Chronic lung disease and developmental delay at 2 years of age in preterm infants

Chronic lung disease (CLD) can increase the risk of early developmental delays, cognitive and language impairment, and poor academic performance. Moreover, predictors and correlates of CLD, such as prolonged mechanical ventilation (MV), are also associated with an increased risk of cognitive impairment. However, the underlying mechanisms of this association have not been identified.
The Extremely Low Gestational Age Newborn (ELGAN) study assessed measures of pulmonary dysfunction as well as prenatal, antenatal, and postnatal exposures and events. The ELGAN investigators evaluated to what extent CLD and its antecedents may influence the risk of developmental delay at 24-months adjusted age, as assessed with the Bayley Scales of Infant Development-2nd Edition (BSID-II), among infants without gross motor function impairments.
Data collected prospectively on 915 infants born before the 28th week of gestation in 2002–2004 were examined. Included infants were assessed at 24 months of age; infants who were not able to walk independently (Gross Motor Function Classification System score <1) and, therefore, more likely to have functionally important fine motor impairments were excluded from the analysis. CLD was defined as receipt of oxygen at 36 weeks’ postmenstrual age. Infants were classified as either not receiving mechanical ventilation (MV) (CLD without MV) or receiving MV (CLD with MV).
In total, 49% of ELGANs had CLD; of these, 14% were receiving MV at 36 weeks’ postmenstrual age. ELGANs without CLD had the lowest risk of a Mental Developmental Index (MDI) or a Psychomotor Developmental Index (PDI) of <55, followed by ELGANs with CLD not receiving MV, and ELGANs with CLD receiving MV (9%, 12%, and 18% for the MDI and 7%, 10%, and 20% for the PDI, respectively). Statistical analysis indicated that the risk of an MDI of <55 was associated with gestational age <25 weeks, single mother, late bacteremia, pneumothorax, and necrotizing enterocolitis. The risk of a PDI of <55 was instead associated with single mother, a complete course of antenatal corticosteroids, early and persistent pulmonary dysfunction, pulmonary deterioration during the second postnatal week, pneumothorax, and pulmonary interstitial emphysema. CLD was not associated with the risk of either a low MDI or a low PDI. However, CLD with MV almost reached, but did not achieve, statistical significance (odds ratio: 1.9 [95% confidence interval: 0.97 3.9]) for the association with a PDI of <55.
These data suggest that it is not CLD, but rather risk factors for CLD, that are more closely linked to developmental delay at 24-months adjusted age. Once these risk factors are considered, CLD imparts no significant additional risk. Both late bacteremia and higher grade NEC have been identified as antecedents of low MDI. What they have in common is a systemic inflammatory response that might lead to cerebral white matter injury. Low PDI seems to be related to factors associated with pulmonary disease (like pneumothorax and pulmonary interstitial emphysema). It is possible that a systemic inflammatory response associated with prolonged MV might increase the likelihood of neonatal brain injury and subsequent disability.

Top