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Cerebral perfusion and neurological examination characterise neonatal opioid withdrawal syndrome: a prospective cohort study
  1. Kristen L Benninger1,2,
  2. Jin Peng3,
  3. Mai-Lan Ho4,
  4. Julia Newton2,
  5. Danny J J Wang5,
  6. Houchun H Hu6,
  7. Ann R Stark7,
  8. Jerome A Rusin4,
  9. Nathalie L Maitre8
  1. 1 Department of Pediatrics and Neonatology, Nationwide Children's Hospital, Columbus, Ohio, USA
  2. 2 Center for Perinatal Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
  3. 3 Research Information Solutions and Innovation Research & Development, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
  4. 4 Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio, USA
  5. 5 Stevens Neuroimaging and Informatics Institute, University of Southern California Keck School of Medicine, Los Angeles, California, USA
  6. 6 Department of Radiology, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
  7. 7 Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
  8. 8 Pediatrics, Emory University, Atlanta, Georgia, USA
  1. Correspondence to Dr Kristen L Benninger, Department of Pediatrics and Neonatology, Nationwide Children's Hospital, Columbus, OH 43215, USA; kristen.benninger{at}nationwidechildrens.org

Abstract

Objective To test the hypothesis that cerebral blood flow (CBF) assessed with arterial spin labelling (ASL) MRI is increased and standardised neurological examination is altered in infants with neonatal opioid withdrawal syndrome (NOWS) compared with those without.

Design Prospective cohort study.

Setting Level IV neonatal intensive care unit and outpatient primary care centre.

Participants Infants with NOWS receiving pharmacological treatment and unexposed controls matched for gestational age at birth and post-menstrual age at MRI.

Main outcomes CBF assessed by ASL on non-sedated 3-Tesla MRI and standardised Hammersmith Neonatal Neurological Examination (HNNE) within 14 days of birth.

Results Thirty infants with NOWS and 31 control infants were enrolled and included in the final analysis. Global CBF across the brain was higher in the NOWS group compared with controls (14.2 mL/100 g/min±5.5 vs 10.7 mL/100 g/min±4.3, mean±SD, Cohen’s d=0.72). HNNE total optimality score was lower in the NOWS group compared with controls (25.9±3.6 vs 28.4±2.4, mean±SD, Cohen’s d=0.81). A penalised logistic regression model including both CBF and HNNE items discriminated best between the two groups.

Conclusions Increased cerebral perfusion and neurological examination abnormalities characterise infants with NOWS compared with those without intrauterine drug exposure and suggest prenatal substance exposure affects fetal brain development. Identifying neurological and neuroimaging characteristics of infants with NOWS can contribute to understanding mechanisms underlying later outcomes and to designing potential new treatments.

  • neonatology
  • neurology
  • toxicology

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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Footnotes

  • Presented at This work was presented at Pediatric Academic Societies Annual Meeting in July 2020.

  • Contributors KLB participated in the conception and design of the study, acquisition, analysis, and interpretation of the data; drafted the initial manuscript; revised all drafts of the manuscript; approved the final manuscript as submitted and is responsible for the overall content as guarantor. JP participated in analysis and interpretation of the data, drafted the initial manuscript, revised drafts of the manuscript and approved the final manuscript as submitted. M-LH participated in acquisition, analysis, and interpretation of the data; revised drafts of the manuscript and approved the final manuscript as submitted. JN participated in conception and design of the study, acquisition and interpretation of the data; revised drafts of the manuscript and approved the final manuscript as submitted. DJJW participated in analysis and interpretation of the data, revised drafts of the manuscript and approved the final manuscript as submitted. HHH participated in the conception and design of the study, acquisition, analysis, and interpretation of the data; revised drafts of the manuscript and approved the final manuscript as submitted. ARS participated in analysis and interpretation of the data, assisted in drafting the initial manuscript, revised all drafts of the manuscript and approved the final manuscript as submitted. JAR participated in acquisition, analysis, and interpretation of the data; revised drafts of the manuscript and approved the final manuscript as submitted. NLM participated in the conception and design of the study, acquisition, analysis, and interpretation of the data; drafted the initial manuscript; revised all drafts of the manuscript and approved the final manuscript as submitted. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests NLM is a consultant for and has equity in Thrive Neuromedical. No funding was obtained from this company and the study is not related to this disclosure. DJJW has equity in Translational MRI that provided the CereFlow software, DJJW was not involved in study design.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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