Acylcarnitine Profiles of Preterm Infants Over the First Four Weeks of Life

Meyburg, Jochen; Schulze, Andreas; Kohlmueller, Dirk; Pöschl, Johannes; Linderkamp, Otwin; Hoffmann, Georg F.; Mayatepek, Ertan

doi:10.1203/00006450-200211000-00018

Cited by 41 publications

(23 citation statements)

References 25 publications

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“…According to the scarce literature available, levels of C 16:1 OH seem not to be influenced significantly by gestational age (Meyburg et al 2002) or those of C 16:1 OH and C 4 DC by the age at sampling (Cavedon et al 2005) and our patients_ data confirm this.…”

Section: Discussionsupporting

confidence: 83%

Newborn screening for methylmalonic acidurias—Optimization by statistical parameter combination

Ho¹,

Kölker²,

Abdoh

et al. 2008

J of Inher Metab Disea

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With the introduction of tandem mass spectrometry, newborn screening for disorders of propionate metabolism became widely available. However, there is controversy whether population screening for these disorders should be performed. The most widely used primary metabolite C(3) itself has a poor specificity or lacks 100% sensitivity for milder forms and/or defects of cobalamin metabolism. Strategies to improve specificity have included the calculation of metabolite ratios (e.g. C(3)/C(2)) or second-tier strategies with analysis of methylmalonic acid or 2-methylcitric acid from the primary screening specimen. We report the results of a new statistical approach to identify parameter combinations that allow for 100% sensitivity as well as increased specificity. The promising results of this alternative approach will have to be substantiated on larger data sets.

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Section: Discussionsupporting

confidence: 83%

Newborn screening for methylmalonic acidurias—Optimization by statistical parameter combination

Ho¹,

Kölker²,

Abdoh

et al. 2008

J of Inher Metab Disea

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“…The normative levels and postnatal changes in plasma carnitine in the preterm neonate are now well characterized [36], [37], [38]. Sick preterm neonates who do not receive carnitine supplementation via the enteral or parenteral route continue to have lower tissue carnitine levels [39], [40], [41], [42] which drop further, and thus may develop a state of relative tissue carnitine deficiency.…”

Section: Introductionmentioning

confidence: 99%

Carnitine Deficiency in OCTN2−/− Newborn Mice Leads to a Severe Gut and Immune Phenotype with Widespread Atrophy, Apoptosis and a Pro-Inflammatory Response

et al. 2012

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We have investigated the gross, microscopic and molecular effects of carnitine deficiency in the neonatal gut using a mouse model with a loss-of-function mutation in the OCTN2 (SLC22A5) carnitine transporter. The tissue carnitine content of neonatal homozygous (OCTN2−/−) mouse small intestine was markedly reduced; the intestine displayed signs of stunted villous growth, early signs of inflammation, lymphocytic and macrophage infiltration and villous structure breakdown. Mitochondrial β-oxidation was active throughout the GI tract in wild type newborn mice as seen by expression of 6 key enzymes involved in β-oxidation of fatty acids and genes for these 6 enzymes were up-regulated in OCTN2−/− mice. There was increased apoptosis in gut samples from OCTN2−/− mice. OCTN2−/− mice developed a severe immune phenotype, where the thymus, spleen and lymph nodes became atrophied secondary to increased apoptosis. Carnitine deficiency led to increased expression of CD45-B220+ lymphocytes with increased production of basal and anti-CD3-stimulated pro-inflammatory cytokines in immune cells. Real-time PCR array analysis in OCTN2−/− mouse gut epithelium demonstrated down-regulation of TGF-β/BMP pathway genes. We conclude that carnitine plays a major role in neonatal OCTN2−/− mouse gut development and differentiation, and that severe carnitine deficiency leads to increased apoptosis of enterocytes, villous atrophy, inflammation and gut injury.

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“…Recent echocardiographic, magnetic resonance and CT imaging studies indicate that preterm infants have larger left atria and lower diastolic function than term infants (14)(15)(16)(17), suggesting that the heart failure among young adults who were born preterm has developmental origins. Serum from preterm infants was shown to have higher levels of malonyl-carnitine and lower levels of palmatoylcarnitine than serum from term infants born (62), suggesting a link between preterm birth and reduced FASN activity. Preterm infants often require mechanical ventilation, steroids, and other therapeutic interventions that make it difficult to identify the direct effects of supplemental oxygen on their cardiovascular health.…”

Section: Discussionmentioning

confidence: 93%

Neonatal hyperoxia inhibits proliferation of atrial cardiomyocytes by suppressing fatty acid synthesis

Cohen

Yee

Porter

et al. 2020

Preprint

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Preterm birth increases the risk for pulmonary hypertension and heart failure in adulthood.Oxygen therapy can damage the immature cardiopulmonary system and may be partially responsible for the cardiovascular disease in adults born preterm. We previously showed that exposing newborn mice to hyperoxia causes pulmonary hypertension by 1 year of age that is preceded by a poorly understood loss of pulmonary vein cardiomyocyte proliferation. We now show that hyperoxia also inhibits the proliferation of left atrial cardiomyocytes and causes diastolic heart failure by thinning the walls of the left atrium and disrupting its ability to pump effectively. Transcriptomic profiling showed that neonatal hyperoxia permanently suppressed fatty acid synthase (Fasn), stearoyl-CoA desaturase 1 (Scd1) and other fatty acid synthesis genes in the atria of mice, the HL-1 line of mouse atrial cardiomyocytes and left atrial tissue explanted from human infants. Suppressing Fasn or Scd1 reduced HL-1 cell proliferation while overexpressing these genes maintained their expansion in hyperoxic conditions, suggesting hyperoxia directly inhibits atrial cardiomyocyte proliferation by repressing Fasn and Scd1. Pharmacologic interventions that restore Fasn, Scd1 and other fatty acid synthesis genes in atrial cardiomyocytes may thus provide a way of ameliorating the adverse effects of supplemental oxygen on preterm infants.

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Acylcarnitine Profiles of Preterm Infants Over the First Four Weeks of Life

Cited by 41 publications

References 25 publications

Newborn screening for methylmalonic acidurias—Optimization by statistical parameter combination

Newborn screening for methylmalonic acidurias—Optimization by statistical parameter combination

Carnitine Deficiency in OCTN2−/− Newborn Mice Leads to a Severe Gut and Immune Phenotype with Widespread Atrophy, Apoptosis and a Pro-Inflammatory Response

Neonatal hyperoxia inhibits proliferation of atrial cardiomyocytes by suppressing fatty acid synthesis

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