Fetal growth restriction linked to reduced lung function in early adulthood

Fetal growth restriction impaired intrauterine lung development and led to reduced measures of lung function later in life, according to a study published in Annals of the American Thoracic Society.

“We found reduced large and small airway function in [monochorionic] twins with selective (fetal growth restriction [FGR]),” Yasmin Salem, a PhD student in the division of pediatric respiratory medicine and allergology at the University Hospital of Bern in Switzerland, and colleagues wrote. “Low birth weight was associated with lung function impairment, and this association was independent of gestational age and body growth. Therefore, our results support the hypothesis that FGR impairs intrauterine lung development with persistent reduction of lung function in later life.”

In a case-controlled study, Salem and colleagues analyzed 20 monochorionic twin pairs (mean age, 18.4 years; mean gestational age, 33.6 weeks; 45% male) from the University Hospital of Bern’s database to determine whether a relationship exists between birth weight and lung function — assessed using spirometry, body plethysmography, multiple-breath washout and MRI — in adulthood.

Each twin pair included one twin with FGR, considered the case, with the other twin considered the counterpart. Researchers assessed differences in their lung function using paired t tests, and they used mixed linear models to determine the relationship between birth weight and outcomes.

Of the total cohort, the mean difference in birth weight within the pairs was 575 g (range, 270-1,130).

Low birth weight appeared associated with lower measures of lung function, as demonstrated by mean differences between the twins with FGR and their counterparts of –0.64 (95% CI, –0.98 to –0.3) for FEV₁ z scores and –0.55 (95% CI, –0.92 to –0.18) for FVC z scores.

Researchers further found that both values of lung volume increased when factoring in additional birth weight. Per 500 g of birth weight, the z score for FEV₁ increased by 0.5 (95% CI, 0.35-0.65) and the z score for FVC increased by 0.44 (95% CI, 0.31-0.57).

Spirometry also showed an association between low birth weight and lower maximal forced expiratory flow (mean difference = –0.37; 95% CI, –0.79 to 0.06), as well as lower flow when 75% of FVC has been exhaled (mean difference = –0.2; 95% CI, –0.52 to 0.12).

Researchers also found that lower birth weight was linked to a lower total lung capacity z score (mean difference = –0.35; 95% CI, –0.71 to 0.01) and a higher residual volume/total lung capacity z score (mean difference = 0.23; 95% CI, –0.17 to 0.62).

Additionally, on multiple-breath washout, researchers observed elevated ventilation inhomogeneity within acinar airways in the twins with FGR compared with their counterparts (mean difference = 0.033; 95% CI, 0.012-0.054), which was also related to low birth weight.

Researchers reported that structural and functional MRI outcomes did not differ between the twins. Also, their original results persisted when adjusting for study height.

“The exact mechanisms of reduced lung function in relation to fetal growth are highly complex and not fully understood,” Salem and colleagues wrote. “One of the main hypotheses is that an adverse intrauterine environment leads to a number of fetal adaptations during a critical time window of development, including distinct epigenetic changes. This interaction should be subject to future studies, ideally assessing prenatal changes in FGR in relation to birth weight and lung function within large longitudinal datasets.”