Abstract
Introduction:
Preterm children with bronchopulmonary dysplasia (BPD) are at increased risk for intermittent and chronic respiratory symptoms during childhood and adult life. Identifying children at higher risk for respiratory morbidities in the outpatient setting could help improve long-term outcomes. In this study, we hypothesized that a family history of asthma is a risk factor for higher acute care usage and respiratory symptoms in preterm infants/children with BPD, following initial discharge home.
Methods:
Subjects were recruited from the Johns Hopkins Bronchopulmonary Dysplasia outpatient clinic between January 2008 and February 2020 (n=827). Surveys were administered to caregivers and demographics and clinical characteristics were obtained through chart review.
Results:
Demographic features associated with family history of asthma included public health insurance, lower median household income and non-white race. Children with a family history of asthma had higher odds of emergency department (ED) visits, systemic steroid use, nighttime respiratory symptoms, and activity limitations. There was no association between family history of asthma and BPD severity.
Conclusion:
This study found that children with BPD and a family history of asthma (FHA) were more likely to have respiratory symptoms and acute care usage during the first three years of life and that FHA was associated with lower socioeconomic status. Although there was no association between family history of asthma and BPD severity, a family history of asthma could predict an increased likelihood of both ED visits and need for systemic steroids in infants/children with BPD followed in the outpatient setting.
Keywords: Prematurity, Bronchopulmonary dysplasia, family history of asthma, respiratory outcomes, outpatient
Introduction
Prematurity is defined as birth occurring before 37 weeks gestation and accounts for approximately 10% of all births in the United States. (1) Bronchopulmonary dysplasia (BPD) is the most common cause of chronic lung disease in infancy and affects at least 10,000-15,000 preterm infants annually in the United States. (2) Advances in neonatal care, such as changes in ventilation strategies, administration of exogenous surfactant, and use of systemic steroids, have increased survival rates of preterm infants. As such, this has been reflected in an overall decrease in infant mortality from pulmonary causes, especially in extremely low birth weight (ELBW) premature infants. (3) Nevertheless, even with improvements in neonatal care, the incidence of BPD has remained unchanged (4, 5) with some children having chronic respiratory symptoms and morbidities that persist throughout childhood and adult life. (6, 7)
As rates of BPD are stable or increasing and more extremely low birth weight infants are surviving to NICU discharge, there is an ongoing need to identify risk factors associated with respiratory morbidities after NICU discharge, to help optimize patient care and improve long-term pulmonary health. Children with BPD are at higher risk for rehospitalization yet identifying risk factors that predict respiratory morbidities in this population, can be elusive. (8) As a consequence, outpatient healthcare providers may not be able to accurately identify those children who would benefit from closer monitoring in the outpatient setting. Early identification and closer monitoring of children at higher risk for adverse respiratory outcomes following NICU discharge, may help mitigate respiratory morbidities reported in children and adults with a history of BPD. (9, 10)
Several studies have also found an association between preterm birth and higher rates of wheezing and asthma during childhood.(11-13) However, it is unclear whether a family history of asthma in preterm infants is associated with BPD severity or increased frequency of respiratory symptoms and acute care usage during the first three years of life. Data from older studies have suggested a relationship between “old” BPD and first or second degree relatives with a history of asthma. (14) However other studies demonstrated no difference in severity of BPD in children and a family history of asthma (15, 16) or if family history of asthma is associated with an increase risk for respiratory symptoms after NICU discharge.
Furthermore, in contrast to infants with BPD in the NICU, the contributions of specific NICU interventions, gestational age and birth weight on respiratory outcomes in the outpatient setting, remains unclear. In this study we hypothesized that a family history of asthma is a risk factor for more severe BPD as well as higher rates of acute care usage and respiratory symptoms in preterm infants/children with BPD in the outpatient setting. To address this question, we retrospectively reviewed data from children recruited from an outpatient BPD clinic between 2008 and 2020.
Methods
Population and Study Design:
A retrospective chart review was performed on subjects (n=827) recruited from Johns Hopkins Bronchopulmonary Dysplasia clinic between January 2008 to February 2020. All subjects received their outpatient BPD care at a single center at time of data collection, however they were discharged from multiple NICUs. All subjects were born at less than 37 weeks gestation and had a diagnosis of BPD by NIH consensus definition. (17) This study was approved by Johns Hopkins Institutional Review Board (Protocol #NA_00051884) and all caregivers were consented.
Demographics and Clinical Data:
Demographics and clinical characteristics were obtained through chart review. Race/ethnicity was reported by caregivers. Birthweight percentile was corrected for gestational age. (18) Median household income was estimated based on residential zip codes and 2019 American Community Survey data from the U.S. Census. Family history of asthma was ascertained through chart review (n=542) and questionnaires (n=285); there were no differences in the rates of parental history of asthma (P=0.37) or familial history of asthma (P=0.38) by source of family history. Any family member with asthma is defined as any family, including parents, who are diagnosed with asthma. Acute care for respiratory issues and chronic symptom outcome variables were collected through questionnaires at visits between ages 0-3 years.
Statistical Methods:
Chi square and t-tests were performed to compare demographic data or clinical characteristics and parental/family history of asthma (Tables 2 and 3). Associations between a parental/family history of asthma (independent variable) and respiratory outcomes (dependent variable) were tested for using logistic regression adjusted for possible confounders, age at time of clinic visit, and BPD severity (Tables 4 and 5). Regressions were clustered by subject to account for ascertainment of outcomes at potentially more than one clinic visit per subject. Stata IC 15 was used for analyses. Results deemed statistically significant had a P value equal to or less than 0.05.
Table 2.
Any Parental History of Asthma
| Mean ± S.D. [Range] |
Entire Study Population (n = 827) |
Any Parental History of Asthma (n = 265) |
No Parental History of Asthma (n = 562) |
P Value | |
|---|---|---|---|---|---|
| Sex (% female) | 42.6% | 40.8% | 43.4% | 0.47 | |
| Race/ethnicity (% non-white) | 64.0% | 70.9% | 60.7% | 0.004 | |
| Gestational age (weeks) | 26.8 ± 2.6 [22.3, 36.9] | 26.9 ± 2.6 [22.3, 35.1] | 26.7 ± 2.6 [22.7, 36.9] | 0.38 | |
| Birth weight (grams) | 922 ± 408 [380, 4200] | 918 ± 414 [390, 4200] | 924 ± 406 [380, 3370] | 0.85 | |
| (n = 816) | (n = 263) | (n = 553) | |||
| Length of initial admission (months) | 4.5 ± 2.7 [0.1, 26.5] | 4.4 ± 2.4 [0.7, 15.6] | 4.5 ± 2.8 [0.1, 26.5] | 0.53 | |
| (n = 826) | (n = 561) | ||||
| BPD severity (%) | Mild | 14.1% | 17.2% | 12.6% | 0.19 |
| Moderate | 36.6% | 34.1% | 37.8% | ||
| Severe | 49.3% | 48.6% | 49.6% | ||
| (n = 789) | (n = 249) | (n = 540) | |||
| Oxygen (% yes) | 42.4% | 38.5% | 44.3% | 0.11 | |
| Oxygen amount at hospital discharge (LPM) | 0.38 ± 0.38 [0.03, 2.00] | 0.41 ± 0.40 [0.03, 2.00] | 0.36 ± 0.37 [0.03, 2.00] | 0.31 | |
| (n = 351) | (n = 102) | (n = 249) | |||
| Tracheostomy (% yes) | 5.3% | 6.0% | 5.0% | 0.53 | |
| Vent (% yes) | 4.1% | 5.3% | 3.6% | 0.24 | |
| Diuretics (% yes) | 62.8% | 61.9% | 63.3% | 0.70 | |
| Inhaled corticosteroids (% yes) | 80.1% | 82.6% | 78.8% | 0.20 | |
| Pulmonary hypertension after 36 weeks (% yes) | 17.3% | 14.7% | 18.5% | 0.18 | |
| Pulmonary anti-hypertensives (% yes) | 5.4% | 4.9% | 5.7% | 0.64 | |
| Gastrostomy tube (% yes) | 30.4% | 27.6% | 31.9% | 0.21 | |
| Nissen fundoplication (% yes) | 18.5% | 15.9% | 19.8% | 0.18 | |
| Public insurance (% yes) | 56.6% | 61.5% | 54.3% | 0.050 | |
| Median household income ($ ‘000s) | 76.3 ± 26.6 [28.5, 186.6] | 73.4 ± 27.2 [28.5, 186.6] | 77.7 ± 26.2 [28.5, 156.8] | 0.030 | |
Table 3.
Any Familial History of Asthma
| Mean ± S.D. [Range] |
Entire Study Population (n = 827) |
Any Familial History of Asthma (n = 476) |
No Familial History of Asthma (n = 351) |
P Value | |
|---|---|---|---|---|---|
| Sex (% female) | 42.6% | 40.8% | 45.0% | 0.22 | |
| Race/ethnicity (% non-white) | 64.0% | 69.8% | 56.1% | <0.001 | |
| Gestational age (weeks) | 26.8 ± 2.6 [22.3, 36.9] | 26.8 ± 2.7 [22.3, 36.9] | 26.8 ± 2.6 [22.7, 36.0] | 0.70 | |
| Birth weight (grams) | 922 ± 408 [380, 4200] | 917 ± 430 [380, 4200] | 929 ± 378 [390, 3181] | 0.68 | |
| (n = 816) | (n = 471) | (n = 345) | |||
| Length of initial admission (months) | 4.5 ± 2.7 [0.1, 26.5] | 4.4 ± 2.5 [0.1, 24.5] | 4.5 ± 2.9 [0.7, 26.5] | 0.50 | |
| (n = 826) | (n = 350) | ||||
| BPD severity (%) | Mild | 14.1% | 14.8% | 13.1% | 0.79 |
| Moderate | 36.6% | 36.4% | 36.9% | ||
| Severe | 49.3% | 48.8% | 50.0% | ||
| (n = 789) | (n = 453) | (n = 336) | |||
| Oxygen (% yes) | 42.4% | 40.3% | 45.3% | 0.15 | |
| Oxygen amount at hospital discharge (LPM) | 0.38 ± 0.38 [0.03, 2.00] | 0.40 ± 0.41 [0.03, 2.00] | 0.35 ± 0.33 [0.03, 2.00] | 0.18 | |
| (n = 351) | (n = 192) | (n = 159) | |||
| Tracheostomy (% yes) | 5.3% | 5.7% | 4.8% | 0.60 | |
| Vent (% yes) | 4.1% | 5.0% | 2.9% | 0.12 | |
| Diuretics (% yes) | 62.8% | 60.5% | 66.0% | 0.11 | |
| Inhaled corticosteroids (% yes) | 80.1% | 82.6% | 76.6% | 0.035 | |
| Pulmonary hypertension after 36 weeks (% yes) | 17.3% | 15.6% | 19.7% | 0.12 | |
| Pulmonary anti-hypertensives (% yes) | 5.4% | 4.8% | 6.3% | 0.37 | |
| Gastrostomy tube (% yes) | 30.4% | 29.2% | 32.2% | 0.36 | |
| Nissen fundoplication (% yes) | 18.5% | 18.7% | 18.2% | 0.87 | |
| Public insurance (% yes) | 56.6% | 62.4% | 48.7% | <0.001 | |
| Median household income ($ ‘000s) | 76.3 ± 26.6 [28.5, 186.6] | 73.6 ± 26.2 [28.5, 186.6] | 80.1 ± 26.6 [28.5, 156.8] | 0.001 | |
Additional analysis: Kaplan-Meier analysis for the 351 subjects who received supplemental oxygen after initial hospital discharge did not demonstrate any differences in the median ages of weaning for those who had a parental history of asthma (log rank p value: 0.08) or familial history of asthma (log rank p value: 0.78) compared to those without such a history.
Table 4.
Clinical Outcomes with any Parental History of Asthma
| OR + SE [95% C.I.] |
Odds ratio with any parental history of asthma* |
P value | Adjusted odds ratio with any parental history of asthma** |
P value | |
|---|---|---|---|---|---|
| Acute Care | Emergency department visits | 1.50 ± 0.23 [1.10, 2.03] (n=734 with 1625 visits) |
0.009 | 1.40 ± 0.22 [1.03, 1.89] (n=734 with 1625 visits) |
0.030 |
| Hospital readmissions | 1.08 ± 0.19 [0.77, 1.53] (n=735 with 1625 visits) |
0.65 | 1.00 ± 0.18 [0.71, 1.41] (n=735 with 1625 visits) |
1.00 | |
| Antibiotics | 1.03 ± 0.17 [0.75, 1.42] (n=735 with 1619 visits) |
0.84 | 1.08 ± 0.17 [0.79, 1.47] (n=735 with 1619 visits) |
0.63 | |
| Systemic steroids | 1.51 ± 0.26 [1.08, 2.12] (n=731 with 1616 visits) |
0.016 | 1.44 ± 0.24 [1.05, 1.99] (n=731 with 1616 visits) |
0.025 | |
| Chronic symptoms and medication use |
Trouble breathing (wheeze, cough, etc) |
1.32 ± 0.19 [1.00, 1.74] (n=729 with 1594 visits) |
0.049 | 1.25 ± 0.17 [0.96, 1.63] (n=729 with 1594 visits) |
0.09 |
| Nighttime symptoms | 1.57 ± 0.29 [1.09, 2.26] (n=726 with 1585 visits) |
0.016 | 1.49 ± 0.26 [1.06, 2.11] (n=726 with 1585 visits) |
0.022 | |
| Activity limitations | 1.33 ± 0.27 [0.90, 1.97] (n=720 with 1546 visits) |
0.15 | 1.27 ± 0.23 [0.89, 1.83] (n=720 with 1546 visits) |
0.19 | |
| Rescue medication use | 1.35 ± 0.22 [0.99, 1.86] (n=726 with 1562 visits) |
0.06 | 1.26 ± 0.19 [0.94, 1.69] (n=726 with 1562 visits) |
0.13 | |
Odds ratios were generated through clustered logistic regression models with clinic visits (prior to 3 years of age) clustered by individual. Both history of asthma (independent variable) and outcomes (dependent variable) were coded as no=0 and yes=1.
Regressions were adjusted for age at the time of clinic visit, race/ethnicity, log of median household income, public insurance, use of inhaled corticosteroids, and severity of BPD (as a dummy categorical variable).
Table 5.
Clinical Outcomes with any Familial History of Asthma
| OR + SE [95% C.I.] |
Odds ratio with any familial history of asthma* |
P value | Adjusted odds ratio with any familial history of asthma** |
P value | |
|---|---|---|---|---|---|
| Acute Care | Emergency department visits | 1.77 ± 0.28 [1.30, 2.41] (n=734 with 1625 visits) |
<0.001 | 1.55 ± 0.24 [1.14, 2.11] (n=734 with 1625 visits) |
0.005 |
| Hospital readmissions | 1.31 ± 0.22 [0.94, 1.83] (n=735 with 1625 visits) |
0.11 | 1.15 ± 0.20 [0.82, 1.61] (n=735 with 1625 visits) |
0.42 | |
| Antibiotics | 1.09 ± 0.16 [0.83, 1.45] (n=735 with 1619 visits) |
0.51 | 1.07 ± 0.15 [0.82, 1.41] (n=735 with 1619 visits) |
0.61 | |
| Systemic steroids | 1.55 ± 0.25 [1.14, 2.12] (n=731 with 1616 visits) |
0.006 | 1.36 ± 0.21 [1.00, 1.85] (n=731 with 1616 visits) |
0.048 | |
| Chronic symptoms and medication use |
Trouble breathing (wheeze, cough, etc) |
1.18 ± 0.15 [0.92, 1.52] (n=729 with 1594 visits) |
0.20 | 1.11 ± 0.14 [0.86, 1.43] (n=729 with 1594 visits) |
0.42 |
| Nighttime symptoms | 1.60 ± 0.26 [1.16, 2.20] (n=726 with 1585 visits) |
0.004 | 1.45 ± 0.24 [1.05, 2.00] (n=726 with 1585 visits) |
0.024 | |
| Activity limitations | 1.61 ± 0.29 [1.13, 2.30] (n=720 with 1546 visits) |
0.009 | 1.46 ± 0.26 [1.21, 1.86] (n=720 with 1546 visits) |
0.035 | |
| Rescue medication use | 1.02 ± 0.15 [0.77, 1.35] (n=726 with 1562 visits) |
0.89 | 0.89 ± 0.12 [0.67, 1.17] (n=726 with 1562 visits) |
0.40 | |
Odds ratios were generated through clustered logistic regression models with clinic visits (prior to 3 years of age) clustered by individual. Both history of asthma (independent variable) and outcomes (dependent variable) were coded as no=0 and yes=1.
Regressions were adjusted for age at the time of clinic visit, race/ethnicity, log of median household income, public insurance, use of inhaled corticosteroids, and severity of BPD (as a dummy categorical variable).
Results
Family History of Asthma:
Of the 827 BPD subjects in the cohort, 32% had a parental history of asthma, whereas 57.6% of subjects had at least one family member with a history of asthma (Table 1). A maternal family history of asthma, paternal history of asthma, and history of asthma in both parents was found in 21.9%, 14.2% and 4% of our BPD subjects respectively.
Table 1.
Family History of Asthma
| History of Asthma | Number of infants/children (n = 827) |
|---|---|
| Mother | 181 (21.9%) |
| Father | 117 (14.2%) |
| Both parents | 33 (4.0%) |
| Any parent | 265 (32.0%) |
| Any non-parental family member | 324 (39.2%) |
| Any family member | 476 (57.6%) |
Demographics and Clinical Characteristics:
Subjects with parental history of asthma were more likely to be non-white (P=0.004), have public insurance (P=0.050), and have a lower estimated median household income (P=0.030) (Table 2). No differences were found for other demographic or clinical characteristics, including BPD severity (P=0.19) or inhaled corticosteroid use (P=0.20). Similarly, a family history of asthma was also associated with being non-white (P<0.001), having public insurance (P<0.001), and a lower household income (P=0.001) (Table 3). Daily inhaled corticosteroid use was also associated with a family history of asthma (P=0.035), but other demographic and clinical characteristics were not, including BPD severity (P=0.79).
Acute Care Use:
In adjusted logistic regressions, subjects with a parental history of asthma were 1.4 times more likely to have an emergency department (ED) visit for respiratory reasons (P=0.030) and to require systemic steroids (P=0.025), but not more likely to require hospitalization (P=1.00) (Table 4). Similarly, subjects with a familial history of asthma were 1.6 times more likely to have an ED visit for respiratory reasons (P=0.005), 1.4 times more likely to require systemic steroids (P=0.048), but again not more likely to require hospitalization (P=0.42) (Table 5).
Chronic respiratory Symptoms:
Subjects with a parental history of asthma were 1.5 times more likely to have nocturnal symptoms (P=0.022) in adjusted logistic regressions, but not other reported chronic symptomatology. (Table 4) Subjects with a family history of asthma were also 1.5 times more likely to have nocturnal symptoms (P=0.024) in addition to activity limitations (P=0.035) (Table 5).
Discussion
In this study we found that children with BPD and a family history of asthma were more likely to require an ED visit, be prescribed systemic steroids and report respiratory symptoms during the first three years of life when compared to children without a family history of asthma. We also noted that children who identified as non-white were more likely to have a family history of asthma. Additionally, a family history of asthma in children with BPD, was also associated with having public insurance and residing in households with lower median income. After adjusting for race, median household income, and public insurance however, differences in clinical outcomes for ED visits, systemic steroid use, nighttime symptoms, and activity limitations persisted between BPD children with and without a family history of asthma, suggesting that other factors may be involved. Recognition that a family history of asthma is a risk factor for respiratory symptoms and acute care usage in children with BPD can help identify those children who may be at higher risk for respiratory morbidities in the first three years of life.
Other studies have reported an association between family history of asthma and BPD and subsequent respiratory symptoms. (14, 16, 19) In 1985, Bertrand et. al., reported that school age preterm children with airflow obstruction on pulmonary function testing, were more likely to have mothers with airway reactivity by histamine challenge; indicating that genetics may contribute to the obstructive phenotype in preterm children. (19) Nickerson and Taussig also found that a higher number of infants with radiographic evidence of BPD, had first or second degree relatives with physician-diagnosed asthma compared to preterm infants without BPD. (14) Hagan et. al., reported that a family history of asthma was associated with longer need for supplemental oxygen in VLBW infants suggesting a link between BPD severity and family history of asthma. (20) Although we did not find an association between BPD severity and family history of asthma, these older studies suggest that an association exists between family history of asthma and higher likelihood of respiratory morbidities and radiographic abnormalities in preterm children with BPD after NICU discharge.
Our study did not address whether a link between family history of asthma and respiratory morbidities continues to be a risk factor in older children and young adults with a history of BPD. It has been shown that preterm birth increases the likelihood of airflow obstruction in children and adults. (21-23) Identifying children in early life who may be at higher risk for pulmonary morbidities post NICU, could potentially improve long-term respiratory outcomes. For instance, children with BPD and a family history of asthma may benefit from closer outpatient follow-up and more timely treatment of their respiratory symptoms. Additionally, since most alveolar growth occurs within the first two years of life (24), closer follow-up of these individuals may help to mitigate pulmonary symptoms and exacerbations and promote healthier lung growth. This in turn could improve lung function trajectories, modifying risk for early onset chronic obstructive pulmonary disease (COPD) in young adults with a history of BPD. (7)
In addition to family history of asthma, other reasons may underlie the increased frequency of respiratory symptoms and persistent airflow obstruction reported in children and young adults with a history of BPD. (25) (26) These reasons include structural and functional abnormalities from early lung injury, dysanaptic airway growth from preterm birth and poor nutrition, post NICU environmental exposures such as secondhand smoke, and a genetic predisposition towards airway reactivity. Nevertheless, identifying children in the outpatient setting who have a family history of asthma has predictive power in determining which children with BPD may be at increased risk for emergency department visits, systemic steroid usage, nighttime symptoms, and activity limitation. Future studies are needed to determine if closer outpatient management and early interventions can improve long-term pulmonary function in these children.
In our study we found that lower socioeconomic class, family history of asthma and non-white racial demographics were associated with a higher likelihood of respiratory symptoms in children with BPD in the outpatient setting. These are also risk factors for childhood asthma. (27, 28) After adjusting for race/ethnicity and socioeconomic status in our BPD subjects we still found significant differences in clinical outcomes for ED visits, systemic steroid use, nighttime symptoms, and activity limitations between those with and without a family history of asthma. Nevertheless, we recognize that these adjustments may not perfectly account for these confounding effects and the possibility exist that children in our cohort have asthma and that BPD is not related to the outcomes.
Limitations include the retrospective nature of the study from a single center outpatient clinic. Although subjects were seen at a single outpatient center, they were discharged from many different NICUs across the state of Maryland and likely received variable care. Therefore, regardless of type of inpatient care and BPD severity at 36 weeks post menstrual age, our findings highlight the importance of family history of asthma as a recognizable factor in predicting outpatient respiratory outcomes in children with BPD. Another potential limitation to our study is that although we had a large study population, our subjects primarily lived in an urban setting and thus our results may not be generalizable to rural or other geographic areas. Additional analyses of other factors, such as smoke exposure, environmental factors, or breastfeeding, were not included in the analysis. Prospective studies will be needed to validate findings presented in this study.
In summary, we found that a family history of asthma was associated with a higher likelihood of respiratory symptoms and emergency room visits in children with BPD following initial hospital discharge. Results from this study indicate that children with BPD who have a family history of asthma are at increased risk for respiratory symptoms and should be monitored more closely to mitigate risk of increased respiratory morbidities in the outpatient setting.
ACKNOWLEDGEMENTS
The authors wish to thank the families who participated in this study. Funding sources included the National Institutes of Health, the Johns Hopkins Eudowood Board, Thomas Wilson Foundation and the Children’s Hospital of Philadelphia.
Funding/Support:
This work was supported by the National Institutes of Health (Bethesda, MD, USA )( SAM: R01 HL114800), the Johns Hopkins Eudowood Foundation (BCA: Fellowship grant), the Children’s Hospital of Philadelphia (JMC), and the Thomas Wilson Foundation (JMC).The funding sources had no involvement in the writing of the manuscript or the decision to submit.
REFERENCES
- 1.Martin JA, Hamilton BE, Osterman MJK, Driscoll AK. Births: Final Data for 2019. Natl Vital Stat Rep 2021; 70: 1–51. [PubMed] [Google Scholar]
- 2.Jensen EA, Schmidt B. Epidemiology of bronchopulmonary dysplasia. Birth Defects Res A Clin Mol Teratol 2014; 100: 145–157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Patel RM, Kandefer S, Walsh MC, Bell EF, Carlo WA, Laptook AR, Sánchez PJ, Shankaran S, Van Meurs KP, Ball MB, Hale EC, Newman NS, Das A, Higgins RD, Stoll BJ. Causes and timing of death in extremely premature infants from 2000 through 2011. The New England journal of medicine 2015; 372: 331–340. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, Laptook AR, Sánchez PJ, Van Meurs KP, Wyckoff M, Das A, Hale EC, Ball MB, Newman NS, Schibler K, Poindexter BB, Kennedy KA, Cotten CM, Watterberg KL, D'Angio CT, DeMauro SB, Truog WE, Devaskar U, Higgins RD. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. Jama 2015; 314: 1039–1051. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Davidson LM, Berkelhamer SK. Bronchopulmonary Dysplasia: Chronic Lung Disease of Infancy and Long-Term Pulmonary Outcomes. J Clin Med 2017; 6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Greenough A Long-term respiratory consequences of premature birth at less than 32 weeks of gestation. Early human development 2013; 89 Suppl 2: S25–27. [DOI] [PubMed] [Google Scholar]
- 7.Caskey S, Gough A, Rowan S, Gillespie S, Clarke J, Riley M, Megarry J, Nicholls P, Patterson C, Halliday HL, Shields MD, McGarvey L. Structural and Functional Lung Impairment in Adult Survivors of Bronchopulmonary Dysplasia. Annals of the American Thoracic Society 2016; 13: 1262–1270. [DOI] [PubMed] [Google Scholar]
- 8.Smith VC, Zupancic JA, McCormick MC, Croen LA, Greene J, Escobar GJ, Richardson DK. Rehospitalization in the first year of life among infants with bronchopulmonary dysplasia. J Pediatr 2004; 144: 799–803. [DOI] [PubMed] [Google Scholar]
- 9.Islam JY, Keller RL, Aschner JL, Hartert TV, Moore PE. Understanding the Short- and Long-Term Respiratory Outcomes of Prematurity and Bronchopulmonary Dysplasia. American journal of respiratory and critical care medicine 2015; 192: 134–156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Collaco JM, McGrath-Morrow SA. Respiratory Phenotypes for Preterm Infants, Children, and Adults: Bronchopulmonary Dysplasia and More. Annals of the American Thoracic Society 2018; 15: 530–538. [DOI] [PubMed] [Google Scholar]
- 11.Fierro JL, Passarella M, Lorch SA. Prematurity as an Independent Risk Factor for the Development of Pulmonary Disease. The Journal of pediatrics 2019; 213: 110–114. [DOI] [PubMed] [Google Scholar]
- 12.Kotecha SJ, Watkins WJ, Lowe J, Granell R, Henderson AJ, Kotecha S. Comparison of the Associations of Early-Life Factors on Wheezing Phenotypes in Preterm-Born Children and Term-Born Children. Am J Epidemiol 2019; 188: 527–536. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Sonnenschein-van der Voort AM, Arends LR, de Jongste JC, Annesi-Maesano I, Arshad SH, Barros H, Basterrechea M, Bisgaard H, Chatzi L, Corpeleijn E, Correia S, Craig LC, Devereux G, Dogaru C, Dostal M, Duchen K, Eggesbø M, van der Ent CK, Fantini MP, Forastiere F, Frey U, Gehring U, Gori D, van der Gugten AC, Hanke W, Henderson AJ, Heude B, Iñiguez C, Inskip HM, Keil T, Kelleher CC, Kogevinas M, Kreiner-Møller E, Kuehni CE, Küpers LK, Lancz K, Larsen PS, Lau S, Ludvigsson J, Mommers M, Nybo Andersen AM, Palkovicova L, Pike KC, Pizzi C, Polanska K, Porta D, Richiardi L, Roberts G, Schmidt A, Sram RJ, Sunyer J, Thijs C, Torrent M, Viljoen K, Wijga AH, Vrijheid M, Jaddoe VW, Duijts L. Preterm birth, infant weight gain, and childhood asthma risk: a meta-analysis of 147,000 European children. The Journal of allergy and clinical immunology 2014; 133: 1317–1329. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Nickerson BG, Taussig LM. Family history of asthma in infants with bronchopulmonary dysplasia. Pediatrics 1980; 65: 1140–1144. [PubMed] [Google Scholar]
- 15.de Winter JP, van Sonderen L, van den Anker JN, Merth IT, Brand R, van Bel F, Zonderland HM, Quanjer PH. Respiratory illness in families of preterm infants with chronic lung disease. Archives of disease in childhood Fetal and neonatal edition 1995; 73: F147–152. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Evans M, Palta M, Sadek M, Weinstein MR, Peters ME. Associations between family history of asthma, bronchopulmonary dysplasia, and childhood asthma in very low birth weight children. Am J Epidemiol 1998; 148: 460–466. [DOI] [PubMed] [Google Scholar]
- 17.Jobe AH, Bancalari E. Bronchopulmonary dysplasia. American journal of respiratory and critical care medicine 2001; 163: 1723–1729. [DOI] [PubMed] [Google Scholar]
- 18.Oken E, Kleinman KP, Rich-Edwards J, Gillman MW. A nearly continuous measure of birth weight for gestational age using a United States national reference. BMC Pediatr 2003; 3: 6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Bertrand JM, Riley SP, Popkin J, Coates AL. The long-term pulmonary sequelae of prematurity: the role of familial airway hyperreactivity and the respiratory distress syndrome. The New England journal of medicine 1985; 312: 742–745. [DOI] [PubMed] [Google Scholar]
- 20.Hagan R, Minutillo C, French N, Reese A, Landau L, LeSouef P. Neonatal chronic lung disease, oxygen dependency, and a family history of asthma. Pediatr Pulmonol 1995; 20: 277–283. [DOI] [PubMed] [Google Scholar]
- 21.Jobe AH. Mechanisms of Lung Injury and Bronchopulmonary Dysplasia. Am J Perinatol 2016; 33: 1076–1078. [DOI] [PubMed] [Google Scholar]
- 22.Balinotti JE, Chakr VC, Tiller C, Kimmel R, Coates C, Kisling J, Yu Z, Nguyen J, Tepper RS. Growth of lung parenchyma in infants and toddlers with chronic lung disease of infancy. Am J Respir Crit Care Med 2010; 181: 1093–1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Filbrun AG, Popova AP, Linn MJ, McIntosh NA, Hershenson MB. Longitudinal measures of lung function in infants with bronchopulmonary dysplasia. Pediatr Pulmonol 2011; 46: 369–375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Thurlbeck WM. Postnatal human lung growth. Thorax 1982; 37: 564–571. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Greenough A Long-term pulmonary outcome in the preterm infant. Neonatology 2008; 93: 324–327. [DOI] [PubMed] [Google Scholar]
- 26.Lombardi E, Fainardi V, Calogero C, Puglia M, Voller F, Cuttini M, Rusconi F. Lung function in a cohort of 5-year-old children born very preterm. Pediatr Pulmonol 2018; 53: 1633–1639. [DOI] [PubMed] [Google Scholar]
- 27.Bao Y, Chen Z, Liu E, Xiang L, Zhao D, Hong J. Risk Factors in Preschool Children for Predicting Asthma During the Preschool Age and the Early School Age: a Systematic Review and Meta-Analysis. Curr Allergy Asthma Rep 2017; 17: 85. [DOI] [PubMed] [Google Scholar]
- 28.Assari S, Moghani Lankarani M. Poverty Status and Childhood Asthma in White and Black Families: National Survey of Children's Health. Healthcare (Basel) 2018; 6. [DOI] [PMC free article] [PubMed] [Google Scholar]