Abstract
Objective:
To compare the abilities of bronchopulmonary dysplasia (BPD) definitions to predict hospital charges as a surrogate of disease complexity.
Methods:
Retrospective study of infants admitted to the neonatal intensive care unit (NICU) <32 weeks gestational age. Subjects were classified according to the Canadian Neonatal Network (CNN), the National Institute of Child Health and Human Development (NICHD 2018), and Jensen BPD definitions as none, mild (1), moderate (2), or severe (3) BPD. Spearman’s correlation was performed to evaluate the association of BPD definitions with health economics outcomes.
Results:
168 infants were included with mean birth weight of 1197 g and mean gestational age of 28.4 weeks. More infants were classified as no BPD according to CNN definition (79%) in comparison to NICHD 2018 (64.3%) and Jensen (59.5%) definitions. There were fewer infants as the grade of severity increased for all definitions, this was most linear for Jensen definition with grade 1 present in 25%, grade 2 in 12.5%, and grade 3 in 3%. A stronger correlation with NICU length of stay, NICU hospital charges, NICU charges per day, and first year of life hospital charges was detected for Jensen definition (correlation coefficient of 0.58, 0.66, 0.64, 0.67 respectively) in comparison to CNN and NICHD 2018 definitions (p<0.0001).
Conclusion:
Jensen BPD definition had the strongest correlation with first year health economics outcomes in our study. Validating recent BPD definitions using population-based data is imperative to improve family counseling and enhance the designs of quality improvement initiatives and therapeutic research studies targeting patient-centric outcomes.
Keywords: Bronchopulmonary dysplasia, Health economics, Neonatal intensive care, Outcome, Preterm infants
Introduction
Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity 1 and is associated with abnormal pulmonary function, more frequent hospitalization, and increased resource utilization throughout childhood 2-8. The understanding of BPD pathogenesis, prevention, diagnosis, and management has evolved over the past fifty years 9, as has its definition. Using a binary definition of BPD has been recognized to be inadequate to describe the disease severity spectrum or accurately predict respiratory outcomes after discharge from the neonatal intensive care unit (NICU) 10.
In 2001, a workshop of experts organized by the National Institute of Child Health and Human Development (NICHD) first introduced a BPD severity grading system based on oxygen use at 36 weeks postmenstrual age (PMA) with infants requiring a fraction of inspired oxygen (FiO2) < 30% as moderate BPD and those requiring positive pressure ventilation or FiO2 ≥ 30% as severe BPD 11. Recently, several other BPD severity grading systems have been proposed due to substantial changes in different aspects of neonatal care. First, an analysis of the Canadian Neonatal Network (CNN) data showed that the use of oxygen and positive pressure respiratory support at 40 weeks PMA was the best predictor for serious respiratory morbidity and neurosensory impairment at 18–21 months. This outperformed the use of oxygen level alone, and the traditionally used 36 weeks PMA as BPD point of assessment 12. Second, the NICHD published a revision of its 2001 definition in 2018 with consideration of recent trends in respiratory treatment strategies such as using low flow nasal cannula with 100% oxygen or high flow nasal cannula with room air. The definition includes three severity grades and accounts for the subset of infants who die before 36 weeks PMA due to respiratory failure from lung disease that cannot be attributed to other neonatal morbidities 13. Most recently, Jensen et al. analyzed 18 prespecified BPD definitions according to the respiratory support level and supplemental oxygen at 36 weeks PMA to determine which definition best correlated with early childhood morbidity. The author demonstrated that a grading system based on respiratory support regardless of oxygen level best predicted late death or serious respiratory morbidity at 18–26 months corrected age 14. Jensen definition classified BPD severity in infants at 36 weeks PMA into: grade 1 if require 2 L/min nasal cannula or less, grade 2 if require more than 2 L/min nasal cannula or other forms of non-invasive ventilation support, and grade 3 if require invasive mechanical ventilation 14.
Identifying infants with BPD at risk of respiratory morbidity post discharge is imperative from a clinical perspective to better counsel families and arrange for specialized pulmonology follow up 15. It is also important for consistent reporting to various data registries to allow enhanced measurement of process improvement and to refine the design of future clinical trials targeting infants at risk for longstanding complications 13. However, how well these BPD definitions predict long term pulmonary and health care outcomes through childhood in the general population requires validation 10; 12; 14; 16.
BPD has been shown to be a key contributor to the large health care burden associated with prematurity, including longer hospital stay, higher hospital costs and charges, and more frequent rehospitalization of affected patients through the first year of life 17; 18. However, neither study evaluated for correlation with the severity of the disease 17; 18. The objective of this study is to compare between recently proposed BPD severity grading systems 12-14 to determine the definition that is most predictive of health economics impacts through the first year of life as a surrogate of disease complexity and resource utilization.
Methods
Study population and data collection:
This is a retrospective study of infants admitted to the NICU at the Children’s Hospital of Orange County (CHOC), Orange, CA, a quaternary level referral center with a specialized extremely low birth weight care program 19. Infants included were those admitted within the first 30 days of life between January 2017 and December 2018 with gestational age less than 32 weeks who survived to 36 weeks PMA. Subjects were excluded if there were major congenital malformations or if they were transferred to another facility before 36 weeks PMA. CHOC has no maternity services; all study subjects were outborn, including only those admitted in the first 30 days of life to sample a relatively homogenous group. The study was approved by the hospital institutional review board. Most of the study clinical variables were extracted from a local database established through participation in the Children’s Hospital Neonatal Consortium. Prospectively defined variables are abstracted by a trained data abstractor from the electronic medical record and entered into a web-based data collection tool 20. The authors reviewed the medical records for the clinical variables which were not readily available in the database, such as post NICU discharge hospitalizations and emergency room visits. The hospital financial department provided financial data for initial hospitalization and first year of life for the cohort of patients who met inclusion criteria. A financial analyst was given a list of subjects’ medical record numbers and provided the investigators with the cohort NICU and first year of life hospital charges. The analyst was blinded to all clinical information.
BPD severity grading comparison:
We classified the study cohort based on the level of oxygen and/or respiratory support as grade 0 (none), 1 (mild), 2 (moderate), or 3 (severe) BPD, according to the CNN 12, NICHD 2018 13 and Jensen 14 definitions. The time of assessment for oxygen/respiratory support was 36 weeks PMA for the NICHD 2018 and Jensen, and 40 weeks PMA for the CNN categorization, as shown to be best predictive for long term outcomes in their report 12. Infants discharged home with no respiratory support before the time of assessment (36 or 40 weeks PMA) were considered to have no BPD. Details of the three grading systems are shown in Table 1. We omitted respiratory treatment modes that were not used in our hospital, such as oxygen hood and non-invasive high-frequency ventilation.
Table 1.
BPD severity grading according to the CNN (12), NICHD 2018 (13) and Jensen (14) definitions
| CNN | NICHD 2018 | Jensen | |
|---|---|---|---|
| Grade 1 or mild | NC <0.1 L/min, FiO2 100% | NC <1 L/min, FiO2 22-70% | NC ≤2 L/min |
| NC <1.5 L/min, FiO2 21-99% | NC 1-3 L/min, FiO2 22-29% | ||
| CPAP, NIPPV or NC ≥3 L/min, FiO2 21% | |||
| Grade 2 or moderate | NC ≥0.1 L/min, FiO2 100% | NC <1 L/min, FiO2 ≥70% | NC >2 L/min |
| NC ≥1.5 L/min, FiO2 21-29% | NC 1-3 L/min, FiO2 ≥30% | CPAP or NIPPV | |
| CPAP or NIPPV, FiO2 21-29% | CPAP, NIPPV or NC ≥3 L/min, FiO2 22-29% | ||
| Mechanical ventilation, FiO2 21% | |||
| Grade 3 or severe | NC ≥1.5 L/min, FiO2 ≥30% | CPAP, NIPPV or NC ≥3 L/min, FiO2 ≥30% | Mechanical ventilation |
| CPAP or NIPPV, FiO2 ≥30% | Mechanical ventilation, FiO2 >21% | ||
| Mechanical ventilation |
Time of assessment is 36 weeks PMA except for CNN at 40 weeks PMA
Abbreviations: BPD = bronchopulmonary dysplasia; CPAP = continue positive airway pressure; FiO2 = fraction of inspired oxygen; NC = nasal cannula; NIPPV = non-invasive positive pressure ventilation; PMA = postmenstrual age
Outcomes:
We evaluated which of the three recent BPD severity grading systems best predicted health economics impacts through the first year of life, including hospital charges for initial NICU stay and first year of life, NICU length of stay (LOS), and hospital charges per day. Secondary outcomes included the number of hospitalizations and emergency department visits post NICU discharge.
Statistical analysis:
Spearman’s correlation was used to evaluate the association of each of the three BPD grading systems with health economics outcomes. The best definition was determined to be the one with the strongest correlations. Next, relevant maternal, perinatal, and neonatal characteristics of the different severity grades for the best definition were summarized and compared. The summary statistics are provided as mean (standard deviation- SD) for continuous variables or frequency (proportions) for categorical variables. For continuous variables, ANOVA was used to test the difference between groups. Categorical variables were examined by Chi-square test. All analyses were performed with SAS version 9.4 and R version 4.0.
Results
Baseline characteristics:
One hundred eighty-eight infants less than 32 weeks gestational age were admitted during the study period. 168 met inclusion criteria, and 20 were excluded due to death (18) or transfer to another facility (2) before 36 weeks PMA. The perinatal, maternal, neonatal characteristics, and outcomes of the study cohort are shown in Table 2. Half of the infants were born to Hispanic mothers, 90% received antenatal steroids, and 29% were intubated in the delivery room. The cohort mean birth weight was 1197 g and mean gestational age 28.4 weeks. The average age at admission to the NICU was 4.7 days, and 63% of infants were admitted immediately after birth at an adjacent physically joined adult hospital with maternity services. The Median age of admission (interquartile range) was 1 (1,5) days, with 135 (80%) infants admitted during the first week of life. More than half of the study subjects required mechanical ventilation at some point during their NICU stay. Ninety-seven percent were discharged home, at average 39.8 weeks PMA, with 20.8% requiring gastrostomy and/or home oxygen therapy. Additional details of the cohort characteristics and outcomes are shown in Table 2.
Table 2.
Maternal, perinatal, neonatal characteristics and outcomes of the study cohort
| Variable | N = 168 |
|---|---|
| Maternal race, n (%) | |
| White | 55 (32.7) |
| Black | 5 (3) |
| Hispanic | 84 (50) |
| Other | 24 (14.3) |
| Chorioamnionitis, n (%) | 14 (8.3) |
| Maternal Diabetes, n (%) | 28 (16.7) |
| Maternal Hypertension, n (%) | 36 (21.4) |
| Antenatal steroids, n (%) | 151 (90) |
| Antenatal magnesium sulfate, n (%) | 123 (73.2) |
| Multiple gestation, n (%) | 39 (23.2) |
| Cesarean delivery, n (%) | 113 (67.3) |
| 5-minute Apgar, median (IQR) | 8 (7-9) |
| Delivery room intubation, n (%) | 50 (29.7) |
| Birth weight, mean ± SD (g) | 1197 ± 393 |
| Gestational age, mean ± SD (weeks) | 28.4 ± 2.4 |
| Male sex, n (%) | 86 (51.2) |
| Age at admission, mean ± SD (days) | 4.7 ± 7.1 |
| Admitted immediately after birth, n (%) | 106 (63.1) |
| Surfactant, n (%) | 48 (28.6) |
| Postnatal systemic steroids for evolving BPD, n (%) | 22 (13) |
| Any mechanical ventilation, n (%) | 88 (52.4) |
| Length of stay, mean ± SD (days) | 76.5 ± 40 |
| Postmenstrual age at discharge, mean ± SD (weeks) | 39.8 ± 4 |
| Outcome after 36 weeks PMA, n (%) | |
| Home | 163 (97) |
| Transferred | 4 (2.4) |
| Died | 1 (0.6) |
| Home oxygen, n (%) | 18 (10.7) |
| Gastrostomy, n (%) | 22 (13.1) |
| Gastrostomy and/or home oxygen, n (%) | 35 (20.8) |
| Tracheostomy, n (%) | 2 (1.2) |
| Emergency room visits, median (IQR) | 0 (0-1) |
| Hospitalization post NICU discharge in first year of life, median (IQR) | 0 (0-0) |
| NICU hospital charges, median (IQR) | $1,098,665 ($682,008-$1,821,019) |
| NICU hospital charges per day, median (IQR) | $16,399 ($14,671-$18,532) |
| First year of life hospital charges, median (IQR) | $1,189,950 ($709,588-$1,941,107) |
BPD severity classification:
The distribution of BPD severity grades according to the CNN, NICHD 2018, and Jensen definitions are shown in Table 3. More infants were classified as no BPD according to the CNN definition (79%) in comparison to the NICHD 2018 (64.3%) and Jensen (59.5%) definitions. Generally, the number of infants decreased as the grade of severity increased for the three definitions, which was most linear for the Jensen definition. Specifically, grade 1 BPD was present in 42 infants (25%), grade 2 in 21 (12.5%), and grade 3 in 5 (3%). The CNN classification had one less subject than the other definitions due to death before 40 weeks PMA.
Table 3.
Distribution of bronchopulmonary dysplasia severity grades according to the CNN, NICHD 2018 and Jensen definitions
| Bronchopulmonary dysplasia | CNN (n=167) a | NICHD 2018 (n=168) |
Jensen (n=168) |
|---|---|---|---|
| Grade 0 or none, n (%) | 132 (79) | 108 (64.3) | 100 (59.5) |
| Grade 1 or mild, n (%) | 12 (7.2) | 21 (12.5) | 42 (25) |
| Grade 2 or moderate, n (%) | 19 (11.4) | 34 (20.2) | 21 (12.5) |
| Grade 3 or severe, n (%) | 4 (2.4) | 5 (3) | 5 (3) |
CNN classification had one less subject due to death prior to 40 weeks PMA
Predicting health economics impacts:
Spearman’s correlation coefficients between the three BPD definitions and the outcomes of NICU LOS, NICU hospital charges, NICU charges per day, the first year of life hospital charges, number of emergency room visits, and number of post NICU discharge hospitalizations are presented in Table 4. Compared to the CNN and NICHD 2018 definitions, a stronger correlation was detected for Jensen definition with NICU LOS, NICU hospital charges, NICU charges per day, and first year of life hospital charges. The correlation coefficients for Jensen definition for these measures ranged from 0.58 to 0.67, which is commonly interpreted as large 21. Comparing the same cohort of subjects, Jensen definition showed the best correlation of greater first year of life hospital charges with increasing BPD severity grade in comparison to the CNN and NICHD 2018 definitions (correlation score of 0.67 vs 0.5 vs 0.64), the same significant correlations were detected for NICU LOS, NICU charges and NICU charges per day (p <0.0001). According to the Jensen definition, there was a stepwise increase in these four measures in correlation with increasing BPD severity grade compared to the CNN and NICHD 2018 definitions (shown in Fig. 1). None of the three definitions had a strong correlation with the number of emergency room visits (correlation coefficients range 0.01–0.08) or hospitalizations (correlation coefficients range 0.13–19) post NICU discharge through the first year of life (Table 4).
Table 4.
Correlations between CNN, NICHD 2018 and Jensen BPD definitions and health economic outcomes
| Definition | NICU Length of stay |
NICU charges |
NICU charges per day |
First year hospital charges |
Emergency room visits |
Hospitalizations |
|---|---|---|---|---|---|---|
| CNN | 0.42 | 0.49 | 0.51 | 0.50 | 0.08 | 0.19 |
| NICHD 2018 | 0.52 | 0.63 | 0.61 | 0.64 | 0.01 | 0.13 |
| Jensen | 0.58 | 0.66 | 0.64 | 0.67 | 0.03 | 0.13 |
Fig. 1.
Study cohort median and ranges for NICU charges (a), NICU charges per day (b), first year of life hospital charges (c) and NICU length of stay (d) according to the CNN, NICHD 2018 and Jensen grading system
To statistically compare the correlation coefficients listed in Table 4, we used Williams’s modification of Hotelling’s test. This test is designed to compare two correlations with a single variate in common on the same group of subjects 22. For NICHD 2018 vs Jensen, the difference of correlations p values were; first year of charges (p = 0.028), NICU charges (p = 0.053), length of stay (p = 0.109) and charges per day (p = 0.134), and for CNN vs Jensen, p values were; first year of charges (p = <0.001), NICU charges (p = 0.002), length of stay (p = 0.002) and charges per day (p = 0.359).
Comparing the characteristics and outcomes of BPD grades according to Jensen definition:
As Jensen definition was determined to have the strongest correlations with outcomes of interest, relevant characteristics and outcomes of the different grades of severity were summarized and compared with grades 2 and 3 were combined due to smaller numbers of grade 3 (Table 5). Grades 2/3 BPD group in comparison to grade 1 BPD and no BPD groups had lower Apgar score and more delivery room intubations (61% vs 35% vs 19%, p = 0.00001). They were of lesser birth weight (946 ± 325 g vs 962 ± 274 g vs 1361 ± 368 g, p <0.0001) and gestational age (26.4 wk vs 27.3 wk vs 29.4 wk, p <0.0001), more likely to receive surfactant (53% vs 40% vs 17%, p = 0.0001) and postnatal systemic steroids for evolving BPD (46% vs 14% vs 4%, p < 0.0001). They were referred at a later age (8.3 vs 5.3 vs 3.5 days, p = 0.006) and were less likely to be born at the adjacent hospital (26.9% vs 57.1% vs 75%, p = <0.0001). Half of grades 2/3 BPD infants were technology dependent upon discharge needing gastrostomy feeding and/or home oxygen (50% vs 35% vs 7%, p <0.00001). Among the study cohort, one infant (0.6%) died after 36 weeks PMA, and two (1.2%) received a tracheostomy, all three patients were categorized as grade 2/3 BPD. Primary outcomes of interests (hospital charges and LOS) increased exponentially from no BPD to grade 2/3. There were no differences in maternal race, antenatal steroids, mode of delivery, infant sex, number of emergency room visits, or rehospitalizations. Other characteristics and outcomes are displayed in Table 5.
Table 5.
Comparing the characteristics and outcomes of BPD grades according to Jensen definition
| Variable | No BPD (n=100) |
Grade 1 (n=42) |
Grade 2/3 (n=26) |
P Value |
|---|---|---|---|---|
| Maternal race, n (%) | 0.46 | |||
| White | 34 (34) | 16 (38.1) | 5 (19.3) | |
| Black | 2 (2) | 1 (2.4) | 2 (7.7) | |
| Hispanic | 48 (48) | 20 (47.6) | 16 (61.5) | |
| Other | 16 (16) | 5 (11.9) | 3 (11.5) | |
| Chorioamnionitis, n (%) | 8 (8) | 3 (7.1) | 3 (11.5) | 0.85 |
| Maternal Diabetes, n (%) | 19 (19) | 5 (12) | 4 (15.4) | 0.62 |
| Maternal Hypertension, n (%) | 23 (23) | 12 (28.6) | 1 (3.9) | 0.02 |
| Antenatal steroids, n (%) | 89 (89) | 38 (90.5) | 24 (92.3) | 1.0 |
| Antenatal magnesium sulfate, n (%) | 70 (70) | 36 (85.7) | 17(65.4) | 0.08 |
| Multiple gestation, n (%) | 27 (27) | 10 (23.8) | 2 (7.7) | 0.1 |
| Cesarean delivery, n (%) | 64 (64) | 30 (71.4) | 19 (73) | 0.58 |
| 5-minute Apgar, median (IQR) | 8 (7-9) | 7.5 (6-8) | 7 (4-8) | <0.0001 |
| Delivery room intubation, n (%) | 19 (19) | 15 (35.7) | 16 (61.5) | 0.0001 |
| Birth weight, mean ± SD (g) | 1361 ±368 | 962 ± 274 | 946 ± 325 | <0.0001 |
| Gestational age, mean ± SD (weeks) | 29.4 ± 2 | 27.3 ± 2 | 26.4 ± 2 | <0.0001 |
| Male sex, n (%) | 49 (49) | 25 (59.5) | 12 (46) | 0.44 |
| Age at admission, mean ± SD (days) | 3.5 ± 6 | 5.3 ± 7 | 8.3 ± 8 | 0.006 |
| Admitted immediately after birth, n (%) | 75 (75) | 24 (57.1) | 7 (26.9) | <0.0001 |
| Surfactant, n (%) | 17 (17) | 17 (40.5) | 14(53.8) | 0.0001 |
| Postnatal systemic steroids for evolving BPD, n (%) | 4 (4) | 6 (14.3) | 12 (46.1) | <0.0001 |
| Any mechanical ventilation, n (%) | 31 (31) | 34 (81) | 23 (88.5) | <0.0001 |
| Length of stay, mean ± SD (days) | 57.5 (27) | 93.4 (26) | 122.4 (52) | <0.0001 |
| Postmenstrual age at discharge, mean ± SD (weeks) | 37.9 (3) | 41.2 (2) | 45 (6) | <0.0001 |
| Outcome after 36 weeks PMA, n (%) | 0.08 | |||
| Home | 99 (99) | 40 (95) | 24 (92) | |
| Transferred | 1 (1) | 2 (4.7) | 1 (3.8) | |
| Died | 0 | 0 | 1 (3.8) | |
| Home oxygen, n (%) | 1 (1) | 8 (19) | 9 (34) | <0.0001 |
| Gastrostomy, n (%) | 6 (6) | 8 (19) | 8 (30.7) | 0.001 |
| Gastrostomy and/or home oxygen, n (%) | 7(7) | 15 (35.7) | 13 (50) | <0.0001 |
| Tracheostomy, n (%) | 0 | 0 | 2 (7.7) | 0.02 |
| Emergency room visits, median (IQR) | 0 (0-1) | 0 (0-1) | 0 (0-1) | 0.66 |
| Hospitalization post NICU discharge in first year of life, median (IQR) | 0 (0-0) | 0 (0-0) | 0 (0-1) | 0.26 |
| NICU hospital charges, median (IQR) | $752,613 ($553,437-$1,115,556) | $1,598,908 ($1,191,935-$2,255,114) | $2,477,816 ($1,817,260-$3,135,409) | < 0.0001 |
| NICU hospital charges per day, median (IQR) | $15,296 ($14,126-$16,494) | $18,095 ($16,491-$19,188) | $19,835 ($18,524-$22,557) | < 0.0001 |
| First year of life hospital charges, median (IQR) | $781,827 ($58,2124-$1,209,824) | $1,734,908 ($1,231,798-$2,354,562) | $2,607,489 ($1,902,391-$3,214,301) | < 0.0001 |
Discussion
BPD is the most common morbidity of preterm birth and is associated with high resource utilization during and after NICU stay 1; 17; 18; 23. Finding a BPD definition that predicts meaningful outcomes to parents, clinicians, and researchers has been pursued by many. Recently, Isayama 12 and Jensen 14 analyzed large data sets and proposed BPD definitions which predicted long term outcomes in their studies. Meanwhile, the NICHD in 2018 suggested a newer BPD grading system based on expert consensus considering newer modes of respiratory care 13. Traditionally reported outcomes in neonatal literature are dichotomous (yes/no), such as death, respiratory morbidity, or neurodevelopmental delays. In our study, we analyzed economics effects, including hospital charges as a surrogate to measure the BPD severity spectrum to evaluate which BPD definition best predicts the first year of life outcomes.
In our analysis of 168 very preterm infants admitted to the NICU in the first 30 days of life, categorizing BPD severity at 36 weeks PMA, according to Jensen definition, had the strongest correlation with health economics outcomes through the first year of life in comparison to the CNN or NICHD 2018 definitions. The results support Jensen et al. evidence-based approach to define BPD, as they analyzed 18 prespecified BPD definitions at 36 weeks PMA to determine which best correlated with early childhood morbidity. The authors proposed a grading system based on respiratory support alone regardless of the oxygen level that predicted late death or serious respiratory morbidity at 18–26 months corrected age in 81% of their study population 14. Jensen BPD grading system is data-driven and easy to apply outside research settings.
Applying the CNN and NICHD 2018 BPD grading systems, more infants were classified as grade 2 (11.4% and 20.2%) than grade 1 (7.2% and 12.5%), which does not correspond well with common severity distribution and is unexpected if a normal distribution is assumed. This may be explained by grade 2 criteria for both definitions, including a heterogeneous group of infants whose respiratory support ranged from low flow nasal cannula to mechanical ventilation. In contrast, the distribution according to Jensen definition revealed a linear decrease in the number of infants as BPD severity increased, with grade 1 BPD in 42 infants (25%), grade 2 in 21 (12.5%), and grade 3 in 5 (3%).
Evaluating optimal endpoints for BPD assessment remains an important research question 24. In our analysis, we utilized 36 weeks PMA for categorizing the study cohort as per Jensen and the NICHD 2018 definition, and 40 weeks PMA for the CNN definition. There were more infants with no BPD according to the CNN definition (79% vs 59–64%); we speculate that this is related to the resolution of feeding difficulties and respiratory control immaturity by 40 weeks PMA, and therefore identifying mostly those with parenchymal or airway disease as BPD. However, the CNN BPD severity classification had the weakest correlation with health economics outcomes in our analysis.
First year hospital charges were heavily driven by initial NICU hospitalization charges, similar to previous reports 17; 18. BPD rate is inversely related to gestational age and is commonly associated with other prematurity morbidities such as retinopathy of prematurity and intraventricular hemorrhage. Prior studies showed that after controlling for birth weight, gestational age, and sociodemographic characteristics, BPD was associated with the highest increase in costs in comparison to other prematurity morbidities 25. Although we have not adjusted for possible confounding factors that may contribute to the primary outcomes, we analyzed charges per day to account for varying length of stay, and it was found to be significantly higher for grade 2/3 in comparison to grade 1 or no BPD.
Our study has limitations, including being a retrospective design at a single center, a relatively small cohort, and outcomes limited to one year of age. However, our cohort is contemporary with NICU hospitalization inclusive of 2017 and 2018. Thus only one year outcomes were available at the time of analysis. The study data set is limited to a single hospital system, which allowed access to granular data and categorizing the study subjects according to the three BPD severity grading systems. Prior large studies of BPD health care burden did not evaluate for correlation with disease severity 17; 18. Our cohort length of stay and hospital charges are comparable to those reported in larger cohorts 17; 18; 26. The reported health economics outcomes were limited to hospital charges only, as the analysis did not include costs, physician charges, medications, supplies, home nursing, or care givers income loss. Moreover, health care services received at facilities that are not affiliated with our hospital were not included. However, in our region pediatric subspecialty care is rare outside of our hospital system. We also did not analyze the impact of evolving BPD which may lead to hospital death prior to 36 weeks PMA.
This study is the first to compare the newer BPD definitions for predicting health economics impact through the first year of life, which may represent an objective surrogate for BPD severity and outcomes. Our analysis showed that the BPD severity grading by Jensen 14 had the best prediction of health economics impact through the first year in the study cohort of 168 infants born less than 32 weeks gestational age. Determining the most predictive BPD grading system will enhance the design of quality improvement initiatives and therapeutic research studies targeting patient-centric outcome measures (i.e. BPD grade) rather than a dichotomous measure such as oxygen requirement at 36 weeks PMA, which includes infants with diverse long term outcomes, combining patients requiring low flow nasal cannula and invasive ventilation in the same group. We think identifying patients at 36 weeks PMA according to Jensen grading system may serve as a proxy for outcome measure, which helps provide families with better anticipatory guidance and prioritize specialized and preventive care after NICU discharge. Future work should attempt to validate the recent BPD definitions, using population-based data, for measures crucial to improve the population health of infants with BPD.
Acknowledgment
The authors acknowledge the assistance of Mr. Bill Rohde, Vice President Finance, Ms. Jennifer Liu, financial analyst, and Megan Norton, RN, data coordinator, at Children’s Hospital of Orange County, Orange, CA.
Funding: This work was partially supported by grant UL1 TR001414 from the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through the Biostatistics, Epidemiology and Research Design Unit.
Abbreviation:
- BPD
Bronchopulmonary dysplasia
- CNN
Canadian Neonatal Network
- NICHD
National Institute of Child Health and Human Development
- NICU
Neonatal intensive care unit
- PMA
Postmenstrual age
Footnotes
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
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