1. Addressing the Challenge of Neonatal Mortality
Addressing the challenge of neonatal mortality in 15 minutes is itself a challenge so I would like to preface my remarks by saying that what I am going to present is a very partial coverage of the topic in both senses of the word “partial”.
Simon Cousens

2. Millennium Development Goal 4
Reduce by two-thirds, between 1990 and 2015, the under 5 mortality rate
The Millenium Development Goals are a set of 8 goals, agreed to in 2000 that all 193 UN member states have agreed to. The fourth of these refers to reducing child mortality and the target set is a two-thirds reduction in the under 5 mortality rate between 1990 and 2015.

3. Millennium Development Goal 4
This figure is based on estimates from the Inter-Agency Group for Child Mortality which brings together UN agencies, WHO, World Bank, Unicef, and UN population Division, to produce annual estimates of child mortality. The figure shows that U5MR is estimated to have declined from 88/1000 livebirths in 1990 to 57 per 1000 live births in 2010, a decline of 35% over 20 years. The MDG target is 29 (red line). To achieve MDG 4 at global level would require U5MR to be halved between 2010 and In terms of absolute numbers of deaths, these reduced from 12 million in 1990 to 7.6 million in 2010.
Source: Levels and trends in Child Mortality. Report Estimates developed by the Inter-agency Group for Mortality Estimation.

4. Millennium Development Goal 4
An increasingly important component of U5 mortality is neonatal mortality, that is deaths during the first 28 days of life.
On this slide I have added the estimated trend in neonatal mortality, work undertaken with Mikkel Oestergaard, Colin Mathers and others at WHO. Between 1990 and 2009 the estimated global NMR declined from 33.2 to 23.9 per 1000 – a 28% reduction while the proportion of under-5 deaths occurring in the neonatal period increased from 37% to 41%. 4 and a half million to about 3 and a quarter million in 2009
It is clear that MDG4 will not be achieved without reducing neonatal mortality.
Sources: Levels and trends in Child Mortality. Report Estimates developed by the Inter-agency Group for Mortality Estimation.
Oestergaard et al. PLoS Med :e

5. Geographical distribution of neonatal mortality in 2009
Region
NMR
% of neonatal deaths
High income
3.6
1.4%
sub-Saharan Africa
35.9
34%
South East Asia
30.7
36%
The figures I have just shown give an indication of what is happening at a global level but there are of course major disparities in neonatal mortality across regions. This figure shows estimated NMRs by country in 2009 – the darker the colour the higher the NMR.
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In high income countries the NMR is around three and a half per 1000 and these countries contribute less than 2% of global deaths. Two regions sub-Saharan Africa and South East Asia, account for 70% of all neonatal deaths and experience neonatal mortality rates almost 10 times those in high income countries.
There are also differences in trends with sub-Saharan Africa experiencing the smallest relative decline – of about 18% - between 1990 and 2009.
Source: Oestergaard et al. PLoS Med :e

6. This is a story from the BBC website reporting on a “miracle baby”, born in the north of England, very early at 23 weeks gestation and weighing about 650 grams. After 7 weeks of intensive care she is about to leave hospital.
It is easy to think when living in a country like the UK and hearing stories like this that preventing neonatal deaths requires very high tech and expensive equipment and treatment.
In fact, many neonatal deaths occurring in low and middle income countries could be prevented with rather easily.....

7. Neonatal mortality rates in England and Wales
This figure shows the neonatal mortality rate for England and Wales over time.
The series starts in 1921 when the NMR was 35/ about what it is in sub-Saharan Africa now. By 2002 the NMR is down to about 4.
When did the “miracle” of neonatal intensive care become available?
Sometime around here (indicate time around ) by which time NMR was already below 15/1000
This reduction from was achieved through free ANC, the arrival of antibiotics and improved in basic care techniques around delivery and postnatally.
Source: ONS mortality statistics (

8. Community-based care: a seminal paper from India
Bang et al. Lancet :
Implemented a home care package in a rural setting with high NMR
Trained village health workers to perform home visits, to promote breastfeeding and thermal management, in simple techniques to manage birth asphyxia, and to treat infections
In 1999 a highly influential paper was published by Abhay Bang and his colleague from India. The paper reported the results of a study conducted in Gadchiroli District, Maharashtra State in which a newborn home care package was implemented in a rural setting with very high NMR. In the intervention area female village health workers were recruited (approximately 1 per 1000 population) and trained to perform home visits during pregnancy and postnatally, to promote breastfeeding and thermal management and in simple techniques to manage birth asphyxia and treating infections, including giving injectable antibiotics.

9.  Community-based care: a seminal paper from India Treatment of sepsis
c. 60% reduction in NMR
This figure compares neonatal mortality rates in the intervention area (dotted line) and the two control areas. At baseline mortyality was similar in both groups and high at around 60/ By the third year of intervention, mortality had declined by about 60% in the intervention arm compared with the control arm, with most of the reduction apparently in sepsis deaths. Despite limitations in the study design, which essentially compared one intervention area with two control areas, and doubts about how replicable the intervention in Gadchiroli was – it involved village health workers making postnatal home visits – the results were sufficiently striking to stimulate a number of studies of community-based interventions, particularly in Asia and later in this presentation I will summarise results from a couple of recently published trials in which I was involved.
Source: Bang et al. Lancet :

10. The Lancet Neonatal Survival Series (2005)
Abhay Bang’s study was an important stimulus to the research community, but I would like to think that the publication in 2005 of the Lancet Neonatal Survival Series was an important stimulus to the wider public health community. The series followed on from the very influential Child Survival Series, published in 2003, and sought to encourage public health action to address neonatal mortality in high burden settings.
Editors: JE Lawn and S Cousens

11. Only about half of this reduction was through community-based care
Developed a model to estimate how many neonatal deaths could be prevented by increasing coverage of a package of relatively simple, cost-effective interventions
Estimated that 36-67% of neonatal deaths in 75 high mortality countries could be averted by high coverage (90%) with 16 interventions
Only about half of this reduction was through community-based care
Following the lead of the Child Survival Series a key piece was the development of a model to estimate how many neonatal deaths could be averted if we could increase coverage of existing, know effective interventions. Based on this model, and considering a range of effectiveness estimates, we estimated that between one third and two thirds of neonatal deaths in 75 high burden countries could be averted if high coverage could be achieved. An important point to note, however, when considering this estimate compared with the results of Abhay Bang’s study was that only about half of this reduction was achieved through community-based care with the remaining 50% dependent on outreach services or facility-based care.
Source: Lancet :

12. Lives Saved Tool (LiST)
Freely available software tool for programme planners
Subsequently the model was passed on to the Futures Institute which had developed the Spectrum a freely available software package which provides policy makers with an analytical tool to support the decision-making process. Supervised by Neff Walker at Johns Hopkins the Futures Institute developed the Lives Saved Tool (LiST for short) which estimates the impact of scaling up interventions on maternal, neonatal and child mortality as a module within Spectrum. The slide shows the cover of a supplement to the International Journal of Epidemiology which sets out the evidence base for the intervention effectiveness estimates used in LiST, and to which a number of LSHTM staff contributed.
LiST is now being widely used by agencies, large NGOs, foundations and individual countries to aid decision making.
Agencies: WHO, UNICEF,PAHO, GAVI, Global Fund, Bilateral: DFID, USAID, Canadian CIDA: Large NGOs: Save the children, PSI, World Vision, Foundations: Gates, Clinton, CIFF, Countries: Burkina Faso, Niger, Nigeria, Ethiopia, Uganda, India (including several states), China

13. Two recent studies: The Hala Trial, Pakistan
I said earlier that I would briefly summarise the results of two recently published trials, both conducted in Pakistan and led by Zulfiqar Bhutta and his team at the Aga Khan University. The first trial, which I shall refer to as the Hala trial, was published at the begging of last year.
Lancet :

14. The Hala Trial, Pakistan
Intervention:
Lady Health Workers (LHWs) trained in preventive newborn care
Dais (TBAs) trained in basic newborn care
Communities encouraged to establish Community Health Committees
16 clusters randomised:
Approximately 23,000 live births identified over a 30 month period
In 1994 Pakistan established a cadre of workers called Lady Health Workers. Lady Health workers are generally young women, resident in local communities and with at least 8 years of formal schooling who receive training over 15 months and are paid a salary by the Ministry of Health. Each LHW covers a population of and provides antenatal care contraceptive advice, growth monitoring and immunisation services. The emphasis is on recognition of problems and referral rather than home-based management.
As part of the intervention LHWs received an extra 6 days of training in newborn care including training in mouth-to-mouth resuscitation. However, unlike the Bang study they were not provided with antibiotics.
A second component of the intervention involved training of TBAs in basic newborn care including clean delivery and basic resuscitation and links with LHWs established.
As a third component intervention communities were encouraged to establish community health committees to liaise with LHWs and establish emergency transport funds.
A cluster randomised trial was conducted in 16 clusters where, with a total population of about 320,000. Clusters were defined by the catchment areas of primary health care facilities which are responsible for supervising LHWs.
The primary outcome was all-cause neonatal mortality and approximately 23,000 livebirths were identified during the course of the trial and
Primary outcome: all-cause neonatal mortality
Lancet :

15. The Hala Trial, Pakistan
Intervention clusters
Control clusters
Risk ratio
(95% c.i.)
NMR
43.0
49.1
0.85 (0.76, 0.96)
P=0.02
Trial differed from other community-based trials in region in that intervention principally delivered through government health system rather than workers employed by research team.
 lower intervention coverage than has been reported in other trials
 smaller mortality impact
Despite limitations, encouraging that public sector programme promoting preventive care can produce health benefits
In brief, the trial estimated a 15% reduction in neonatal mortality, which is quite a lot smaller than has been reported in some of the other community-based trials in Asia which have been reported in recent years. One important way in which the Hala trial differed from other trials is that it was conducted largely through the existing health system using government health workers – the LHWs - rather than workers recruited by the research team specifically for the research.
This may explain the lower coverage achieved in Hala compared with some other trials. For example in the Gadchiroli trial it was reported that in the third year of the intervention 93% of newborns received postnatal home visits from village health workers. In Hala only about one third of mother in the intervention arm reported receiving a home visit from the LHW within the first 3 days.
Nevertheless, despite these limitations, a public sector programme promoting preventive care was able to produce health benefits.

16. Cord care
WHO recommends dry cord care BUT in a Cochrane review from 2004
all 21 trials were conducted in hospitals
all but one in high income settings
no systemic infections or deaths in any of the trials
Source: Zupan et al. Cohrane Database Syst Rev : CD001057

17. Cord care compared with dry cord care
A subsequent community-based trial of topical chlorhexidine in Nepal reported:
a 75% reduction in severe omphalitis
a 24% reduction in neonatal mortality
compared with dry cord care
Chlorhexidine is a chemical disinfectant, effective against both Gram positive and Gram negative bacteria, though less effective against some gram negative bacteria.
Trial in Nepal reported a 24% reduction in neonatal mortality but the confidence interval around the estimate of mortality reduction was wide and included no effect.
Source: Mullany et al. Lancet :

18. Chlorhexidine trial, Pakistan
Very recently (two weeks ago) a further two trials were published in the Lancet, one from Pakistan and one from Bangladesh. I am going to describe briefly the trial in Pakistan .
Lancet :

19. Chlorhexidine trial, Pakistan
187 clusters randomly allocated in 2x2 factorial design
2 interventions
Chlorhexidine (daily for 2 weeks) vs dry cord care
Handwashing promotion vs no handwashing promotion
Interventions delivered through Dais
Facility births excluded
9741 livebirths enrolled over 18 months
Study conducted in Dadu district of Sindh province c. 400kms north of Karachi. Clusters were defined by the catchment areas of active TBAs (at least 2 deliveries per month)

20. Chlorhexidine trial, Pakistan
Neonatal mortality
Neonatal deaths (NMR)
Risk ratio
(95% c.i.) P
No handwashing promotion
147 (29.1)
1.0
Handwashing promotion
140 (29.9)
1.08
(0.79, 1.48)
0.62
Dry cord care
176 (36.1)
Chlorhexidine
111 (22.8)
(0.45, 0.85)
0.003

21. Chlorhexidine
“We could argue that more research is needed—questions certainly exist about the duration and timing of application and about external validity. Evidence from high-mortality populations in Africa would be useful. Nevertheless, to demand more evidence of effectiveness might be to repeat an old public health debate: if the need is clear, the possibilities attractive, and the risk low, how much evidence is necessary before we act on plausible findings?”
Trial from Bangladesh published at the same time.
Osrin and Hill. Commentary. Lancet :

22. The challenge of neonatal mortality: what needs to be done?
Effective interventions are available: how do we make sure they reach mother’s and newborns?
Improve the quality and quantity of data available to:
assist rational policy making
Monitor progress

23. Acknowledgements
Joy Lawn, Zulfiqar Bhutta, Gary Darmstadt, Hannah Blencowe, Susana Scott, Neff Walker, Mikkel Oestergaard, Colin Mathers and many others

24. 25-50% of neonatal deaths occur within the first 24 hours
75% of deaths occur within the first week
 1.7% of babies die in the first week of life
Figure: Daily risk of death during first month of life based on analysis of 47 DHS datasets (1995—2003) with neonatal deaths.Deaths in first 24 h recorded as occurring on day 0, or possibly day 1, depending on interpretation of question and coding of response. Preference for reporting certain days (7, 14, 21, and 30) is apparent.
Source: Lancet :

25. 3 main causes: infections, complications of prematurity and intrapartum related deaths (asphyxia)
Figure has changed a bit, a smaller proportion of deaths due to tetanus now but key features remain the same.
Source: Lancet :

26. The Hala Trial, Pakistan
Household practices
Intervention clusters
Control clusters P
Women having contact with LHW during pregnancy
44% (31-56)
26% (15-37)
0.05
Women delivering in a facility
54% (48-61)
44% (34-53)
0.07
Home deliveries with Clean Delivery Kit
35% (27-43)
3% (2-5)
<0.0001
Initiated breastfeeding within 30 minutes
43% (33-52)
27%(19-36)
0.03
Delayed bathing > 6h
50% (39-60)
27% (17-38)
0.008
PNC visit by LHW within 3 days
34% (19-48)
13% (6-20)
0.005

27. Chlorhexidine trial, Pakistan
Omphalitis
Live births
Cases (%)
Risk ratio
(95% c.i.) P
No handwashing promotion
5052
266 (5.3%)
1.0
Handwashing promotion
4689
209 (4.5%)
0.83
(0.61, 1.13)
0.24
Dry cord care
4874
309 (6.3%)
Chlorhexidine
4867
166 (3.4%)
0.58
(0.41, 0.82)
0.002