Pediatric Research最新文献

Background: Limited data exist on population-level mortality outcomes related to extreme neonatal hyperbilirubinemia (EHB) and this study examines trends in annual infant mortality rate (IMR) attributed to hemolytic and perinatal jaundice among Germany, France, Italy, Portugal, Greece and Spain from 1990 to 2019.

Methods: Data on annual incident cases and disability-adjusted life years were collected from the 2019 Global Burden of Disease study. Live birth cohort data were sourced from UN World Population Prospects. We quantified temporal trends, with relative percent changes. Average annual percent changes (AAPCs) were evaluated using the Joinpoint Regression Program.

Results: EHB-related infant mortality decreased from 21.4 (95%CI: 16.1, 27.1) in 1990 to 4.2 (95%CI: 1.9, 7.6) per million live births in 2019. Germany demonstrated lowest AAPC of -3.2% (95% CI: -3.8, -2.5), while Portugal had the highest AAPC of -8.6% (95% CI -11.9, -5.1) in reducing infant mortality due to EHB. There were distinct divergences in the trajectories of declining EHB mortality among the studied countries.

Conclusion: This study highlights a significant decline in infant mortality due to extreme hyperbilirubinemia, emphasizing the need for national surveillance and tailored guidelines to prevent bilirubin induced neurological damage.

Impact: This cross-sectional analysis revealed a marked decline in infant mortality rates attributed to extreme hyperbilirubinemia across the selected European countries. The rates of decline varied significantly between countries, demonstrating notable heterogeneity in mortality trends when stratified by age at death. Implementing data-driven surveillance systems can optimize the alignment of equitable healthcare services, strengthen accountability measures, and identify critical operational inefficiencies. In the European Union, country-specific hyperbilirubinemia guidelines should be reinforced to ensure effective screening and post-discharge follow-up protocols that are tailored to risk burden and available healthcare resources.

Neonatal G6PD deficiency (G6PDd) prevalence explains its recent recognition as a major contributory cause of extreme hyperbilirubinemia (EHB). Disparate global EHB burden reveals comparative racial prevalence of leading conditions, Rh negativity and G6PDd: 15-17% vs. < 5% in Caucasians, 4 to 8% vs. up to 17% in Blacks and 0.1 to 4% vs. 5-8% in Asians, respectively. G6PDd also burdens malaria endemic countries planning malarial elimination. Binary expression of male G6PDd is reliably diagnostic but is complex and uncertain for heterozygous females. Unlike the RhD disease and its prevention, the medical and hematological life burdens of female G6PDd and heterozygosity have been vastly understudied. Three silent global health crises intersect: EHB, Malaria, and women's health. Regardless of race, sex, or geography, clinical practice needs optimization with dual (phenotypic and genotypic) screening to allow women plan and anticipate safe pregnancies, birthing, breastfeeding and enjoy their newborns' healthy childhood in a society freed of malaria.

Background: Tetralogy of Fallot (TOF) is a common congenital heart disease (CHD) but the impact of the variants of the HAND1 gene promoter region has not been explored.

Methods: DNA from blood samples of 612 subjects (300 sporadic TOF patients and 312 healthy controls) was sequenced to identify variants in the HAND1 gene promoter region that were further tested by cellular function experiments including dual-luciferase reporter gene assays, electrophoretic mobility shift analysis (EMSA), and bioinformatics analysis using JASPAR, a transcription factor binding site database.

Results: Eight variants in HAND1 gene promoter region were identified with 3 only found in TOF patients including one novel g.3639 G > T. All 3 variants significantly reduced the transcriptional activity of HAND1 gene promoter in an in vitro reporter assay (p < 0.05). JASPAR analysis indicated that these variants may alter the binding sites of transcription factors, potentially associated with TOF formation.

Conclusions: In the promoter region of HAND1gene of TOF patients, 3 variants were found only in the patients including one found for the first time. These variants decreased transcription factor activity. Therefore, the present study implies the role of HAND1 gene in the pathogenesis of TOF and further provides new insights into the genetic basis of TOF formation.

Impact: Sequencing of DNA from 612 human subjects (300 TOF patients and 312 healthy controls) identified 8 variants in the promoter region of HAND1 gene with 3 found only in TOF including 1 newly identified. Reduced transcriptional activity at these 3 variants was confirmed by dual-luciferase reporter gene assay and EMSA assay. Predictions from the JASPAR database suggest altered binding sites of transcription factors by the variants. We for the first time demonstrate variants in the HAND1 promoter and that cause cellular dysfunction. The variants identified may have a pathological role in the formation of TOF.

Background: This study aimed to identify large duplications (>5 Mb) that are harmless through long-term clinical follow-ups of fetuses and phenotype analyses of carrier family members.

Methods: We retrospectively analyzed fetuses undergoing prenatal diagnosis and who had >5 Mb chromosomal duplications. Routine karyotyping and single-nucleotide polymorphism array analysis were performed to identify the source and location information of the duplicated segments. Genotype-phenotype analyses were conducted based on genetic information and phenotypes during postnatal follow-up.

Results: Eight eligible cases were included. All fetuses carried maternal or paternal duplications ranging in length from 5.3 to 12.2 Mb. The locations were as follows: 2q32.3q33.1 (Chr2:192322509-199548704), 4q22.1 (Chr4: 88347368-93602855), 4q34.2q35.2 (Chr4:176956406-189189971), 4q34.3q35.2 (Chr4:180613345-189353740), 5p14.3p14.1 (Chr5:19093749-28557664), 10q22.2q23.2 (Chr10:77448435-88786593), 12q21.31q21.32 (Chr12:81983257-87322734), and 13q14.11q14.2 (Chr13: 40825382-47633710). Karyotyping revealed that these duplications occurred within their respective chromosomal regions, except in pedigrees 6 and 7. In the eight pedigrees, the coordinates and lengths of duplicated segments in family members were matched with those in fetuses. Neither the fetuses nor other carriers were clinically symptomatic.

Conclusion: Our findings revealed that the eight pedigrees carrying duplications >5 Mb were asymptomatic, providing new data to inform genetic counseling for the observed segments.

Impact: We focused on unrelated fetuses among eight pedigrees who carried duplications of different chromosomal segments. These duplications had been stably transmitted through 2 or 3 generations of normal individuals. Importantly, phenotypic abnormalities were lacking, which was unexpected given that the maximum segment size was approximately 12.2 Mb. We found that duplications in these regions were benign in the context of prenatal genetic counseling. These results provide a foundation for addressing genotype-phenotype correlations. To our knowledge, this is the first description of normal phenotypes in individuals with duplications in these regions.

Backgrounds: Pediatric patients with congenital heart disease (CHD) often require surgical repair using cardiopulmonary bypass. Despite advancements, mortality and complication rates remain significant.

Methods & results: We prospectively examined 101 patients undergoing congenital cardiac surgery, identifying a mortality rate of 4.0% and a complication rate of 31.6%. Neonates and infants exhibited multiple complications more frequently. Prolonged bypass time was significantly associated with complications, with each additional 30 min increasing the odds by 1.46 times (95% CI 1.01-2.10, p = 0.042). We further investigated the involvement of damage-associated molecular pattern (DAMP) molecules by proteomics and ELISA. Plasma levels of DAMPs, including histones and high mobility group box 1 (HMGB1), were significantly elevated in the complication group. As these molecules target Toll-like receptor (TLR)2 and TLR4, mRNA expression of TLR2 and TLR4 in neutrophils was upregulated in the complication group. In vitro and in vivo analyses demonstrated that histones and HMGB1 induced the formation of neutrophil extracellular traps (NETs). This finding aligned with greater NETs formation observed at the end of CPB and during the postoperative period in neonates and infants who developed postoperative complications.

Conclusion: Targeting NETs and associated DAMPs may provide a novel therapeutic approach to mitigate complications in this patient population.