Association between admission temperature and mortality and major morbidity in preterm infants born at fewer than 33weeks\u27 gestation

Importance: Neonatal hypothermia has been associated with higher mortality and morbidity; therefore, thermal control following delivery is an essential part of neonatal care. Identifying the ideal body temperature in preterm neonates in the first few hours of lifemay be helpful to reduce the risk for adverse outcomes. Objectives: To examine the association between admission temperature and neonatal outcomes and estimate the admission temperature associated with lowest rates of adverse outcomes in preterm infants born at fewer than 33 weeks\u27 gestation.. Design, Setting, And Participants: Retrospective observational study at 29 neonatal intensive care units in the Canadian Neonatal Network. Participants included 9833 inborn infants born at fewer than 33 weeks\u27 gestation who were admitted between January 1, 2010, and December 31, 2012.. Exposure: Axillary or rectal body temperature recorded at admission.. Main Outcomes And Measures: The primary outcomewas a composite adverse outcome defined as mortality or any of the following: severe neurological injury, severe retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infection. The relationships between admission temperature and the composite outcome as well as between admission temperature and the components of the composite outcome were evaluated using multivariable analyses.. Results: Admission temperatures of the 9833 neonates were distributed as follows: lower than 34.5°C (1%); 34.5°C to 34.9°C (1%); 35.0°C to 35.4°C (3%); 35.5°C to 35.9°C (7%); 36.0°C to 36.4°C (24%); 36.5°C to 36.9°C (38%); 37.0°C to 37.4°C (19%); 37.5°C to 37.9°C (5%); and 38.0°C or higher (2%). After adjustment for maternal and infant characteristics, the rates of the composite outcome, severe neurological injury, severe retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, and nosocomial infection had a U-shaped relationship with admission temperature (a \u3e 0 [P \u3c .05]). The admission temperature at which the rate of the composite outcome was lowest was 36.8°C (95%CI, 36.7°C-37.0°C). Rates of severe neurological injury, severe retinopathy of prematurity, necrotizing enterocolitis (95%CI, 36.3°C-36.7°C), bronchopulmonary dysplasia, and nosocomial infection (95%CI, 36.9°C-37.3°C) were lowest at admission temperatures ranging from 36.5°C to 37.2°C.. Conclusions And Relevance: The relationship between admission temperature and adverse neonatal outcomes was U-shaped. The lowest rates of adverse outcomes were associated with admission temperatures between 36.5°C and 37.2°C.

Secular trends in age at menarche among women born between 1955 and 1985 in Southeastern China

Abstract Background Improvements in socioeconomic conditions and population health have been linked to declining age at menarche. In China, secular trends in age at menarche following extensive economic reform during recent decades have not been thoroughly investigated. This study examined the overall trend in age at menarche and assessed differences in the rate of change of age at menarche over time, and between urban and rural populations and education levels in southeastern China. Methods Age at menarche was retrospectively collected from 1,167,119 Han Chinese women born 1955–1985, who registered in the Perinatal Health Care Surveillance System in 19 cities and counties in two southeast provinces during 1993–2005. Multivariable linear regression was used to estimate trends in age at menarche overall and stratified by urban/rural residence and education level. Results Age at menarche declined by 0.33 [95% CI 0.33, 0.32] years/decade overall, with the fastest decline in women born in 1966–1975. For the earliest birth cohorts (1955–1965), age at menarche declined faster in urban versus rural regions, and for women with high school education or above versus primary school or less. In contrast, age at menarche declined slower among urban women born 1976–1985, and among those with higher education born 1966–1985. Conclusions Mean age at menarche declined for women born in 1955–1985 in southeast China. Further study is warranted to identify specific factors contributing to earlier age at menarche and associated health outcomes

Possible Catch-Up Developmental Trajectories for Children with Mild Developmental Delay Caused by <i>NAA15</i> Pathogenic Variants

Variants in NAA15 are closely related to neurodevelopmental disorders (NDDs). In this study, we investigated the spectrum and clinical features of NAA15 variants in a Chinese NDD cohort of 769 children. Four novel NAA15 pathogenic variants were detected by whole-exome sequencing, including three de novo variants and one maternal variant. The in vitro minigene splicing assay confirmed one noncanonical splicing variant (c.1410+5G>C), which resulted in abnormal mRNA splicing. All affected children presented mild developmental delay, and catch-up trajectories were noted in three patients based on their developmental scores at different ages. Meanwhile, the literature review also showed that half of the reported patients with NAA15 variants presented mild/moderate developmental delay or intellectual disability, and possible catch-up sign was indicated for three affected patients. Taken together, our study expanded the spectrum of NAA15 variants in NDD patients. The affected patients presented mild developmental delay, and possible catch-up developmental trajectories were suggested. Studying the natural neurodevelopmental trajectories of NDD patients with pathogenic variants and their benefits from physical rehabilitations are needed in the future for precise genetic counseling and clinical management

Single Point Mutation from E22-to-K in Aβ Initiates Early-Onset Alzheimer’s Disease by Binding with Catalase

Amyloid-beta (Aβ) is a critical etiological factor for late-onset familial Alzheimer’s disease (AD). However, an early-onset AD has been found to be related with an Aβ mutation in glutamic acid 22-to-lysine (Italian type E22K). Why only one single point mutation at E22 residue induces AD remains unclear. Here, we report that a Chinese familial AD pedigree with E22K mutation was associated with higher levels of serum hydrogen peroxide (H2O2) and lower activity of catalase (a H2O2 degrading enzyme) than controls. Further, we found that E22K binding with catalase caused more severe H2O2 accumulation in the brains of E22K-injected rats than Aβ-injected rats. Unexpectedly, H2O2 bound with the mutation site 22K residue of E22K and elicited more rapid aggregation of E22K than Aβ in vitro. Moreover, H2O2 acted with E22K synergistically to induce higher cellular toxicity than with Aβ. Notably, intrahippocampal infusion of E22K led to more severe plaque deposition, neuron death, and more rapid memory decline than Aβ-injected rats. However, L-cysteine, a H2O2 scavenger, not only prevented self-aggregation of E22K but also reduced H2O2-promoted E22K assembly in vitro; subsequently, it alleviated Alzheimer-related phenotypes. Hence, E22K binding with catalase promotes the early onset of familial AD, and L-cys may reverse this disease