Abstract

Objective

To identify specific risk factors for epilepsy for individuals born extremely preterm.

Study Design

In a prospective cohort study, at 10-year follow-up, children were classified as having epilepsy or seizures not associated with epilepsy. We evaluated for association of perinatal factors using time-oriented, multinomial logistic regression models.

Results

Of the 888 children included in the study, 66 had epilepsy and 39 had seizures not associated with epilepsy. Epilepsy was associated with an indicator of low socioeconomic status, maternal gestational fever, early physiologic instability, postnatal exposure to hydrocortisone, cerebral white matter disease and severe bronchopulmonary dysplasia. Seizure without epilepsy was associated with indicators of placental infection and inflammation, and hypoxemia during the first 24 postnatal hours.

Conclusions

In children born extremely preterm, epilepsy and seizures not associated with epilepsy have different risk profiles. Though both profiles included indicators of infection and inflammation, the profile of risk factors for epilepsy included multiple indicators of endogenous vulnerability.

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Acknowledgements

We gratefully acknowledge the contributions of their subjects, and their subjects’ families, as well as those of their colleagues. Participating institutions (site principal investigator and colleagues): Baystate Medical Center, Springfield MA (Rachana Singh, Bhavesh Shah, Debby Klein); 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); 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 [deceased], 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).

Funding

This study was supported by grants from the National Institute of Neurological Disorders and Stroke (5U01NS040069–05; 2R01NS040069 − 06A2), the National Institute of Child Health and Human Development (5P30HD018655–34), and the Office of the National Institutes of Health Director (1UG3OD023348–01).

Author information

Affiliations

  1. Baystate Children’s Hospital, Springfield, MA, USA

    • Rachana Singh
    •  & Bhavesh Shah
  2. Department of Pediatrics, Division of Pediatric Neurology, Boston Medical Center and Boston University School of Medicine, Boston, MA, USA

    • Laurie M. Douglass
    • , Timothy C. Hereen
    •  & Karl C. K. Kuban
  3. University of North Carolina, Chapel Hill, NC, USA

    • T. Michael O’Shea
  4. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    • Carl E. Stafstrom
  5. Neuroepidemiology Unit, Department of Neurology, Boston Children’s Hospital, Boston, MA, USA

    • Elizabeth N. Allred
    •  & Alan Leviton
  6. Department of Neurology, Harvard Medical School, Boston, MA, USA

    • Elizabeth N. Allred
    •  & Alan Leviton
  7. Department of Pediatrics, East Carolina University Brody School of Medicine, Greenville, NC, USA

    • Stephen Engelke

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  1. on behalf of ELGAN Study Group

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    The authors declare that they have no conflict of interest.

    Corresponding author

    Correspondence to Rachana Singh.

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    DOI

    https://doi.org/10.1038/s41372-019-0355-4