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Introduction: Newborn screening for Duchenne muscular dystrophy can be performed via a first-tier creatine kinase-MM measurement followed by reflex testing to second-tier molecular analysis of the DMD gene. In order to establish appropriate cut-offs for the creatine kinase-MM screen, factors that influence creatine kinase-MM in newborns were investigated., Materials and Methods: Creatine kinase-MM data from a consented pilot study in New York State were collected over a two-year period and combined with de-identified validation data and analyzed. Univariate analysis and multiple linear regression analysis were performed., Results: The analysis indicated that age of newborn at specimen collection, gestational age and birth weight were significant influencers of CK-MM levels in newborns. In addition, to a lesser extent, sex, race/ethnicity and seasonal temperature also affect CK-MM levels in newborns., Conclusions: To reduce false positive and false negative cases, newborn screening programs should be cognizant of factors that influence CK-MM when determining cut-offs for the assay. Variability based on age at specimen collection and birth weight are primarily observed within the first week of life. Therefore, particularly during this time period, multi-tiered cut-offs based on age of collection and lower cut-offs for premature and low birth weight babies are recommended. Other cut-off determinants may include sex, race/ethnicity and seasonal temperature., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Wadsworth Center, New York State Department of Health. Published by Elsevier Inc. All rights reserved.)

Introduction: This study examined hydroxyurea usage in young children with sickle cell anemia within New York State (NYS). The cohort was 273 children with sickle cell anemia born in NYS in 2006-2009 and enrolled essentially continuously in Medicaid for the first 4 years of life., Methods: Medicaid data were used to examine hydroxyurea usage in this group by age at first prescription fill, persistence, region, treatment institution, and year. Log-binomial regression models were used to estimate the likelihood of receiving hydroxyurea treatment. Data from birth through 2014 for all members of the study group were assembled and analyzed in 2015., Results: About 25% of the cohort had at least one filled hydroxyurea prescription by their fifth birthday, and nearly 40% by the end of the study period. The mean proportion of days covered for the first year of therapy was 56.3%. Adherence was also assessed by calculating medication possession ratios for individual treatment periods. Slightly more than one third of treated children showed 80% coverage by these measures. There was a consistent, but not statistically significant, trend toward younger age at first fill. Significant regional and treatment center differences in initiation of hydroxyurea use, but not in persistence after initiation, were noted among NYS centers., Conclusions: Subsequent to clinical studies demonstrating safety, current NYS-wide use of hydroxyurea in young children with sickle cell anemia appears to be widespread and increasing. However, practice differences between treatment centers and inadequate adherence may limit the full disease-modifying effects of hydroxyurea., (Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Because of lack of worldwide standardization of influenza virus surveillance, comparison between countries of impact of a pandemic is challenging. For that, other approaches to allow internationally comparative serosurveys are welcome., Objectives: Here we explore the use of neonatal screening dried blood spots to monitor the trends of the 2009 influenza A (H1N1) pdm virus by the use of a protein microarray., Study Design: We contacted colleagues from neonatal screening laboratories and asked for their willingness to participate in a study by testing anonymized neonatal screening bloodspots collected during the course of the pandemic. In total, 7749 dried blood spots from 13 countries in 5 continents where analyzed by using a protein microarray containing HA1 recombinant proteins derived from pandemic influenza A (H1N1) 2009 as well as seasonal influenza viruses., Results: Results confirm the early start of the pandemic with extensive circulation in the US and Canada, when circulation of the new virus was limited in other parts of the world. The data collected from sites in Mexico suggested limited circulation of the virus during the early pandemic phase in this country. In contrast and to our surprise, an increase in seroprevalence early in 2009 was noted in the dataset from Argentina, suggestive of much more widespread circulation of the novel virus in this country than in Mexico., Conclusions: We conclude that this uniform serological testing of samples from a highly standardized screening system offers an interesting opportunity for monitoring population level attack rates of widespread diseases outbreaks and pandemics., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, contributes to carcinogenesis through its role in the regulation of cytochrome P450 1 (CYP1)-catalyzed metabolism of carcinogens. Here, we investigated genetic and epigenetic mechanisms that affect AhR expression. Analyses of the human AHR proximal promoter in MCF-7 human breast cancer cells using luciferase assays and electrophoretic mobility shift assays revealed multiple specificity protein (Sp) 1 binding sequences that are transcriptional activators in vitro. The regulation of AhR expression was evaluated in long-term estrogen exposed (LTEE) MCF-7 cells, which showed increased AhR expression, enhanced CYP1 inducibility, and increased capacity to form DNA adducts when exposed to the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. The increased AhR expression in LTEE cells was found not to result from increased mRNA stability, differential RNA processing, or decreased DNA methylation. Analysis of the AHR proximal promoter region using chromatin immunoprecipitation confirmed that enhanced expression of AhR in LTEE cells involves changes in histone modifications, notably decreased trimethylation of histone 3, lysine 27. Upon further examination of the GC-rich Sp1-binding region, we confirmed that it contains a polymorphic (GGGGC)(n) repeat. In a population of newborns from New York State, the allele frequency of (GGGGC)(n) was n = 4 > 5 ≫ 6, 2. Circular dichroism spectroscopy revealed the ability of sequences of this GC-rich region to form guanine-quadruplex structures in vitro. These studies revealed multiple levels at which AhR expression may be controlled, and offer additional insights into mechanisms regulating AhR expression that can ultimately impact carcinogenesis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: We aimed to prepare dried-blood spot (DBS) quality control (QC) materials for lysosomal storage disease (LSD) screening tests and to determine optimum blood and DBS storage conditions., Methods: We compared enzyme activities of five LSD markers in adult blood, umbilical-cord blood, and leukocyte-reduced blood. We measured activities in liquid blood and DBSs after predetermined intervals at controlled temperatures and humidities., Results: Lysosomal-enzyme activity levels in umbilical-cord blood mimicked those in newborn screening samples. Lysosomal-enzyme activities in leukocyte-reduced blood were lower than in LSD-positive patient samples. Enzyme activities were stable in refrigerated liquid blood for 32 days and in frozen DBSs stored at low humidity for a year. Activity losses from DBSs after 34 days at 37±1°C were 35%-66% in low humidity and 61%-100% in high humidity., Conclusions: Umbilical-cord blood is the preferred matrix for LSD-normal DBS QC materials. Leukocyte-reduced blood is lysosomal enzyme-deficient. Failure to control humidity during DBS storage results in loss of lysosomal-enzyme activities., (Published by Elsevier Inc.)

Objective: The aim of this study was to develop a newborn screening algorithm for Krabbe disease., Design and Methods: We measured the galactocerebrosidase activity of 139,074 anonymous newborns, 56 known carriers, and 16 Krabbe patients using a tandem mass spectrometry method. The activities were converted to percentages of daily mean activity (%DMA), and the results from diseased and normal populations were used to establish cutoffs., Results: The absolute activities for the newborns ranged from 0.17 to 355 micromol/L h (N=139,074) and activities for Krabbe-positive controls ranged from 0.08 to 0.48 micromol/L h (N=16, n=91 measurements) while activities for carriers ranged from 0.28 to 2.71 micromol/L h (N=56, n=72 measurements). Cutoffs were set based on results from Krabbe-positive and carrier controls and the newborn population distribution., Conclusions: The algorithm and cutoffs we propose provided 100% detection of all positive controls with 60/100,000 screen positive results predicted. In the course of this study, one anonymous newborn was predicted to have Krabbe disease based on enzyme activity and subsequent DNA analysis.