ArticleScientific reports2020
Mendelian randomization and experimental IUGR reveal the adverse effect of low birth weight on lung structure and function.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Emphysema in an 11-month-old boy with alpha-1 antitrypsin deficiency.Pediatric investigation · 2026Article
- Association of birth weight with lung function and the mediating role of gut microbiota: A STROBE 2-step Mendelian randomization study.Medicine · 2025Article
- Seeing pulmonary hypertension through a paediatric lens: a viewpoint.The European respiratory journal · 2024Article
- Association of Fetal Lung Development Disorders with Adult Diseases: A Comprehensive Review.Journal of personalized medicine · 2024Review
- Perinatal origins of bronchopulmonary dysplasia-deciphering normal and impaired lung development cell by cell.Molecular and cellular pediatrics · 2023Review
- Maternal and perinatal obesity induce bronchial obstruction and pulmonary hypertension via IL-6-FoxO1-axis in later life.Nature communications · 2022Article
- Non-linear association of birth weight with lung function and risk of asthma: A population-based study.Frontiers in public health · 2022Article
- Intrauterine Growth Restriction Induces Adulthood Chronic Metabolic Disorder in Cardiac and Skeletal Muscles.Frontiers in nutrition · 2022Article
- Perinatal Nutritional and Metabolic Pathways: Early Origins of Chronic Lung Diseases.Frontiers in medicine · 2021Review
- An Early Sign? Low Birth Weight and Childhood Respiratory Infections as Predictors of Chronic Cough in Adult Asthma.Open respiratory archivesArticle
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intrauterine growth restriction (IUGR) and low birth weigth (LBW) are risk factors for neonatal chronic lung disease. However, maternal and fetal genetic factors and the molecular mechanisms remain unclear. We investigated the relationship between LBW and lung function with Mendelian randomisation analyses and studied angiogenesis in a low protein diet rat model of IUGR. Our data indicate a possible association between LBW and reduced FEV1 (p = 5.69E-18, MR-PRESSO) and FVC (6.02E-22, MR-PRESSO). Complimentary, we demonstrated two-phased perinatal programming after IUGR. The intrauterine phase (embryonic day 21) is earmarked by a reduction of endothelial cell markers (e.g. CD31) as well as mRNA expression of angiogenic factors (e.g., Vegfa, Flt1, Klf4). Protein analysis identified an activation of anti-angiogenic mTOR effectors. In the postnatal phase, lung capillaries (< 20 µm) were significantly reduced, expression of CD31 and VE-Cadherin were unaffected, whereas SMAD1/5/8 signaling and Klf4 protein were increased (p < 0.01). Moreover, elevated proteolytic activity of MMP2 and MMP9 was linked to a 50% reduction of lung elastic fibres. In conclusion, we show a possible link of LBW in humans and reduced lung function in adulthood. Experimental IUGR identifies an intrauterine phase with inhibition of angiogenic signaling, and a postnatal phase with proteolytic activity and reduced elastic fibres.
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