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Reduced lung function during childhood in identical twins with discordant fetal growth: a cohort study
Jip A Spekman1, Joël Israëls2, Ilja de Vreede2
1Neonatology, Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Centre, Leiden, the Netherlands.
Insights
Selective fetal growth restriction (sFGR) in identical twins significantly impairs lung development, leading to reduced lung function and increased respiratory risks later in life.
Area of Science:
- Pediatric Pulmonology
- Fetal Medicine
- Genetics
Background:
- Fetal growth restriction (FGR) adversely impacts lung development, increasing respiratory issues later in life.
- Studies on FGR and lung function in singletons are confounded by various factors.
- Investigating identical twins with selective FGR (sFGR) minimizes genetic and maternal confounding factors.
Purpose of the Study:
- To assess the impact of sFGR on lung function in genetically identical twins.
- To determine if in-utero growth restriction affects lung development and function.
Main Methods:
- Lung function tests (spirometry) were conducted on identical twins with sFGR (birthweight discordance ≥20%).
- Key outcomes included forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO).
- Lung function was compared between the smaller (sFGR) and larger co-twin.
Main Results:
- Thirty-nine twin pairs aged 5-17 years were analyzed.
- Smaller twins exhibited significantly lower z-scores for FEV1, FVC, and DLCO compared to their larger co-twins.
- These differences persisted even after accounting for reduced lung volume.
Conclusions:
- Genetically identical twins with sFGR show reduced lung volumes and diffusion capacity.
- Adverse intrauterine conditions negatively impact lung development and function.
- sFGR may contribute to increased respiratory morbidity in later life.
Background:
Fetal growth restriction (FGR) can negatively affect lung development, leading to increased respiratory morbidity and reduced lung function later in life. Studies regarding the impact of FGR on lung function in singletons are influenced by genetic, obstetric, and maternal factors. To overcome these confounding factors, we aim to investigate lung function in identical twins with selective FGR (sFGR).
Methods:
Lung function assessments were performed in identical twins with sFGR born in our centre between March 1, 2002, and December 31, 2017, aged between 5 and 17 years. sFGR was defined as birthweight discordance ≥20%. Outcome measures consisted of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and transfer factor for carbon monoxide (DLCO) and were compared between the smaller and larger twin.
Findings:
Thirty-nine twin pairs performed spirometry of sufficient quality. Median gestational age at birth was 34.3 (interquartile range (IQR) 32.1-36.0) weeks with median birthweights of 1500 (IQR 1160-1880) grams and 2178 (IQR 1675-2720) grams for the smaller and larger twin, respectively. Smaller twins had significantly lower z-scores for FEV1 (-0.94 versus -0.41, p = 0.0015), FVC (-0.56 versus -0.06, p < 0.0001) and DLCO (-0.50 versus 0.00, p < 0.0001) compared to larger co-twins.
Interpretation:
Although being genetically identical, sFGR in identical twins is associated with a reduction in static and dynamic lung volume and a reduction in lung diffusion, even when taking the reduced lung volume into account. This indicates that adverse growth conditions in utero negatively affect lung development and function, potentially contributing to an increase in respiratory morbidities later in life.
Funding:
The Dutch Heart Foundation and The Bontius Foundation.
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