Robb T1, Sabir H1,2, Jary S1, Thoresen M1,3, Chakkarapani E.1

Institution(s)

1 Translational Health Sciences, St Michael’s Hospital, Bristol Medical School, University of Bristol, UK

2 Neonatology and Pediatric Critical Care Medicine, University Bonn Children’s Hospital, Germany.

3 Division of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

Introduction (include hypothesis)

In infants cooled for neonatal encephalopathy (NE), C-reactive protein (CRP), a marker of inflammation, is elevated earlier in infants exposed to risk factors for infection (rf infection+) compared to non-exposed infants (rf infection-).1 CRP response is influenced by sex.2 Furthermore, inflammatory responses contribute to brain injury in NE.3 We therefore investigated whether there is a sex dependent difference in the inflammatory response profile in NE controlling for rf infection status and how it is related to the neurodevelopmental outcome.

Methods (include source of funding and ethical approval if required)

Of 236 infants cooled between 2006-2017, 45 were excluded. In 191 infants (106 male), we recorded NE severity (aEEG severity prior to TH), rf-infection (membranes ruptured >18hours (h), maternal fever >38°C, group B streptococcus vaginal colonisation), CRP and White blood cell (WBC) 12hrly until 168h. Adverse outcome: death or Bayley-III cognitive/language composite or motor score <85 or any grade of cerebral palsy or severe hearing/visual impairment assessed at 18-24 months. Median CRP and WBC: median of 12hrly data from 0 to 168h. Sex effect on median CRP/WBC assessed using multiple linear regression stratified by outcome.

Results

Of 191 infants, 12 died and 163 underwent Bayley examination. 52/191 infants had adverse outcome. In the adverse outcome group, female sex was associated with lower median CRP (β: -21.1 mg/L, 95%CI:-36.5, -5.7) and higher WBC (β: 4.1 x109/ L, 95%CI:1.0, 7.1) independent of Rf-infection status and severity of NE. In the adverse outcome group, temporal course of CRP and WBC demonstrated that females compared to males had lower CRP at 24h, 36h, 48h, 60h, 72h and 96h and higher WBC at 36h, 48h, 60h and 72h. No independent effect of Rf-infection status on temporal profile or median CRP or WBC in the adverse outcome group was noted. In the favourable outcome group, being exposed to Rf-infection was associated with higher median CRP (β: 6.7 mg/L, 95% CI: 0.8, 12.7) independent of sex and NE severity. No independent sex effect on median CRP or WBC observed in the favourable outcome group.

Conclusions

There is a sex dependent CRP and white blood cell response in infants cooled for NE, which is only seen in those with adverse neurodevelopmental outcome. Females with adverse outcome had a lower CRP and higher white blood cell count response than males independent of risk factors for infection or severity of NE.

References (include acknowledgement here if appropriate) 1. Chakkarapani E, et al. Archives of Disease in Childhood – Fetal and Neonatal Edition 2014;99:F458-F463. 2. Mackenzie, K E .et al. Pediatric diabetes 2009;10:44-51. 3. Hagberg H, et al. Nat Rev Neurol.2015;11:192-208.