Global Perinatal Health

The greatest burden of perinatal asphyxia falls in low and mid-resource settings where it is unclear whether therapeutic hypothermia is safe and effective. In sub-Saharan Africa, neo natal encephalopathy related to perinatal asphyxia is 10-20 times more common than in the developed world. Globally, perinatal asphyxia is responsible for 42 million disability life adjusted years, double that due to diabetes and three quarters of that due to HIV/AIDS. Almost one quarter of the world’s 4 million annual neonatal deaths are caused by perinatal asphyxia and 99% of these deaths occur in low and mid-resource settings.

Fig 1: Global distribution of neonatal deaths (WHO, 2000). 99% of neonatal deaths occur in low and mid resource settings.

Sub Saharan Africa

As part of the UCL Uganda Women’s health Initiative we performed a pilot study of cooling at Mulago Hospital, Kampala, Uganda in 2008. Mulago Hospital is a large teaching hospital in Kampala and has an annual birth rate in excess of 20,000 births per year. Following on from this study we are now investigating Associations between Birth Asphxia and infection amongst newborns in Africa:

The ABAaNA Study

Dr Cally Tann received Research Training Fellowship funding for 3 years from the London School of Hygiene and Tropical Medicine and the Wellcome Trust to perform this study. Supervisors: Professor Alison Elliott, Dr Nikki Robertson.

Aim of the study

• to understand the causal chain of pre-disposing factors, exposures and events, specifically the role of perinatal infection, in the development of neonatal encephalopathy
• to identify intrinsic and modifiable risk factors to develop preventative strategies to reduce neonatal mortality and morbidity from neonatal encephalopathy in this setting.

Study plan
Over the 18-month study period, 300 case and 300 control infants will be enrolled from infants born at Mulago Hospital in Kampala, Uganda. The anticipated prevalence estimates of the main exposures of interest are malaria 10%, HIV 10-15%, chorioamnionitis 25% (40% in HIV positive women), neonatal bacteraemia 2%.

Cases will be infants, born at 37 weeks gestation and identified after delivery with moderate/severe neonatal encephalopathy which will be defined as a Thompson score >5 within 24 hours of delivery. Control infants will be term babies (37 weeks gestation) unaffected by neonatal encephalopathy recruited during the same period as the cases. Control infants will be identified prior to delivery using randomly generated numbers to highlight entries on the labour ward admission log.

India

In 2009 we performed a feasibility study of whole body cooling in a public sector hospital (~25,000 births per year) in South India (Calicut Medical College, Kozhikode, Kerala) in two phases. The first phase was a prospective observational study (n=22) to examine the clinical profile and brain tissue injury in outborn and inborn infants with NE admitted to the neonatal unit by serial cranial ultrasound (cUS) imaging (day 1, 3, 7), amplitude integrated electroencephalogram (aEEG) (1st 24 hours; Olympus CFM), EEG (day 3 to 4) and magnetic resonance imaging (MRI).

The second phase was a pilot randomised controlled trial (n=33) to examine the cooling efficacy of a low-tech ‘natural servo controlled’ cooling mattress made from phase changingmaterial (PCM) which had been validated in our laboratory. PCM mattress (melting point 32oC) effectively induced and maintained cooling with a similar temperature stability to the Tecotherm device used in the TOBY trial; minimal additional nursing interventions (e.g. use of blankets if rectal temperature (TR) <33ºC or additional PCM blocks if TR >34ºC) were required to maintain target temperature.

Drs Thayyil and Robertson organised two International Symposiaon Neonatal Neurology and Therapeutic Hypothermia (ISNNTH) (http://www.isnnth.com/home) in India (New Delhi and Kochi, India) in Dec 2009. The consensus opinion among the Indian academic neonatologists was that the safety and efficacy data from the cooling trials conducted in the high income countries should not be extrapolated to the Indian settings and rigorous evaluation of hypothermia should be undertaken urgently in this population; until further evidence is available normothermia should continue as the standard of care in NE.