Review of clinical trials and guidelines for children and youth with mucopolysaccharidosis: outcome selection and measurement.

Background: To inform the development of a core outcome set (COS) for children and youth with mucopolysaccharidoses (MPS), we aimed to identify all outcomes and associated outcome measurement instruments that are reported in recent clinical trials and recommended as measurements in clinical management guidelines.

Methods: To identify English-language clinical trials and guidelines pertaining to MPS published between 2011 and mid-2021, we applied a comprehensive peer-reviewed search strategy to relevant databases and registers on May 16, 2021. Two reviewers independently screened retrieved citations and then full-text articles to determine eligibility for inclusion.

Mediation of genetic susceptibility to obesity through eating behaviours in children.

Background/objectives: Few studies have examined the putative mediating role of eating behaviours linking genetic susceptibility and body weight. The goal of this study was to investigate the extent to which two polygenic scores (PGSs) for body mass index (BMI), based on child and adult data, predicted BMI through over-eating and fussy eating across childhood.

Subjects/methods: The study sample involved 692 participants from a birth cohort study.

Outcomes of pregnancies with varying levels of nuchal translucency measurements: A population-based retrospective study in Ontario, Canada.

Introduction: Nuchal translucency prenatal ultrasound is widely used to screen for chromosomal abnormalities. An elevated nuchal translucency has been associated with adverse outcomes such as pregnancy loss; however, extant studies investigating these associations have had important limitations, including selection bias. This study aimed to investigate the association between nuchal translucency measurements and pregnancy outcome, specifically, a composite of pregnancy loss, termination, stillbirth, or neonatal death.

Pregnancies with 'double-positive' multiple marker screening results: a population-based study in Ontario, Canada.

Background: Multiple marker screening is offered to pregnant individuals in many jurisdictions to screen for trisomies 21 and 18. On occasion, the result is 'double-positive'-a screening result that is unexpectedly positive for both aneuploidies. Although this occurs rarely, the paucity of available evidence about the outcomes of these pregnancies hinders patient counselling.

Ultrasonographic Fetal Nuchal Translucency Measurements and Cytogenetic Outcomes.

Importance: Ultrasonographic measurement of fetal nuchal translucency is used in prenatal screening for trisomies 21 and 18 and other conditions. A cutoff of 3.5 mm or greater is commonly used to offer follow-up investigations, such as prenatal cell-free DNA (cfDNA) screening or cytogenetic testing.

Guidelines for reporting pediatric and child health clinical trial protocols and reports: study protocol for SPIRIT-Children and CONSORT-Children.

Background: Despite the critical importance of clinical trials to provide evidence about the effects of intervention for children and youth, a paucity of published high-quality pediatric clinical trials persists. Sub-optimal reporting of key trial elements necessary to critically appraise and synthesize findings is prevalent. To harmonize and provide guidance for reporting in pediatric controlled clinical trial protocols and reports, reporting guideline extensions to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) guidelines specific to pediatrics are being developed: SPIRIT-Children (SPIRIT-C) and CONSORT-Children (CONSORT-C).

Assessing the quality and value of metabolic chart data for capturing core outcomes for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

Background: Generating rigorous evidence to inform care for rare diseases requires reliable, sustainable, and longitudinal measurement of priority outcomes. Having developed a core outcome set for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, we aimed to assess the feasibility of prospective measurement of these core outcomes during routine metabolic clinic visits.

Methods: We used existing cohort data abstracted from charts of 124 children diagnosed with MCAD deficiency who participated in a Canadian study which collected data from birth to a maximum of 11 years of age to investigate the frequency of clinic visits and quality of metabolic chart data for selected outcomes.

Relationship Between Gestational Weight Gain and Health Service Utilization in Early Childhood: A Retrospective Cohort Study.

Objective: Gestational weight gain (GWG) outside recommended ranges can negatively impact both the woman and child. The long-term effects of below-recommended or above-recommended GWG on the child are unclear.

Methods: This retrospective cohort study used a population-based birth registry of 258,005 live births to evaluate the relationship between maternal GWG and paediatric health service use.

Patient and public involvement in pragmatic trials: online survey of corresponding authors of published trials.

Background: There are few data on patient and public involvement (PPI) in pragmatic trials. We aimed to describe the prevalence and nature of PPI within pragmatic trials, describe variation in prevalence of PPI by trial characteristics and compare prevalence of PPI reported by trial authors to that reported in trial publications.

Methods: We applied a search filter to identify pragmatic trials published from 2014 to 2019 in MEDLINE.

Exome and genome sequencing for rare genetic disease diagnosis: A scoping review and critical appraisal of clinical guidance documents produced by genetics professional organizations.

Purpose: Exome and genome sequencing have rapidly transitioned from research methods to widely used clinical tests for diagnosing rare genetic diseases. We sought to synthesize the topics covered and appraise the development processes of clinical guidance documents generated by genetics professional organizations.

Methods: We conducted a scoping review of guidance documents published since 2010, systematically identified in peer-reviewed and gray literature, using established methods and reporting guidelines.

Maternal weight and paediatric health use: mediating role of adverse birth outcomes: a retrospective cohort study.

Background: Maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) above or below recommendations have been associated with increased paediatric health service utilization as well as increased risk of adverse birth outcomes, including small for gestational age (SGA) and preterm birth (PTB). SGA and PTB are associated with numerous adverse health outcomes in the child, including delayed growth, motor and cognitive impairment. Previous research has identified birth weight and gestational age on the causal pathway in the association between maternal pre-pregnancy BMI and child hospital admissions, there are no studies to date to quantify this relationship across other areas of health service utilization, nor the impact of gestational weight gain.

Paper II: thematic framework analysis of registry-based randomized controlled trials provided insights for designing trial ready registries.

Objectives: Registry-based randomized controlled trials (RRCTs) are increasingly used, promising to address challenges associated with traditional randomized controlled trials. We identified strengths and limitations reported in planned and completed RRCTs to inform future RRCTs.

Study Design And Setting: We conducted an environmental scan of literature discussing conceptual or methodological strengths and limitations of using registries for trial design and conduct (n = 12), followed by an analysis of RRCT protocols (n = 13) and reports (n = 77) identified from a scoping review.

Paper I: Heterogeneous use of registry data for participant identification and primary outcome ascertainment is found in registry-based randomized controlled trials: A scoping review.

Objectives: Registry-based randomized controlled trials (RRCTs) have potential to address limitations of traditional clinical trials. To describe their current use, information on planned and published RRCTs was identified and synthesized.

Study Design And Setting: A scoping review of published RRCT protocols and reports was conducted.

Ethical and practical considerations related to data sharing when collecting patient-reported outcomes in care-based child health research.

Purpose: The collection and use of patient reported outcomes (PROs) in care-based child health research raises challenging ethical and logistical questions. This paper offers an analysis of two questions related to PROs in child health research: (1) Is it ethically obligatory, desirable or preferable to share PRO data collected for research with children, families, and health care providers? And if so, (2) What are the characteristics of a model best suited to guide the collection, monitoring, and sharing of these data?

Methods: A multidisciplinary team of researchers, providers, patient and family partners, and ethicists examined the literature and identified a need for focus on PRO sharing in pediatric care-based research. We constructed and analyzed three models for managing pediatric PRO data in care-based research, drawing on ethical principles, logistics, and opportunities to engage with children and families.

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.

Validation of gestational age determination from ultrasound or a metabolic gestational age algorithm using exact date of conception in a cohort of newborns conceived using assisted reproduction technologies.

Background: Accurate estimates of gestational age in pregnancy are important for the provision of optimal care. Although current guidelines generally recommend estimating gestational age via first-trimester ultrasound measurement of crown-rump length, error associated with this method can range from 3 to 8 days of gestation. In pregnancies resulting from assisted reproductive technology, estimated due date can be calculated on the basis of the age of the embryo and the date of embryo transfer, arguably providing the most accurate estimates possible.

Bridging clinical care and research in Ontario, Canada: Maximizing diagnoses from reanalysis of clinical exome sequencing data.

We examined the utility of clinical and research processes in the reanalysis of publicly-funded clinical exome sequencing data in Ontario, Canada. In partnership with eight sites, we recruited 287 families with suspected rare genetic diseases tested between 2014 and 2020. Data from seven laboratories was reanalyzed with the referring clinicians.

The Impact of Patient and Family Engagement in Child Health Research: A Scoping Review.

Objective: To identify impacts of patient and family engagement in child health research on the research process, research teams, and patient and family partners.

Study Design: A scoping review was conducted using the MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and Web of Science databases. English-language studies were included if they described ≥1 impact of patient and family engagement on child health research (age <18 years), researchers, or patient and family partners.