Long-term burden of respiratory complications associated with extreme prematurity: An analysis of US Medicaid claims.

BACKGROUND: Infants born extremely premature (EP) (<28 weeks gestational age) are at high risk of complications, particularly bronchopulmonary dysplasia (BPD), which can develop into chronic lung disease (CLD). METHODS: The burden of respiratory complications in EP infants up to 2 years corrected age (CA) was evaluated using real-world data from the US Medicaid program. Data recorded between 1997 and 2018 on EP infants without major congenital malformations were collected from Medicaid records of six states. EP infants were divided into three cohorts: BPD, CLD, and without BPD or CLD. The incidence of respiratory conditions, respiratory medication use, and healthcare resource utilization were compared between the BPD cohort and CLD cohort versus the cohort without BPD or CLD, using unadjusted and adjusted generalized linear models. RESULTS: A total of 4462 EP infants were identified (17.4% of all premature infants in the database). Of these, BPD and CLD were diagnosed in 61.9% and 72.1%, respectively, and 14.5% were diagnosed with neither BPD nor CLD. Compared with infants without BPD or CLD, infants with BPD or CLD had more complications and a longer length of birth hospitalization stay. Respiratory distress syndrome was the most frequently reported complication (94.6%, 92.5%, and 82.3% of EP infants in the BPD, CLD, and without BPD or CLD cohorts, respectively). After the birth hospitalization, respiratory conditions, respiratory medication use, and incidence rates of rehospitalizations, emergency room visits, and outpatient visits were higher for infants with BPD or CLD. Rehospitalization occurred in 50.5%, 51.6%, and 27.3% of EP infants with BPD, CLD, or without BPD or CLD, respectively; most hospitalizations occurred for respiratory-related reasons. CONCLUSION: In this analysis of a large population of EP infants up to 2 years CA, respiratory conditions were prevalent after the birth hospitalization and were associated with high rates of medication and healthcare resource utilization.

Burden of Comorbidities and Healthcare Resource Utilization Among Medicaid-Enrolled Extremely Premature Infants.

Background: The effect of gestational age (GA) on comorbidity prevalence, healthcare resource utilization (HCRU), and all-cause costs is significant for extremely premature (EP) infants in the United States. Objectives: To characterize real-world patient characteristics, prevalence of comorbidities, rates of HCRU, and direct healthcare charges and societal costs among premature infants in US Medicaid programs, with respect to GA and the presence of respiratory comorbidities. Methods: Using International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification codes, diagnosis and medical claims data from 6 state Medicaid databases (1997-2018) of infants born at less than 37 weeks of GA (wGA) were collected retrospectively. Data from the index date (birth) up to 2 years corrected age or death, stratified by GA (EP, ≤28 wGA; very premature [VP], >28 to <32 wGA; and moderate to late premature [M-LP], ≥32 to <37 wGA), were compared using unadjusted and adjusted generalized linear models. Results: Among 25 573 premature infants (46.1% female; 4462 [17.4%] EP; 2904 [11.4%] VP; 18 207 [71.2%] M-LP), comorbidity prevalence, HCRU, and all-cause costs increased with decreasing GA and were highest for EP. Total healthcare charges, excluding index hospitalization and all-cause societal costs (US dollars), were 2 to 3 times higher for EP than for M-LP (EP $74 436 vs M-LP $27 541 and EP $28 504 vs M-LP $15 892, respectively). Conclusions: Complications of preterm birth, including prevalence of comorbidities, HCRU, and costs, increased with decreasing GA and were highest among EP infants during the first 2 years in this US analysis.

Neonatal Intensive Care Utilization and Postdischarge Newborn Outcomes: A Population-based Study of Texas Medicaid Insured Infants.

OBJECTIVE: To test the hypothesis that newborn infants cared for in hospitals with greater utilization of neonatal intensive care experienced fewer postdischarge adverse events. STUDY DESIGN: We developed 3 retrospective population-based cohorts of Texas Medicaid insured singletons born in 2010-2014 (very low birth weight [VLBW n = 11 139], late preterm [n = 57 509], and non-preterm [n = 664 447]) who received care in higher volume hospitals with level III/IV neonatal intensive care units (NICUs). Measures of NICU care were hospital-level risk adjusted NICU admission rates, special care days (days of nonroutine care) per infant, and the percent of intensive (highest billable care code) special care days. The units of analysis were hospitals (n = 80) and the primary outcome was an adverse event, (defined as admission, emergency department visit, or death) within 30 days postdischarge. RESULTS: Higher use of NICU care at a hospital level was not associated with lower postdischarge 30-day adverse event. Infants cared for in hospitals with above vs below median special care day rates experienced slightly higher postdischarge adverse event per 100 infants (VLBW: 14.01 [95% CI 12.74-15.27] vs 11.84 [10.52-13.16], P < .05; late preterm: 7.33 [6.68-7.97] vs 6.28 [5.87-6.69], P < .01; non-preterm: 4.47 [4.17-4.76] vs 3.97 [3.75-4.18], P < .01). Weak positive associations (Pearson correlations of 0.31-0.37, P < .01) were observed for adverse event with special care days; in no instance was a negative association observed between NICU utilization and adverse event. CONCLUSION: Higher utilization of NICU care was not associated with lower rates of short-term events suggesting that there may be opportunities to safely decrease admission rates and length of NICU stays.

Hypertension in neonates treated with intravitreal bevacizumab for retinopathy of prematurity.

OBJECTIVE: To investigate if preterm neonates developed systemic hypertension after intravitreal bevacizumab for retinopathy of prematurity. METHODS: Patients who received treatment between January 1, 2011 and January 31, 2019 were eligible for inclusion. Patients with pre-existing hypertension, congenital eye disease, or who were discharged within 72 h of treatment were excluded. Charts were reviewed for baseline data, co-morbidities, and the development of systemic hypertension within 4 weeks post treatment. RESULTS: After exclusions, 64 patients were analyzed. New-onset systemic hypertension was identified in 44 (69%) infants. There were no statistical differences in the demographic characteristics or presence of co-morbidities between the hypertensive and non-hypertensive groups. Of those who developed hypertension, the majority presented within the first week post treatment (55%). CONCLUSIONS: The majority of infants who received intravitreal bevacizumab developed new-onset systemic hypertension after treatment. Further studies may explore hypertension as a potential side effect of bevacizumab in the neonatal population.

Unbiasing costs? An appraisal of economic assessment alongside randomized trials in neonatology.

Economic evaluations performed alongside randomized controlled trials benefit from the protections against bias inherent in randomization. In this systematic review, we assessed the frequency and quality of economic assessments alongside randomized controlled trials of interventions in neonates published between 1990 and 2016. Over that period, 58 economic assessments were published, corresponding to approximately 2% of RCTs. We noted significant methodological limitations of these studies, including limitation of included costs to the health sector or payer rather than broader categories such as family or community expenditures (81%), short time horizon for cost measurement (less than one year in 60%), lack of reporting of uncertainty (26%), and infrequent analysis of costs and effects in a single metric (combined in 45%). Strategies for improving the quality and frequency of economic evaluations in neonatology are discussed, including selection of appropriate trials, funding, and peer review.

The financial burden on families of infants requiring neonatal intensive care.

While the high costs of neonatal intensive care have been a topic of increasing study, the financial impact on families have been less frequently reported or summarized. We conducted a systematic review of the literature using Pubmed/Medline and EMBASE (1990-2020) for studies reporting estimates of out-of-pocket costs or qualitative estimates of financial burden on families during a neonatal intensive care unit stay or after discharge. 44 studies met inclusion criteria, with 25 studies providing cost estimates. Cost estimates primarily focused on direct non-medical out-of-pocket costs or loss of productivity, and there was a paucity of cost estimates for insurance cost-sharing. Available estimates suggest these costs are significant to families, cause significant stress, and may impact care received by patients. More high-quality studies estimating the entirety of out-of-pocket costs are needed, and particular attention should be paid to how these costs directly impact the care of our high-risk population.

Prevalence of chronic respiratory morbidity, length of stay, inpatient readmissions, and costs among extremely preterm infants with bronchopulmonary dysplasia.

Objective: To evaluate the prevalence of chronic respiratory morbidity (CRM) in preterm infants (born ≤28 weeks gestational age (GA)) and compare healthcare resource utilization and costs among infants with/without CRM, and with/without bronchopulmonary dysplasia (BPD).Methods: Commercial claims data from the Truven MarketScan database were retrospectively analyzed. Included infants were born ≤28 weeks GA and admitted to a neonatal intensive care unit (January 2009-June 2016). Continuous insurance eligibility was required from birth through 1 year (CRM/no CRM cohorts) or ≥3 months (BPD/no BPD cohorts) CA or death.Results: CRM analysis included 1782 infants; 29.0% had CRM. BPD analysis included 2805 infants; 61.1% had BPD. The mean birth hospital length of stay was longer in infants with CRM versus those with no CRM (p < 0.0001). In infants with CRM or BPD, hospital readmission rates were significantly increased versus those without (both p < 0.0001). Total health care costs were significantly higher in infants with CRM (p = 0.0488) and BPD (p < 0.0001) versus those without. After birth hospitalization, outpatient visits and hospital readmissions accounted for most of the costs for the CRM and BPD cohorts.Conclusion: CRM and BPD following extremely preterm birth impose a significant health care burden.

Airway management protocol for conjoined twins delivery.

OBJECTIVE: Conjoined twin deliveries require collaborative preparation by multiple specialties for successful airway management. Literature regarding neonatal airway management after conjoined twin delivery is limited to case reports. We present a case series of conjoined twins and introduce an airway management protocol for conjoined twin delivery. METHODS: The medical records of conjoined twins and their mothers at a tertiary care center were reviewed from April 2016 to December 2018. The NCBI database was queried for literature regarding preparation for neonatal airway management after conjoined twins delivery. RESULTS: Five sets of conjoined twins were delivered. Of 10 neonates, all required bag valve mask ventilation. Other airway interventions included continuous positive airway pressure (7), endotracheal intubation (6), and direct laryngoscopy with telescopic video evaluation (1). No patients required ex-utero intrapartum treatment or emergent tracheostomy. A protocol for airway management is described and special considerations are discussed, including anatomic variations, equipment list, operating room staffing and layout, multidisciplinary prenatal conference, and airway imaging review. CONCLUSION: Conjoined twin deliveries have significant implications for the otolaryngologist and require multidisciplinary collaboration. An airway management protocol allows for a standardized process to secure the neonatal airway and optimize patient outcomes.

Hypertension and Neuroimaging Changes After Bevacizumab for Retinopathy of Prematurity.

Bevacizumab is a human monoclonal immunoglobulin G1 antibody to vascular endothelial growth factor indicated in several adult diseases. Emerging literature and expert opinion support the off-label use of intravitreal bevacizumab in the treatment of retinopathy of prematurity (ROP), a common disease process seen in premature neonates. One of the most common side effects of systemic therapy in adults is hypertension; however, this has not been well described in infants receiving bevacizumab for ROP. In this report, we review a case of a former 25-week premature infant treated for stage 3 ROP with administration of intravitreal bevacizumab. The immediate posttreatment course was uncomplicated; however, at 10 days posttreatment, he developed new-onset systemic hypertension. In addition, neuroimaging revealed new areas of vasogenic edema, which improved over time. To the best of our knowledge and after a review of the literature, neither of these effects has been described in neonates after intravitreal bevacizumab for ROP.

Neonatal Intensive Care Variation in Medicaid-Insured Newborns: A Population-Based Study.

OBJECTIVE: To assess the contribution of maternal and newborn characteristics to variation in neonatal intensive care use across regions and hospitals. STUDY DESIGN: This was a retrospective population-based live birth cohort of newborn infants insured by Texas Medicaid in 2010-2014 with 2 subcohorts: very low birth weight (VLBW) singletons and late preterm singletons. Crude and risk-adjusted neonatal intensive care unit (NICU) admission rates, intensive and intermediate special care days, and imaging procedures were calculated across Neonatal Intensive Care Regions (n = 21) and hospitals (n = 100). Total Medicaid payments were calculated. RESULTS: Overall, 11.5% of live born, 91.7% of VLBW, and 37.6% of infants born late preterm were admitted to a NICU, receiving an average of 2 days, 58 days, and 5 days of special care with payments per newborn inpatient episode of $5231, $128 075, and $10 837, respectively. There was little variation across regions and hospitals in VLBW NICU admissions but marked variation for NICU admissions in late preterm newborn infants and for special care days and imaging rates in all cohorts. The variation decreased slightly after health risk adjustment. There was moderate substitution of intermediate for intensive care days across hospitals (Pearson r VLBW -0.63 P < .001; late preterm newborn -0.53 P < .001). CONCLUSIONS: Across all risk groups, the variation in NICU use was poorly explained by differences in newborn illness levels and is likely to indicate varying practice styles. Although the "right" rates are uncertain, it is unlikely that all of these use patterns represent effective and efficient care.

Health Care Burden of Bronchopulmonary Dysplasia Among Extremely Preterm Infants.

Background: Infants born extremely preterm are at high risk of developing bronchopulmonary dysplasia (BPD). This study aimed to assess the incremental health care burden of BPD and associated comorbidities among extremely preterm infants in the United States. Methods: Health service claims in the Premier Perspective database were retrospectively analyzed for infants born at ≤28 weeks gestation who were admitted to neonatal intensive care during birth hospitalization and survived to a postmenstrual age of ≥36 weeks. Gestational age (GA) at birth and BPD status of infants was determined based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes recorded in the database. Results: Of the 12,017 infants included, 4,904 (40.8%) had BPD. BPD increased with decreasing GA: 67.4% of infants born at <24 weeks GA had BPD vs. 28.7% of those born at 27-28 weeks. Infants with BPD had significantly longer hospital stays following birth than those without (mean [standard deviation (SD)] 102 [34] vs. 83 [24] days, respectively, P < 0.001), and incurred higher total charges (mean [SD] $799,499 [$535,528] vs. $588,949 [$377,137], respectively, P < 0.001). Mean total charges incurred during index hospitalization decreased as GA at birth increased, with GA having a bigger effect than presence or absence of BPD. During their first year, infants with BPD had a higher in-hospital late mortality rate than those without (1.9 vs. 0.6%), and were more likely to have two or more hospital encounters following birth hospitalization (58.0 vs. 48.2%). Among infants who had two or more encounters after discharge, those with BPD experienced a higher percentage of pulmonary symptoms than those without (46.3 vs. 38.9%). Comparison with infants who did not have BPD, retinopathy of prematurity, or intraventricular hemorrhage showed that BPD is the main complication contributing to increased length of stay, costs, in-hospital mortality, and additional health care encounters. Conclusion: BPD is a key contributor to the large health care burden associated with extremely preterm birth. However, GA at birth has a bigger effect on health care costs for extremely preterm infants than the presence of BPD.

The cost of necrotizing enterocolitis in premature infants.

Necrotizing enterocolitis (NEC), a common morbidity of prematurity, affects 5-10% of premature infants with a birthweight <1500 g. The added cost remains unclear. Multiple studies report the cost of care for an infant with NEC as higher than that of well premature infants, but these studies are fraught with limitations. Surgical intervention and type of surgery appear to impact overall costs. Health care resource utilization extends beyond the birth hospitalization, particularly in those infants requiring surgery, and persists to at least three years of age. This narrative review of the literature reveals a paucity of studies and significant methodological deficiencies in most included studies. Further studies of the cost of NEC need to address the issues of significant confounding in this complex population.

Effect of prenatal diagnosis on hospital costs in complete transposition of the great arteries.

OBJECTIVE: Prenatal diagnosis of congenital heart disease (CHD) is associated with improved clinical outcomes, yet its impact on the cost of hospitalization is not well described. We hypothesized that prenatal diagnosis of complete transposition of the great arteries (d-TGA) results in lower total hospital costs compared with postnatal diagnosis. METHODS: Retrospective analysis of infants with d-TGA repaired at our center from July 2006 to 2014. Total charges from initial hospitalization until discharge were converted to costs using the cost-to-charge ratio and then converted into 2016 dollars using the consumer price index. A direct cost comparison from the hospital perspective was performed between groups. A secondary analysis included the cost of prenatal diagnosis. RESULTS: Thirty-three infants with d-TGA were identified; 8 with and 25 without prenatal diagnosis. There was no difference in baseline characteristics. Mean direct cost of hospitalization was higher in infants without prenatal diagnosis ($108 014 ± $51 305 vs $88 305 ± $22 896, P = .31). On secondary analysis, the cost of prenatal diagnosis was negligible compared with total hospital cost. CONCLUSIONS: Total cost of initial hospitalization was higher for infants without prenatal diagnosis of d-TGA. Prenatal diagnosis not only improves clinical outcomes but may also be cost saving in the current era of increasing health care costs.

Cholestasis and Hepatic Iron Deposition in an Infant With Complex Glycerol Kinase Deficiency.

We present a 6-week-old male infant with persistent hyperbilirubinemia, hypertriglyceridemia, elevated creatine kinase levels, and transaminitis since the second week of life. When he developed hyperkalemia, clinical suspicion was raised for adrenal insufficiency despite hemodynamic stability. A full endocrine workup revealed nearly absent adrenocorticotropic hormone. Coupled with his persistent hypertriglyceridemia (peak of 811 mg/dL) and elevated creatine kinase levels (>20 000 U/L), his corticotropin level lead to a clinical diagnosis of complex glycerol kinase deficiency (GKD), also known as Xp21 deletion syndrome. This complex disorder encompasses the phenotype of Duchenne muscular dystrophy, GKD, and congenital adrenal hypoplasia due to the deletion of 3 contiguous genetic loci on the X chromosome. Our case exemplifies the presentation of this disorder and highlights the important lesson of distinguishing between adrenal hypoplasia congenita and congenital adrenal hyperplasia, as well as the sometimes subtle presentation of adrenal insufficiency. To our knowledge, it is also the first reported case of complex GKD deficiency with the additional finding of hepatic iron deposition, which may indicate a potential area for exploration regarding the pathogenesis of liver injury and cholestasis seen in cortisol-related endocrinopathies.

Supply-Side Disruption in Cocaine Production Associated With Cocaine-Related Maternal and Child Health Outcomes in the United States.

OBJECTIVES: To investigate the effects of precursor chemical regulation aimed at reducing cocaine production on cocaine-related maternal and newborn hospital stays in the United States. METHODS: We analyzed monthly counts of maternal and neonatal stays from January 2002 through December 2013 by using a quasi-experimental interrupted time series design. We estimated the preregulation linear trend, postregulation change in linear trend, and abrupt change in level. RESULTS: The number of monthly cocaine-related maternal and neonatal stays decreased by 221 and 128 stays, respectively, following the cocaine precursor regulation change. We also observed a further decline in per-month maternal and neonatal stays of 18 and 8 stays, respectively. CONCLUSIONS: A supply-side disruption in the United States cocaine market was associated with reduced hospital stays for 2 vulnerable populations: pregnant women and newborns. Results support findings that federal precursor regulation can positively reduce cocaine availability in the United States.