Real world external validation of metabolic gestational age assessment in Kenya.

Using data from Ontario Canada, we previously developed machine learning-based algorithms incorporating newborn screening metabolites to estimate gestational age (GA). The objective of this study was to evaluate the use of these algorithms in a population of infants born in Siaya county, Kenya. Cord and heel prick samples were collected from newborns in Kenya and metabolic analysis was carried out by Newborn Screening Ontario in Ottawa, Canada.

Development and external validation of machine learning algorithms for postnatal gestational age estimation using clinical data and metabolomic markers.

Background: Accurate estimates of gestational age (GA) at birth are important for preterm birth surveillance but can be challenging to obtain in low income countries. Our objective was to develop machine learning models to accurately estimate GA shortly after birth using clinical and metabolomic data.

Methods: We derived three GA estimation models using ELASTIC NET multivariable linear regression using metabolomic markers from heel-prick blood samples and clinical data from a retrospective cohort of newborns from Ontario, Canada.

Families' healthcare experiences for children with inherited metabolic diseases: protocol for a mixed methods cohort study.

Introduction: Children with inherited metabolic diseases (IMDs) often have complex and intensive healthcare needs and their families face challenges in receiving high-quality, family centred health services. Improvement in care requires complex interventions involving multiple components and stakeholders, customised to specific care contexts. This study aims to comprehensively understand the healthcare experiences of children with IMDs and their families across Canada.

Core Outcome Sets for Medium-Chain Acyl-CoA Dehydrogenase Deficiency and Phenylketonuria.

Background: Evidence to guide treatment of pediatric medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency and phenylketonuria (PKU) is fragmented because of large variability in outcome selection and measurement. Our goal was to develop core outcome sets (COSs) for these diseases to facilitate meaningful future evidence generation and enhance the capacity to compare and synthesize findings across studies.

Methods: Parents and/or caregivers, health professionals, and health policy advisors completed a Delphi survey and participated in a consensus workshop to select core outcomes from candidate lists of outcomes for MCAD deficiency and PKU.

Metabolic gestational age assessment in low resource settings: a validation protocol.

Preterm birth is the leading global cause of neonatal morbidity and mortality. Reliable gestational age estimates are useful for quantifying population burdens of preterm birth and informing allocation of resources to address the problem. However, evaluating gestational age in low-resource settings can be challenging, particularly in places where access to ultrasound is limited.

What is in a Name? Parent, Professional and Policy-Maker Conceptions of Consent-Related Language in the Context of Newborn Screening.

Newborn bloodspot screening programs are some of the longest running population screening programs internationally. Debate continues regarding the need for parents to give consent to having their child screened. Little attention has been paid to how meanings of consent-related terminology vary among stakeholders and the implications of this for practice.

External validation of postnatal gestational age estimation using newborn metabolic profiles in Matlab, Bangladesh.

This study sought to evaluate the performance of metabolic gestational age estimation models developed in Ontario, Canada in infants born in Bangladesh. Cord and heel prick blood spots were collected in Bangladesh and analyzed at a newborn screening facility in Ottawa, Canada. Algorithm-derived estimates of gestational age and preterm birth were compared to ultrasound-validated estimates.

Incidental screen positive findings in a prospective cohort study in Matlab, Bangladesh: insights into expanded newborn screening for low-resource settings.

Background: Newborn screening programs are essential preventative public health initiatives but are not widely available in low-resource settings. The objective of this study was to describe the frequency and nature of screen positive determinations as made by a Canadian newborn screening program in a cohort of infants born in Matlab, Bangladesh. Dried newborn cord and heel-prick blood spot samples collected as part of a validation study nested within a preterm birth research cohort were collected between January 2017 and July 2018 and analyzed in a Canadian newborn screening laboratory where the laboratory's disease panel and screening thresholds were applied.

Metabolic Signatures of Cystic Fibrosis Identified in Dried Blood Spots For Newborn Screening Without Carrier Identification.

Cystic fibrosis (CF) is a complex multiorgan disorder that is among the most common fatal genetic diseases benefiting from therapeutic interventions early in life. Newborn screening (NBS) for presymptomatic detection of CF currently relies on a two-stage immunoreactive trypsinogen (IRT) and cystic fibrosis transmembrane conductance regulator (CFTR) mutation panel algorithm that is sensitive but not specific for identifying affected neonates with a low positive predictive value. For the first time, we report the discovery of a panel of CF-specific metabolites from a single 3.

Metabolic profiles derived from residual blood spot samples: A longitudinal analysis.

Secondary use of newborn screening dried blood spot samples include use for biomedical or epidemiological research. However, the effects of storage conditions on archival samples requires further examination. The objective of this study was to determine the utility of residual newborn samples for deriving reliable metabolic gestational age estimates.

Temporal Signal Pattern Recognition in Mass Spectrometry: A Method for Rapid Identification and Accurate Quantification of Biomarkers for Inborn Errors of Metabolism with Quality Assurance.

Mass spectrometry (MS)-based metabolomic initiatives that use conventional separation techniques are limited by low sample throughput and complicated data processing that contribute to false discoveries. Herein, we introduce a new strategy for unambiguous identification and accurate quantification of biomarkers for inborn errors of metabolism (IEM) from dried blood spots (DBS) with quality assurance. A multiplexed separation platform based on multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) was developed to provide comparable sample throughput to flow injection analysis-tandem MS (FIA-MS/MS) but with greater selectivity as required for confirmatory testing and discovery-based metabolite profiling of volume-restricted biospecimens.

Experiences of caregivers of children with inherited metabolic diseases: a qualitative study.

Background: We sought to understand the experiences of parents/caregivers of children with inherited metabolic diseases (IMD) in order to inform strategies for supporting patients and their families. We investigated their experiences regarding the management of disease, its impact on child and family life, and interactions with the health care system.

Methods: From four Canadian centres, we conducted semi-structured telephone interviews with parents/caregivers of children with an IMD who were born between 2006 and 2015 and who were participating in a larger cohort study.

Consent for newborn screening: parents' and health-care professionals' experiences of consent in practice.

Consent processes for newborn bloodspot screening (NBS) are variable, with a lack of descriptive research that depicts how the offer of NBS is made to parents. We explored the experience, in practice, of consent for NBS. Semistructured interviews in two Canadian provinces were held with: (1) parents of children offered NBS (n=32); and (2) health-care professionals involved in the NBS process (n=19).

Metabolic Clinic Atlas: Organization of Care for Children with Inherited Metabolic Disease in Canada.

Introduction: Nearly all children in Canada with an inherited metabolic disease (IMD) are treated at one of the country's Hereditary Metabolic Disease Treatment Centres. We sought to understand the system of care for paediatric IMD patients in Canada in order to identify sources of variation and inform future research priorities.

Methods: Treatment centres were contacted by email and invited to complete a web-based survey.