Umbilical cord blood metabolomics reveal distinct signatures of dyslipidemia prior to bronchopulmonary dysplasia and pulmonary hypertension

Michael R. La Frano, Johannes F. Fahrmann, Dmitry Grapov, Theresa L. Pedersen, John W. Newman, Oliver Fiehn, Mark Underwood, Karen Mestan, Robin H Steinhorn, Stephen Wedgwood

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Pulmonary hypertension (PH) is a common consequence of bronchopulmonary dysplasia (BPD) and remains a primary contributor to increased morbidity and mortality among preterm infants. Unfortunately, at the present time, there are no reliable early predictive markers for BPD-associated PH. Considering its health consequences, understanding in utero perturbations that lead to the development of BPD and BPD-associated PH and identifying early predictive markers is of utmost importance. As part of the discovery phase, we applied a multiplatform metabolomics approach consisting of untargeted and targeted methodologies to screen for metabolic perturbations in umbilical cord blood (UCB) plasma from preterm infants that did (n ☓ 21; cases) or did not (n ☓ 21; controls) develop subsequent PH. A total of 1,656 features were detected, of which 407 were annotated by metabolite structures. PH-associated metabolic perturbations were characterized by reductions in major choline-containing phospholipids, such as phosphatidylcholines and sphingomyelins, indicating altered lipid metabolism. The reduction in UCB abundances of major choline-containing phospholipids was confirmed in an independent validation cohort consisting of UCB plasmas from 10 cases and 10 controls matched for gestational age and BPD status. Subanalyses in the discovery cohort indicated that elevations in the oxylipins PGE1, PGE2, PGF2a, 9-and 13-HOTE, 9-and 13-HODE, and 9-and 13-KODE were positively associated with BPD presence and severity. This expansive evaluation of cord blood plasma identifies compounds reflecting dyslipidemia and suggests altered metabolite provision associated with metabolic immaturity that differentiate subjects, both by BPD severity and PH development.

Original languageEnglish (US)
Pages (from-to)L870-L881
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume315
Issue number5
DOIs
StatePublished - Nov 1 2018

Fingerprint

Bronchopulmonary Dysplasia
Metabolomics
Dyslipidemias
Fetal Blood
Pulmonary Hypertension
Choline
Premature Infants
Phospholipids
Oxylipins
Sphingomyelins
Alprostadil
Phosphatidylcholines
Lipid Metabolism
Dinoprostone
Gestational Age
Morbidity
Mortality
Health

Keywords

  • Bronchopulmonary dysplasia
  • Lipids
  • Metabolomics
  • Oxylipins
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Umbilical cord blood metabolomics reveal distinct signatures of dyslipidemia prior to bronchopulmonary dysplasia and pulmonary hypertension. / La Frano, Michael R.; Fahrmann, Johannes F.; Grapov, Dmitry; Pedersen, Theresa L.; Newman, John W.; Fiehn, Oliver; Underwood, Mark; Mestan, Karen; Steinhorn, Robin H; Wedgwood, Stephen.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 315, No. 5, 01.11.2018, p. L870-L881.

Research output: Contribution to journalArticle

La Frano, Michael R. ; Fahrmann, Johannes F. ; Grapov, Dmitry ; Pedersen, Theresa L. ; Newman, John W. ; Fiehn, Oliver ; Underwood, Mark ; Mestan, Karen ; Steinhorn, Robin H ; Wedgwood, Stephen. / Umbilical cord blood metabolomics reveal distinct signatures of dyslipidemia prior to bronchopulmonary dysplasia and pulmonary hypertension. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2018 ; Vol. 315, No. 5. pp. L870-L881.
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abstract = "Pulmonary hypertension (PH) is a common consequence of bronchopulmonary dysplasia (BPD) and remains a primary contributor to increased morbidity and mortality among preterm infants. Unfortunately, at the present time, there are no reliable early predictive markers for BPD-associated PH. Considering its health consequences, understanding in utero perturbations that lead to the development of BPD and BPD-associated PH and identifying early predictive markers is of utmost importance. As part of the discovery phase, we applied a multiplatform metabolomics approach consisting of untargeted and targeted methodologies to screen for metabolic perturbations in umbilical cord blood (UCB) plasma from preterm infants that did (n ☓ 21; cases) or did not (n ☓ 21; controls) develop subsequent PH. A total of 1,656 features were detected, of which 407 were annotated by metabolite structures. PH-associated metabolic perturbations were characterized by reductions in major choline-containing phospholipids, such as phosphatidylcholines and sphingomyelins, indicating altered lipid metabolism. The reduction in UCB abundances of major choline-containing phospholipids was confirmed in an independent validation cohort consisting of UCB plasmas from 10 cases and 10 controls matched for gestational age and BPD status. Subanalyses in the discovery cohort indicated that elevations in the oxylipins PGE1, PGE2, PGF2a, 9-and 13-HOTE, 9-and 13-HODE, and 9-and 13-KODE were positively associated with BPD presence and severity. This expansive evaluation of cord blood plasma identifies compounds reflecting dyslipidemia and suggests altered metabolite provision associated with metabolic immaturity that differentiate subjects, both by BPD severity and PH development.",
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AU - La Frano, Michael R.

AU - Fahrmann, Johannes F.

AU - Grapov, Dmitry

AU - Pedersen, Theresa L.

AU - Newman, John W.

AU - Fiehn, Oliver

AU - Underwood, Mark

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AU - Steinhorn, Robin H

AU - Wedgwood, Stephen

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AB - Pulmonary hypertension (PH) is a common consequence of bronchopulmonary dysplasia (BPD) and remains a primary contributor to increased morbidity and mortality among preterm infants. Unfortunately, at the present time, there are no reliable early predictive markers for BPD-associated PH. Considering its health consequences, understanding in utero perturbations that lead to the development of BPD and BPD-associated PH and identifying early predictive markers is of utmost importance. As part of the discovery phase, we applied a multiplatform metabolomics approach consisting of untargeted and targeted methodologies to screen for metabolic perturbations in umbilical cord blood (UCB) plasma from preterm infants that did (n ☓ 21; cases) or did not (n ☓ 21; controls) develop subsequent PH. A total of 1,656 features were detected, of which 407 were annotated by metabolite structures. PH-associated metabolic perturbations were characterized by reductions in major choline-containing phospholipids, such as phosphatidylcholines and sphingomyelins, indicating altered lipid metabolism. The reduction in UCB abundances of major choline-containing phospholipids was confirmed in an independent validation cohort consisting of UCB plasmas from 10 cases and 10 controls matched for gestational age and BPD status. Subanalyses in the discovery cohort indicated that elevations in the oxylipins PGE1, PGE2, PGF2a, 9-and 13-HOTE, 9-and 13-HODE, and 9-and 13-KODE were positively associated with BPD presence and severity. This expansive evaluation of cord blood plasma identifies compounds reflecting dyslipidemia and suggests altered metabolite provision associated with metabolic immaturity that differentiate subjects, both by BPD severity and PH development.

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