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Understanding the role of the placenta in neonatal encephalopathy and outcome

Pediatric Research (2023)Cite this article

Globally neonatal encephalopathy (NE) continues to be one of the highest causes of neonatal mortality and childhood morbidity with 24% of newborn death due to intrapartum complications/brain injury.1,2 Its incidence has remained static for decades despite the increasing rates of caesarean birth, intrapartum monitoring and improved maternal health surveillance. Low- and middle-income countries (LMIC) have the highest burden of this disease1,3 with 99% of neonatal death due to NE occurring in LMIC.4 The reason for this is multifactorial and in part is due to the health and nutrition of the mother coupled with limited ability to access medical and antenatal healthcare. The placenta has come into focus in recent years with increasing research into its role in the brain health.5 It is widely accepted that placental pathology is associated with neonatal morbidity and mortality5,6 but the specifics of this relationship remain unclear particular its contribution to brain injury and outcome. The maternal–placental–fetal (MPF) triad concept is gaining much traction in neonatal and histopathology research.7 Improving our understanding of how each element of this triad interlink has the potential to identify placental risk factors for hypoxic ischaemia (HI) leading to NE. This has the potential to modify the clinical journey for an affected MPF triad to avoid NE. This is particularly important for understanding the pathogenesis of NE in LMIC. NE is an overarching term for all babies who have neurological dysfunction at birth or develop encephalopathy within the first week of life.8 There are many causes for NE, including HI, stroke, brain malformation, genetic, metabolic and infection, with HI recognised as the most common aetiology.8,9 The type and timing of HI causing brain injury in NE varies. Only 30–40% are associated with an intrapartum sentinel event and the other causes of ischaemia remain incompletely understood with an assumption that it involves the placenta.10 This is likely to be true for LMIC also.

A recent study by Thayyil et al. has shown therapeutic hypothermia (TH) to increase the mortality rate while having no improvement on the death/neurodevelopmental outcome combined. This study reported a low incidence of sentinel events with a high incidence of white matter injury and early seizure burden.4 This supports the theory that a high proportion of NE cases in LMIC are likely related to subacute/chronic HI. With this type of injury, underlying placental pathology likely plays a greater role in the pathogenesis. The resultant injury is more likely resistant to the therapeutic effects of TH due to the remote proximity of the insult to the commencement of therapy. Understanding the relationship between placental pathology, brain imaging patterns and outcome could give a better understanding as to timing of brain injury.5 Research in the area is essential to reduce the incidence of HI and develop new strategies for brain protection for affected babies.

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Funding

Funding for this research was provided by The Rotunda Foundation. Funders had no involvement in the research or manuscript preparation.

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  1. Royal College of Surgeons Ireland (RCSI), Dublin, Ireland

    Aine Fox & Breda Hayes

  2. Department of Neonatology, Rotunda Hospital, Dublin, Ireland

    Aine Fox & Breda Hayes

  3. Department of Histopathology, Rotunda Hospital, Dublin, Ireland

    Emma Doyle

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  1. Aine Fox
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Correspondence to Aine Fox.

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Fox, A., Doyle, E. & Hayes, B. Understanding the role of the placenta in neonatal encephalopathy and outcome. Pediatr Res (2023). https://doi.org/10.1038/s41390-023-02921-7

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