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Original article
Perinatal risk factors for neonatal encephalopathy: an unmatched case-control study
  1. Cally J Tann1,2,3,
  2. Margaret Nakakeeto4,5,
  3. Barbara A Willey6,
  4. Margaret Sewegaba2,5,
  5. Emily L Webb6,
  6. Ibby Oke7,
  7. Emmanuel Derek Mutuuza4,
  8. Donald Peebles3,
  9. Margaret Musoke4,
  10. Kathryn A Harris7,
  11. Neil J Sebire8,
  12. Nigel Klein8,
  13. Jennifer J Kurinczuk9,
  14. Alison M Elliott1,2,
  15. Nicola J Robertson3
  1. 1 Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK
  2. 2 MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda
  3. 3 Institute for Women’s Health, University College London, London, UK
  4. 4 Neonatal Medicine, Mulago University Hospital, Kampala, Uganda
  5. 5 Uganda Women’s Health Initiative, Kampala, Uganda
  6. 6 MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK
  7. 7 Department of Microbiology, Virology and Infection Prevention and Control, Great Ormond Street Hospital For Children NHS Trust, London, UK
  8. 8 Institute for Child Health, University College London, London, UK
  9. 9 National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  1. Correspondence to Dr Cally J Tann, Clinical Research Department/MARCH Centre, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK; cally.tann{at}lshtm.ac.uk

Abstract

Objective Neonatal encephalopathy (NE) is the third leading cause of child mortality. Preclinical studies suggest infection and inflammation can sensitise or precondition the newborn brain to injury. This study examined perinatal risks factor for NE in Uganda.

Design Unmatched case–control study.

Setting Mulago National Referral Hospital, Kampala, Uganda.

Methods 210 term infants with NE and 409 unaffected term infants as controls were recruited over 13 months. Data were collected on preconception, antepartum and intrapartum exposures. Blood culture, species-specific bacterial real-time PCR, C reactive protein and placental histology for chorioamnionitis and funisitis identified maternal and early newborn infection and inflammation. Multivariable logistic regression examined associations with NE.

Results Neonatal bacteraemia (adjusted OR (aOR) 8.67 (95% CI 1.51 to 49.74), n=315) and histological funisitis (aOR 11.80 (95% CI 2.19 to 63.45), n=162) but not chorioamnionitis (aOR 3.20 (95% CI 0.66 to 15.52), n=162) were independent risk factors for NE. Among encephalopathic infants, neonatal case fatality was not significantly higher when exposed to early neonatal bacteraemia (OR 1.65 (95% CI 0.62 to 4.39), n=208). Intrapartum antibiotic use did not improve neonatal survival (p=0.826). After regression analysis, other identified perinatal risk factors (n=619) included hypertension in pregnancy (aOR 3.77), male infant (aOR 2.51), non-cephalic presentation (aOR 5.74), lack of fetal monitoring (aOR 2.75), augmentation (aOR 2.23), obstructed labour (aOR 3.8) and an acute intrapartum event (aOR 8.74).

Conclusions Perinatal infection and inflammation are independent risk factors for NE in this low-resource setting, supporting a role in the aetiological pathway of term brain injury. Intrapartum antibiotic administration did not mitigate against adverse outcomes. The importance of intrapartum risk factors in this sub-Saharan African setting is highlighted.

  • Neonatal Encephalopathy
  • Risk Factors
  • Uganda
  • Infection

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/archdischild-2017-312744

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    Footnotes

    • Contributors CJT, JJK, NK, NJS, DP, KAH, AME and NJR designed the study and were involved in data interpretation and report writing. CJT implemented and led the study. Data analysis was conducted by CJT and BAW, ELW and JJK provided statistical support. CJT, MN, MS, MM, NN, IO, EDM and PN participated in data collection. CJT, PN and KAH performed the molecular assays. MN, JM, AME and NJR provided logistical support. All authors reviewed and approved the final version. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. CJT affirms that the manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

    • Funding The study was funded by a Wellcome Trust Bloomsbury Clinical Fellowship in International Health to CT (094016/Z/10/Z). The Wellcome Trust had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

    • Competing interests None declared.

    • Ethics approval London School of Hygiene & Tropical Medicine, Uganda Virus Research Institute and Uganda National Council of Science & Technology.

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

    • Data sharing statement Data from this study will be made available for further research to anyone with an interest in relevant further study, subject to proper acknowledgements and on contacting the corresponding author.