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Very preterm birth, low birth weight may increase risk for suboptimal lung function in adulthood

Very preterm birth or very low birth weight may put a person at risk for not reaching full airway growth potential in early adulthood, according to a study published in The Lancet Respiratory Medicine.

In the meta-analysis, the researchers evaluated individual participant data from 11 cohort studies, which included 935 participants born very preterm or with very low birth weight and 722 control participants. Expiratory airflow was tested at a mean age of 21 years.

The mean z scores for expiratory flow rates were close to the expected value of 0 in the control group. However, they were reduced in the very preterm or very low birth weight group for forced expiratory volume in 1 second (FEV₁; –0.06 vs. –0.81), with a mean reduction of 0.78 (P < .0001). The same was true for forced vital capacity (FVC; –0.15 vs. –0.38), with a mean reduction of 0.25 (P = .0012); FEV₁/FVC ratio (0.14 vs. –0.64), with a mean reduction of 0.74 (P < .0001); and forced expiratory flow at 25% to 75% (FEF_25-75%; –0.04 vs. –0.95), with a mean reduction of 0.88 (P < .0001).

In the very preterm or very low birth weight group, 23% to 29% had z scores below the fifth percentile for FEV₁, FVC, FEV₁/FVC ratio and FEF_25-75% and 11% had FVC scores below the fifth percentile — proportions that exceeded those in the control group, which were close to the expected value of 5%.

Subgroup analyses

Expiratory airflow testing after age 21 years was performed in 669 participants, including 360 who were born very preterm or with very low birth weight and 309 controls. The rate of change in z scores with age in this older group was lower in the very preterm or very low birth weight participants when compared with controls. In the control group, there was a strong association between FVC z score and age that was not seen among the very preterm or very low birth weight group. FEV₁/FVC ratio z scores decreased more in the control group, but the association was not statistically significant after adjustment for baseline scores.

A total of 117 participants born very preterm or with very low birth weight and 53 controls underwent expiratory airflow testing twice, at age 18 and age 25 years. Both groups demonstrated comparable increases in FEV₁ z scores from age 18 to 25 years. Increases in FVC z scores were also noted, but the change was less in the very preterm or very low birth weight group.

In univariable and multivariable analyses, FEV₁ z score was higher with antenatal corticosteroid treatment and lower in men or those who had bronchopulmonary dysplasia. FVC z score was increased in those who had antenatal steroids or were current smokers and was decreased in those who had bronchopulmonary dysplasia. FEV₁/FVC ratio z score and FEF_25-75% z score were also lower in men or those with bronchopulmonary dysplasia.

The researchers noted, however, that the data were mostly derived from participants born before the availability of exogenous surfactants. Inclusion criteria also varied across the studies included in the meta-analysis and some data were missing or inconsistently collected. Therefore, the study results should be viewed within the context of these limitations, they wrote.

Clinical considerations

Overall, these findings indicate that children born very preterm or with very low birth weight may experience significant respiratory problems in adulthood, according to the researchers.

“Individuals who survived very preterm birth or very low birth weight during the era of modern intensive care are not reaching their full airway growth potential in early adulthood, already being more likely to have clinically important reductions in airflow (values below the fifth percentile) at this age than individuals born with normal birth weight or at term. This disadvantage is exacerbated by bronchopulmonary dysplasia in the neonatal period. In individuals born very preterm or with very low birth weight, unless their rate of decline in airflow is lower than that which normally occurs with age in adulthood, many will develop [chronic obstructive pulmonary disorder] later in adult life,” they wrote.

In an accompanying editorial, Shyamali C. Dharmage, MD, PhD; Dinh S. Bui, MPH; Jennifer L. Perret, MD; and Caroline J. Lodge, PhD, all from the Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, noted that this study supports consideration of secondary intervention strategies to prevent lung disease in this patient population.

“Physicians of adult patients need to appreciate the long-term influences of very preterm birth or very low birth weight on lung function, and should consider adults who were born prematurely to be at high risk of lung function deficits,” they wrote. “Although the potential interaction between very preterm birth or very low birth weight and further lung problems should be investigated, the current evidence on interactions between different risk factors for lung function deficits at a population level can inform secondary preventive strategies that could be advocated for this high-risk population.” – by Melissa Foster

Disclosures: One study author reports he has received grants from the Academy of Finland, the European Commission, the Novo Nordisk Foundation, the Foundation for Pediatric Research (Helsinki), the Foundation for Cardiovascular Research (Helsinki), the Foundation for Diabetes Research (Helsinki), the Sigrid Juselius Foundation, the Signe and Ane Gyllenberg Foundation, the Juho Vainio Foundation and the Yrjö Jahnsson Foundation. Another study author reports he has received personal fees from Merck and grants from GlaxoSmithKline, Boehringer Ingelheim, Chiesi, Novartis and AstraZeneca. All other authors report no relevant financial disclosures.