Evaluating visual imagery for participant understanding of research concepts in genomics research.

Informed consent is crucial for participant understanding, engagement, and partnering for research. However, current written informed consents have significant limitations, particularly for complex topics such as genomics and biobanking. Our goal was to identify how participants visually conceptualize terminology used in genomics and biobanking research studies, which might provide a novel approach for informed consent. An online convenience sample was used from May to July 2020 to collect data. Participants were asked to draw 10 randomly chosen words out of 32 possible words commonly used in consent forms for genomics and biobanking research. An electronic application captured drawings that were downloaded into a qualitative software program for analysis. A total of 739 drawings by 269 participants were captured. Participants were mostly female (61.3%), eight different race/ethnicities were represented (15.6% Black, 13.8% Hispanic), and most had some college education (68.8%). Some words had consistent visual themes such as different types of risky activities for risk or consistent specific images such as a double helix for DNA. Several words were frequently misunderstood (e.g., ascend for assent), while others returned few submissions (e.g., phenotype or whole genome sequencing). We found that although some words used in genomics and biobanking research were visually conceptualized in a common fashion, but misunderstood or less well-known words had no, few, or mistaken drawings. Future research can explore the incorporation of visual images to improve participant comprehension during consent processes, and how to utilize visual imagery to address more challenging concepts.

Tibial quantitative ultrasound compared to dual-energy X-ray absorptiometry in preterm infants.

OBJECTIVE: The gold standard for diagnosing metabolic bone disease in pediatrics is dual-energy x-ray absorptiometry (DXA). Bone quantitative ultrasound (QUS) has increasing applications. This study compared the relationship of DXA to QUS in preterm infants. DESIGN: Prospective observational study of preterm infants ≤32 weeks gestation or ≤1800 grams at birth. DXA scans measuring bone mineral content (BMC) and tibial QUS scans measuring bone speed of sound (SOS) were obtained near term gestation. RESULTS: 41 infants had bone scans at mean corrected gestation 37.7 ± 2.1 weeks. BMC and SOS showed weak inverse correlation (R2 0.163, p < 0.01). BMC and SOS correlated with parameters at corrected gestational age at the time of the bone scans (p < 0.05-0.001). SOS correlated with birth gestational age (p < 0.001), not BMC. CONCLUSIONS: A statistically significant weak inverse correlation between DXA and QUS was observed. QUS may have advantages over DXA.

Hospital-level variation in genetic testing in children's hospitals' neonatal intensive care units from 2016 to 2021.

PURPOSE: This study aimed to examine variation in genetic testing between neonatal intensive care units (NICUs) across hospitals over time. METHODS: We performed a multicenter large-scale retrospective cohort study using NICU discharge data from the Pediatric Hospital Information System database between 2016 and 2021. We analyzed the variation in the percentage of NICU patients who had any genetic testing across hospitals and over time. We used a multivariable multilevel logistic regression model to investigate the potential association between patient characteristics and genetic testing. RESULTS: The final analysis included 207,228 neonates from 38 hospitals. Overall, 13% of patients had at least 1 genetic test sent, although this varied from 4% to 50% across hospitals. Over the study period, the proportion of patients tested increased, with the increase disproportionately borne by hospitals already testing high proportions of patients. On average, patients who received genetic testing had higher illness severity. Controlling for severity, however, only minimally reduced the degree of hospital-level variation in genetic testing. CONCLUSION: The percentage of NICU patients who undergo genetic testing varies among hospitals and increasingly so over time. Variation is largely unexplained by differences in severity between hospitals. The degree of variation suggests that clearer guidelines for NICU genetic testing are warranted.

Rapid genome sequencing identifies a novel de novo SNAP25 variant for neonatal congenital myasthenic syndrome.

Congenital myasthenic syndrome (CMS) is a group of 32 disorders involving genetic dysfunction at the neuromuscular junction resulting in skeletal muscle weakness that worsens with physical activity. Precise diagnosis and molecular subtype identification are critical for treatment as medication for one subtype may exacerbate disease in another (Engel et al., Lancet Neurol 14: 420 [2015]; Finsterer, Orphanet J Rare Dis 14: 57 [2019]; Prior and Ghosh, J Child Neurol 36: 610 [2021]). The SNAP25-related CMS subtype (congenital myasthenic syndrome 18, CMS18; MIM #616330) is a rare disorder characterized by muscle fatigability, delayed psychomotor development, and ataxia. Herein, we performed rapid whole-genome sequencing (rWGS) on a critically ill newborn leading to the discovery of an unreported pathogenic de novo SNAP25 c.529C > T; p.Gln177Ter variant. In this report, we present a novel case of CMS18 with complex neonatal consequence. This discovery offers unique insight into the extent of phenotypic severity in CMS18, expands the reported SNAP25 variant phenotype, and paves a foundation for personalized management for CMS18.

Evaluating use of changing technologies for rapid next-generation sequencing in pediatrics.

BACKGROUND: Rapid next-generation sequencing (NGS) offers the potential to shorten the diagnostic process and improve the care of acutely ill children. The goal of this study was to report our findings, including benefits and limitations, of a targeted NGS panel and rapid genome sequencing (rGS) in neonatal and pediatric acute clinical care settings. METHODS: Retrospective analysis of patient characteristics, diagnostic yields, turnaround time, and changes in management for infants and children receiving either RapSeq, a targeted NGS panel for 4500+ genes, or rGS, at the University of Utah Hospital and Primary Children's Hospital, from 2015 to 2020. RESULTS: Over a 5-year period, 142 probands underwent rapid NGS: 66 received RapSeq and 76 rGS. Overall diagnostic yield was 39%. In the majority of diagnostic cases, there were one or more changes in clinical care management. Of note, 7% of diagnoses identified by rGS would not have been identified by RapSeq. CONCLUSIONS: Our results indicate that rapid NGS impacts acute pediatric care in real-life clinical settings. Although affected by patient selection criteria, diagnostic yields were similar to those from clinical trial settings. Future studies are needed to determine relative advantages, including cost, turnaround time, and benefits for patients, of each approach in specific clinical circumstances. IMPACT: The use of comprehensive Mendelian gene panels and genome sequencing in the clinical setting allows for early diagnosis of patients in neonatal, pediatric, and cardiac intensive care units and impactful change in management. Diagnoses led to significant changes in management for several patients in lower acuity inpatient units supporting further exploration of the utility of rapid sequencing in these settings. This study reviews the limitations of comparing sequencing platforms in the clinical setting and the variables that should be considered in evaluating diagnostic rates across studies.

Comparison of levonorgestrel level and creamatocrit in milk following immediate versus delayed postpartum placement of the levonorgestrel IUD.

BACKGROUND: Breastfeeding and postpartum contraception critically influence infant and maternal health outcomes. In this pilot study, we explore the effects of timing and duration of postpartum levonorgestrel exposure on milk lipid and levonorgestrel content to establish baseline data for future research. METHODS: This sub-study recruited a balanced convenience sample from 259 participants enrolled in a parent randomized controlled trial comparing immediate to delayed (4-8 weeks) postpartum levonorgestrel IUD placement. All planned to breastfeed, self-selected for sub-study participation, and provided the first sample at 4-8 weeks postpartum (before IUD placement for the delayed group) and the second four weeks later. We used the Wilcoxon rank sum (inter-group) and signed rank (intra-group) tests to compare milk lipid content (creamatocrit) and levonorgestrel levels between groups and time points. RESULTS: We recruited 15 participants from the immediate group and 17 from the delayed group with 10 and 12, respectively, providing both early and late samples. Initially, median levonorgestrel concentration of the immediate group (n = 10) (32.5 pg/mL, IQR: 24.8, 59.4) exceeded that of the delayed group (n = 12) (17.5 pg/mL, IQR: 0.0, 25.8) (p = 0.01). Four weeks later, the values aligned: 26.2 pg/mL (IQR: 20.3, 37.3) vs. 28.0 pg/mL (IQR: 25.2, 40.8). Creamatocrits were similar between both groups and timepoints. CONCLUSIONS: Immediate postpartum levonorgestrel IUD placement results in steady, low levels of levonorgestrel in milk without apparent effects on lipid content. These findings provide initial support for the safety of immediate postpartum levonorgestrel IUD initiation, though the study was not powered to detect noninferiority between groups. TRIAL REGISTRATION: This randomized controlled trial was registered with ClinicalTrials.gov (Registry No. NCT01990703) on November 21, 2013.