Applying trace element geochemistry of archaeological bone to study the coevolution of environmental change and human health in the Roman Empire.

Technological change has affected human health dating back to at least the Neolithic agricultural revolution. Growing evidence indicates widespread environmental pollution began with metallurgical practices and continues today. Environmental exposures to trace elements released from these practices have the potential to alter human body composition, such as bone mineral chemistry, especially for elements that are not homeostatically regulated.

Breastfeeding, growth, and lung disease in the first 3 years of life in children with cystic fibrosis.

Background: The 2009 cystic fibrosis (CF) infant care guidelines recommend breastmilk as the initial feeding but do not address if/when it should be fortified or supplemented with formula to promote optimal growth and pulmonary health.

Methods: We conducted a prospective multi-center cohort study in breastfed and formula-fed infants that included 172 infants with CF who were born during 2012-17, enrolled after newborn screening at age 1.9 ± 1.

Update on advances in cystic fibrosis towards a cure and implications for primary care clinicians.

During the past quarter century, the diagnosis and treatment of cystic fibrosis (CF) have been transformed by molecular sciences that initiated a new era with discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The knowledge gained from that breakthrough has had dramatic clinical impact. Although once a diagnostic dilemma with long delays, preventable deaths, and irreversible pathology, CF can now be routinely diagnosed shortly after birth through newborn screening programs.

Vitamin D status and variable responses to supplements depend in part on genetic factors in adults with cystic fibrosis.

Vitamin D sufficiency has been difficult to achieve consistently in patients with cystic fibrosis (CF), even with robust oral supplements. To assess vitamin D status and resistance to supplementation, we studied 80 adults using 25-hydroxyvitamin D (25OHD) determinations and whole genome sequencing to construct polygenic risk scores (PRS) that aggregate variants associated with vitamin D status. The results revealed that 30 % of patients were below the threshold of 30 ng/mL and thus should be regarded as insufficient despite normal vitamin E status, a reflection of adherence to fat soluble vitamin supplementation.

Why cystic fibrosis newborn screening programs have failed to meet original expectations… thus far.

This Commentary summarizes what the author has learned in 46 years of research on newborn screening (NBS) for cystic fibrosis (CF) combined with healthcare and public health practice. The original expectation was that screening for this relatively common, life-threatening genetic disorder would lead to consistently timely diagnoses in the neonatal period and be equitable. Unfortunately, this ambitious goal has not been achieved in the USA despite the availability of an excellent, although imperfect, 2-tiered screening test employing immunoreactive trypsinogen (IRT) and DNA analysis for pathogenic variants in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR).

Impact of intrinsic and extrinsic risk factors on early-onset lung disease in cystic fibrosis.

Background: Although respiratory pathology is known to develop in young children with cystic fibrosis (CF), the determinants of early-onset lung disease have not been elucidated.

Objective: We aimed to determine the impact of potential intrinsic and extrinsic risk factors during the first 3 years of life, testing the hypothesis that both contribute significantly to early-onset CF lung disease.

Design: We studied 104 infants born during 2012-2017, diagnosed through newborn screening by age 3 months, and evaluated comprehensively to 36 months of age.

Late Diagnosis in the Era of Universal Newborn Screening Negatively Affects Short- and Long-Term Growth and Health Outcomes in Infants with Cystic Fibrosis.

Newborn screening for cystic fibrosis was fully implemented in the US by 2010, but delays in timeliness of evaluation for infants with positive newborn screening tests persist. Through evaluation of national patient registry data, we determined that late initiation of cystic fibrosis care is associated with poorer long-term nutritional outcomes.

Variation in cystic fibrosis newborn screening algorithms in the United States.

Rationale: Cystic fibrosis (CF) newborn screening (NBS) algorithms in the United States vary by state. Differences in CF NBS algorithms could potentially affect the detection rate of CF newborns and lead to disparities in CF diagnosis amongst different racial and ethnic groups.

Objectives: Generate a database of CF NBS algorithms in the United States and identify processes that may potentially lead to missed diagnoses or lead to healthcare disparities.

Refinement of newborn screening for cystic fibrosis with next generation sequencing.

Background: Newborn screening for cystic fibrosis (CF) has been underway universally in the United States for more than a decade, as well in most European countries, and algorithms have been evolving throughout this period with quality improvement projects as immunoreactive trypsinogen (IRT) determinations alone have been transformed to a 2-tier strategy with DNA analyses.

Objective: To apply next generation sequencing (NGS) as a screening method to expand the DNA tier and identify substantially more variants in the CF transmembrane conductance regulator (CFTR) gene to enhance sensitivity and equity while minimizing incidental findings.

Design: Sequential evaluation and improvement plan in three phases using algorithm modifications coupled to statewide follow up and analysis of screening outcomes.

Parental Preferences about Policy Options Regarding Disclosure of Incidental Genetic Findings in Newborn Screening: Using Videos and the Internet to Educate and Obtain Input.

Our objective was to develop and test a new approach to obtaining parental policy guidance about disclosure of incidental findings of newborn screening for cystic fibrosis (CF), including heterozygote carrier status and the conditions known as CFTR-related metabolic syndrome (CRMS) and/or cystic fibrosis screen positive inconclusive diagnosis, CFSPID. The participants were parents of infants up to 6 months old recruited from maternity hospitals/clinics, parent education classes and stores selling baby products. Data were collected using an anonymous, one-time Internet-based survey.

Detection of disease-causing CFTR variants in state newborn screening programs.

Background: Newborn screening (NBS) algorithms for cystic fibrosis (CF) vary in the United State of America and include different cystic fibrosis transmembrane conductance regulator (CFTR) variants. CFTR variant distribution varies among racial and ethnic groups.

Objective: Our objectives were to identify differences in detection rate by race and ethnicity for CFTR variant panels, identify each US state detection rate for CFTR variant panels, and describe the rate of false-negative NBS and delayed diagnoses by race and ethnicity.

Genetic factors help explain the variable responses of young children with cystic fibrosis to vitamin D supplements.

Background & Aims: Children with cystic fibrosis (CF) are susceptible to fat-soluble vitamin deficiencies unless supplemented, but even large doses of vitamin D may not prevent low 25-hydroxyvitamin D (25OHD) concentrations. The explanation for these vitamin D non-responders has been elusive. We utilized data from whole genome sequencing (WGS) to test the hypothesis that genetic variations predict responsiveness to vitamin D supplementation in a prospective cohort study of children with CF in the first 3 years of life.

Newborn Screening for Cystic Fibrosis: A Qualitative Study of Successes and Challenges from Universal Screening in the United States.

Cystic fibrosis (CF) newborn screening (NBS) was universally adopted in 2009 in the United States. Variations in NBS practices between states may impact the timing of diagnosis and intervention. Quantitative metrics can provide insight into NBS programs (NBSP), but the nuances cannot be elucidated without additional feedback from programs.

Disparities in first evaluation of infants with cystic fibrosis since implementation of newborn screening.

Objective: We evaluated whether implementation of cystic fibrosis (CF) newborn screening (NBS) leads to equitable timeliness of initial evaluation. We compared age at first event (AFE, age at sweat test, encounter and/or care episode) between infants categorized as Black/African American, American Indian/ Native Alaskan, Asian, and/or Hispanic and/or other (Group 1) to White and not Hispanic infants (Group 2).

Methods: This retrospective cohort study from the Cystic Fibrosis Foundation Patient Registry (CFFPR) included infants born 2010-2018.

Defining and identifying early-onset lung disease in cystic fibrosis with cumulative clinical characteristics.

Background: Because of the heterogeneity in cystic fibrosis (CF) lung disease among young children, a clinical method to identify early-onset lung disease is needed.

Objective: To develop a CF early-onset lung disease (CFELD) scoring system by utilizing prospectively collected longitudinal data on manifestations in the first 3 years of life.

Design: We studied 145 infants born during 2012-2017, diagnosed through newborn screening by age 3 months, and followed to 36 months of age.

Vitamins A, D, E status as related to supplementation and lung disease markers in young children with cystic fibrosis.

Background: The variable response to fat-soluble vitamin supplementation in young children with cystic fibrosis (CF), and factors contributing to this variability, remain under-investigated.

Objective: To determine if recommended supplement doses normalize serum vitamins A (retinol), D (25-hydroxy-vitamin D, 25OHD), and E (α-tocopherol), and identify factors predictive of achieving sufficiency, in children with CF in the first 3 years of life.

Design: We studied 144 infants born during 2012-2017 and diagnosed with CF through newborn screening.

Challenging the dogma of the healthy heterozygote: Implications for newborn screening policies and practices.

Heterozygous (carrier) status for an autosomal recessive condition is traditionally considered to lack significance for an individual's health, but this assumption has been challenged by a growing body of evidence. Carriers of several autosomal recessive disorders and some X-linked diseases are potentially at risk for the pathology manifest in homozygotes. This minireview provides an overview of the literature regarding health risks to carriers of two common autosomal recessive conditions on the Recommended Uniform Screening Panel: sickle cell disease [sickle cell trait (SCT)] and cystic fibrosis (CF).

Outcomes of infants born during the first 9 years of CF newborn screening in the United States: A retrospective Cystic Fibrosis Foundation Patient Registry cohort study.

Introduction: Newborn screening (NBS) for cystic fibrosis (CF) was implemented in all US states and DC by 2010. This hypothesis-generating study was designed to form the basis of additional analyses and to plan quality improvement initiatives. The aims were to describe the outcomes of infants with CF born during the first 9 years of universal NBS.

Newborn Screening for CF across the Globe-?

Newborn screening (NBS) for cystic fibrosis (CF) has been performed in many countries for as long as four decades and has transformed the routine method for diagnosing this genetic disease and improved the quality and quantity of life for people with this potentially fatal disorder. Each region has typically undertaken CF NBS after analysis of the advantages, costs, and challenges, particularly regarding the relationship of benefits to risks. The very fact that all regions that began screening for CF have continued their programs implies that public health and clinical leaders consider early diagnosis through screening to be Currently, many regions where CF NBS has not yet been introduced are considering options and in some situations negotiating with healthcare authorities as policy and economic factors are being debated.

Vulnerable Child Syndrome and Newborn Screening Carrier Results for Cystic Fibrosis or Sickle Cell.

Objectives: To measure parental perceptions of child vulnerability, as a precursor to developing a population-scale mechanism to mitigate harm after newborn screening.

Study Design: Participants were parents of infants aged 2-5 months. Parental perceptions of child vulnerability were assessed with an adapted version of the Vulnerable Baby Scale.