Association of early-life factors with prematurity-associated lung disease: prospective cohort study.

Kylie Hart,W John Watkins,Sailesh Kotecha,Sarah J Kotecha,A John Henderson,Michael Cousins

doi:10.1183/13993003.01766-2021

Abstract

BackgroundAlthough bronchopulmonary dysplasia (BPD) is associated with lung function deficits in childhood, many who develop BPD have normal lung function in childhood and many without BPD, including those born at 33–34 weeks of gestation, have lung dysfunction in childhood. Since the predictability of BPD for future lung deficits is increasingly doubted, we prospectively recruited preterm-born children to identify early-life factors associated with lung function deficits after preterm birth.MethodsFrom 767 children aged 7–12 years who had their respiratory symptoms assessed, and had spirometry before and after a bronchodilator in our Respiratory Health Outcomes in Neonates (RHiNO) study, 739 (544 preterm-born at ≤34 weeks of gestation and 195 term-born) had satisfactory lung function. Data were analysed using multivariable logistic regression and mediation.ResultsWhen preterm-born children were classified according to their lung function, low lung function (prematurity-associated lung disease (PLD)) was associated with BPD, gestation and intra-uterine growth restriction (IUGR) on univariable logistic regression analyses. However, on multivariable logistic regression analyses, gestation (β= –0.153, se 0.051; p=0.003) and IUGR (OR 1.783, 95% CI 1.06–3.00; p=0.029) remained significantly associated with later deficits of lung function, but BPD (OR 0.99, 95% CI 0.52–1.89; p=0.974) did not. Mediation analyses confirmed these results.ConclusionsAlthough traditionally BPD has been associated with low lung function in later life, the data show that gestation and IUGR are significantly associated with PLD in childhood, but BPD is not. By identifying children with PLD, we can better understand the underlying mechanisms and develop optimal therapies.

Highlights

Bronchopulmonary dysplasia (BPD) is associated with lung function deficits in childhood, many who develop bronchopulmonary dysplasia (BPD) have normal lung function in childhood, and many without BPD including those born at 33-34 weeks’ gestation, have lung dysfunction in childhood
Conclusions: traditionally BPD has been associated with low lung function in later life, these data show that gestation and intrauterine growth restriction (IUGR) are significantly associated with PLD in childhood but BPD is not
To identify which early risk factors were associated with low lung function observed after preterm-birth, we classified pretermborn children into those with %FEV1 ≤85% (PTlow) and %FEV1 >85% (PTc) groups (Table 1)

Summary

Introduction

Bronchopulmonary dysplasia (BPD) is associated with lung function deficits in childhood, many who develop BPD have normal lung function in childhood, and many without BPD including those born at 33-34 weeks’ gestation, have lung dysfunction in childhood. On multivariable logistic regression analyses, gestation (Beta=-0.153, SE: 0.051, p=0.003) and intrauterine growth restriction (odds ratio 1.783, 95% confidence interval: 1.06, 3.00, p=0.029) remained significantly associated with later deficits of lung function but BPD (0.99; 0.52, 1.89, p=0.974) did not By identifying children with PLD, we can better understand the underlying mechanisms and develop optimal therapies It is well-established that prematurity is associated with long-term respiratory deficits in childhood and young adulthood[1,2,3,4,5]. As summarised by our systematic review[1], most individual studies reported decreased spirometry after preterm-birth, including those who did and did not develop BPD but in general were small in size They did not permit detailed analyses of which early life factors may be important in the development of future lung function deficits. Since BPD is increasingly questioned for predicting future lung function deficits[15, 16], it is important to assess which early life factors including gestation, BPD, intrauterine growth restriction (IUGR), sex, etc. may be important in these future lung function deficits in preterm-born children

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Results

Conclusion