Clinical efficacy and acceptability of remote fetal heart rate self-monitoring in Southern China.

BACKGROUND: Compared to traditional fetal heart rate monitoring (FHR) for the outpatients in clinic, remote FHR monitoring shows real-time assessment of fetal wellbeing at home. The clinical function of remote FHR monitoring in pregnant wome in outpatient is still unclear. OBJECTIVE: To explore the feasibility of remote FHR self-monitoring in singleton pregnant women from southern China. STUDY DESIGN: This prospective cohort study was conducted at one tertiary center in southern China. Pregnant women used a mobile cardiotocogram device to measure the FHR at least once a week until delivery in the remote group. For the control group, pregnant women underwent traditional FHR monitoring once a week in the outpatient clinic. The rate of cesarean section, risk of postpartum hemorrhage and adverse neonatal outcomes were compared between the two groups. All the pregnant women completed a questionnaire survey to evaluate their acquisition of remote FHR self-monitoring. RESULTS: Approximately 500 women were recruited in the remote FHR self-monitoring group (remote group), and 567 women were recruited in the traditional FHR monitoring group (control group). The women in the remote FHR monitoring group were more likely to be nulliparous (P < 0.001), more likely to have a higher education level (P < 0.001) and more likely to be at high risk (P = 0.003). There was no significant difference in the risk of cesarean section (P = 0.068) or postpartum hemorrhage (P = 0.836) between the two groups. No difference in fetal complications was observed across groups, with the exception of the incidence of NICU stays, which was higher in the remote group (12.0% vs. 8.3%, P = 0.044). The questionnaire survey showed that the interval time (P = 0.001) and cost (P = 0.010) of fetal heart rate monitoring were lower in the remote group. Regarding age, prepregnancy BMI, risk factors, education level, maternal risk and household income, senior high school (OR 2.86, 95% CI 1.67-4.90, P < 0.001), undergraduate (OR 2.96, 95% CI 1.73-5.06, P < 0.001), advanced maternal age (OR 1.42, 95% CI 1.07-1.89, P = 0.015) and high-risk pregnancy (OR 1.61, 95% CI 1.11-2.35, P = 0.013) were independent factors for pregnant women to choose remote fetal monitoring. Multiparty (OR 0.33, 95% CI 0.21-0.51, P < 0.001), full-time motherhood (OR 0.47, 95% CI 0.33-0.678, P < 0.001) and high household income (OR 0.67, 95% CI 0.50-0.88, P = 0.004) were negatively correlated with the choice of remote FHR self-monitoring. CONCLUSION: Remote FHR self-monitoring technology has a lower cost and shows potential clinical efficacy for the outpatient setting in southern China. This approach does not increase the risk of cesarean section or adverse neonatal outcomes. It is acceptable among nulliparous pregnant women with a high education level, high household income or high risk. Further research is needed to assess the impact of this technology on obstetric outcomes in different health settings.

Elevated first-trimester hepcidin level is associated with reduced risk of iron deficiency anemia in late pregnancy: a prospective cohort study.

Background: Iron deficiency (ID) and iron deficiency anemia (IDA) during pregnancy are highly prevalent worldwide. Hepcidin is considered an important biomarker of iron status. Currently, few longitudinal cohort studies have assessed the potential causal relationship between hepcidin and ID/IDA. Therefore, we aimed to investigate the association of first-trimester maternal serum hepcidin with third-trimester ID/IDA risk in a prospective cohort. Methods: Total of 353 non-ID/IDA pregnant women at 11-13 weeks' gestation were enrolled in Southern China and followed up to 38 weeks of gestation. Data on demography and anthropometry were obtained from a structured questionnaire at enrollment. Iron biomarkers including hepcidin were measured at enrollment and follow-up. Regression models were used to evaluate the association of first-trimester hepcidin with third-trimester ID/IDA risk. Results: Serum hepcidin levels substantially decreased from 19.39 ng/mL in the first trimester to 1.32 ng/mL in the third trimester. Incidences of third-trimester ID and IDA were 46.2 and 11.4%, respectively. Moreover, moderate and high levels of first-trimester hepcidin were positively related to third-trimester hepcidin (log-transformed ß = 0.51; 95% CI = 0.01, 1.00 and log-transformed ß = 0.66; 95% CI = 0.15, 1.17). Importantly, elevated first-trimester hepcidin was significantly associated with reduced risk of third-trimester IDA (OR = 0.38; 95% CI = 0.15, 0.99), but not with ID after adjustment with potential confounders. Conclusion: First-trimester hepcidin was negatively associated with IDA risk in late pregnancy, indicating higher first-trimester hepcidin level may predict reduced risk for developing IDA. Nonetheless, given the limited sample size, larger studies are still needed.

Effects of a school-based lifestyle intervention on ideal cardiovascular health in Chinese children and adolescents: a national, multicentre, cluster-randomised controlled trial.

BACKGROUND: The prevalence of ideal cardiovascular health among Chinese children and adolescents is alarmingly low. We aimed to examine whether a school-based lifestyle intervention against obesity would improve ideal cardiovascular health. METHODS: In this cluster-randomised controlled trial, we included and randomly assigned schools from the seven regions of China to intervention or control (1:1), stratified by province and school grade (grades 1-11; ages 7-17 years). Randomisation was done by an independent statistician. The 9-month intervention consisted of school promotion for diet, exercise, and self-monitor of obesity-related behaviours and the control group was no promotion. The primary outcome, assessed at both baseline and 9 months, was ideal cardiovascular health (six or more ideal cardiovascular health behaviours [non-smoking, BMI, physical activity, and diet] and factors [total cholesterol, blood pressure, and fasting plasma glucose]). We did intention-to-treat analysis and multilevel modelling. This study was approved by the ethics committee of Peking University, Beijing, China (ClinicalTrials.gov, NCT02343588). FINDINGS: 30 629 students in the intervention group and 26 581 students in the control group from 94 schools with any follow-up cardiovascular health measures were analysed. At follow-up, 22·0% (1139/5186) of the intervention group and 17·5% (601/3437) in the control group met ideal cardiovascular health. Overall, the intervention was associated with ideal cardiovascular health behaviours (three or more; odds ratio 1·15; 95% CI 1·02-1·29), but not other ideal cardiovascular health metrics after adjusting for covariates. The intervention had higher effects on ideal cardiovascular health behaviours in primary school students aged 7-12 years (1·19; 1·05-1·34) than secondary school students aged 13-17 years (p<0·0001), with no apparent sex difference (p=0·58). The intervention protected senior students aged 16-17 years from smoking (1·23; 1·10-1·37) and improved ideal physical activity in primary school students (1·14; 1·00-1·30) but was associated with lower odds of ideal total cholesterol in primary school boys (0·73; 0·57-0·94). INTERPRETATION: This school-based intervention, focused on diet and exercise, was effective in improving ideal cardiovascular health behaviours in Chinese children and adolescents. Early intervention might benefit cardiovascular health over the life course. FUNDING: The Special Research Grant for Non-profit Public Service of the Ministry of Health of China (201202010) and Guangdong Provincial Natural Science Foundation (2021A1515010439).

MFN1 augmentation prevents retinal degeneration in a Charcot-Marie-Tooth type 2A mouse model.

Charcot-Marie-Tooth disease type 2A (CMT2A), the most common inherited peripheral axonal neuropathy, is associated with more than 100 dominant mutations, including R94Q as the most abundant mutation in the Mitofusin2 (MFN2) gene. CMT2A is characterized by progressive motor and sensory loss, color-vision defects, and progressive loss of visual acuity. We used a well-established transgenic mouse model of CMT2A with R94Q mutation on MFN2 gene (MFN2 R94Q ) to investigate the functional and morphological changes in retina. We documented extensive vision loss due to photoreceptor degeneration, retinal ganglion cell and their axonal loss, retinal secondary neuronal and synaptic alternation, and Müller cell gliosis in the retina of MFN2 R94Q mice. Imbalanced MFN1/MFN2 ratio and dysregulated mitochondrial fusion/fission result in retinal degeneration via P62/LC3B-mediated mitophagy/autophagy in MFN2 R94Q mice. Finally, transgenic MFN1 augmentation (MFN2 R94Q :MFN1) rescued vision and retinal morphology to wild-type level via restoring homeostasis in mitochondrial MFN1/MFN2 ratio, fusion/fission cycle, and PINK1-dependent, Parkin-independent mitophagy.

Application of ITO Method in Determination of Special Half-Sibling Relationship.

OBJECTIVES: To identify whether the relationship between Zhang A, Zhang B, Zhang C and Zhang X is the half-sibling relationship whose mother is sister (hereinafter referred to as the special half-sibling relationship) or the common first cousin relationship and discuss the application of ITO method in discriminating the special kinship. METHODS: DNA was extracted from blood stain of four identified individuals, PowerPlex® 21 System and AGCU 21+1 STR kit were used to detect autosomal STR genetic markers. Investigator® Argus X-12 QS kit was used to detect the X chromosome STR genetic markers, the special half-sibling index (SHSI) and first cousin index (FCI) and their likelihood ratio (LR) were calculated by ITO method. RESULTS: The LR results of SHSI to FCI, which were calculated based on autosomal STR genotyping and the analysis of X-STR genotyping results suggested that the relationship between Zhang A, Zhang B, Zhang C and Zhang X was inclined to be a special half-sibling relationship. CONCLUSIONS: For the identification of special kinship, it is necessary to comprehensively apply various genetic markers according to the case. After the conclusion that shared alleles cannot be excluded from the analysis, ITO method can be further used to establish discriminant assumptions according to the specific case to obtain objective and reliable identification opinions.

Genetic analysis of tri-allelic patterns at the CODIS STR loci.

In the routine of autosomal STR genotyping for forensic aims, tri-allelic patterns could be occasionally observed at a single locus in phenotypically normal individuals. Two predominant types of tri-allelic variants have been nominated. Uneven intensities of three alleles are normally considered as the Type 1 pattern, and balanced height of three alleles are considered as the Type 2 pattern. In this study, the prevalence of tri-allelic patterns at the CODIS STR loci was investigated in global populations based on previous reports. The frequencies of the Type 1 and Type 2 pattern manifest a correlation with the germline mutation rates at the CODIS STR loci. The irregular high frequencies of the Type 2 pattern at TPOX with low germline mutation rates could attribute to the stable inheritance of genomic rearrangement from ancestral origin. Furthermore, results from genetic pattern analysis show that only a single allele from STRs with the Type 1 pattern could be transmitted from parents to offsprings, while a single allele and a combination of two alleles from STRs with the Type 2 pattern present an equal opportunity of transmission from parents to offsprings. Altogether, these results provide a genetic portrait of STRs with tri-allelic patterns, which will help the genetic interpretation of tri-allelic patterns in forensic practice.

Genetic polymorphism and phylogenetic analyses of 21 non-CODIS STR loci in a Chinese Han population from Shanghai.

BACKGROUND: Short tandem repeats (STRs) are essential genetic markers for forensic applications and population estimations; thus the population genetics of STR loci have been extensively studied and discussed. METHODS: In the present study, we detected 21 autosomal noncombined DNA index system (non-CODIS) STR loci in a Chinese Han population from Shanghai, calculated their forensic parameters and analyzed their genetic relationships with reported reference populations in mainland China. RESULTS: A total of 173 alleles were observed, with corresponding allele frequencies from 0.0020 to 0.5512. The cumulative power of discrimination (CPD) and the cumulative probability of exclusion (CPE) values of the 21 STR loci were 0.999999999999999999997337058271 and 0.99999953732495, respectively. The results of interpopulation differentiation, phylogenetic, multidimensional scaling, and structure analyses indicated a closer genetic relationship of the studied population with Han populations from other regions of China than with other populations. CONCLUSIONS: The 21 STR loci exhibited high genetic polymorphism in the studied Shanghai_Han population and could be used for forensic applications and population genetic studies.

Restoring mitofusin balance prevents axonal degeneration in a Charcot-Marie-Tooth type 2A model.

Mitofusin-2 (MFN2) is a mitochondrial outer-membrane protein that plays a pivotal role in mitochondrial dynamics in most tissues, yet mutations in MFN2, which cause Charcot-Marie-Tooth disease type 2A (CMT2A), primarily affect the nervous system. We generated a transgenic mouse model of CMT2A that developed severe early onset vision loss and neurological deficits, axonal degeneration without cell body loss, and cytoplasmic and axonal accumulations of fragmented mitochondria. While mitochondrial aggregates were labeled for mitophagy, mutant MFN2 did not inhibit Parkin-mediated degradation, but instead had a dominant negative effect on mitochondrial fusion only when MFN1 was at low levels, as occurs in neurons. Finally, using a transgenic approach, we found that augmenting the level of MFN1 in the nervous system in vivo rescued all phenotypes in mutant MFN2R94Q-expressing mice. These data demonstrate that the MFN1/MFN2 ratio is a key determinant of tissue specificity in CMT2A and indicate that augmentation of MFN1 in the nervous system is a viable therapeutic strategy for the disease.

Characterization of the extra copy of TPOX locus with tri-allelic pattern.

BACKGROUND: An STR locus with tri-allelic pattern is occasionally observed in routine forensic casework. The extra copy of TPOX locus with tri-allelic pattern in populations has been assumed to be inserted into an X chromosome, which took place forth before the Bantu expansion in Africa. Nonetheless, the exact location of the duplication and the form of rearrangement in the human genome has not been clarified yet. RESULTS: In this study, we investigated the extra copy of type 2 tri-allelic pattern at TPOX in various populations. While allele 10 is the major third allele in Africa, allele 11 appears more frequent in America and overwhelming in Chinese and Korean populations, which might attribute to the population substructures. Results from the investigation of family cases showed that the transmission of the extra allele had a similar genetic pattern of autosomal genes. Furthermore, a whole-genome sequencing followed by bioinformatics analysis revealed that the intact form of chromosomal duplication and rearrangement occurred ~ 407 kb away from the authentic TPOX locus on chromosome 2 in two cases. The breakpoints of the insertion were further validated in most other tri-allelic subjects, which can imply the identical origin from the ancestral extra copy. Nevertheless, de novo chromosomal duplication and rearrangement at thyroid peroxidase gene occur in populations. CONCLUSIONS: Instead of the extra allele 10 in African populations, the main third allele at TPOX with tri-allelic pattern is allele 11 in Chinese and Korean populations. The insertion of the extra copy into chromosome 2 occurs in most subjects with tri-allelic pattern at TPOX and demonstrates the transmission of the third allele from parents to offspring. The breakpoints of the ancestral extra copy are defined, which shows evidence of its inheritance from African populations. In addition, the simple validation method would help improve tri-allelic pattern calling, distinguish de novo chromosomal rearrangements, and also count the frequencies among different geographic regions. Therefore, the statistical interpretation of tri-allelic pattern at TPOX could be enhanced during forensic practice.

Null alleles and sequence variations at primer binding sites of STR loci within multiplex typing systems.

Rare variants are widely observed in human genome and sequence variations at primer binding sites might impair the process of PCR amplification resulting in dropouts of alleles, named as null alleles. In this study, 5 cases from routine paternity testing using PowerPlex®21 System for STR genotyping were considered to harbor null alleles at TH01, FGA, D5S818, D8S1179, and D16S539, respectively. The dropout of alleles was confirmed by using alternative commercial kits AGCU Expressmarker 22 PCR amplification kit and AmpFℓSTR®. Identifiler® Plus Kit, and sequencing results revealed a single base variation at the primer binding site of each STR locus. Results from the collection of previous reports show that null alleles at D5S818 were frequently observed in population detected by two PowerPlex® typing systems and null alleles at D19S433 were mostly observed in Japanese population detected by two AmpFℓSTR™ typing systems. Furthermore, the most popular mutation type appeared the transition from C to T with G to A, which might have a potential relationship with DNA methylation. Altogether, these results can provide helpful information in forensic practice to the elimination of genotyping discrepancy and the development of primer sets.

Mutation analysis of 19 autosomal short tandem repeats in Chinese Han population from Shanghai.

The mutation of short tandem repeat (STR) loci is affected by several factors, such as sex, age, and DNA architectures. Previous studies have shown a different profile of mutation rates at autosomal STR loci among populations. It is important to provide population data and reveal underlying factors influencing the evaluation of STR mutation rates. In this study, we performed a comprehensive analysis on the mutation of 19 autosomal STR loci through 124,773 parent-child allelic transfers from 5846 paternity testing cases. A total of 197 mutations were observed including 187 single-step mutations. The observed mutation rates ranged from 0.15 × 10-3 (TH01) to 4.57 × 10-3 (FGA), and the average mutation rate across all the 19 loci was 1.58 × 10-3. Furthermore, the average mutation rate of STR loci increases with the paternal conception ages and remains relatively stable in different maternal age groups, which suggest the profile of paternal conception ages as a potential factor influencing the evaluation of STR mutation rates and the ratio of paternal versus maternal mutation rate in populations. Multidimensional scaling analysis (MDS) shows a difference in the profile of mutation rates at 13 CODIS STR loci among ethnical groups. Based on our data, our results support that short alleles are biased towards expansion mutation and longer alleles favor contraction mutation. In conclusion, our results provide useful information for further investigation on STR mutation in forensic genetics and population genetics.

Identification and characterization of the highly polymorphic locus D14S739 in the Han Chinese population.

AIM: To systemically select and evaluate short tandem repeats (STRs) on the chromosome 14 and obtain new STR loci as expanded genotyping markers for forensic application. METHODS: STRs on the chromosome 14 were filtered from Tandem Repeats Database and further selected based on their positions on the chromosome, repeat patterns of the core sequences, sequence homology of the flanking regions, and suitability of flanking regions in primer design. The STR locus with the highest heterozygosity and polymorphism information content (PIC) was selected for further analysis of genetic polymorphism, forensic parameters, and the core sequence. RESULTS: Among 26 STR loci selected as candidates, D14S739 had the highest heterozygosity (0.8691) and PIC (0.8432), and showed no deviation from the Hardy-Weinberg equilibrium. 14 alleles were observed, ranging in size from 21 to 34 tetranucleotide units in the core region of (GATA)9-18 (GACA)7-12 GACG (GACA)2 GATA. Paternity testing showed no mutations. CONCLUSION: D14S739 is a highly informative STR locus and could be a suitable genetic marker for forensic applications in the Han Chinese population.

Identification of mammalian species using the short and highly variable regions of mitochondrial DNA.

The mitochondrial DNA (mtDNA) typing is useful for the species determination of degraded samples and the nucleotide diversity of target fragments across species is crucial for the discrimination. In this study, the short and highly polymorphic regions flanked by two conserved termini were sought by the sequence alignment of mtDNA across species and two target regions located at 12S rRNA gene were characterized. Two universal primer sets were developed that appear to be effective for a wide variety of mammalian species, even for domestic birds. The two target regions could be efficiently amplified using their universal primer sets on degraded samples and provide sufficient information for species determination. Therefore, the two short and highly variable target regions might provide a high discriminative capacity and should be suitable for the species determination of degraded samples.

FUS-regulated RNA metabolism and DNA damage repair: Implications for amyotrophic lateral sclerosis and frontotemporal dementia pathogenesis.

Cytoplasmic inclusion of RNA binding protein FUS/TLS in neurons and glial cells is a characteristic pathology of a subgroup of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dysregulation of RNA metabolism caused by FUS cytoplasmic inclusion emerges to be a key event in FUS-associated ALS/FTD pathogenesis. Our recent discovery of a FUS autoregulatory mechanism and its dysregulation in ALS-FUS mutants demonstrated that dysregulated alternative splicing can directly exacerbate the pathological FUS accumulation. We show here that FUS targets RNA for pre-mRNA alternative splicing and for the processing of long intron-containing transcripts, and that these targets are enriched for genes in neurogenesis and gene expression regulation. We also identify that FUS RNA targets are enriched for genes in the DNA damage response pathway. Together, the data support a model in which dysregulated RNA metabolism and DNA damage repair together may render neurons more vulnerable and accelerate neurodegeneration in ALS and FTD.

Deletion mapping of the regions with AMELY from two Chinese males.

The amelogenin (AMEL) is widely used in many multiplex PCR kits for gender determination. However, the null of amelogenin Y (AMELY) can result in the incorrect genotyping of male samples as females. In this study, we report the deletion of AMELY in two cases with a deletion frequency of 0.019% (2/10526) in our laboratory. The deletion region with AMELY was mapped by using other twelve loci, which shows the class I deletion pattern. Further, the Y chromosome short tandem repeat (Y-STR) typing shows that these two cases share the same haplotype with other two cases from previous reports. The haplogroup of the two cases was predicted as O3 haplogroup with a 100% probability. Altogether, this study will provide evidence to further demonstrate the deletion of AMELY in Chinese population.

ALS-associated FUS mutations result in compromised FUS alternative splicing and autoregulation.

The gene encoding a DNA/RNA binding protein FUS/TLS is frequently mutated in amyotrophic lateral sclerosis (ALS). Mutations commonly affect its carboxy-terminal nuclear localization signal, resulting in varying deficiencies of FUS nuclear localization and abnormal cytoplasmic accumulation. Increasing evidence suggests deficiencies in FUS nuclear function may contribute to neuron degeneration. Here we report a novel FUS autoregulatory mechanism and its deficiency in ALS-associated mutants. Using FUS CLIP-seq, we identified significant FUS binding to a highly conserved region of exon 7 and the flanking introns of its own pre-mRNAs. We demonstrated that FUS is a repressor of exon 7 splicing and that the exon 7-skipped splice variant is subject to nonsense-mediated decay (NMD). Overexpression of FUS led to the repression of exon 7 splicing and a reduction of endogenous FUS protein. Conversely, the repression of exon 7 was reduced by knockdown of FUS protein, and moreover, it was rescued by expression of EGFP-FUS. This dynamic regulation of alternative splicing describes a novel mechanism of FUS autoregulation. Given that ALS-associated FUS mutants are deficient in nuclear localization, we examined whether cells expressing these mutants would be deficient in repressing exon 7 splicing. We showed that FUS harbouring R521G, R522G or ΔExon15 mutation (minor, moderate or severe cytoplasmic localization, respectively) directly correlated with respectively increasing deficiencies in both exon 7 repression and autoregulation of its own protein levels. These data suggest that compromised FUS autoregulation can directly exacerbate the pathogenic accumulation of cytoplasmic FUS protein in ALS. We showed that exon 7 skipping can be induced by antisense oligonucleotides targeting its flanking splice sites, indicating the potential to alleviate abnormal cytoplasmic FUS accumulation in ALS. Taken together, FUS autoregulation by alternative splicing provides insight into a molecular mechanism by which FUS-regulated pre-mRNA processing can impact a significant number of targets important to neurodegeneration.

Bisulfite genomic sequencing of DNA from dried blood spot microvolume samples.

DNA methylation is an important event in epigenetic changes in cells, and a fundamental regulator of gene transcription. Bisulfite genomic sequencing is a powerful technique used in studies of DNA methylation. However, the established procedures often require relatively large amounts of DNA. In everyday practice, samples submitted for analysis might contain very small amounts of poor quality material, as is often the case with forensic stain samples. In this study, we assess a modified, more efficient method of bisulfite genomic sequencing. Genomic DNA extracted from 3-mm dried blood spots using QIAamp micro kit was treated with sodium bisulfite (using EpiTect kit). Subsequent methylation-specific PCR (MSP) followed by DNA sequencing displayed the differentially methylated region of imprinted gene SNRPN. Our results show that this new combination of efficient DNA extraction and bisulfite treatment provides high quality conversion of unmethylated cytosine to uracil for bisulfite genomic sequencing analysis. This reliable method substantially improves the DNA methylation analysis of forensic stain samples.

Should chronic hepatitis B mothers breastfeed? a meta analysis.

BACKGROUND: Hepatitis B virus (HBV) exists in the breast milk of chronic hepatitis B (CHB) mothers. The authors use a meta-analytic technique to quantify the evidence of an association between breastfeeding and risk of CHB infection among the infants vaccinated against HBV. METHODS: Literature search is performed up to 2010 on the relationship between infantile CHB infection within one-year follow up after immunization with the third-dose hepatitis B vaccine and breastfeeding. Two reviewers independently extract the data and evaluate the methodological quality. A random-effects model is employed to systematically combine the results of all included studies. RESULTS: Based on data from 32 studies, 4.32% (244/5650) of infants born of CHB mothers develop CHB infection. The difference in risk of the infection between breastfed and formula-fed infants (RD) is -0.8%, (95% confidence interval [CI]: -1.6%, 0.1%). Analysis of the data from 16 of the studies finds that RD for mothers who are positive for the HBeAg and/or the HBV DNA, 0.7% (95%CI: -2.0%, 3.5%), is similar to that for those who are negative for these infectivity markers, -0.5% (95%CI: -1.7%, 0.6%). CONCLUSIONS: Breast milk is infectious; yet, breastfeeding, even by mothers with high infectivity, is not associated with demonstrable risk of infantile CHB infection, provided that the infants have been vaccinated against HBV at birth.