Abstract
Background:
Congenital diaphragmatic hernia (CDH) represents a spectrum of lung hypoplasia, and consequent pulmonary hypertension (PH) is an important cause of postnatal morbidity and mortality. We studied biomarkers at the maternal–fetal interface to understand factors associated with the persistence of PH.
Methods:
Maternal and cord blood samples from fetuses with CDH and unaffected controls were analyzed using a human 39plex immunoassay kit. Cellular trafficking between the mother and the fetus was quantified using quantitative real-time PCR for nonshared alleles. Biomarker profiles were then correlated with CDH severity on the basis of the degree of PH.
Results:
Cord blood levels of epidermal growth factor, platelet-derived growth factor, and several inflammatory mediators increased significantly as the severity of CDH increased, whereas maternal levels of growth factors and mediators decreased significantly with CDH severity. Maternal cells were increased in fetuses with severe CDH as compared with controls, with elevated levels of the CXC chemokine ligand-10 in patients with the highest trafficking.
Conclusion:
Patients with CDH demonstrate proinflammatory and chemotactic signals in fetal blood at the time of birth. Because some of these molecules have been implicated in the development of PH, prenatal strategies targeting specific molecular pathways may be useful adjuncts to current fetal therapies.
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Acknowledgements
We thank the physicians and nurses at the University of California, San Francisco Labor and Delivery Unit and the Fetal Treatment Center for their assistance with sample collection; Qizhi Tang, Peter Oishi, and Jeff Fineman for helpful discussions; and our patients for their gracious participation in this research project.
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Fleck, S., Bautista, G., Keating, S. et al. Fetal production of growth factors and inflammatory mediators predicts pulmonary hypertension in congenital diaphragmatic hernia. Pediatr Res 74, 290–298 (2013). https://doi.org/10.1038/pr.2013.98
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DOI: https://doi.org/10.1038/pr.2013.98
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