Hsu CJ, Schraw JM, Rasmussen SA, et al. Structural birth defects and leukemia risk in children with Down syndrome. Sci Rep. Published online December 11, 2025. doi:10.1038/s41598-025-31340-3

Abstract

Birth defects are associated with increased cancer risk in the general pediatric population, yet their impact on leukemia risk in children with Down syndrome (DS) remains uncertain. We assessed this using data from 26,660 children with DS in the Genetic Overlap Between Anomalies and Cancer in Kids Registry Linkage Study. Among them, 71.9% had at least one major birth defect, predominantly involving the cardiac (64.2%), musculoskeletal (21%), and gastrointestinal systems (6.8%). The cumulative incidence of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) was comparable in children with and without co-occurring defects. Adjusted hazard ratios (aHR) for ALL and AML in children with versus without co-occurring major birth defects were 1.12 (95% confidence interval [CI]: 0.80-1.56) and 1.09 (95% CI: 0.76-1.58), respectively. Overall, no consistent patterns were seen between organ system-level defects and ALL. However, in terms of specific defects, we identified that anophthalmia/microphthalmia (aHR: 2.83, 95% CI: 1.16-6.92) was associated with ALL and tetralogy of Fallot (aHR: 2.40, 95% CI: 1.27-4.55) was associated with AML. While children with DS experience a higher prevalence of birth defects, these defects do not appear to strongly influence leukemia risk, unlike the elevated risk observed in the general pediatric population (< 18 years).

 

Koops A, Howell R, Allred RP, Jeon HN, Shumate C. Staff experiences with electronic initial case reports for birth defects surveillance in Texas. Birth Defects Res. 2025;117(12):e70002. doi:10.1002/bdr2.70002

Abstract

Background: Electronic case reporting (eCR) is increasingly used by public health agencies to support disease surveillance. Its utility for birth defects surveillance remains unexplored. This project aimed to evaluate birth defects surveillance staff experiences and perceptions of eCR data to identify its challenges, benefits, and opportunities for improvement in birth defects surveillance.

Methods: Two virtual, 1-h focus groups were conducted with 15 staff from the Texas Birth Defects Registry (TBDR) who had participated in a pilot evaluation of electronic initial case reports (eICRs). The focus groups explored staff experiences with identifying and abstracting cases from eICRs and how these experiences compared to abstraction from electronic health records (EHRs). Discussions followed a structured interview guide with six broad question categories. Detailed notes were taken during the sessions and analyzed using thematic analysis to identify common themes and patterns.

Results: Thematic analysis identified six key themes related to the eICR: Structure; Quality and Completeness; Comparison with EHRs; Technical and Workflow Challenges; Usefulness and Potential Applications; and Recommendations to Strengthen its Utility for Birth Defect Surveillance.

Conclusions: Staff reported that while eCR offers potential advantages, such as serving as a data source for case-finding, significant challenges remain. These include issues with eICR structure, data completeness, and integration into existing workflows. Recommended improvements include better organization of eICR data, inclusion of additional clinical details, and development of standardized abstraction protocols. These findings can inform strategies to optimize eCR for birth defects surveillance and point to the need for national guidelines.

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Langan LM, Bain FL, Snow CC, et al. Spatially informed wastewater differentiation among locations during an ongoing measles outbreak in Texas, USA. ACS Environ Au. 2025;5(6):543-549. Published 2025 Sep 16. doi:10.1021/acsenvironau.5c00122

Abstract

Though reverse transcription-quantitative polymerase chain reaction (RT-qPCR), RT digital PCR (RT-dPCR), and RT digital droplet PCR (RT-ddPCR) are commonly used for wastewater-based epidemiology and surveillance (WBE/WBS), differences among the platforms exist. While RT-ddPCR has been suggested as an ideal approach to use globally for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monitoring, access to RT-qPCR instrumentation is more widely available in many regions, and it is more economical. Subsequently, a larger number of studies have used RT-qPCR for SARS-CoV-2 wastewater monitoring, along with additional pathogens that can be detected with WBS. In this study, we employed RT-qPCR and RT-dPCR platforms for the comparative detection of vaccine (A genotype Edmonston) and wild-type (D8 genotype) measles RNA from wastewater in nearby cities separated by <50 km during an ongoing measles outbreak in Texas, USA, in addition to several other locations up to 30-1400 km from the outbreak location. The limit of detection (LOD) for each methodology was evaluated using a synthetic gBlock DNA gene fragment of known concentrations, with comparable LODs identified for both the RT-dPCR (∼0.5 gc/μL) and RT-qPCR (∼0.4 gc/μL) platforms. Using composite supernatant-solid wastewater samples, RNA aliquots were analyzed on each platform in parallel. The RT-qPCR platform demonstrated a higher detection rate than RT-dPCR for the vaccine strain quantified in wastewater samples, with equivalent detections for the wild-type strain in both platforms, and notable differences in the gene copies quantified in wastewater based on the platform. Our study identifies that regardless of PCR methodology employed, WBS is a particularly valuable approach for the spatially informed differentiation of measles during rapid response to an active outbreak.

 

Shafer S, Stuteville H, Varney SM. Clinical outcomes of pediatric metformin exposures reported to the National Poison Data System®. Clin Toxicol (Phila). Published online November 26, 2025. doi:10.1080/15563650.2025.2587773

Abstract

Introduction: Prior studies suggest metformin exposures in young pediatric patients are low risk, and a triage threshold of 85 mg/kg can be used to reduce unnecessary evaluations. Our objective was to analyze single-substance metformin exposures using the National Poison Data System® to describe the clinical course, outcome, and mg/kg dose of metformin exposures in children under six years old. The secondary objective was to describe outcomes in patients divided into safe (≤85 mg/kg reported dose) and caution (>85 mg/kg reported dose) categories.

Methods: Using the National Poison Data System®, we analyzed single-substance metformin exposures from 2011-2021 in patients under six years old. We defined two categories of metformin overdose patients: safe (≤85 mg/kg reported dose), who could be managed at home, and caution (>85 mg/kg reported dose), who should be sent to a healthcare facility. Data were summarized with medians with interquartile ranges for continuous variables and percentages for categorical variables.

Results: There were 8,762 single-substance metformin exposures reported from 2011-2021. Most patients (6,493, 74.1%) were managed in a non-healthcare setting. Critical care admissions accounted for 73 (3.4%) exposures. For the 1,270 (14.5%) patients who had mg/kg data available, 1,081 (85.1%) were in the safe category with ingestions ≤85 mg/kg, while 189 (14.9%) were in the caution category with ingestions >85 mg/kg.

Discussion: Data were limited due to 59.4% of cases missing follow-up information. However, in patients with follow-up information available, most cases were managed on site (74.1%) and only 2.5% of cases required hospitalization. Caution range patients had ten times more admissions (6%) than safe range patients (0.6%).

Conclusion: Most exploratory pediatric single-agent metformin exposures were safe and could be managed at home. The ≤85 mg/kg threshold identifies exposures with expected good outcome requiring little to no medical management.