Home Medicine Congenital diaphragmatic hernia: endotracheal fluid phospholipidic profile following tracheal occlusion in an experimental model
Article
Licensed
Unlicensed Requires Authentication

Congenital diaphragmatic hernia: endotracheal fluid phospholipidic profile following tracheal occlusion in an experimental model

  • Gloria Pelizzo EMAIL logo , Maria Chiara Mimmi , Jose Luis Peiro , Mario Marotta , Francesco Amoroso , Mario Fusillo , Veronica Carlini and Valeria Calcaterra
Published/Copyright: August 11, 2016

Abstract

Objective:

To compare endotracheal fluid (EF) and amniotic fluid (AF) phospholipidic profile changes following tracheal occlusion (TO) in the congenital diaphragmatic hernia (CDH) fetal lamb model, in order to support the efficacy of TO on lung maturity.

Methods:

A diaphragmatic defect was induced at 70 days’ gestation, TO was carried out at day 102 and cesarean section at 136 days’ gestation. EF and AF samples, collected at delivery, were evaluated using mass spectrometry (the analysis focused on palmitoyloleoyl-phosphatidylcholine [POPC, PC(18:1/16:0)], dipalmitoyl-phosphatidylcholine [DPPC, PC(16:0/16:0)] and sphingomyelins [SMs]).

Results:

The effects of CDH and TO were different on AF and EF. POPC levels were higher than DPPC levels in AF of healthy lambs. Following induction of the diaphragmatic malformation, an evident decrease in POPC was noted, while a substantial return to normal POPC levels and an increased DPPC peak were prompted by the TO. After CDH induction, a decrease in N-palmitoyl-D-sphingomyelin [SM(d18:1/16:0)] was revealed (P<0.01) and an increased peak in SMs in AF was prompted by the TO (P=0.05). While the most represented phosphatidylcholine (PC) species in EF of healthy lambs was DPPC, CDH induced a decrease in the DPPC peak and treatment with TO induced its partial recovery. SMs were detectable only in healthy EF samples.

Conclusion:

The phospholipid recovery profile following TO suggests the potential role of this therapy in restoring processes involved in surfactant-mediated lung maturation, even though other interactions involved in AF turnover should be considered. Moreover, these metabolites could be used as biomarkers of fetal pulmonary development.


Corresponding author: Professor Gloria Pelizzo, Pediatric Surgery Unit, Fondazione IRCCS Policlinico S. Matteo and University of Pavia, P.le Golgi n.2, 27100 Pavia, Italy, Tel.: +390382502910, Fax: +390382502926

Acknowledgments

We wish to acknowledge Dr. Annalisa De Silvestri for statistical support, the Fondazione IRCCS Policlinico San Matteo of Pavia for supporting the project “Prenatal therapy for congenital malformations” the “Associazione Bambini con la CCAM” for supporting research in our Pediatric Surgery Unit and L. Kelly MSc for English revision of the article.

  1. Funding sources: None.

References

[1] Liu M, Post M. Invited review: mechanochemical signal transduction in the fetal lung. J Appl Physiol. 2000;89:2078–84.10.1152/jappl.2000.89.5.2078Search in Google Scholar

[2] Sanchez-Esteban J, Cicchiello LA, Wang Y, Tsai SW, Williams LK, Torday JS, et al. Mechanical stretch promotes alveolar epithelial type II cell differentiation. J Appl Physiol. 2001;91:589–95.10.1152/jappl.2001.91.2.589Search in Google Scholar

[3] Sanchez-Esteban J. Mechanical forces in fetal lung development: opportunities for translational research. Front Pediatr. 2013;1:51.10.3389/fped.2013.00051Search in Google Scholar

[4] Badillo A, Gingalewski C. Congenital diaphragmatic hernia: treatment and outcomes. Semin Perinatol. 2014;38:92–6.10.1053/j.semperi.2013.11.005Search in Google Scholar

[5] Haroon J, Chamberlain RS. An evidence-based review of the current treatment of congenital diaphragmatic hernia. Clin Pediatr (Phila). 2013;52:115–24.10.1177/0009922812472249Search in Google Scholar

[6] Leeuwen L, Fitzgerald DA. Congenital diaphragmatic hernia. J Paediatr Child Health. 2014:50:667–73.10.1111/jpc.12508Search in Google Scholar

[7] Losty PD. Congenital diaphragmatic hernia: where and what is the evidence? Semin Pediatr Surg. 2014;23:278–82.10.1053/j.sempedsurg.2014.09.008Search in Google Scholar

[8] McHoney M. Congenital diaphragmatic hernia. Early Hum Dev. 2014;90:941–46.10.1016/j.earlhumdev.2014.09.013Search in Google Scholar

[9] Deprest JAM, Veerle A, Evrard K, Verbeken EK, Perales AJ, Delaere PR, et al. Tracheal side effects of endoscopic balloon tracheal occlusion in the fetal lamb model. Eur J Obstet Gynecol Reprod Biol. 2000;92:119–26.10.1016/S0301-2115(00)00435-8Search in Google Scholar

[10] Deprest J, Gucciardo L, Eastwood P, Zia S, Jimenez J, Russo F, et al. Medical and regenerative solutions for congenital diaphragmatic hernia: a perinatal perspective. Eur J Pediatr Surg. 2014;24:270–77.10.1055/s-0034-1382262Search in Google Scholar PubMed

[11] Ruano R, Peiro JL, da Silva MM, Campos JA, Carreras E, Tannuri U, et al. Early fetoscopic tracheal occlusion for extremely severe pulmonary hypoplasia in isolated congenital diaphragmatic hernia: preliminary results. Ultrasound Obstet Gynecol. 2013;42:70–6.10.1002/uog.12414Search in Google Scholar PubMed

[12] Jani JC, Nicolaides KH, Gratacós E, Valencia CM, Doné E, Martinez JM, et al. Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol. 2009;34:304–10.10.1002/uog.6450Search in Google Scholar PubMed

[13] Chiu PP. New Insights into Congenital Diaphragmatic Hernia – a Surgeon’s introduction to CDH animal models. Front Pediatr. 2014;2:36.10.3389/fped.2014.00036Search in Google Scholar PubMed PubMed Central

[14] Zani A, Zani-Ruttenstock E, Pierro A. Advances in the surgical approach to congenital diaphragmatic hernia. Semin Fetal Neonatal Med. 2014;19:364–69.10.1016/j.siny.2014.09.002Search in Google Scholar PubMed

[15] Luks FI, Wild YK, Piasecki GJ, De Paepe ME. Short-term tracheal occlusion corrects pulmonary vascular anomalies in the fetal lamb with diaphragmatic hernia. Surgery. 2000;128:266–72.10.1067/msy.2000.107373Search in Google Scholar PubMed

[16] Davis RP, Mychaliska GB. Neonatal pulmonary physiology. Semin Pediatr Surg. 2013;22:179–84.10.1053/j.sempedsurg.2013.10.005Search in Google Scholar PubMed

[17] Joe P, Wallen LD, Chapin CJ, Lee CH, Allen L, Han VK, et al. Effects of mechanical factors on growth and maturation of the lung in fetal sheep. Am J Physiol. 1997;272:L95–105.10.1152/ajplung.1997.272.1.L95Search in Google Scholar PubMed

[18] Fanos V, Atzori L, Makarenko K, Melis GB, Ferrazzi E. Metabolomics application in maternal-fetal medicine. Biomed Res Int. 2013;2013:720514.10.1155/2013/720514Search in Google Scholar PubMed PubMed Central

[19] Cohn BR, Fukuchi EY, Joe BN, Swanson MG, Kurhanewicz J, Yu J, et al. Calculation of gestational age in late second and third trimesters by ex vivo magnetic resonance spectroscopy of amniotic fluid. Am J Obstet Gynecol. 2010;203:76. e1–76.e10.10.1016/j.ajog.2010.01.046Search in Google Scholar PubMed

[20] Cohn BR, Joe BN, Zhao S, Kornak J, Zhang VY, Iman R, et al. Quantitative metabolic profiles of 2nd and 3rd trimester human amniotic fluid using (1)H HR-MAS spectroscopy. MAGMA. 2009;22:343–52.10.1007/s10334-009-0184-0Search in Google Scholar PubMed PubMed Central

[21] Joe BN, Vahidi K, Zektzer A, Chen MH, Clifton MS, Butler T, et al. (1)H HR-MAS spectroscopy for quantitative measurement of choline concentration in amniotic fluid as a marker of fetal lung maturity: inter- and intraobserver reproducibility study. J Magn Reson Imaging. 2008;28:1540–45.10.1002/jmri.21592Search in Google Scholar

[22] Mimmi MC, Ballico M, Amoroso F, Calcaterra V, Marotta M, Peiro JL, et al. Phospholipid profile of amniotic fluid in ovine model of congenital diaphragmatic hernia (CDH): the effect of fetal tracheal occlusion. J Proteome Res. 2015;14: 1465–71.10.1021/pr501120xSearch in Google Scholar

[23] Pelizzo G, Mimmi MC, Ballico M, Marotta M, Goruppi I, Peiro JL, et al. Congenital pulmonary malformations: metabolomic profile of lung phenotype in infants. J Matern Fetal Neonatal Med. 2014;4:1–12.10.3109/14767058.2014.991708Search in Google Scholar

[24] Pelizzo G, Ballico M, Mimmi MC, Peirò JL, Marotta M, Federico C, et al. Metabolomic profile of amniotic fluid to evaluate lung maturity: the diaphragmatic hernia lamb model. Multidiscip Respir Med. 2014;9:54.10.1186/2049-6958-9-54Search in Google Scholar

[25] Brace RA, Cheung CY. Regulation of amniotic fluid volume: evolving concepts. Adv Exp Med Biol. 2014;814:49–68.10.1007/978-1-4939-1031-1_5Search in Google Scholar

[26] Dunn WB, Broadhurst D, Begley P, Zelena E, Francis-McIntyre S, Anderson N, et al. Human Serum Metabolome (HUSERMET) Consortium: procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat Protoc. 2011;6:1060–83.10.1038/nprot.2011.335Search in Google Scholar

[27] Zhu ZJ, Schultz AW, Wang J, Johnson CH, Yannone SM, Patti GJ, et al. Liquid chromatography quadrupole time-of-flight mass spectrometry characterization of metabolites guided by the METLIN database. Nat Protoc. 2013;8:451–60.10.1038/nprot.2013.004Search in Google Scholar

[28] Papadakis K, Luks FI, De Paepe ME, Piasecki GJ, Wesselhoeft CW Jr. Fetal lung growth after tracheal ligation is not solely a pressure phenomenon. J Pediatr Surg. 1997;32:347–51.10.1016/S0022-3468(97)90208-6Search in Google Scholar

[29] Goerke J. Pulmonary surfactant: functions and molecular composition. Biochim Biophys Acta. 1998;1408:79–89.10.1016/S0925-4439(98)00060-XSearch in Google Scholar

[30] Akella A, Deshpande SB. Pulmonary surfactants and their role in pathophysiology of lung disorders. Indian J Exp Biol. 2013;51:5–22.Search in Google Scholar

[31] Parra E, Pérez-Gil J. Composition, structure and mechanical properties define performance of pulmonary surfactant membranes and films. Chem Phys Lipids. 2015;185C:153–75.10.1016/j.chemphyslip.2014.09.002Search in Google Scholar PubMed

[32] Lang CJ, Postle AD, Orgeig S, Possmayer F, Bernhard W, Panda AK, et al. Dipalmitoylphosphatidylcholine is not the major surfactant phospholipid species in all mammals. Am J Physiol Regul Integr Comp Physiol. 2005;289:R1426–39.10.1152/ajpregu.00496.2004Search in Google Scholar

[33] Brace RA. Progress toward understanding the regulation of amniotic fluid volume: water and solute fluxes in and through the fetal membranes. Placenta. 1995;16:1–18.10.1016/0143-4004(95)90077-2Search in Google Scholar

[34] Gilbert WM, Brace RA. The missing link in amniotic fluid volume regulation: intramembranous absorption. Obstet Gynecol. 1989;74:748–54.Search in Google Scholar

[35] Jang PR, Brace RA. Amniotic fluid composition changes during urine drainage and tracheoesophageal occlusion in fetal sheep. Am J Obstet Gynecol. 1992;167:1732–41.10.1016/0002-9378(92)91768-6Search in Google Scholar

[36] Serriere S, Barantin L, Seguin F, Tranquart F, Nadal-Desbarats L. Impact of prenatal stress on 1H NMR-based metabolic profiling of rat amniotic fluid. MAGMA. 2011;24:267–75.10.1007/s10334-011-0260-0Search in Google Scholar PubMed

[37] Wagle S, Bui A, Ballard PL, Shuman H, Gonzales J, Gonzales LW. Hormonal regulation and cellular localization of fatty acid synthase in human fetal lung. Am J Physiol. 1999;277:L381–90.10.1152/ajplung.1999.277.2.L381Search in Google Scholar PubMed

[38] Rooney SA. Lung surfactant. Environ Health Perspect. 1984;55:205–26.10.1289/ehp.8455205Search in Google Scholar PubMed PubMed Central

[39] Alaggio R, Midrio P, Sgrò A, Piovan G, Guzzardo V, Donato R, et al. Congenital diaphragmatic hernia: focus on abnormal muscle formation. J Pediatr Surg. 2015;50:388–93.10.1016/j.jpedsurg.2014.08.005Search in Google Scholar PubMed

  1. The authors stated that there are no conflicts of interest regarding the publication of this article.

Received: 2015-9-28
Accepted: 2016-7-18
Published Online: 2016-8-11
Published in Print: 2017-2-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Fetal diagnosis and therapy: a continously evolving discipline
  4. Highlight articles
  5. Prenatally diagnosed fetal tumors of the head and neck: a systematic review with antenatal and postnatal outcomes over the past 20 years
  6. Prenatal screening for microcephaly: an update after three decades
  7. Fetal echocardiography: reference values for the Chinese population
  8. Multi-fetal pregnancy reduction (MFPR) to twins or singleton – medical justification and ethical slippery slope
  9. Combined screening test for trisomy 21 – is it as efficient as we believe?
  10. Fetal loss following invasive prenatal testing: a comparison of transabdominal chorionic villus sampling, transcervical chorionic villus sampling and amniocentesis
  11. Comparison of adverse perinatal outcomes after single-needle and double-needle CVS techniques
  12. Prenatal decision-making in the second and third trimester in trisomy 21-affected pregnancies
  13. Role of collagen type IV in the pathogenesis of increased prenasal thickness in Down syndrome fetuses: sonographic and immunohistological findings
  14. Congenital diaphragmatic hernia: endotracheal fluid phospholipidic profile following tracheal occlusion in an experimental model
  15. Original articles
  16. The effect of intraumbilical fetal nutrition via a subcutaneously implanted port system on amino acid concentration by severe IUGR human fetuses
  17. Anti-inflammatory Elafin in human fetal membranes
  18. Recombinant vascular endothelial growth factor 121 injection for the prevention of fetal growth restriction in a preeclampsia mouse model
  19. Estimation of fetal weight by ultrasonography after preterm premature rupture of membranes: comparison of different formulas
  20. Congress Calendar
  21. Congress Calendar
Downloaded on 31.12.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jpm-2015-0334/html
Scroll to top button