1. Correlation of developmental outcome with severity of bronchopulmonary dysplasia in extremely low gestational age neonates
Karen Belen, Chengqiu Lu, Narges Afshar, Cecilia de Cabo, Man Yi, John Minski and R. John Baier
Department of Pediatrics • University of Manitoba • Children’s Hospital
Abstract
Introduction: The development of bronchopulmonary dysplasia (BPD) is associated with an increased risk of developmental delay (DD). At our institution, nasal CPAP on room air is commonly used for treatment of apnea of prematurity and many infants are on minimal support (room air CPAP or nasal cannula) at 36 weeks postmenstrual age (PMA) and are difficult to classify as to severity of BPD using the current NIH consensus definition of BPD.
Objective: This study aims to classify infants as to the degree of severity of BPD using a modification of the NIH classification and to determine if the severity of BPD using this revised classification system correlates with developmental outcome.
Methods: We undertook a retrospective chart review of premature infants < 29 weeks gestation admitted to the intensive care nursery between January 1, 2009 and December 31, Exclusion criteria were; death before 36 weeks post menstrual age (PMA), congenital respiratory anomalies, complex heart disease and transfer out of province. Data was abstracted from the medical records and linked with data from the developmental follow up clinic for assessment of impact of BPD severity on developmental outcomes. BPD severity was scored as described below.
Results: 237 infants were included in the study. They had an average birth weight of 1005±238 grams and gestation 26.7±1.3 weeks. BPD developed in 106 out of 237 infants (45%) and the frequencies per the modified classification were BPD1-mild (n=71, 30%), BPD2-mild to moderate (n=49, 21%), BPD3-moderate to severe (n=48, 20%) and BPD4-severe (n=9, 5%) (76%) patients were seen for follow up at 17±6 months. BPD (any support at 36 weeks) was associated with increased risk for severe DD (cognitive score <70) (11/91 vs. 1/90; p=0.003) and for a cognitive score <85 (45/91 vs. 15/90; p<0.001). The risk for DD increased with increasing severity of BPD. For those infants on nCPAP of <7 cm H2O at 36 weeks or the risk of severe DD was low (0/39).
Conclusion: Increasing severity of BPD using the proposed severity grading was associated with increasing risk of severe DD but not for the development of cerebral palsy. Infants with mild and mild to moderate BPD did not have a significantly increased risk for severe DD compared to infants without BPD. Infants with BPD who are receiving nCPAP <7 cm H2O at 36 weeks PMA have low risk of severe DD in our population.
Introduction
The development of BPD is one of the important factors in determining developmental outcome in preterm birth. The current (NIH consensus) definition of BPD assess the degree of severity of BPD at 36 weeks based on the supplemental oxygen and mode of respiratory support. At our institution, nasal CPAP on room air is commonly used for treatment of apnea of prematurity and many infants are on minimal support (room air CPAP or nasal cannula) at 36 weeks postmenstrual age (PMA) and are difficult to classify as to severity of BPD using the current NIH consensus definition of BPD.
This study aims to classify infants as to the degree of severity of BPD using a modification of the NIH classification and to determine if the severity of BPD using this revised classification system correlates with developmental outcomes.
Results
285 infants admitted to NICU
44 deaths (15%)
4 infants transferred out of province before 36 weeks
57 infants with no follow-up data
180 surviving infants with follow up data (76% of survivors)
Birth weight 984±234 grams
Gestation 26.6±1.3 weeks
Male 53%
Any antenatal steroids 85%
Complete course 61%
PDA 57%
Severe Developmental Delay
Severe Developmental Delay
Odds ratio
95% CI
P Value
Gestation (weeks)
1.38
0.284
BPD Severity
4.19
0.002
Severe IVH (Grade 3 and 4)
6.72
0.010
ROP treatment
4.60
0.052
Early or late onset BSI
3.67
0.110
PDA
0.49
0.402
Moderate and Severe Developmental Delay
Odds ratio
95% CI
P Value
Gestation (weeks)
0.94
0.69
BPD Severity
1.65
0.008
Severe IVH (Grade 3 and 4)
3.15
0.009
ROP treatment
2.25
0.073
Early or late onset BSI
1.53
0.248
PDA
0.875
Frequency of BPD and its severity in follow up group
BPD defined as any respiratory support at 36 weeks post menstrual age (PMA) developed in 91 (51%) infants. Infants classified as mild BPD were free of any respiratory support at 36 weeks PMA.
Materials and Methods
Retrospective chart review
< 29 weeks age gestation admitted to NICU
January 1, and December 31, 2015
Exclusion criteria were death before 36 weeks PMA, congenital respiratory anomalies, complex heart disease and transfer out of province
Linked with data from high risk follow up clinic
Bayley 2
MDI<85
Cerebral palsy
Audiology
BPD severity scoring system
Seen in follow up
N=180
Not seen
N=57
P Value
Gestation (weeks
26.6±1.3
26.9±1.0
0.056
Birth weight (grams)
984±234
1080±241
0.011
BPD at 36 weeks PMA
48%
28%
0.008
Severe IVH (Grade 3 and 4)
18% 8%
0.072
ROP treatment
15% 4%
0.067
Early or late onset BSI
40%
22%
0.016
Severe intestinal disease*
17%
16%
0.867
NEC
6.5%
3.9%
0.497
PDA
57%
41%
0.045
Multivariate Analysis of Developmental Outcomes
The severity of BPD remained a significant predictor of both severe and moderate developmental delay when adjusted for confounders by logistic regression. After adjustment for confounders severity of BPD was not significantly associated with hearing loss.
No BPD
N=36
Mild BPD
N=53
Mild to Moderate BPD
N=42
Moderate to severe BPD
Severe BPD
N=7
P Value
Severe Developmental Delay
1 (3%)
2 (5%)
5 (12%)
4 (57%)
<0.001
Cognitive score <85
6 (16%)
9 (17%)
17 (41%)
22 (52%)
6 (86%)
Cerebral palsy
0.366
Conclusions
Increasing severity of BPD using the proposed severity grading was associated with increasing risk of moderate and severe DD but not for the development of cerebral palsy. Infants with mild and mild to moderate BPD did not have a significantly increased risk for severe DD compared to infants without BPD.
Comparison of infants seen in follow-up to infants not seen in follow-up
Infants seen in follow up tended to be less mature, of lower birth weight and more major complications than those who were not seen. Severity of BPD was also lower in infants that were not seen in follow up.
*Severe intestinal disease: NEC, spontaneous intestinal perforation or any intestinal problem that was treated with gut rest and antibiotics >3 days
Severity of BPD and Developmental Outcomes
Increasing severity of BPD was associated with increasing risk of development delay (p<0.001) and hearing impairment (p=0.012) There was no relationship between BPD severity and subsequent development of cerebral palsy (p=0.336). There were no infants who were blind.