote penile growth. The average penis length and glans width were increased by 1.46 cm and 0.62 cm, respectively. The most frequent mutations were p.R227Q (39.1%, 54/138), p.Q6* (15.2%, 21/138), p.G203S (12.3%, 17/138), and p.R246Q (11.6%, 16/138). In 64 patients who were followed up, 43 had a one-stage operation and 21 had a staged operation, and there were significant differences in external masculinization score (EMS) ( P = 0.008) and the average number of operation required to cure ( P < 0.001) between one-stage and staged operations. PHS had a positive effect ( P < 0.001) on penile development. The p.R227Q mutation was associated with higher EMS and less severe hypospadias. One-stage surgery can be selected if conditions permit. The growth and development of children are acceptable in the long term, but penis growth remains unsatisfactory. Long-term complications of hypospadias should be considered during puberty.

Early recombinant human growth hormone treatment improves mental development and alleviates deterioration of motor function in infants and young children with Prader-Willi syndrome.

BACKGROUND: Recombinant human growth hormone (rhGH) therapy has shown to improve height and body composition in children with Prader-Willi syndrome (PWS), the evidence of early rhGH treatment on motor and mental development is still accumulating. This study explored the time effect on psychomotor development, anthropometric indexes, and safety for infants and young children with PWS. METHODS: A phase 3, single-arm, multicenter, self-controlled study was conducted in six sites. Patients received rhGH at 0.5 mg/m2/day for first four weeks, and 1 mg/m2/day thereafter for up to 52 weeks. Motor development was measured using Peabody Developmental Motor Scales-second edition, mental development using Griffiths Development Scales-Chinese (GDS-C). Height standard deviation score (SDS), body weight SDS, and body mass index (BMI) SDS were also assessed. RESULTS: Thirty-five patients were enrolled totally. Significant improvements were observed in height, body weight, and BMI SDS at week 52; GDS-C score showed significant improvement in general quotient (GQ) and sub-quotients. In a linear regression analysis, total motor quotient (TMQ), gross motor quotient (GMQ), and fine motor quotient were negatively correlated with age; however, treatment may attenuate deterioration of TMQ and GMQ. Changes in GQ and locomotor sub-quotient in < 9-month group were significantly higher than ≥ 9-month group. Mild to moderate severity adverse drug reactions were reported in six patients. CONCLUSION: Fifty-two-week treatment with rhGH improved growth, BMI, mental development, and lessened the deterioration of motor function in infants and young children with PWS. Improved mental development was more pronounced when instituted in patients < 9 months old.

Clinical Incidence and Characteristics of Newly Diagnosed Type 1 Diabetes in Chinese Children and Adolescents: A Nationwide Registry Study of 34 Medical Centers.

Objective: To investigate the clinical incidence and characteristics of type 1 diabetes mellitus (T1DM) of children and adolescents at the time of initial diagnosis in China. Methods: Data on all pediatric patients with newly diagnosed T1DM were retrospectively collected from 34 medical centers in 25 major cities in China from January 2015 to January 2020. Patients were classified into three age groups: <5 years, 5 to <10 years, and ≥10 years of age. The same patient population was also categorized into diabetic ketoacidosis (DKA) and non-DKA groups based on clinical criteria. Results: The mean annual clinical incidence of T1DM was 3.16/100,000 from the years 2015 to 2019. A total of 6,544 patients with newly diagnosed T1DM aged 0-16 years (median 7.84 ± 3.8) were studied [ages <5 years (29.3%), 5 to <10 years (38.7%), and ≥10 years (32%)], 52.4% of them were women. In total, 90.5% of the cases were occurred in individuals without a family history. Patients had lower C-peptide (CP) and body mass index (BMI) z scores when compared with healthy children, 41.8% of them had measurable T1DM-related antibodies and 52.7% had DKA. Among all three age groups, the <5 years group had the lowest BMI z score, CP, and glycated hemoglobin (HbA1c) on average, while it had the highest incidence rate of DKA (56.9%). Compared to the non-DKA group, the DKA group was significantly younger, with a lower BMI z score and CP, higher antibody positive rate, HbA1c, and the rate of insulin pump therapy. Conclusion: The clinical incidence of T1DM in children and adolescents in China was 3.16/100,000. Patients with DKA at the first diagnosis of T1DM have a worse ß-cell function. Public health measures for the prevention and treatment of T1DM should focus on preschoolers (aged <5 years) in particular, considering the severity and the highest frequency of DKA in this age group. More efforts should be dedicated to early screening and diagnosis of the T1DM.

Hydrocephalus presented as the prominent symptom of severe 5,10-methylenetetrahydrofolate reductase deficiency in an infant: A case report.

Hyperhomocysteinemia is a common medical condition observed in patients with aminoaciduria. Deficiency in cystathionine beta-synthase, metabolism of cobalamin associated C, peroxiredoxin 1, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase, LMBR1 domain containing 1, 5-methyltetrahydrofolate-homocysteine methyltransferase or 5,10-methylenetetrahydrofolate reductase (MTHFR) all can result in an elevation in plasma homocysteine, which has been reported to be a risk factor of vascular events, such as atherosis, acute myocardial infarction and cerebral stroke. Hyperhomocysteinemia due to the deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR; also known as 5,10-methyl THR reductase) is an autosomal recessive rare disease caused by defects in the MTHFR gene. The clinical manifestations of this disorder are heterogeneous, ranging from asymptomatic to severe neurological disorders. However, hydrocephalus has seldomly been reported in patients with MTHFR deficiency. The present study thus describes a case of severe MTHFR deficiency in an infant, whose main manifestation was hydrocephalus. The clinical course and genotype of the patient were also examined. Specifically, a 4-month-old boy with hydrocephalus was admitted to hospital. Clinical examinations and genetic sequencing of the patient were performed to determine the probable causative factors. A physical examination revealed that the patient had developmental delay and progressive hydrocephalus. Amino acid analysis of the blood revealed an enhancement in serum homocysteine levels and a decrease in blood methionine and free carnitine levels. The organic acid levels in urine were normal. Therefore, he was diagnosed with hyperhomocysteinemia. Targeted next-generation sequencing was performed to determine the pathogenetic gene in this case. A paternal mutation c.1530G>A (p.K510K) and a maternal mutation c.233C>A (p.S78X) were identified. Previous experimental evidence indicated that these two mutations were all pathogenic; therefore, this patient was ultimately diagnosed with MTHFR deficiency. The patient in described herein study presented with severe progressive hydrocephalus in association with a delayed developmental milestone. According to the clinical and genetic tests, the patient was diagnosed with severe MTHFR deficiency. It thus is recommended that screening for metabolites and performing gene sequencing in infants presenting with undisclosed hydrocephalus.

Efficacy and safety of human chorionic gonadotropin combined with human menopausal gonadotropin and a gonadotropin-releasing hormone pump for male adolescents with congenital hypogonadotropic hypogonadism.

BACKGROUND: Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH. METHODS: Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0-3 months) and a follow-up phase (3-12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance). RESULTS: Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ±â€Š2.3 mL and 4.1 ±â€Š1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ±â€Š1.8 cm and 5.1 ±â€Š1.6 cm (P < 0.05, t = 3.083), the PD reached 2.4 ±â€Š0.5 cm and 2.0 ±â€Š0.6 cm (P < 0.05, t = 2.224), respectively, in the two groups. At the end of 6 months of treatment, biomarkers were in normal range in the two groups. Compared with the GnRH group, the testosterone (T) level and growth of PL and PD were significantly greater in the hCG/hMG group (all P < 0.05). While the TV of both groups increased, the difference was not statistically significant (P > 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference. CONCLUSIONS: The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.

A novel heterozygous MKRN3 nonsense mutation in a Chinese girl with idiopathic central precocious puberty: A case report.

RATIONALE: Central precocious puberty (CPP) is caused by the premature activation of the hypothalamic-pituitary-gonadal axis. Recently, the makorin ring finger protein 3 (MKRN3) mutations represent the most common genetic defects associated with CPP. However, the MKRN3 mutation is relatively rare in Asian countries. Here, we identified a novel heterozygous MKRN3 nonsense mutation (p. Gln363) causing CPP in a Chinese girl. PATIENT CONCERNS: The index case is a 7-year-old Chinese girl who presented rapidly progressive precocious puberty with the onset of menstrual period 2 months after breast development, the advanced bone age (11 years), and the accelerated growth velocity (10 cm/year). Her basal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, as well as the peak LH/FSH values after the gonadotropin-releasing hormone (GnRH) stimulation test were significantly elevated.Pelvic B ultrasound showed the presence of ovarian follicles with diameters ≥0.4 cm. Uterine length also indicated the onset of puberty. Contrast-enhanced magnetic resonance imaging (MRI) did not disclose any abnormality in the pituitary. Additionally, our present case was obese companies with impaired glucose tolerance (IGT) at the baseline assessment. Genetic analysis revealed a novel heterozygous nonsense mutation (c1087C>T; p. Gln363) in the maternally imprinted MKRN3, which inherited from the girl's father. DIAGNOSIS: Combined with the symptoms, hormonal data, and the results of the pelvic B ultrasound, the girl was diagnosed as CPP. INTERVENTIONS: The girl has been treated with a GnRH analog (3.75 mg every 4 wks) for 1 year and 5 months. OUTCOMES: The puberty signs have since not progressed during the follow-up period, which indicates that the GnRH analogs treatment is effective. LESSONS: This case was obese companied with IGT at the baseline assessment and exhibited stronger LH/FSH response to GnRH stimulation test. Therefore, clinicians should highlight the importance of weight management and the long-term follow-up to monitor the adverse health outcomes, especially for the polycystic ovary syndrome in later life.

Clinical, biochemical, molecular and therapeutic characteristics of four new patients of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency.

Thirty patients with mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS) deficiency, which is a rare autosomal recessive disorder caused by HMGCS2 gene mutation are known. Here, we present four new patients with this disease. The characteristics including several metabolites of patients were recorded. Next-generation targeted sequencing and multiple sequence alignment of PCR amplified products allowed for mutational analysis of HMGCS2. Minigene assay transcript analysis confirmed pathogenicity of a splice site mutation. All cases had recurrent episodes with infections while they had no symptoms during intermissions. Patient 1, a girl, showed recurrent severe metabolic acidosis after infections from 8 months old and presented with weakness, vomiting and lethargy but had normal blood glucose. After treatment, she revived completely. Patients 2, 3 and 4 were boys who showed episodes of hypoglycemia since 8, 27 and 10 months of age, respectively. Glucose infusion reversed the symptoms. All four patients had hepatomegaly and abdominal imaging showed fatty livers. Serum free fatty acid increased. Urinary dicarboxylic acids and urinary 4-hydroxy-6-methyl-2pyrone presented. Diagnosis was confirmed by HMGCS2 gene analysis and 7 mutations (p.R188H, p.F420S, p.R206C, IVS2 + 1G > T, p.E401*, p.A450Pfs*7 and p.Q427*) of this gene were found. Here we report on the characteristics and genetics of four new patients with HMGCS deficiency. This study will enrich our knowledge of this rare autosomal recessive disorder.

Final adult height of children with idiopathic short stature: a multicenter study on GH therapy alone started during peri-puberty.

BACKGROUND: To evaluate the efficacy of GH in improving FAH in ISS children in a multicenter study. METHODS: A real-world observation was carried out. Children with ISS in seven hospitals in China were enrolled. The height gains standard deviation score and the height gain over the target height were evaluated. RESULTS: There were 344 ISS patients (217 boys and 127 girls). The baseline average age of boys and girls was 12.7 and 11.7 years, with bone age of 11.7 and 10.1 years, respectively. The baseline height SDS of boys and girls was - 3.07 and - 2.74, and the FAH SDS was - 1.91 and - 1.38, respectively. Compared with the baseline height SDS, the FAH SDS was significantly increased in both boys and girls (both P = 0.0000). The FAH SDS was the highest (gain by 1.54 SD) in the ≥2y treatment course group. Two hundred eighteen patients (218/344, 63.4%) had a FAH SDS > - 2 SD. Among these patients, girls in the 1-2y treatment course group and ≥ 2y group had a FAH SDS higher than TH SDS. Even in the control group, a spontaneous catch-up growth of 1.16 SD was observed. A multivariate linear regression model was used to analyze the results, with FAH SDS as the dependent variable. It was found that the treatment course and baseline height SDS in the boys' model were statistically significant (P < 0.05), whereas the baseline height SDS and baseline bone age significantly affected the girls' FAH SDS (P < 0.05). CONCLUSIONS: Both girls and boys of ISS improved FAH by GH therapy even if treatments begin over 10 years old and majority of them reached TH. Some peri-puberty ISS will have a spontaneous height gain. We recommend the course of GH treatment more than 2 years for girls, and longer courses for boys.

The diagnosis of cystinosis in patients reveals new CTNS gene mutations in the Chinese population.

Background Cystinosis is a rare autosomal-recessive disorder caused by a defective transport of cystine across the lysosomal membrane. Previous studies have mapped cystinosis to the CTNS gene which is located on chromosome 17p13, and various CTNS mutations have been identified to correlate them with this disease. Methods We analyzed six patients from five unrelated families who were diagnosed with cystinosis in our hospital. We described the diagnostic procedures for all the patients and proposed alternative therapies for cystinosis patients instead of using cysteamine, an orphan drug which was commercially unavailable in China. Moreover, genetic analysis of all patients' samples was carried out to identify novel CTNS gene mutations. Results and conclusions The patients in this study were followed up from 1 to more than 10 years to monitor their growth and development, which indicated that the alternative therapies we used were helpful to ameliorate the complications of the cystinosis patients without cysteamine. Furthermore, by sequencing the patients' genome, we identified novel mutations in the CTNS gene including: c.477C > G (p.S159R), c.274C > T (p.Q92X) and c.680A > T (p.E227V); these mutations were only observed in cystinosis patients and had never been reported in any other populations, suggesting they might be specific to Chinese cystinosis patients.

Clinical and Molecular Spectrum of Glutamate Dehydrogenase Gene Defects in 26 Chinese Congenital Hyperinsulinemia Patients.

OBJECTIVE: To characterize the genotype and phenotype of Chinese patients with congenital hyperinsulinism (CHI) caused by activating mutations in GLUD1, the gene that encodes mitochondrial enzyme glutamate dehydrogenase (GDH). METHODS: The clinical data of glutamate dehydrogenase hyperinsulinism (GDH-HI) patients were reviewed, and gene mutations were confirmed by whole exome sequencing (WES) and Sanger DNA sequencing. RESULTS: Twenty-six patients with GDH-HI heterozygous missense mutations were identified from 240 patients diagnosed as congenital hyperinsulinism over past 15 years. The median age at onset was 8 months (range: 1 day of life to 3 years). Seizure disorder was common in our cohort of patients (23/26). Four patients had normal serum ammonia levels; the median serum concentration was 101 µmol/L (range: 37-190 µmol/L). Hypoglycemic symptoms could be triggered by fasting or protein meals in all patients while blood glucose could be well controlled in all patients with diazoxide. Dosage of diazoxide could be reduced by protein restriction. Attempts to lower ammonia levels failed with different therapies such as protein restriction, benzoate, or N-carbamoyl glutamate. In follow-up, 15 of 26 patients had normal intelligence. Eleven patients developed epilepsy at the age of 6 months to 11 years. De novo mutations in GLUD1 were found in 24 cases, and dominant inheritance was observed in the other two; all were heterozygous. A total of 35% (9/26) patients carried c.1493C>T (p.S445L) mutation. CONCLUSIONS: Phenotypic heterogeneity of GDH-HI patients was observed within the Chinese cohort in the present study. The fact that most patients had a GLUD1 p. S445L mutation implies that this site could be a hotspot in Chinese patients. A high frequency of GDH-HI with normal ammonia has been reported in this study. Hence, GLUD1 mutational analysis may be an important method to differential diagnosis of GDH-HI from other diazoxide-responsive CHI in Chinese patients.

Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies.

OBJECTIVE: We assessed the efficacy and safety of a weekly pegylated human growth hormone (PEG-rhGH) (Jintrolong) vs daily rhGH for children with growth hormone deficiency (GHD). DESIGN: Phase II and III, multicenter, open-label, randomized controlled trials. METHODS: 108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively. Patients in the phase II study were randomized 1:1:1 to weekly Jintrolong (0.1 mg/kg/week PEG-rhGH complex), weekly Jintrolong (0.2 mg/kg/week PEG-rhGH complex) or daily rhGH (0.25 mg/kg/week) for 25 weeks. Patients in the phase III study were randomized in a 2:1 ratio to weekly Jintrolong (0.2 mg/kg/week) or daily rhGH (0.25 mg/kg/week) for 25 weeks. The primary endpoint for both studies was height velocity (HV) increase at the end of treatment. Other growth-related parameters, safety and compliance were also monitored. RESULTS: The phase II study established the preliminary efficacy, safety and recommended dose of Jintrolong PEG-rhGH. In the phase III study, we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment (from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year) vs daily rhGH (from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year) at the end of treatment (P < 0.05). Additionally, significantly greater improvement in the height standard deviation scores was associated with Jintrolong throughout the treatment (P < 0.05). Adverse event rates and treatment compliance were comparable between the two groups. CONCLUSION: Jintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH.

Possible role of birth weight on general and central obesity in Chinese children and adolescents: a cross-sectional study.

PURPOSE: According to the developmental origins of health and disease theory, fetal nutrition is associated with obesity and chronic diseases in children and adults. However, previous findings regarding the association between birth weight and childhood obesity have been inconsistent. The aim of the present study was to investigate the relationship between birth weight and childhood obesity in China. METHODS: The 16,580 subjects (8477 boys and 8103 girls) aged 7-17 years, who participated in this study were recruited from a cross-sectional study in six cities in China. Epidemiological data, including birth information, were collected through face-to-face interviews, and anthropometric indices were measured by trained physicians. Overweight and obese cases were defined using sex-specific and age-specific 85th and 95th percentile body mass index (BMI) cutoffs for Han children and adolescents. Central obesity was defined using sex-specific waist-to-height ratio (WHtR) cutoffs (WHtR ≥0.48 in boys and WHtR ≥0.46 for girls). RESULTS: The overall rate of overweight status and obesity was 20.3% in the Chinese children and adolescents and that of central obesity was 18.9%. Subjects were stratified into eight groups according to weight at birth. J-shaped relationships were observed between birth weight and BMI for age Z-score and WHtR. After adjusting for confounders such as gender, gestational age, parental factors, and dietary factors, the risk of overweight and obese status was still higher in the children with higher birth weights than in children with birth weights of 3000-3499 g (3500-3999 g: odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.02-1.28; 4000-4499 g: OR = 1.39, 95% CI = 1.19-1.63; and 4500-4999 g: OR = 1.36, 95% CI = 1.06-1.76). Moderately high birth weight also increased the risk of central obesity. Relative to the children with normal birth weights (3000-3499 g), the adjusted OR and 95% CI were 1.33 (1.13-1.56) in children with birth weights of 4000-4499 g. Children with very low birth weight (lower than 1500 g) had the highest risk of central obesity. The adjusted OR was 2.30 (95% CI: 1.03-5.14) relative to children with birth weights of 3000-3499 g. CONCLUSIONS: Birth weight was associated with obesity in Chinese children and adolescents. J-shaped relationships were observed between birth weight and BMI and WHtR in childhood, and very low birth weight was associated with a mild increase in the risk of central obesity in Chinese children and adolescents.