Predictors of venous thromboembolism among infants in children's hospitals in the United States: a retrospective Pediatric Health Information Study.

OBJECTIVES: Examine: (1) Prevalence of diagnosed venous thromboembolism (VTE) in infants <6 months discharged from U.S. NICUs; (2) Associations between sociodemographic and clinical factors and VTE; (3) Secondary outcomes related to VTE. STUDY DESIGN: Multivariable logistic regressions examined associations between VTE and sociodemographic and clinical factors among infants <6 months discharged from Pediatric Health Information System (PHIS) NICUs between 2016 and 2019. RESULTS: Of 201,033 infants, 2720 (1.35%) had diagnosed VTE. Birthweight 300-1000 g (aOR 3.14, 95% CI 2.54-3.88), 1000-1500 g (aOR 1.77, 95% CI 1.40-2.42) versus 2500-3999 g, and public (aOR 1.18, 95% CI 1.02-1.37) versus private insurance were associated with increased odds of VTE, as were CVC, TPN, mechanical ventilation, infection, ECMO, and surgery. All types of central lines (non-tunneled and tunneled CVCs, PICCs, and umbilical catheters) had higher odds of VTE than not having that type of line. CVCs in upper versus lower extremities had higher odds of VTE. CONCLUSION: Infants with risk factors may require monitoring for VTE. Results may inform VTE prevention.

Diagnosing newborns with suspected mitochondrial disorders: an economic evaluation comparing early exome sequencing to current typical care.

PURPOSE: To determine the value of early exome sequencing (eES) relative to the current typical care (TC) in the diagnosis of newborns with suspected severe mitochondrial disorders (MitD). METHODS: We used a decision tree-Markov hybrid to model neonatal intensive care unit (NICU)-related outcomes and costs, lifetime costs and quality-adjusted life-years among patients with MitD. Probabilities, costs, and utilities were populated using published literature, expert opinion, and the Pediatric Health Information System database. Incremental cost-effectiveness ratios (ICER) and net monetary benefits (NMB) were calculated from lifetime costs and quality-adjusted life-years for singleton and trio eES, and TC. Robustness was assessed using univariate and probabilistic sensitivity analyses (PSA). Scenario analyses were also conducted. RESULTS: Findings indicate trio eES is a cost-minimizing and cost-effective alternative to current TC. Diagnostic probabilities and NICU length-of-stay were the most sensitive model parameters. Base case analysis demonstrates trio eES has the highest incremental NMB, and PSA demonstrates trio eES had the highest likelihood of being cost-effective at a willingness-to-pay (WTP) of $200,000 relative to TC, singleton eES, and no ES. CONCLUSION: Trio and singleton eES are cost-effective and cost-minimizing alternatives to current TC in diagnosing newborns suspected of having a severe MitD.

The association of inborn status and resource utilization among neonates who received extracorporeal membrane oxygenation.

BACKGROUND: Many studies have established that extracorporeal membrane oxygenation (ECMO) can be a cost-effective treatment in some populations, but limited data exist on which factors are associated with length of stay (LOS) and total hospital costs. This study aimed to determine if inborn (i.e., cared for in their birth hospitals) neonates who receive ECMO have different resource utilization and outcomes compared to outborn (i.e., not cared for in their birth hospitals) neonates who receive ECMO. METHODS: A retrospective cohort study was conducted using the Healthcare Cost and Utilization Project's Kids' Inpatient Database from 1997-2012. Neonates (infants, <28 days) placed on ECMO were categorized as either inborn or outborn. Salient clinical characteristics were compared between groups. A multivariable analysis was performed to identify the factors associated with length of stay (LOS), total hospital costs, and mortality in these two patient populations. RESULTS: Of 5,152 neonates receiving ECMO, 800 were inborn and 4,352 were outborn. Inborn neonates were more frequently diagnosed with cardiac-related diagnoses (70.5% vs 62.1%, p < 0.001). After adjusting for demographics and hospital-level factors, inborn neonates had longer hospital LOS (13.2 days, 95% CI, 8.7-18.7; p < 0.001), higher total encounter costs ($62,000, 95% CI, 40,000-85,000; p < 0.001) and higher mortality (OR 2.4, 95% CI 1.9-2.9; p < 0.001) compared to outborn neonates. CONCLUSIONS: Inborn neonates placed on ECMO were more frequently diagnosed with cardiac-related diseases or congenital diaphragmatic hernia, had longer LOS, higher total encounter costs, and higher mortality rates relative to their outborn counterparts, and likely represent a higher risk population. These two populations of infants may be inherently different and their differences should be further explored to inform decision making about optimal site of delivery.

Impact of Confounding on Cost, Survival, and Length-of-Stay Outcomes for Neonates with Hypoplastic Left Heart Syndrome Undergoing Stage 1 Palliation Surgery.

The objective of this analysis was to update trends in LOS and costs by survivorship and ECMO use among neonates with hypoplastic left heart syndrome (HLHS) undergoing stage 1 palliation surgery using 2016 data from the Healthcare Cost and Utilization Project Kids' Inpatient Database. We identified neonates ≤ 28 days old with HLHS undergoing Stage 1 surgery, defined as a Norwood procedure with modified Blalock-Taussig (BT) shunt, Sano modification, or both. Multivariable regression with year random effects was used to compare LOS and costs by hospital region, case volume, survivorship, and ECMO vs. no ECMO. An E-value analysis, an approach for conducting sensitivity analysis for unmeasured confounding, was performed to determine if unmeasured confounding contributed to the observed effects. Significant differences in total costs, LOS, and mortality were noted by hospital region, ECMO use, and sub-analyses of case volume. However, other than ECMO use and mortality, the maximum E-value confidence interval bound was 1.71, suggesting that these differences would disappear with an unmeasured confounder 1.71 times more associated with both the outcome and exposure (e.g., socioeconomic factors, environment, etc.) Our findings confirm previous literature demonstrating significant resource utilization among Norwood patients, particularly those undergoing ECMO use. Based on our E-value analysis, differences by hospital region and case volume can be explained by moderate unobserved confounding, rather than a reflection of the quality of care provided. Future analyses on surgical quality must account for unobserved factors to provide meaningful information for quality improvement.

Cost effectiveness of vitamin c supplementation for pregnant smokers to improve offspring lung function at birth and reduce childhood wheeze/asthma.

OBJECTIVE: To determine the implications of supplemental vitamin C for pregnant tobacco smokers and its effects on the prevalence of pediatric asthma, asthma-related mortality, and associated costs. STUDY DESIGN: A decision-analytic model built via TreeAge compared the outcome of asthma in a theoretical annual cohort of 480,000 children born to pregnant smokers through 18 years of life. Vitamin C supplementation (500 mg/day) with a standard prenatal vitamin was compared to a prenatal vitamin (60 mg/day). Model inputs were derived from the literature. Deterministic and probabilistic sensitivity analyses assessed the impact of assumptions. RESULT: Additional vitamin C during pregnancy would prevent 1637 cases of asthma at the age of 18 per birth cohort of pregnant smokers. Vitamin C would reduce asthma-related childhood deaths and save $31,420,800 in societal costs over 18 years per birth cohort. CONCLUSION: Vitamin C supplementation in pregnant smokers is a safe and inexpensive intervention that may reduce the economic burden of pediatric asthma.

Zebrafish mutations in gart and paics identify crucial roles for de novo purine synthesis in vertebrate pigmentation and ocular development.

Although purines and purinergic signaling are crucial for numerous biochemical and cellular processes, their functions during vertebrate embryonic development have not been well characterized. We analyze two recessive zebrafish mutations that affect de novo purine synthesis, gart and paics. gart encodes phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase, a trifunctional enzyme that catalyzes steps 2, 3 and 5 of inosine monophosphate (IMP) synthesis. paics encodes phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase, a bifunctional enzyme that catalyzes steps 6 and 7 of this process. Zygotic gart and paics mutants have pigmentation defects in which xanthophore and iridophore pigmentation is almost completely absent, and melanin-derived pigmentation is significantly decreased, even though pigment cells are present in normal amounts and distributions. Zygotic gart and paics mutants are also microphthalmic, resulting from defects in cell cycle exit of proliferative retinoblasts within the developing eye. Maternal-zygotic and maternal-effect mutants demonstrate a crucial requirement for maternally derived gart and paics; these mutants show more severe developmental defects than their zygotic counterparts. Pigmentation and eye growth phenotypes in zygotic gart and paics mutants can be ascribed to separable biosynthetic pathways: pigmentation defects and microphthalmia result from deficiencies in a GTP synthesis pathway and an ATP synthesis pathway, respectively. In the absence of ATP pathway activity, S phase of proliferative retinoblasts is prolonged and cell cycle exit is compromised, which results in microphthalmia. These results demonstrate crucial maternal and zygotic requirements for de novo purine synthesis during vertebrate embryonic development, and identify independent functions for ATP and GTP pathways in mediating eye growth and pigmentation, respectively.