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@ARTICLE{Hoermann:1038463,
      author       = {Hoermann, H. and van Faassen, M. and Roeper, M. and
                      Hagenbeck, C. and Herebian, D. and Muller Kobold, AC. and
                      Dukart, Jürgen and Kema, IP. and Mayatepek, E. and
                      Meissner, T. and Kummer, S.},
      title        = {{A}ssociation of {F}etal {C}atecholamines {W}ith {N}eonatal
                      {H}ypoglycemia},
      journal      = {JAMA pediatrics},
      volume       = {178},
      number       = {6},
      issn         = {2168-6203},
      address      = {Chicago, Ill.},
      publisher    = {American Medical Association},
      reportid     = {FZJ-2025-01459},
      pages        = {577-585},
      year         = {2024},
      abstract     = {Importance: Perinatal stress and fetal growth restriction
                      increase the risk of neonatal hypoglycemia. The underlying
                      pathomechanism is poorly understood. In a sheep model,
                      elevated catecholamine concentrations were found to suppress
                      intrauterine insulin secretion, followed by hyperresponsive
                      insulin secretion once the adrenergic stimulus
                      subsided.Objective: To determine whether neonates with risk
                      factors for hypoglycemia have higher catecholamine
                      concentrations in umbilical cord blood (UCB) and/or amniotic
                      fluid (AF) and whether catecholamines are correlated with
                      postnatal glycemia.Design, setting, and participants: In a
                      prospective cohort study of 328 neonates at a tertiary
                      perinatal center from September 2020 through May 2022 in
                      which AF and UCB were collected immediately during and after
                      delivery, catecholamines and metanephrines were analyzed
                      using liquid chromatography with tandem mass spectrometry.
                      Participants received postnatal blood glucose (BG)
                      screenings.Exposure: Risk factor for neonatal
                      hypoglycemia.Main outcomes and measures: Comparison of
                      catecholamine and metanephrine concentrations between
                      at-risk neonates and control participants, and correlation
                      of concentrations of catecholamines and metanephrines with
                      the number and severity of postnatal hypoglycemic
                      episodes.Results: In this study of 328 neonates (234 in the
                      risk group: median [IQR] gestational age, 270 [261-277]
                      days; and 94 in the control group: median [IQR] gestational
                      age, 273 [270-278] days), growth-restricted neonates showed
                      increased UCB median (IQR) concentrations of norepinephrine
                      (21.10 [9.15-42.33] vs 10.88 [5.78-18.03] nmol/L; P < .001),
                      metanephrine (0.37 [0.13-1.36] vs 0.12 [0.08-0.28] nmol/L; P
                      < .001), and 3-methoxytyramine (0.149 [0.098-0.208] vs 0.091
                      [0.063-0.149] nmol/L; P = .001). Neonates with perinatal
                      stress had increased UCB median (IQR) concentrations of
                      norepinephrine (22.55 [8.99-131.66] vs 10.88 [5.78-18.03]
                      nmol/L; P = .001), normetanephrine (1.75 [1.16-4.93] vs 1.25
                      [0.86-2.56] nmol/L; P = .004), and 3-methoxytyramine (0.120
                      [0.085-0.228] vs 0.091 [0.063-0.149] nmol/L; P = .008) (P <
                      .0083 was considered statistically significant).
                      Concentrations of UCB norepinephrine, metanephrine, and
                      3-methoxytyramine were negatively correlated with AF
                      C-peptide concentration (rs = -0.212, P = .005; rs = -0.182,
                      P = .016; and rs = -0.183, P = .016, respectively [P < .017
                      was considered statistically significant]). Concentrations
                      of UCB norepinephrine, metanephrine, and 3-methoxytyramine
                      were positively correlated with the number of hypoglycemic
                      episodes (BG concentration of 30-45 mg/dL) (rs = 0.146, P =
                      .01; rs = 0.151, P = .009; and rs = 0.180, P = .002,
                      respectively). Concentrations of UCB metanephrine and
                      3-methoxytyramine were negatively correlated with the lowest
                      measured BG concentration (rs = -0.149, P = .01; and rs =
                      -0.153, P = .008, respectively).Conclusions and relevance:
                      Neonates at risk for hypoglycemia displayed increased
                      catecholamine and metanephrine concentrations that were
                      correlated with postnatal hypoglycemic episodes and lower BG
                      levels; these results are consistent with findings in a
                      sheep model that fetal catecholamines are associated with
                      neonatal β-cell physiology and that perinatal stress or
                      growth restriction is associated with subsequent neonatal
                      hyperinsulinemic hypoglycemia. Improving the
                      pathomechanistic understanding of neonatal hypoglycemia may
                      help to guide management of newborns at risk for
                      hypoglycemia.},
      cin          = {INM-7},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {5252 - Brain Dysfunction and Plasticity (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5252},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {38557708},
      UT           = {WOS:001197556000001},
      doi          = {10.1001/jamapediatrics.2024.0304},
      url          = {https://juser.fz-juelich.de/record/1038463},
}