Distinct protein patterns related to postnatal development in small for gestational age preterm infants
Pediatric Research, vol. 97, pp. 1722–1731
Abstract
BACKGROUND: Preterm infants, especially those born small for gestational age (SGA), are at risk of short-term and long-term health complications. Characterization of changes in circulating proteins postnatally in preterm infants may provide valuable fundamental insights into this population. Here, we investigated postnatal developmental patterns in preterm infants and explored protein signatures that deviate between SGA infants and appropriate for gestational age (AGA) infants using a mass spectrometry (MS)-based proteomics workflow. METHODS: Longitudinal serum samples obtained at postnatal days 0, 3, 7, 14, and 28 from 67 preterm infants were analyzed using unbiased MS-based proteomics. RESULTS: 314 out of 833 quantified serum proteins change postnatally, including previously described age-related changes in immunoglobulins, hemoglobin subunits, and new developmental patterns, e.g. apolipoproteins (APOA4) and terminal complement cascade (C9) proteins. Limited differences between SGA and AGA infants were found at birth while longitudinal monitoring revealed 69 deviating proteins, including insulin-sensitizing hormone adiponectin, platelet proteins, and 24 proteins with an annotated function in the immune response. CONCLUSIONS: This study shows the potential of MS-based serum profiling in defining circulating protein trajectories in the preterm infant population and its ability to identify longitudinal alterations in protein levels associated with SGA. IMPACT: Postnatal changes of circulating proteins in preterm infants have not fully been elucidated but may contribute to development of health complications. Mass spectrometry-based analysis is an attractive approach to study circulating proteins in preterm infants with limited material. Longitudinal plasma profiling reveals postnatal developmental-related patterns in preterm infants (314/833 proteins) including previously described changes, but also previously unreported proteins. Longitudinal monitoring revealed an immune response signature between SGA and AGA infants. This study highlights the importance of taking postnatal changes into account for translational studies in preterm infants.
Authors 12
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Affiliation as printed
Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands
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Amsterdam UMC Location University of Amsterdam · Amsterdam Reproduction Development · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands
Department of Neonatology, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands
Department of Pediatric Endocrinology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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Affiliation as printed
Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands
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Affiliation as printed
Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands
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Hilde van der Staaij Aachen Department of Pediatrics Division of Neonatology, Willem-Alexander Children's Hospital
Leiden University Medical Center · Sanquin · Emma Kinderziekenhuis · Willem-Alexander Kinderziekenhuis · Amsterdam University Medical Centers
Affiliation as printed
Department of Pediatric Hematology, Emma Children's Hospital, Amsterdam University Medical Center, Amsterdam, the Netherlands
Department of Pediatrics, Division of Neonatology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands
Sanquin Research & Lab Services, Sanquin Blood Supply Foundation, Amsterdam, the Netherlands
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Amsterdam Reproduction Development · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands
Department of Pediatric Endocrinology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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Amsterdam UMC Location University of Amsterdam · Amsterdam Reproduction Development
Affiliation as printed
Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands
Department of Neonatology, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands
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Suzanne F Fustolo-Gunnink Aachen Department of Pediatrics Division of Neonatology, Willem-Alexander Children's Hospital
Leiden University Medical Center · Sanquin · Emma Kinderziekenhuis · Willem-Alexander Kinderziekenhuis · Amsterdam University Medical Centers
Affiliation as printed
Department of Pediatric Hematology, Emma Children's Hospital, Amsterdam University Medical Center, Amsterdam, the Netherlands
Department of Pediatrics, Division of Neonatology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands
Sanquin Research & Lab Services, Sanquin Blood Supply Foundation, Amsterdam, the Netherlands
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Affiliation as printed
Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands
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Amsterdam UMC Location University of Amsterdam · Amsterdam Reproduction Development
Affiliation as printed
Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands
Department of Neonatology, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands
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Amsterdam Reproduction Development · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands
Department of Pediatric Endocrinology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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Maartje van den Biggelaar corresponding
Affiliation as printed
Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands. m.vandenbiggelaar@sanquin.nl
Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands
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