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.

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.

Connecting to Early Intervention Services After Neonatal Intensive Care Unit Discharge in a Medicaid Sample.

OBJECTIVE: To describe caregiver perspectives regarding connecting to early intervention (EI) services after neonatal intensive care unit discharge in a Medicaid sample. METHODS: Open-ended semistructured interviews and focus groups were conducted with English- or Spanish-speaking families enrolled in Medicaid in an urban high-risk infant follow-up clinic at a safety-net center, which serves preterm and high-risk term infants. We generated salient themes using inductive-deductive thematic analysis. RESULTS: Thirty-two participants completed the study. The infant's median (interquartile range) birth weight was 1365 (969, 2800) grams; 50% were Hispanic; 31% reported living in a neighborhood with fourth quartile economic hardship. Eighty-one percent were classified as having chronic complex disease per the Pediatric Medical Complexity Algorithm and 63% had a diagnosis of developmental delay. A conceptual model was constructed and the analysis revealed major themes describing families' challenges and ideas to facilitate connection to EI. We identified subthemes related to the person in environment: health care environment/support and socio-economic resources, parent perspectives and built environment; provider level factors such as appointment scheduling, staff limitations, and parent suggestions to improve health care and service navigation, which included improved information sharing, the importance of patient advocates, video resources, early referrals to EI facilitated by the discharging hospital and system workarounds. CONCLUSIONS: The results from this study may provide a granular roadmap for providers to help facilitate referrals to EI services. We identified several ideas such as using advocates and providing transitional resources, including online media, that might improve the connection to EI services.

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.

The association of care transitions measure-15 score and outcomes after discharge from the NICU.

BACKGROUND: Our objectives were (1) to describe Care Transitions Measure (CTM) scores among caregivers of preterm infants after discharge from the neonatal intensive care unit (NICU) and (2) to describe the association of CTM scores with readmissions, enrollment in public assistance programs, and caregiver quality of life scores. METHODS: The study design was a cross-sectional study. We estimated adjusted associations between CTM scores (validated measure of transition) with outcomes using unconditional logistic and linear regression models and completed an E-value analysis on readmissions to quantify the minimum amount of unmeasured confounding. RESULTS: One hundred sixty-nine parents answered the questionnaire (85% response rate). The majority of our sample was Hispanic (72.5%), non-English speaking (67.1%) and reported an annual income of <$20,000 (58%). Nearly 28% of the infants discharged from the NICU were readmitted within a year from discharge. After adjusting for confounders, we identified that a positive 10-point change of CTM score was associated with an odds ratio (95% CI) of 0.74 (0.58, 0.98) for readmission (p = 0.01), 1.02 (1, 1.05) for enrollment in early intervention, 1.03 (1, 1.05) for enrollment in food assistance programs, and a unit change (95% CI) 0.41 (0.27, 0.56) in the Multicultural Quality of Life Index score (p < 0.0001). The associated E-value for readmissions was 1.6 (CI 1.1) suggesting moderate confounding. CONCLUSION: The CTM may be a useful screening tool to predict certain outcomes for infants and their families after NICU discharge. However, further work must be done to identify unobserved confounding factors such as parenting confidence, problem-solving and patient activation.

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.

Association of WIC Participation and Growth and Developmental Outcomes in High-Risk Infants.

The objective of this study was to describe the association of enrollment in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC), the Supplemental Nutrition Assistance Program (SNAP), and infant growth and neurodevelopmental outcomes. Z scores and Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) and Vineland Adaptive/Behavior Scale-II (VABS-II) scores represented primary outcomes. We conducted bivariate analyses and linear regression. Children who were enrolled in WIC or WIC/SNAP had weight z scores U (95% confidence interval [CI]) that were 1.32 (0.42-2.21) or 1.19 (0.16-2.23) units higher. Enrollment in WIC or WIC/SNAP was associated with a higher score (95% CI) of 11.7 U (1.2-22.2 U) or 11.5 (0.1-22.9) for Bayley-III cognitive score and 10.1 U (1.9-19.1 U) or 10.3 (0.9-19.7) for the VABS-II composite score. These findings support increased advocacy for participation in WIC or WIC/SNAP for families with high-risk infants.

Delivery timing after laser surgery for twin-twin transfusion syndrome.

OBJECTIVE: To compare outcomes of twin-twin transfusion syndrome (TTTS) patients who underwent early elective delivery vs. expectant management. STUDY DESIGN: Retrospective study of monochorionic diamniotic twins who underwent laser surgery for TTTS and had dual survivors at 32 weeks. Patients who underwent elective delivery between 32 0/7 to 35 6/7 weeks ("early elective group") were compared with all patients who delivered ≥36 0/7 weeks ("expectant management group"). The primary outcome was a composite of fetal and neonatal morbidity. RESULTS: The final study population was comprised of 15 early elective and 119 expectant management patients. Those in the early elective group were seven times more likely to experience the primary outcome (OR 7.38 [2.01-27.13], p = 0.0026). CONCLUSION: Among patients who underwent laser surgery for TTTS who had dual survivors at 32 weeks, elective delivery prior to 36 weeks did not appear to be protective.

Viewpoints from families for improving transition from NICU-to-home for infants with medical complexity at a safety net hospital: a qualitative study.

BACKGROUND: We have limited information on families' experiences during transition and after discharge from the neonatal intensive care unit. METHODS: Open-ended semi-structured interviews were conducted with English or Spanish- speaking families enrolled in Medicaid in an urban high-risk infant follow up clinic at a safety-net center, which serves preterm and high-risk term infants. We generated salient themes using inductive-deductive thematic analysis. RESULTS: Twenty-one participants completed the study. The infant's median (IQR) birth weight was 1750 (1305, 2641) grams; 71% were Hispanic and 10% were Black non-Hispanic; 62% reported living in a neighborhood with 3-4th quartile economic hardship. All were classified as having chronic disease per the Pediatric Medical Complexity Algorithm and 67% had medical complexity. A conceptual model was constructed and the analysis revealed major themes describing families' challenges and ideas to support transition centered on the parent-child role and parent self-efficacy. The challenges were: (1) comparison to normal babies, (2) caregiver mental health, (3) need for information. Ideas to support transition included, (1) support systems, (2) interventions using mobile health technology (3) improved communication to the primary care provider and (4) information regarding financial assistance programs. Specific subthemes differed in frequency counts between infants with and without medical complexity. CONCLUSIONS: Families often compare their preterm or high-risk infant to their peers and mothers feel great anxiety and stress. However, families often found hope and resilience in peer support and cited that in addition to information needs, interventions using mobile health technology and transition and financial systems could better support families after discharge.

The association of Trisomy 13 and 18 and hospital discharge outcomes among neonates in California: A retrospective cohort study.

BACKGROUND: Despite Trisomy 13 and 18 being among the most fatal congenital anomalies, limited information exists about resource utilization and factors associated with length of stay (LOS) and total hospital charges (THC) for these anomalies. METHODS: We studied data sets of the patient discharge data set from the California Office of Statewide Health Planning and Development from 2006 to 2010, to determine differences in resource utilization for survivors and non-survivors and identify the predictors of LOS and total hospital charges. Descriptive statistics were assessed for demographic and clinical characteristics. General linear regression models were used to identify predictors of LOS and THC. RESULTS: Seventy-six Trisomy 13 and 115 Trisomy 18 patients were identified, for whom inpatient mortality was 27.6% and 20.9%, respectively. In patients with Trisomy 13, after adjusting for gender, ethnicity, advanced directive (DNR), insurance and co-morbidities on multivariate analysis, the provision of more than 96 h of mechanical ventilation was associated with significantly increased LOS (standard error, SE) by 18.0 ± 5.3 days and THC (SE) by $399,000 ± $85,000. In terms of insurance type, patients with private coverage had 10.8 ± 4.9 days more than patients with Medicaid. In patients with Trisomy 18, on multivariate analysis, after adjusting for gender, ethnicity, DNR, insurance and co-morbidities, more than 96 h of mechanical ventilation was associated with increased LOS (SE) by 36.8 ± 6.8 days and THC (SE) by $365,000 ± $59,000. CONCLUSION: Understanding predictors that are associated with longer LOS and higher THC may be associated in hospital resource allocation for this vulnerable population of infants.

Resource utilization patterns using non-invasive ventilation in neonates with respiratory distress syndrome.

OBJECTIVES: To describe the frequency of non-invasive ventilation (NIV) and endotracheal intubation use in neonates diagnosed with respiratory distress syndrome (RDS); to describe resources utilization (length of stay (LOS), charges, costs) among NIV and intubated RDS groups. STUDY DESIGN: Retrospective study from the national Kid's Inpatient Database of the Healthcare Cost and Utilization Project, for the years 1997-2012. Propensity scoring and multivariate regression analysis used to describe differences. RESULTS: A total of 595,254 out of 42,912,090 cases were identified with RDS. There was an increase in NIV use from 6% in 1997 to 17% in 2012. After matching, patients receiving NIV only were associated with shorter LOS: (95%CI) 25 (25.3,25.7) vs. 35 (34.2,34.9) days, decreased costs: ($/1k) 46.1 (45.5,46.8) vs. 65.0 (64.1,66.0), decreased charges: 130.3 (128.6,132.1) vs. 192.1 (189.5,194.6) compared to intubated neonates. CONCLUSION: There was a three-fold increase in NIV use within the 15-year study period. NIV use was associated with decreased LOS, charges and costs compared to intubated patients.

Utilization patterns of extracorporeal membrane oxygenation in neonates in the United States 1997-2012.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) remains one of the most intensive therapies for newborns in the United States. However, there is limited information on resource utilization for neonates receiving ECMO. METHODS: We conducted a retrospective data analysis of the Kids' Inpatient Database from 1997 to 2012. Bivariate and multivariate analysis was completed to identify predictors of LOS, hospital costs and mortality. Cardiac and non-cardiac diagnoses of neonates receiving ECMO were also included in the bivariate and multivariable analysis. RESULTS: Of the 5151 ECMO cases, survival to discharge was 62%. 22% had a principal cardiac diagnosis. After adjusting for covariates, increased mortality was associated with treatment in the midwest compared to the northeast region (aOR=2.0, p<0.01) and decreased among neonates with a non-cardiac diagnosis (aOR=0.4, p<0.01). Living in midwest was associated with longer LOS by 13days and increased hospital costs by 63,000 dollars (p<0.01). When stratified by non-cardiac diagnoses, infants with a diagnosis of congenital diaphragmatic hernia was associated with increased mortality (2.3, p<0.01) and longer LOS (25, p<0.01) and increased costs (11,100, p<0.01). CONCLUSION: Neonates who received ECMO in certain regions of the United States were associated with poorer survival outcomes as well as increased LOS and hospital costs. TYPE OF STUDY: Retrospective study. LEVEL OF EVIDENCE: Level III.

The Role of Extracorporeal Membrane Oxygenation Simulation Training at Extracorporeal Life Support Organization Centers in the United States.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) requires a multidisciplinary healthcare team. The Extracorporeal Life Support Organization publishes training guidelines but leaves specific requirements up to each institution. Simulation training has shown promise, but it is unclear how many institutions have incorporated simulation techniques into ECMO training to date. METHODS: We sent an electronic survey to ECMO coordinators at Extracorporeal Life Support Organization sites in the United States. Participants were asked about training practices and the use of simulation for ECMO training. Descriptive results were reported as the percentage of total responses for each question. Logistic regression was used to identify characteristics associated with simulation use. RESULTS: Of 94 responses (62% response rate), 46% had an ECMO simulation program, whereas 26% report a program is in development. Most (61%) have been in operation for 2 to 5 years. Sixty-three percent use simulation for summative assessment, and 76% have multidisciplinary training. Access to a simulation center [odds ratio (OR) = 4.7, 95% confidence interval (CI) = 1.7-12.5], annual ECMO caseload of greater than 20 (OR = 2.5, 95% CI = 1.5-5.8), and having a pediatric cardiothoracic intensive care unit (OR = 2.8, 95% CI = 1.2-6.7) are each associated with increased likelihood of mannequin-based ECMO simulation. Common scenarios include pump failure (93%), oxygenator failure (90%), and circuit rupture (76%). DISCUSSION: Extracorporeal membrane oxygenation simulation is growing but remains in its infancy. Centers with access to a simulation center, higher caseloads, and pediatric cardiothoracic intensive care units are more likely to have ECMO simulation programs. Extracorporeal membrane oxygenation simulation is felt to be beneficial, and further work is needed to delineate best training practices for ECMO providers.

The impact of preterm birth <37 weeks on parents and families: a cross-sectional study in the 2 years after discharge from the neonatal intensive care unit.

BACKGROUND: Little is known about the quality of life of parents and families of preterm infants after discharge from the neonatal intensive care unit (NICU). Our aims were (1) to describe the impact of preterm birth on parents and families and (2) and to identify potentially modifiable determinants of parent and family impact. METHODS: We surveyed 196 parents of preterm infants <24 months corrected age in 3 specialty clinics (82% response rate). Primary outcomes were: (1) the Impact on Family Scale total score; and (2) the Infant Toddler Quality of Life parent emotion and (3) time limitations scores. Potentially modifiable factors were use of community-based services, financial burdens, and health-related social problems. We estimated associations of potentially modifiable factors with outcomes, adjusting for socio-demographic and infant characteristics using linear regression. RESULTS: Median (inter-quartile range) infant gestational age was 28 (26-31) weeks. Higher Impact on Family scores (indicating worse effects on family functioning) were associated with taking ≥3 unpaid hours/week off from work, increased debt, financial worry, unsafe home environment and social isolation. Lower parent emotion scores (indicating greater impact on the parent) were also associated with social isolation and unpaid time off from work. Lower parent time limitations scores were associated with social isolation, unpaid time off from work, financial worry, and an unsafe home environment. In contrast, higher parent time limitations scores (indicating less impact) were associated with enrollment in early intervention and Medicaid. CONCLUSIONS: Interventions to reduce social isolation, lessen financial burden, improve home safety, and increase enrollment in early intervention and Medicaid all have the potential to lessen the impact of preterm birth on parents and families.

Acetazolamide for the management of chronic metabolic alkalosis in neonates and infants.

In this study, we evaluated the efficacy and safety of acetazolamide in the management of chronic metabolic alkalosis in neonates and infants with chronic respiratory insufficiency. A retrospective chart review of 90 patients treated with acetazolamide between 2006 and 2007 admitted to the neonatal intensive care unit was performed. Blood gases and electrolytes obtained at baseline and by 24 hours after acetazolamide administration were compared. Compared with baseline and after 24 hours of acetazolamide, mean measured serum bicarbonate (29.5±3.7 vs. 26.9±3.8 mEq/L, P<0.001) and base excess (10.0±3.4 vs. 4.8±4.0 mEq/L, P<0.001) were significantly lower. No significant differences in other electrolytes, blood urea nitrogen, and urine output were noted, except for an increased serum chloride and creatinine. Uncompensated respiratory acidosis developed in 4 (3.1%) treatment courses. Acetazolamide may be effective in decreasing serum bicarbonate in carefully selected patients. Its use and safety as an adjunctive therapy for chronic metabolic alkalosis in neonates and infants with chronic respiratory insufficiency needs further study.

Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.

Hospital rates of maternal and neonatal infection in a low-risk population.

BACKGROUND: In 2003, the Agency for Healthcare Quality and Research (AHRQ) published its Quality Indicators for healthcare, and set out methodological criteria for the evaluation of potential candidates. OBJECTIVES: Because perinatal infections may result from poor obstetrical practices, we intended to describe the variability of maternal and congenital neonatal infections across different types of hospital ownership (e.g., not for profit, government), and to assess whether rates of these infections meet criteria as quality indicators. RESEARCH DESIGN: Population-based cohort study. SUBJECTS: All laboring women without maternal, fetal, or placental complications who delivered in California in 1997, and their neonates, as reported through hospital discharge data. MEASURES: A Bayesian hierarchical logistic regression model was used to quantify the effects of both "patient-level" risk factors such as parity and prior cesarean history, and "hospital-level" risk factors such as ownership and teaching status. RESULTS: The 308,841 mother-newborn pairs in this low-risk study population delivered at 281 hospitals; 0.39% had uterine infections and 1.3% had neonatal infections. Hospital ownership and teaching status were strongly associated with perinatal infection. Secondly, methods used to estimate and analyze hospital-specific infection rates identified hospitals with exceptionally high rates. Twenty-eight hospitals had neonatal infection rates that ranged from 3% to 28%. CONCLUSIONS: The methods presented here were consistent with AHRQ methods and criteria for potential Quality Indicators. They also identified hospitals with exceptionally high rates of infectious morbidity. The relationship between hospital ownership and obstetrical practice patterns, and the feasibility of practice improvement, remain to be studied.