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The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Individual symptoms and signs of infectious mononucleosis (IM) are of limited value for diagnosis., Objective: To develop and validate risk scores based on signs and symptoms with and without haematologic parameters for the diagnosis of IM., Design and Setting: Data were extracted from electronic health records of a university health centre and were divided into derivation (9/1/2015-10/31/2017) and a prospective temporal internal validation (11/1/2017-1/31/2019) cohort., Method: Independent predictors for the diagnosis of IM were identified in univariate analysis using the derivation cohort. Logistic regression models were used to develop 2 risk scores: 1 with only symptoms and signs (IM-NoLab) and 1 adding haematologic parameters (IM-Lab). Point scores were created based on the regression coefficients, and patients were grouped into risk groups. Primary outcomes were area under the receiver operating characteristic curve (AUROCC) and classification accuracy., Results: The IM-NoLab model had 4 predictors and identified a low-risk group (7.9% with IM) and a high-risk group (22.2%) in the validation cohort. The AUROCC was 0.75 in the derivation cohort and 0.69 in the validation cohort. The IM-Lab model had 3 predictors and identified a low-risk group (3.6%), a moderate-risk group (12.5%), and a high-risk group (87.6%). The AUROCC was 0.97 in the derivation cohort and 0.93 in the validation cohort., Conclusion: We derived and internally validated the IM-NoLab and IM-Lab risk scores. The IM-Lab score in particular had very good discrimination and have the potential to reduce the need for diagnostic testing for IM., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Preterm birth is defined by the onset of labor at a gestational age shorter than 37 weeks, and it can lead to premature birth and impose a threat to newborns' health. The Puerto Rico PROTECT cohort is a well-characterized prospective birth cohort that was designed to investigate environmental and social contributors to preterm birth in Puerto Rico, where preterm birth rates have been elevated in recent decades. To elucidate possible relationships between metabolites and preterm birth in this cohort, we conducted a nested case-control study to conduct untargeted metabolomic characterization of maternal plasma of 31 women who experienced preterm birth and 69 controls who underwent full-term labor at 24-28 gestational weeks., Results: A total of 333 metabolites were identified and annotated with liquid chromatography/mass spectrometry. Subsequent weighted gene correlation network analysis shows that the fatty acid and carene-enriched module has a significant positive association (P = 8e-04, FDR = 0.006) with preterm birth. After controlling for potential clinical confounders, a total of 38 metabolites demonstrated significant changes uniquely associated with preterm birth, where 17 of them were preterm biomarkers. Among 7 machine-learning classifiers, the application of random forest achieved a highly accurate and specific prediction (AUC = 0.92) for preterm birth in testing data, demonstrating their strong potential as biomarkers for preterm births. The 17 preterm biomarkers are involved in cell signaling, lipid metabolism, and lipid peroxidation functions. Additional modeling using only the 19 spontaneous preterm births (sPTB) and controls identifies 16 sPTB markers, with an AUC of 0.89 in testing data. Half of the sPTB overlap with those markers for preterm births. Further causality analysis infers that suberic acid upregulates several fatty acids to promote preterm birth., Conclusions: Altogether, this study demonstrates the involvement of lipids, particularly fatty acids, in the pathogenesis of preterm birth., (© The Author(s) 2022. Published by Oxford University Press GigaScience.)

Background: Invasive fungal infections in the United States are chronically underdiagnosed and a lack of coordinated surveillance makes the true burden of disease difficult to determine. The purpose of this analysis was to capture mortality-associated burden of risk conditions and fungal infections., Methods: We analyzed data from the National Vital Statistics System from 1999 through 2018 to estimate the mortality attributed to risk conditions and related fungal disease., Results: The number of risk conditions associated with fungal disease is steadily rising in the United States, with 1 047 422 diagnoses at time of death in 2018. While fungal disease decreased substantially from 1999 to 2010, primarily due to the control of human immunodeficiency virus (HIV) infection, the number of deaths with fungal diagnosis has increased in the non-HIV cohort, with significant increases in patients with diabetes, cancer, immunosuppressive disorders, or sepsis., Conclusions: The landscape of individuals at risk for serious fungal diseases is changing, with a continued decline in HIV-associated incidence but increased diagnoses in patients with cancer, sepsis, immunosuppressive disorders, and influenza. Additionally, there is an overall increase in the number of fungal infections in recent years, indicating a failure to control fungal disease mortality in these new immunocompromised cohorts. Improvement in the prevention and management of fungal diseases is needed to control morbidity and mortality in the rising number of immunocompromised and at-risk patients in the United States., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Pregnancy-associated malaria (PAM) has been associated with adverse pregnancy outcomes like preterm birth (PTB) and low birthweight (LBW), which are among the leading causes of infant mortality globally. Rates of PTB and LBW are high in countries with a high burden of malaria. PAM may be a contributing factor to PTB and LBW, but is not well understood., Methods: We conducted a systematic review and meta-analysis of studies examining the relationship between PAM and PTB or LBW using PubMed. The title and abstract of all studies were screened by two reviewers, and the full text of selected studies was reviewed to ensure they met inclusion criteria. Information regarding study characteristics and of PTB and LBW births among women with and without PAM was abstracted for included studies., Results: Our search terms yielded 2237 articles, of which 18 met our final inclusion criteria. Eight studies examined associations between PAM and PTB, and 10 examined associations between PAM and LBW (population size ranging from 35 to 9956 women). The overall risk of LBW was 63% higher among women with PAM compared with women without PAM (95% CI = 1.48-1.80) and the risk of PTB was 23% higher among women with PAM compared with women without PAM (95% CI = 1.07-1.41)., Conclusions: These results indicate that infection with PAM is associated with PTB and LBW. Further understanding of the pathogenesis of disease and the immunologic changes that occur during pregnancy is essential for reducing the disproportional effects this disease has on this vulnerable population., (© The Author(s) [2019]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The goal of eliminating indigenous rubella and congenital rubella syndrome (CRS) in the United States in the near future is now within reach, because rubella incidence has been sustained at record-low levels since the mid-1990s. Effective prevention strategies to eliminate CRS and rubella require improvement in the surveillance of CRS and congenital rubella infection (CRI). The purpose of the workshop was to review rubella and CRS epidemiology, as well as current clinical, diagnostic, and laboratory practices, to determine whether new strategies are needed to achieve and document CRS elimination. Workshop participants agreed that surveillance for CRS must be strengthened, particularly through augmented laboratory capabilities, and the case definition for CRS must be revised to reflect the current scientific information available. Further studies of methods are needed to identify high-risk populations and geographic areas for rubella and CRS and to enhance identification of infants with CRS.

This population-based case-control study was designed to investigate risk indicators for the occurrence of the birth defect craniosynostosis in Colorado. A total of 173 children who underwent craniectomy for craniosynostosis and 759 children without craniosynostosis were included in the study. Multivariable logistic regression analysis of birth certificate data showed that male sex (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.1-2.2), maternal five-year age "increase" (OR = 1.3, 95% CI = 1.1-1.5), plural birth (OR = 3.0, 95% CI = 1.2-7.1) and black maternal race (OR = 0.0, 95 per cent CI = 0.0-0.6) were independently associated with craniosynostosis. There was a weak positive association between craniosynostosis and the altitude of the town closest to the maternal residence, but no association was found with maternal education, marital status, number of previous births, or previous pregnancy termination. The association of craniosynostosis with plural birth is consistent with the hypothesis of fetal head constraint.