Perinatal risk factors for neonatal encephalopathy: an unmatched case-control study

Cally J Tann; Margaret Nakakeeto; Barbara A Willey; Margaret Sewegaba; Emily L Webb; Ibby Oke; Emmanuel Derek Mutuuza; Donald Peebles; Margaret Musoke; Kathryn A Harris; Neil J Sebire; Nigel Klein; Jennifer J Kurinczuk; Alison M Elliott; Nicola J Robertson

doi:10.1136/archdischild-2017-312744

Perinatal risk factors for neonatal encephalopathy: an unmatched case-control study

Arch Dis Child Fetal Neonatal Ed. 2018 May;103(3):F250-F256. doi: 10.1136/archdischild-2017-312744. Epub 2017 Aug 5.

Authors

Cally J Tann^{1

2

3}, Margaret Nakakeeto^{4

5}, Barbara A Willey⁶, Margaret Sewegaba^{2

5}, Emily L Webb⁶, Ibby Oke⁷, Emmanuel Derek Mutuuza⁴, Donald Peebles³, Margaret Musoke⁴, Kathryn A Harris⁷, Neil J Sebire⁸, Nigel Klein⁸, Jennifer J Kurinczuk⁹, Alison M Elliott^{1

2}, Nicola J Robertson³

Affiliations

¹ Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK.
² MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
³ Institute for Women's Health, University College London, London, UK.
⁴ Neonatal Medicine, Mulago University Hospital, Kampala, Uganda.
⁵ Uganda Women's Health Initiative, Kampala, Uganda.
⁶ MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK.
⁷ Department of Microbiology, Virology and Infection Prevention and Control, Great Ormond Street Hospital For Children NHS Trust, London, UK.
⁸ Institute for Child Health, University College London, London, UK.
⁹ National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, 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.

Keywords: Infection; Neonatal Encephalopathy; Risk Factors; Uganda.

MeSH terms

Brain Diseases / etiology*
Case-Control Studies
Female
Humans
Infant
Infant, Newborn
Infant, Newborn, Diseases / etiology*
Logistic Models
Male
Pregnancy
Risk Factors
Term Birth
Uganda

Abstract

MeSH terms

Grants and funding