Screening primary carnitine deficiency in 10 million Chinese newborns: a systematic review and meta-analysis.

BACKGROUND: Primary carnitine deficiency (PCD) is a rare autosomal recessive fatty acid oxidation disorder caused by variants in SLC22A5, with its prevalence and SLC22A5 gene mutation spectrum varying across races and regions. This study aimed to systematically analyze the incidence of PCD in China and delineate regional differences in the prevalence of PCD and SLC22A5 gene variants. METHODS: PubMed, Embase, Web of Science, and Chinese databases were searched up to November 2023. Following quality assessment and data extraction, a meta-analysis was performed on screening results for PCD among Chinese newborns. RESULTS: After reviewing 1,889 articles, 22 studies involving 9,958,380 newborns and 476 PCD cases were included. Of the 476 patients with PCD, 469 underwent genetic diagnosis, revealing 890 variants of 934 alleles of SLC22A5, among which 107 different variants were detected. The meta-analysis showed that the prevalence of PCD in China was 0.05‰ [95%CI, (0.04‰, 0.06‰)] or 1/20 000 [95%CI, (1/16 667, 1/25 000)]. Subgroup analyses revealed a higher incidence in southern China [0.07‰, 95%CI, (0.05‰, 0.08‰)] than in northern China [0.02‰, 95%CI, (0.02‰, 0.03‰)] (P < 0.001). Furthermore, the result of the meta-analysis showed that the frequency of the variant with c.1400C > G, c.51C > G, c.760C > T, c.338G > A, and c.428C > T were 45% [95%CI, (34%, 59%)], 26% [95%CI, (22%, 31%)], 14% [95%CI, (10%, 20%)], 6% [95%CI, (4%, 8%)], and 5% [95%CI, (4%, 8%)], respectively. Among the subgroup analyses, the variant frequency of c.1400C > G in southern China [39%, 95%CI, (29%, 53%)] was significantly lower than that in northern China [79‰, 95%CI, (47‰, 135‰)] (P < 0.05). CONCLUSIONS: This study systematically analyzed PCD prevalence and identified common SLC22A5 gene variants in the Chinese population. The findings provide valuable epidemiological insights and guidance for future PCD screening effects in newborns.

Newborn Screening of 6 Lysosomal Storage Disorders by Tandem Mass Spectrometry.

This study was designed to screen 6 lysosomal storage diseases (LSDs) in neonates using tandem mass spectrometry (MS/MS), and establish cutoff values for these LSDs with 3000 dried blood spots (DBS) samples. Cutoff values for α-L-iduronidase (IDUA), α-galactosidase (GLA), acid beta glucosidase (ABG), ß-galactocerebrosidase (GALC), acid sphingomyelinase (ASM), and acid alpha glucosidase (GAA) were as follows: GLA, > 2.06 µmol/L·h; ABG, > 1.78 µmol/L·h; ASM, > 0.99 µmol/L·h; IDUA, > 1.33 µmol/L·h; GALC, > 0.84 µmol/L·h; and GAA, > 2.06 µmol/L·h. There were 30 positives in initial MS/MS screening test, and 15 samples were still positive with repeat testing. Their parents/guardians were recontacted and DBS samples were collected again for test. Only 1 child showed abnormal GAA enzyme activity after recontacting process, and was diagnosed with Pompe disease after genetic screening. Eventually, cutoff values of 6 specific enzyme activities were established and MS/MS is effective for early LSDs screening.

Biochemical and molecular features of tetrahydrobiopterin deficiency in Fujian Province, southeastern China.

The estimated prevalence of tetrahydrobiopterin deficiency (BH4D) and the mutational spectrum of the causal 6-pyruvoyl-tetrahydropterin synthase (PTS) gene vary widely according to race and region. This study assessed the prevalence and genetic characteristics of BH4D in Fujian Province, southeastern China. A total of 3,204,067 newborns were screened between 2012 and 2022 based on the phenylalanine level and the phenylalanine/tyrosine ratio in dried blood spots. Differential diagnosis was determined by the urine purine spectrum, dihydropteridine reductase activity in red blood cells, and genetic testing. The PTS mutation spectrum and genotypes were determined by next-generation sequencing. A total of 189 newborns were diagnosed with hyperphenylalaninemia (HPA) over the study period, including 159 with phenylalanine hydroxylase deficiency and 30 with BH4D. Therefore, the prevalence of BH4D in Fujian was 9.36 per 1,000,000 live births (30/3,204,067) and the proportion of BH4D among patients with HPA was 15.87% (30/189). A total of 58 PTS alleles were identified in the 29 patients with PTS deficiency (PTPSD), and those alleles were composed of 10 different variants, including eight missense variants and two splice-site variants. The most prevalent variants were c.155A>G, p.Asn52Ser (44.83%); c.259C>T, p.Pro87Ser (39.66%); and c.84-291A>G, p.Tyr27Argfs*8 (3.45%). The predominant genotype was c [155A>G]; [259C>T] (11/29, 37.93%). The prevalence of BH4D and the spectrum of associated PTS mutations were successfully determined for the first time in Fujian Province, southeastern China. Since the mutation spectrum of PTS is region-specific, such data will facilitate molecular diagnosis and genetic counseling in PTPSD cases.

Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China.

BACKGROUND: Glutaric acidemia type 1 (GA1) is a rare autosomal recessive inherited metabolic disorder caused by variants in the gene encoding the enzyme glutaryl-CoA dehydrogenase (GCDH). The estimated prevalence of GA1 and the mutational spectrum of the GCDH gene vary widely according to race and region. The aim of this study was to assess the acylcarnitine profiles and genetic characteristics of patients with GA1 in Fujian Province, southeastern China. RESULTS: From January 2014 to December 2022, a total of 1,151,069 newborns (631,016 males and 520,053 females) were screened using MS/MS in six newborn screening (NBS) centers in Fujian Province and recruited for this study. Through NBS, 18 newborns (13 females and 5 males) were diagnosed with GA1. Thus, the estimated incidence of GA1 was 1 in 63,948 newborns in Fujian province. In addition, 17 patients with GA1 were recruited after clinical diagnosis. All but one patient with GA1 had a remarkable increase in glutarylcarnitine (C5DC) concentrations. The results of urinary organic acid analyses in 33 patients showed that the concentration of glutaric acid (GA) increased in all patients. The levels of C5DC and GA in patients identified via NBS were higher than those in patients identified via clinical diagnosis (P < 0.05). A total of 71 variants of 70 alleles were detected in patients with GA1, with 19 different pathogenic variants identified. The three most prevalent variants represented 73.23% of the total and were c.1244-2 A > C, p.(?) (63.38%), c.1261G > A, p.Ala421Thr (5.63%), and c.406G > T, p.Gly136Cys (4.22%). The most abundant genotype observed was c.[1244-2 A > C]; [1244-2 A > C] (18/35, 52.43%) and its phenotype corresponded to high excretors (HE, GA > 100 mmol/mol Cr). CONCLUSIONS: In conclusion, we investigated the biochemical and molecular features of 35 unrelated patients with GA1. C5DC concentrations in dried blood spots and urinary GA are effective indicators for a GA1 diagnosis. Our study also identified a GCDH variant spectrum in patients with GA1 from Fujian Province, southeastern China. Correlation analysis between genotypes and phenotypes provides preliminary and valuable information for genetic counseling and management.

Characterization of phenylalanine hydroxylase gene variants and analysis of genotype-phenotype correlation in patients with phenylalanine hydroxylase deficiency from Fujian Province, Southeastern China.

BACKGROUND: Phenylalanine hydroxylase deficiency (PAHD) is the most prevalent inherited disorder of amino acid metabolism in China. Its complex phenotype includes many variants and genotypes among different populations. METHODS AND RESULTS: In this study, we analyzed the phenylalanine hydroxylase gene (PAH) variants in a cohort of 93 PAHD patients from Fujian Province. We also assessed genotype and phenotype correlation in patients with PAHD. A total of 44 different pathogenic variants were identified, including five novel variants. The three most prevalent variants among all patents were c.158G > A, p.(Arg53His) (18.03%), c.721C > T, p.(Arg241Cys) (14.75%), and c.728G > A, p.(Arg243Gln) (7.65%). The frequency of the c.158G > A, p.(Arg53His) variant was highest in patients with mild hyperphenylalaninemia, whereas the frequency of the c.1197A > T, p.(Val399 =) and c.331C > T, p.(Arg111Ter) variants was highest in patients with classic phenylketonuria. The most abundant genotypes observed in PAHD patients were c.[158G > A];[728G > A], c.[158G > A];[442-1G > A], and c.[158G > A];[721C > T]. Comparing allelic phenotype to genotypic phenotype values yielded fairly accurate predictions of phenotype, with an overall consistency rate was 85.71% for PAHD patients. CONCLUSIONS: Our study identified a PAH variant spectrum in PAHD patients from Fujian Province, Southeastern China. Quantitative correlation analysis between genotype and phenotype severity is helpful for genetic counseling and management.

Gene diagnosis and pedigree analysis of two Han ethnicity families with propionic acidemia in Fujian.

ABSTRACT: Propionic acidemia is associated with pathogenic variants in PCCA or PCCB gene. We investigated the potential pathogenic variants in PCCA or PCCB genes in Fujian Han population.Two probands and their families of Han ethnicity containing two generations were subject to newborn screening using tandem mass spectrometry, followed by diagnosis using urine gas chromatography mass spectrometry. Sanger sequencing was used to identify potential mutations in PCCA and PCCB genes.Compound heterozygous variants were identified in PCCB gene in two siblings of the first family, the youngest girl showed a novel missense variant c.1381G>C (p.Ala461Pro) in exon 13 and a heterozygous missense variant c.1301C>T (p.Ala434Val) in exon 13, which were inherited respectively from their parents. The oldest boy is a carrier with a novel missense variant c.1381G>C (p.Ala461Pro) in exon 13 which were inherited from his father. In the second family, c.1535G>A homozygous mutations were identified in the baby girl, which were inherited respectively from their parents. In silico analysis, several different types of bioinformatic software were utilized, which predicted that the novel variant c.1381G>C in PCCB gene was damaged. According to ACMG principle, the missense variant c.1381G>C (p.Ala461Pro) in exon 13 was a Variant of Undetermined Significance (VUS).One novel missense variant and two missense variants in PCCB gene were identified in the study. The novel variant of PCCB gene identified VUS was identified for the first time in the Chinese population, which enriched the mutational spectrum of PCCB gene.

Gene spectrum and clinical traits of 10 patients with primary carnitine deficiency.

BACKGROUND: Rare studies focused on the tandem mass spectrometry (MS/MS) findings for the primary carnitine deficiency (PCD) in the neonates in China mainland. In this study, we aim to analyze the gene mutation spectrum of PCD in Fujian Province in China mainland. METHODS: Primary carnitine deficiency (PCD) samples used in this study were selected from 95,453 cases underwent neonatal screening between May 2015 and February 2020. SLC22A5 gene sequencing was performed on the neonates and their parents with C0 level of less than 8.8 µmol/L. RESULTS: Ten patients (male: 7; female: 3) were finally included in this study. Among these patients, nine were neonates, and one was maternal decline of C0 of less than 8.8 µmol/L. The maternal case showed two types of mutations of SLC22A5 including c.760C>T(p.R254*) and c.1400C>G(p.S467C). The other nine neonates showed compound mutations involving nine types in 18 sites, among which two mutations [i.e., c.37G>T(p.E13*) and c.694A>G(p.T232A)] were novel that had never been reported before. Bioinformatic analysis indicated that c.37G>T(p.E13*) was a pathogenic mutation, while the c.694A>G (p.T232A) was considered to be likely pathogenic. CONCLUSION: MS/MS screening on PCD contributed to the early diagnosis and screening. In addition, SLC22A5 gene mutation analysis contributed to the PCD screening.

Association between genetic polymorphism of heme oxygenase 1 promoter and neonatal hyperbilirubinemia: a meta-analysis.

Objective: The association between a (GT)n dinucleotide length polymorphism in the promoter region of heme oxygenase 1 (HMOX1) and the risk of neonatal hyperbilirubinemia remains controversial. This meta-analysis was, therefore, performed with aims to examine the correlation between the HMOX1 (GT)n repeat length polymorphism and neonatal hyperbilirubinemia susceptibility.Materials and methods: We searched the databases including PubMed, Embase, Cochrane Library, China national knowledge infrastructure (CNKI), and Wanfang Data, with all reviewed studies published before 28 June 2018. After the evaluation of quality, we used RevMan to perform the meta-analyses. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the effect of HMOX1 gene promoter polymorphisms on the risk of neonatal hyperbilirubinemia.Results: Seven studies, involving 584 patients with neonatal hyperbilirubinemia and 1655 controls, were included. A statistically significant association was found between the HMOX1 (GT)n repeat length polymorphism and risk of neonatal hyperbilirubinemia under the allele (allele S vs. allele L: OR = 1.81, 95% CI = 1.22-2.67, p = .003), recessive (genotype SS vs. genotypes LS + LL: OR = 1.38, 95% CI = 1.02-1.86, p = .04), dominant (genotypes SS + LS vs. LL: OR = 1.37, 95% CI = 1.01-1.76, p = .01), and homozygous genetic models (genotype SS vs. genotype LL: OR = 1.47, 95% CI = 1.02-2.11, p = .003), but not under the heterozygous genetic model. Interestingly, subgroup analysis revealed that the cutoffs of the S allele < 25 showed significant associations in any of the five genetic models (allele S vs. allele L: OR = 2.26, 95% CI = 1.68-3.05, p < .00001; genotype SS vs. genotypes LS + LL: OR = 2.56, 95% CI = 1.41-4.65, p = .002; genotypes SS + LS vs. genotype LL: OR = 1.82, 95% CI = 1.28-2.59, p = .0009; genotype SS vs. genotype LL: OR = 3.09, 95% CI = 1.50-6.36, p = .002; genotype LS vs. genotype LL: OR = 1.64, 95% CI = 1.11-2.42, p = .01); however, this association was not observed in the cutoffs of the S allele ≥25.Conclusion: The results of this study indicate that there is a significant association between the HMOX1 (GT)n repeat length polymorphism and susceptibility to neonatal hyperbilirubinemia. Newborns carrying shorter (GT)n repeats in the HMOX1 gene promoter may have a higher risk of neonatal hyperbilirubinemia.

Perinatal risk factors for congenital hypothyroidism: A retrospective cohort study performed at a tertiary hospital in China.

Congenital hypothyroidism (CH) is one of the most common neonatal endocrine diseases. This retrospective cohort study aimed to identify the potential perinatal risk factors for CH and to differentiate between transient and permanent CH (TCH and PCH, respectively) as well as determine their prevalence in a southeastern Chinese population.This study was based on an 18-year surveillance of a neonatal CH screening program in a large tertiary hospital. A retrospective review of the maternal and neonatal perinatal exposures was conducted.Of the 205,834 newborns screened between 2000 and 2018, 189 were diagnosed with CH (1/1089). Among the 131 CH patients who again underwent thyroid function testing (TFT) after discontinuation of levothyroxine at the age of 3 years, 61 (46.6%) were diagnosed with PCH and 70 (53.4%) were diagnosed with TCH. In the maternal characteristics model, women aged 35 years or older and those who had thyroid disease and/or diabetes mellitus during pregnancy had increased risk of having an offspring with CH (P = .001, .000, and .001, respectively). Significant associations were found with regard to parity and the risk of CH in the offspring (P = .000). In the neonatal characteristics model, infants with female sex, preterm birth, post-term birth, low birth weight, other birth defects, and those born as part of multiple births (P = .011, .034, .001, .000, .000, and .003, respectively) had increased risk of CH. The rate of newborns with other birth defects was higher in the PCH group than that in the TCH group (P = .008), whereas the rate of maternal thyroid disease, newborns with low birth weight, and newborns with preterm birth was higher in the TCH group than that in the PCH group (P = .041, .020, and .013, respectively). The levothyroxine dose (µg/kg/day) at 1 year, 2 years, and 3 years old was significantly lower in the TCH group than that in the PCH group (P = .000, .000, and .000, respectively).Perinatal factors should be considered during the diagnosis and treatment of CH.

A verification of the application of the non-derivatized mass spectrometry method in newborns screening of metabolic disorders.

It is required that the clinical screening of metabolic disorders in newborns meet International Organization for Standardization 15189-2012 approval. The new tandem mass spectrometry (MS/MS) based screening system and its companion reagent should be independently authenticated before their implementation in clinical diagnosis laboratories.Linearity, stability, accuracy, and precision evaluations were carried out to verify the performance of the Waters ACQUITY TQD MS/MS system with the NeoBase non-derivatized MS/MS PerkinElmer kit for detecting amino acids and acylcarnitine in newborns with metabolic disorders.Statistically, the correlation coefficient (R) of 0.9982 to 0.9999 indicates good linearity. The measurements at the beginning and end of the reagent storage procedure were taken for stability verification. No significant difference was detected between the 2 periods. The amino acid exhibited a degree of bias in the range of 0% to 14.17%, with acylcarnitine's being was in the range of 0% to 14.84%; they consequently passed the quality assessment requirements for clinical laboratories of the China National Centre. The amino acids' within-run, between-run, and day-to-day run precision were 1.19% to 7.68%, 1.63% to 5.01%, and 4.77% to 12.48%, respectively, while the total imprecision was 5.55% to 13.33%. Acylcarnitine's within-run, between-run, and day-to-day run precision was 1.2% to 8.43%, 0.19% to 9.60%, and 2.33% to 10.74%, respectively, while it's total imprecision was 6.57% to 13.99%. The manufacturer declared that the total imprecision of the tests, using Multiple Reaction Monitoring, should be less than or equal to 25% of the coefficient of variation for the kit's high and low-quality control levels.The performance of the non-derivatized MS/MS screening system in detecting the amino acids and acylcarnitines passed the test's requirements. It was maintained in accordance with the routine clinical chemical detection system.

Identification of Genetic Risk Factors for Neonatal Hyperbilirubinemia in Fujian Province, Southeastern China: A Case-Control Study.

To date, the genetic risk factors for neonatal hyperbilirubinemia remain unknown in Southeastern China. This case-control study aimed to identify the genetic risk factors for neonatal hyperbilirubinemia in Fujian, Southeastern China. A total of 286 hyperbilirubinemic newborns were enrolled as a case group, and 250 randomly selected newborns without jaundice or with a bilirubin level that was lower than the threshold required for phototherapy served as controls. The serum levels of total bilirubin, unconjugated bilirubin, and direct bilirubin were measured, and the common genetic loci in UGT1A1, OATP1B1, and HO-1 genes were genotyped. Higher incidence of ABO incompatibility and G6PD deficiency was detected in the case group compared to the control group (P < 0.01). There were significant differences in the frequencies of rs4148323 and rs1805173 genotypes between the case and control groups (P < 0.05). At the rs4148323 locus, the frequencies of GA heterozygotes and AA mutant homozygotes were higher in the case group than in the control group (P < 0.05), and at the rs1805173 locus, the frequencies of LS, MS, and SS genotypes were higher in the case group than in the control group (P < 0.05). A higher frequency of rs4148323 A allele and rs1805173 S allele was detected in the case group compared to the control group (P = 0). Additionally, multivariate logistic regression analysis identified that the mutant genotype of rs4148323 in the UGT1A1 gene, ABO incompatibility, G6PD deficiency, and SS genotype at rs1805173 locus of the HO-1 gene were genetic risk factors of neonatal hyperbilirubinemia. Our data demonstrate that G211 mutation in the UGT1A1 gene, ABO incompatibility, G6PD deficiency, and the SS genotype of the repeats in the promoter region of the HO-1 gene are risk factors for neonatal hyperbilirubinemia in Fujian, Southeastern China.

[Analysis of GCDH gene mutations in 3 patients from Fujian area with glutaric academia type I].

OBJECTIVE: To explore clinical features and mutation types in patients from Fujian area with glutaric academia type I(GA I). METHODS: Serum acylcarnitine and urine organic acid of 3 patients were determined with tandem mass spectrometry and gas chromatographic mass spectrometry. The patients also underwent magnetic resonance imaging analysis for the cranial region. Genomic DNA was extracted from peripheral blood samples, and the 12 exons and flanking regions of the GCDH gene were amplified with PCR and subjected to direct DNA sequencing. One hundred healthy newborns were used as controls. RESULTS: Mutations of the GCDH gene were identified in all of the 3 patients. Two patients have carried compound heterozygous mutations including c.1244-2A>C and c.1147C>T(p.R383C), c.406G>T(p.G136C) and c.1169G>A(p.G390E), respectively. One has carried homozygous c.1244-2A>C mutation. The same mutations were not detected among the 100 healthy newborns. Only one patient received early intervention and did not develop the disease. The other two had irreversible damagesto their intelligence. CONCLUSION: c.1169G>A(p.G390E) is likely pathogenic mutations for GA I patients from Fujianarea. Early screening of neonatal metabolic diseases is crucial for such patients.

Mutation of glucose-6-phosphate dehydrogenase deficiency in Chinese Han children in eastern Fujian.

We aim to investigate the mutation types of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Chinese Han children in eastern Fujian Province.A total of 904 Chinese Han neonates (male: 733 with positive G6PD deficiency and 28 with weakly positive deficiency; female: 73 with positive G6PD deficiency and 70 with weakly positive deficiency) received G6PD screening in our center from January 2014 to December 2016 were included in this study. Additionally, 904 age-matched normal Chinese Han individuals (male: 761; female: 143) were selected as control. Neonatal G6PD deficiency screening was performed through blood sample collection from the heels, using the commercial kits. Multicolor melting curve analysis (MMCA) method was used to determine the G6PD mutation type in the 904 cases. If it failed to detect mutations in the cases with abnormal enzyme activity, the polymerase chain reaction (PCR) and gene sequencing were used to determine the mutation sites. PCR and gene sequencing were used to determine the mutation sites in the 904 individuals with normal enzyme activity. Three most common mutation types in Chinese population were compared between Fujian and other provinces.Among the 904 neonates with abnormal G6PD enzyme activity, 17 mutation types were detected including 15 single point mutations and 7 complex mutations. Three most common mutation types were c.1376G > T, c.1388G > A, and c.95A > G accounted for 72.6% of the total mutations in eastern Fujian.The proportion of mutational types in G6PD and the degree of enzyme activity change in various mutational types were found in the neonates of Fujian Province. Our study may enrich the molecular diagnosis of G6PD deficiency meaning Fujian Province.

[Analysis of CYP21A2 gene mutations among patients with classical steroid 21-hydroxylase deficiency].

OBJECTIVE: To assess the frequencies of CYP21A2 gene mutations among patients from Fujian area with classical 21-hydroxylase deficiency. METHODS: For 19 probands from different families affected with classical steroid 21-hydroxylase deficiency and 74 family members, mutations of the CYP21A2 gene were analyzed with combined nested polymerase chain reaction, Sanger sequencing and multiplex ligation-dependent probe amplification. Time resolved fluorescence immunoassay was performed to determine the level of 17-hydroxyprogesterone (17-OHP) in all family members. Clinical data and laboratory results of the probands and their family members were analyzed. RESULTS: Eleven mutations were identified among the 38 alleles from the 19 probands. 92.1% (35/38) of the mutant CYP21A2 alleles were due to recombination between CYP21A2 and CYP21A1P. Gene conversion and deletions were identified in 84.2% (32/38) and 7.9% (3/38) of the alleles, respectively. IVS2-13A/C>G and chimeras were the most common mutations, which respectively accounted for 34.2% (13/38) and 18.4% (7/38) of all mutant alleles. Among these, IVS2+1G>A and Q318X+356W were first reported in China. 74.3% (55/74) of the family members were carriers of heterozygous mutations. However, no significant difference was found in the 17-OHP levels between carriers and non-carriers (P>0.05). CONCLUSION: There seems to be a specific spectrum of CYP21A2 gene mutations in Fujian area, where IVS2-13A/C>G and chimeras are the most common mutations.

[Association of thyroperoxidase gene polymorphisms with dyshormonogenesis in congenital hypothyroidism].

OBJECTIVE: To assess the association of thyroperoxidase (TPO) gene polymorphisms with dyshormonogenesis in congenital hypothyroidism (CH). METHODS: The 17 exons and flanking introns of the TPO gene from 30 randomly selected samples were sequenced for the selection of single nucleotide polymorphisms (SNPs). In 136 patients with dyshormonogenetic CH and 141 healthy controls from the same region, the selected SNPs were genotyped by polymerase chain reaction (PCR) and direct sequencing or PCR-restriction fragment length polymorphism (RFLP). RESULTS: Six SNPs (rs9678281, rs376413622, rs1126797, rs4927611, rs732609 and rs1126799) were selected to determine the genotype for each sample. Among these, rs4927611 and rs732609 showed a significant difference between the two groups in both allelic and genotypic frequencies. With a recessive model of inheritance, rs732609 CC (OR=0.484, 95%CI: 0.253-0.927, P=0.04) and rs4927611 TT (OR=0.32, 95%CI: 0.112-0.915, P=0.047) were greater in the patients. CONCLUSION: rs4927611 and rs732609 may be associated with dyshormonogenetic CH. rs4927611 TT and rs732609 CC are genotypes associated with potential risk for the disease.

[Risk factors of 125 cases of neonatal congenital hypothyroidism during perinatal period].

OBJECTIVE: To understand the relationship between perinatal factors and congenital hypothyroidism (CH) and provide scientific evidence for the prevention of CH. METHODS: A case-control study was conducted among 125 neonates with CH (case group) and 375 neonates without CH (control group) in Fujian Neonatal Screening Center from January in 2012 to December in 2013. Univariate and multivariate logistic regression analysis were performed to identify the risk factors to CH during perinatal period. RESULTS: Univariate logistic regression analysis indicated that compared with control group, gestational hypertension, gestational diabetes mellitus, gestational thyroid disease and older age of mother were the risk factors to CH, the difference was statistically significant (P < 0.05) and the risk of CH was higher in female babies, preterm babies, post-term babies low birth weight babies, macrosomia, twins, babies with birth defects and infection in cases group than those in control group, the difference was statistically significant (P < 0.05). Multivariate logistic analysis showed that older age of mother (OR = 2.518, 95% CI: 1.186-5.347), gestational diabetes mellitus (OR = 1.904, 95% CI: 1.190-3.045), gestational hypothyroidism or hyperthyroidism (OR = 12.883 and 30.797, 95% CI: 2.055-80.751 and 3.309-286.594), preterm birth (OR = 4.238, 95% CI: 1.269-14.155), and post-term birth (OR = 12.799, 95% CI: 1.257-130.327), low birth weight (OR = 3.505, 95% CI: 1.059-11.601), macrosomia (OR = 3.733, 95% CI: 1.415-9.851), twin or multiparous delivery (OR = 5.493, 95% CI: 1.701-17.735), birth defects (OR = 3.665, 95% CI: 1.604-8.371) and fetal distress (OR = 3.130, 95% CI: 1.317-7.440) were the high risk factors to CH (P < 0.05). CONCLUSION: CH was correlated with mother's age, gestational diabetes, gestational thyroid disease as well as neonate's birth weight and gestational age, foetus number, fetal distress and other complicated birth defects at certain degree. More attention should be paid to perinatal care to reduce risk factors and the incidence of CH.