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Is infection a factor in neonatal encephalopathy?
  1. Karin B Nelson1,2,
  2. Anna A Penn3
  1. 1Children's Hospital National Medical Center, Washington, DC, USA
  2. 2National Institutes of Health, NINDS, Bethesda, Maryland, USA
  3. 3Fetal & Transitional Medicine, Neonatology, Children's National Medical Center, Center for Neuroscience Research, Washington, DC, USA
  1. Correspondence to Dr Karin B Nelson, 5524 Charles Street, Bethesda, MD 20814, USA; nelsonk{at}

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In adults and in very preterm neonates, systemic infection is a well-recognised cause of encephalopathy. Although the manifestations of encephalopathy are very similar in the fetal inflammatory response and in acute hypoxic-ischaemic events, neonatal encephalopathy (NE) in term infants is more often attributed primarily to hypoxia-ischaemia rather than to infection. Is systemic infection an important etiological factor in NE in term and late preterm infants?

A striking 1999 case report1 showed that placental infection with group B streptococcus can cause NE and that the clinical picture can closely mimic both immediate and later signs commonly assumed to indicate birth asphyxia. Many other reports describe associations of placental infections with encephalopathy in term neonates, suggesting that infection, or the resulting inflammation, can indeed underlie NE without an associated sentinel event causing asphyxia. This brief discussion considers the evidence of an infection-NE association, the difficulty of distinguishing infectious from non-infectious inflammation and the way forward.

Most of the evidence relating infection to NE has concerned infections identified during the admission for delivery, usually defined histologically in the placenta, or clinically. Histological evidence includes chorioamnionitis, which is inflammation on the maternal side of the placenta and funisitis on the fetal side, with infiltration of the umbilical cord with inflammatory cells. Clinical evidence of infection includes maternal fever in labour, uterine tenderness, purulent discharge or fetal tachycardia. A third approach to identifying placental infection is by microbiological evaluation. Unfortunately, results of these approaches are often not in agreement,2 ,3 and multiple identification methods are rarely used in the same study.

Histological chorioamnionoitis

McDonald et al4 compared placentas of 93 infants with NE with placentas of normal term controls (n=816) and of random controls (n=387), finding funisitis in 31.2% of NE placentas versus 5.4% and 4.4% of controls (p=0.002). Chorioamnionitis and villitis were …

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  • Contributors KBN, a paediatric neurologist, wrote the main body of this article. AAP, a neonatologist and neuroscientist with special interest in the placenta, contributed a section and made useful suggestions concerning the remainder. AAP is partly supported by NIH Director's New Innovator Award (DP2OD006457).

  • Competing interests None.

  • Provenance and peer review Commissioned; externally peer reviewed.

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