Costs and outcomes associated with the administration of Intravenous Acetaminophen in neonates after esophageal atresia and tracheoesophageal fistula repair.

BACKGROUND: Over the last decade, the intravenous (IV) formulation of acetaminophen (APAP) has gained popularity as a safe and effective first-line analgesic in the neonatal intensive care unit and it is especially useful in peri-operative settings where oral agents are contraindicated. The primary objective was to examine the outcomes and costs associated with the use of IV APAP in combination with opioids versus opioids alone as a pain management strategy after neonatal esophageal atresia (EA) and tracheoesophageal fistula (TEF) repair. METHODS: Data from the Pediatric Health Information System was used to examine 1137 hospitalizations for EA/TEF repair from October 2015 to September 2018. Neonates administered opioids only, or IV APAP in combination with opioids as pain management, were included. RESULTS: Neonates receiving IV APAP experienced a longer median LOS, but a significantly lower mortality rate, a decreased mean daily cost, and reduced opioid use compared to neonates given only opioids. The two groups had no significant differences in pharmacy and total costs. CONCLUSION: Our findings suggest that the use of IV APAP alongside opioids in EA/TEF repair is associated with reduced mortality and opioid use, as well as longer LOS.

Implementation and assessment of an electronic clinical decision support tool to notify clinicians of critical hyperbilirubinemia in preterm neonates less than 35 weeks' gestation.

OBJECTIVES: Critical hyperbilirubinemia in preterm neonates, a condition requiring greater attention, is treated with phototherapy or exchange transfusion when bilirubin results exceed gestational age and age-specific medical decision levels (MDLs) to prevent bilirubin-induced neurologic damage. Conventional evaluation involves multiple manual steps and is poised to inconsistencies and delays. METHODS: We designed and implemented an electronic clinical decision support (CDS) tool to identify and alert neonatal intensive care unit clinicians of critical hyperbilirubinemia with a SmartZone alert. We evaluated the performance of our manual evaluation workflow, the accuracy of the electronic CDS tool, and the outcome of the electronic CDS tool to reduce the time to place orders for interventions. RESULTS: Among the 22 patients who met the criteria to have phototherapy ordered before implementing the electronic CDS tool, 20 (90%) had phototherapy ordered. Fourteen (70%) phototherapy orders were placed less than 24 hours, 4 phototherapy orders were placed 24 to 72 hours, and 2 orders were placed more than 72 hours after bilirubin results exceeded the corresponding MDLs. Among the 15 patients who met the criteria to have phototherapy ordered after implementing the electronic CDS tool, all (100%) received phototherapy orders, with 14 (93%) placed less than 24 hours and 1 order placed less than 48 hours. The electronic CDS tool identified all eligible patients correctly. The proportion of phototherapy ordered less than 24 hours increased from 70% to 93% after the implementation of the electronic CDS tool. CONCLUSIONS: The electronic CDS tool promoted more appropriate and timely intervention orders to manage critical hyperbilirubinemia in preterm neonates.

Cost-effectiveness of nirsevimab and palivizumab for respiratory syncytial virus prophylaxis in preterm infants 29-34 6/7 weeks' gestation in the United States.

BACKGROUND: Respiratory syncytial virus (RSV) hospitalizations have increased since the 2014 guideline update recommended against the use of palivizumab for preterm infants born ≥29 0/7 weeks' gestational age (GA) without additional risk factors. A novel drug candidate, nirsevimab, has been developed for this population. We analyzed the cost-effectiveness of palivizumab/nirsevimab vs. no prophylaxis in this population. METHODS: A hybrid-Markov model predicted the RSV clinical course in the first year of life and sequelae in the subsequent four years for preterm infants from the healthcare and societal perspectives. Model parameters were derived from the literature. We calculated costs and quality-adjusted life-years (QALYs) to produce an incremental cost-effectiveness ratio (ICER) evaluated at a willingness-to-pay threshold of $150,000/QALY. Sensitivity analyses assessed model robustness. A threshold analysis examined nirsevimab pricing uncertainty. RESULTS: Compared to no prophylaxis, palivizumab costs $9572 and $9584 more from the healthcare and societal perspectives, respectively, with 0.0019 QALYs gained per patient over five years, resulting in ICERs >$5 million per QALY from each perspective. Results were robust to parameter uncertainties; probabilistic sensitivity analysis revealed that no prophylaxis had a 100% probability of being cost-effective. The threshold analysis suggested that nirsevimab is not cost-effective when compared to no prophylaxis if the price exceeds $1962 from a societal perspective. CONCLUSION: Palivizumab is dominated by no prophylaxis for preterm infants 29 0/7-34 6/7 weeks' GA with no additional risk factors. Relevant stakeholders should consider alternatives to palivizumab for this population that are both effective and economical.

Neonates with mild hypoxic-ischaemic encephalopathy receiving supportive care versus therapeutic hypothermia in California.

OBJECTIVE: The use of therapeutic hypothermia (TH) for mild hypoxic-ischaemic encephalopathy (HIE) remains controversial and inconsistent. We analysed trends in TH and maternal and infant characteristics associated with short-term outcomes of infants with mild HIE. DESIGN: Retrospective cohort analysis of the California Perinatal Quality Care Collaborative database 2010-2018. E-value analysis was conducted to determine the potential impact of unmeasured confounding. SETTING: California neonatal intensive care units. PATIENTS: 1364 neonates with mild HIE. INTERVENTIONS: Supportive care versus TH. MAIN OUTCOME MEASURES: Factors associated with TH and mortality. RESULTS: The proportion of infants receiving TH increased from 46% in 2010 to 79% in 2018. TH was more likely in the setting of singleton birth (OR 2.69, 95% CI 1.21 to 5.39), no major birth defects (OR 2.18, 95% CI 1.42 to 3.30), operative vaginal delivery (OR 3.04, 95% CI 1.80 to 5.10) and 5-minute Apgar score ≤5 (OR 3.17, 95% CI 2.43 to 4.13). Mortality was associated with small for gestational age (OR 5.79, 95% CI 1.90 to 18.48), <38 weeks' gestation (OR 7.31 95% CI 2.39 to 24.93), major birth defects (OR 11.62, 95% CI 3.97 to 38.00), inhaled nitric oxide (OR 12.73, 95% CI 4.00 to 44.53) and nosocomial infection (OR 7.98, 95% CI 1.15 to 47.03). E-value analyses suggest that unmeasured confounding may have contributed to some of the observed effects. CONCLUSIONS: Variation in management of mild HIE persists, but therapeutic drift has become more prevalent over time. Further studies are needed to assess long-term outcomes alongside resource utilisation to inform evidence-based practice.

The financial burden experienced by families of preterm infants after NICU discharge.

BACKGROUND AND OBJECTIVES: Describe the financial burden and worry that families of preterm infants experience after discharge from the neonatal intensive care unit (NICU). METHODS: We surveyed 365 parents of preterm infants in a cross-sectional study regarding socio-demographics, supplemental security income (SSI), and financial worry. We completed a multivariable logistic regression model to examine the adjusted association of financial worry with modifiable factors. RESULTS: We found that 53% of participants worried about healthcare costs after NICU discharge. After adjusting for socio-demographic and infant characteristics, we identified that, aOR (95% CI), out-of-pocket costs from the NICU index hospitalization, 3.51 (1.7, 7.26) and durable medical equipment use, 2.41 (1.11, 5.23) was associated with increased financial worry while enrollment in SSI, 0.38 (0.19, 0.76) was associated with decreased financial worry. CONCLUSIONS: We identified factors that could contribute to financial burden after NICU discharge that may advise future work to target financial support systems.

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.

Cost-effectiveness analysis of extended extracorporeal membrane oxygenation duration in newborns with congenital diaphragmatic hernia in the United States.

BACKGROUND: The duration of extracorporeal membrane oxygenation (ECMO) has been historically confined in many centers to two weeks. We evaluated the cost-effectiveness of additional weeks on ECMO beyond two weeks for newborns with congenital diaphragmatic hernia (CDH) who may require longer stays to maximize survival potential. METHODS: We modeled lifetime outcomes using a decision tree from the US societal perspective. Survival at discharge, probability of long-term sequelae, direct medical costs, indirect costs, and quality-adjusted life years (QALY) for long-term disability were considered. Considering the nature of severity of CDH, we used $200,000 per QALY as the willingness-to-pay threshold in the base case. RESULTS: The lifetime costs per CDH infant generated from staying on ECMO for ≤2 weeks, 2-3 weeks, and >3 weeks are $473,334, $654,771, $1,007,476, respectively (2018 USD), and the total QALYs gained from each treatment arm are 1.83, 3.6, and 5.05. In the base case, the net monetary benefits are -$108,034 for ECMO ≤2 weeks, $64,258 for 2-3 weeks, and $2955 for >3 weeks. In probabilistic simulations, a duration of ≤2 weeks is dominated by a duration of 2-3 weeks in 65.3% of cases and dominated by > 3 weeks in 60.2% of cases. A duration of 2-3 weeks is more cost-effective than >3 weeks in 68.6% of simulations. CONCLUSION: Our findings suggest that 2-3 weeks of ECMO may be the most cost-effective for CDH infants that are unable to wean off at 2 weeks from the US societal perspective. Regardless of ECMO duration, ECMO use generates positive incremental NMB at WTP of $200,000 if the survival probability is greater than 0.3. Future research must be conducted to evaluate the long-term outcomes and sequelae of CDH patients post-discharge to better inform the clinical decision-making in neonatal intensive care unit.

Economic considerations at the threshold of viability.

Neonatal intensive care for infants born at 22-24 weeks has become more prevalent in the past three decades, but outcomes remain highly variable between centers, in part due to different approaches in management. With this increased frequency of intervention, there has been concern for a concurrent increase in costs of care for survivors. This article reviews the direct medical, direct non-medical, and indirect costs of care for periviable infants and their families, as well as the current limitations of published data. In addition, we highlight the cost-effectiveness of neonatal intensive care and various therapies offered to extremely preterm infants, while also considering the ethical dilemmas inherently tied to periviable decision-making. Strategies to improve the gaps in knowledge on the economic impact of the smallest infants are discussed.

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.

Perils and pitfalls for evaluating economic studies in neonatology.

Health care economics has become an essential topic for all clinicians. Rising health care costs and continued limited resources force hospitals, health networks, and payers to make difficult choices. Economic studies range from those that only focus on costs to those that include costs and outcomes in a single metric, allowing for an assessment of incremental benefit gained from the incremental investment made. This article takes a step by step approach to interpreting the results of an economic evaluation, allowing the reader to critically appraise the results and to understand the implications for their specific patient population.

Cost-effectiveness of probiotics for necrotizing enterocolitis prevention in very low birth weight infants.

OBJECTIVE: To examine the cost-effectiveness of prophylactic probiotics on necrotizing enterocolitis (NEC) prevention in very low birth weight (VLBW) infants. STUDY DESIGN: We built a decision-analytic model using TreeAge. Effectiveness was assessed using quality-adjusted life-years (QALY). Primary outcome was an incremental cost-effectiveness ratio (ICER) expressed as cost per QALY gained. Costs were expressed in 2017 US dollars. Deterministic and probabilistic sensitivity analyses (SA) were performed. RESULTS: For the base case analysis, the ICER of probiotics versus no probiotics for the prevention of NEC in VLBW infants was $1868/QALY. SA revealed that probiotics became cost-saving at a NEC rate of 6.5% and higher or with incremental NEC cost of $37,500 or higher. CONCLUSIONS: Our model demonstrated that prophylactic probiotics were a cost-effective strategy in NEC reduction. SA confirmed that the model is customizable to various clinical settings and thus, can aid in understanding the economic impact of this intervention.

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.

A Cost-Effectiveness Analysis of Rooming-in and Breastfeeding in Neonatal Opioid Withdrawal.

OBJECTIVE: Our cost-effectiveness analysis investigated rooming-in versus not rooming-in to determine optimal management of neonates with neonatal opioid withdrawal (NOW). STUDY DESIGN: A decision-analytic model was constructed using TreeAge to compare rooming-in versus not rooming-in in a theoretical cohort of 23,200 newborns, the estimated annual number affected by NOW in the United States. Additional considerations included the effect of breast milk versus formula milk in evaluating the need for pharmacotherapy. Primary outcomes were needed for pharmacotherapy and neurodevelopment. We assumed a societal perspective in evaluating costs and maternal-neonatal quality-adjusted life years (QALYs) using a willingness-to-pay threshold of $100,000/QALY. Model inputs were derived from literature and varied in sensitivity analyses. RESULTS: Rooming-in resulted in fewer neonates requiring pharmacotherapy when compared with not rooming-in. The rooming-in group had more neonates with intact/mild neurodevelopmental impairment and fewer cases of moderate to severe impairment. Rooming-in resulted in cost savings of $509,652,728 and 12,333 additional QALYs per annual cohort. When the risk ratio of need for pharmacotherapy in rooming-in was varied across a clinically plausible range, rooming-in remained the cost-effective strategy. CONCLUSION: Maternal rooming-in with newborns affected by NOW leads to reduced costs and increased effectiveness. Management strategies should optimize nonpharmacological interventions as first-line treatment.

Monozygotic dichorionic diamniotic twins with large interstitial deletion of chromosome 1p.

We describe twins with an interstitial deletion of chromosome 1 with a severe phenotype compared to previously described cases. As genetic testing is more frequently performed, it is important for clinicians to understand the spectrum of clinical findings that can occur with this particular deletion.