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Systemic Inflammation during the First Postnatal Month and the Risk of Attention Deficit Hyperactivity Disorder Characteristics among 10 year-old Children Born Extremely Preterm

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Abstract

Although multiple sources link inflammation with attention difficulties, the only human study that evaluated the relationship between systemic inflammation and attention problems assessed attention at age 2 years. Parent and/or teacher completion of the Childhood Symptom Inventory-4 (CSI-4) provided information about characteristics that screen for attention deficit hyperactive disorder (ADHD) among 793 10-year-old children born before the 28th week of gestation who had an IQ ≥ 70. The concentrations of 27 proteins in blood spots obtained during the first postnatal month were measured. 151 children with ADHD behaviors were identified by parent report, while 128 children were identified by teacher report. Top-quartile concentrations of IL-6R, TNF-α, IL-8, VEGF, VEFG-R1, and VEGF-R2 on multiple days were associated with increased risk of ADHD symptoms as assessed by a teacher. Some of this increased risk was modulated by top-quartile concentrations of IL-6R, RANTES, EPO, NT-4, BDNF, bFGF, IGF-1, PIGF, Ang-1, and Ang-2. Systemic inflammation during the first postnatal month among children born extremely preterm appears to increase the risk of teacher-identified ADHD characteristics, and high concentrations of proteins with neurotrophic properties appear capable of modulating this increased risk.

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Acknowledgements

This study was supported by The National Institute of Neurological Disorders and Stroke (5U01NS040069-05; 2R01NS040069-06A2), The National Eye Institute (1-R01-EY021820-01), and the National Institute of Child Health and Human Development (5P30HD018655-34).

The authors gratefully acknowledge the contributions of their subjects and their subjects’ families, as well as the contributions of their colleagues.

Participating Institutions and ELGAN Study Collaborators Who Made this Report Possible

Baystate Medical Center, Springfield MA (Bhavesh Shah, Karen Christianson)

Beth Israel Deaconess Medical Center, Boston MA (Camilia R. Martin, Colleen Hallisey, Caitlin Hurley, Miren Creixell)

Brigham & Women’s Hospital, Boston MA (Linda J. Van Marter)

Boston Children’s Hospital, Boston MA (Alan Leviton, Kathleen Lee, Anne McGovern, Elizabeth Allred, Jill Gambardella, Susan Ursprung, Ruth Blomquist)

Massachusetts General Hospital, Boston MA (Robert Insoft, Jennifer G. Wilson, Maureen Pimental)

New England Medical Center, Boston MA (Cynthia Cole, John Fiascone, Janet Madden, Ellen Nylen, Anne Furey)

U Mass Memorial Health Center, Worcester, MA (Francis Bednarek [deceased], Mary Naples, Beth Powers)

Yale-New Haven Hospital, New Haven CT (Richard Ehrenkranz, Joanne Williams, Elaine Romano)

Forsyth Hospital, Baptist Medical Center, Winston-Salem NC (T. Michael O’Shea, Debbie Gordon, Teresa Harold, Gail Hounsell, Debbie Hiatt)

University Health Systems of Eastern Carolina, Greenville NC (Stephen Engelke, Sherry Moseley, Linda Pare, Donna Smart, Joan Wilson)

North Carolina Children’s Hospital, Chapel Hill NC (Carl Bose, Gennie Bose, Janice Wereszczak)

DeVos Children’s Hospital, Grand Rapids MI (Mariel Portenga, Dinah Sutton)

Sparrow Hospital, Lansing MI (Padmani Karna, Carolyn Solomon)

University of Chicago Hospital, Chicago IL (Michael D. Schreiber, Grace Yoon)

William Beaumont Hospital, Royal Oak MI (Daniel Batton, Beth Kring)

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Authors and Affiliations

  1. Boston Children’s Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115-5724, USA

    Elizabeth N. Allred & Alan Leviton

  2. Tufts University School of Medicine, Boston, MA, 02111, USA

    Olaf Dammann

  3. Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, 02115, USA

    Raina N. Fichorova

  4. University of North Carolina School of Medicine, Chapel Hill, NC, USA

    Stephen R Hooper & Thomas Michael O’Shea

  5. The University of Chicago Medicine Comer Children’s Hospital, Chicago, IL, USA

    Scott J Hunter & Megan N. Scott

  6. Boston University School of Medicine, Boston, MA, USA

    Robert M. Joseph

  7. Boston Medical Center and Boston University School of Medicine, Boston, MA, USA

    Karl Kuban

Authors
  1. Elizabeth N. Allred
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  2. Olaf Dammann
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  3. Raina N. Fichorova
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  4. Stephen R Hooper
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  5. Scott J Hunter
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  6. Robert M. Joseph
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  7. Karl Kuban
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  8. Alan Leviton
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  9. Thomas Michael O’Shea
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  10. Megan N. Scott
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Consortia

The ELGAN Study ADHD symptoms writing group for the ELGAN Study Investigators

Corresponding author

Correspondence to Alan Leviton.

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The authors report no conflict of interest, financial or otherwise.

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Allred, E.N., Dammann, O., Fichorova, R.N. et al. Systemic Inflammation during the First Postnatal Month and the Risk of Attention Deficit Hyperactivity Disorder Characteristics among 10 year-old Children Born Extremely Preterm. J Neuroimmune Pharmacol 12, 531–543 (2017). https://doi.org/10.1007/s11481-017-9742-9

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