1. Necrotising Enterocolitis: Population approaches
4/19/2017
Necrotising Enterocolitis: Population approaches
This final talk of the day will focus on how the data collected by you provides population-based data which can be used to further our understanding of devastating diseases such as NEC.
I will describe some of challenges in conducting NEC-related research and how the data you contribute may help resolve some these issues in the UKNC- NEC study .
Cheryl Battersby
Clinical Research Fellow
Neonatal Data Analysis Unit

2. Necrotising Enterocolitis
Infant mortality in UK:
Overall ↓
NEC associated ↑ (Rees et al 2008)
Affects up to 10% of low birth weight babies,
30-50% mortality (Lin and Stoll 2006)
Long-term complications (Stoll et al 2004)
Limited preventive and treatment strategies
Limited knowledge of risk factors beyond low gestational age and birth weight
With improving survival of preterm infants, the population of babies at risk of developing NEC is increasing
Therefore although overall infant mortality in the UK is falling, NEC associated mortality is on the rise.
It Approximately affects up to... Although the exact uK figures are unknown
Longterm complications include neurodevelopmental delay, gastrointestinal PN-associated cholestasis, liver failure, and short bowel syndrome
Despite rising incidence there are limited preventive and treatment strategies are known .
And little is known about specific risk factors beyond prematurity and low birth weight

3. Enteral feeding: A common dilemma
Enteral feeding is widely believed to influence the susceptibility to NEC
A common dilemma on daily ward rounds are about feeding –whether we should feed today, what milk if mums milk is not available, how fast to advance….. yet the optimum feeding strategy remains unknown.
This systematic review highlights the need for further research as most randomised controlled trials performed have been inadequately powered to look at the outcome of NEC

4. First step: A population approach
To provide:
A case-definition used consistently
Sample sizes needed for future studies
Current feeding practices
Baseline incidence and systematic surveillance
However, before we embark on further interventional randomised CT
a few fundamental first steps need to be taken in an observational study- Using a population approach
This will provide data to develop a case-definition for NEC which is currently lacking,, Variations in case definition across studies invalidates comparative analyses , makes it difficult to pool data, and to use “NEC” as an outcome in clinical trials.
It will also inform us about sample sizes needed , current enteral feeding practices across a geographically –defined area.as Im sure you appreciate this can differ widely across the country ,
Estimate the baseline incidence rate of NEC and systematic surveillance

5. NEC Surveillance: Practical challenges
History tells us that using questionnaires to conduct NEC surveillance studies to estimate incidence of NEC is challenging.
These 2 studies both used different case-definitions for NEC , one performed in the 1980s and another in 2010 were both limited by a Poor response rate of 50-60%.

6. Observational studies: A novel approach
The Challenges
What is needed
Low incidence and small sample sizes
Collaboration
An evidence-based case-definition
Variations in use of case-definitions
Paucity of population-based data
Population-based incidence and systematic surveillance
SO we do need further observational studies but a different approach is required to resolve some of the challenges.
Because of the relatively low incidence of NEC in individual units , it is difficult to achieve sample sizes required to power studies. What we need is collaboration between many neonatal units nationally and perhaps internationally.
We need to develop an evidence-based case-defintion and apply it consistently across studies.
There is a paucity of population-based data and even large databases worldwide often limit data to those from the very low birth weight / this data is therefore not/ generalisable. And does not tell us population incidence . What we need is data from all babies at risk of NEC in a population and monitor temporal trends
Majority of studies have been retrospective case-control studies from single institutions – with its own limitations
What we need is the capture of data PROSPECTIVELY as part of routine clinical care
Retrospectively collected data
Prospectively collected routine data

7. UK Neonatal Collaborative NEC STUDY
NIHR funded
Medicines for Neonates Programme
CRN portfolio adopted study
140 (86%) neonatal units: 41 level 3, 61 level 2, 38 level 1
Many of you will be involved in the UKNC-NEC STUDY . NIHR funded study which is part of the Medicines for Neonates Programme, and has been adopted into the Clinical research network portfolio
86% of neonatal units in England are participating in the study including the majority of tertiary units . Including 10 complete networks
Thank you to all of you who have joined the UKNC-NEC study Group, committed to entering high quality electronic data which will help fulfill the aims of this study. WHICH ARE......

8. Aims To determine the population incidence of NEC in England
To establish an objective case-definition for NEC
3) To identify enteral-feed related factors that precede onset of NEC in order to inform the design of future interventional randomised controlled trials

9. Method
Analyse data collected from all babies admitted to participating neonatal units over an 18 month period
November May 2013
Dependent on the quality of data
Interim analyses on data completeness will be performed and fed back to units
Data collected by you over an 18 month period will be analysed

10. Data Analysis Report by network using established case-definition
AIM 1: To determine the population incidence of NEC in England
Report by network using established case-definition
AIM 2: To establish an objective case-definition for NEC
Which best predicts the "gold-standard" confirmatory evidence of NEC:
“NEC on histology of resected bowel
OR visual inspection at laparotomy
OR visual inspection at post mortem examination”
The population incidence will be reported by network and therefore complete network participation is encouraged.
Cases of NEC will be identified using a case-defintiion developed as part of this study, which .... Best predicts.....
Which is limited to...

11. Abdominal x-ray performed ad-hoc form
You will be familiar with this simple way of capturing the clinical signs, x-ray appearances and outcomes, These will contribute to establishing a case definition and to estimating the incidence of NEC .

12. AIM 3: Enteral-feed related antecedents of NEC
Hypothesis: “There is an association between enteral-feed related factors and NEC” Method: Comparing the outcome (NEC or no NEC) between groups of patients with different enteral-feed exposures Statistical analysis: A selection of statistical methods to adjust for confounding factors
For the third aim, The outcome of NEC or no NEC will be compared between groups of patients with diff enteral-feed explosures using the case-definition
A selection of statistical methods including propensity score will be ..

13. Enteral-feed related exposures
Days (from birth) to first feed
Type of first feed (Maternal Expressed Breast Milk, Human Donor Milk, Formula)
Days to reach 120ml/kg/day
Summary measure of type of feed up to development of NEC:
1) Exclusive maternal breast milk
2) Maternal breast milk with breast milk fortifier
3) Exclusive human donor milk
4) Human donor milk with breast milk fortifier
5) Exclusive formula
6) Mixed human (maternal or donor) milk
7) Mixed human (maternal or donor) milk and formula
8) Nil by mouth
The different enteral-feed exposures include days to first feed, type of first feed, rate of advancement of feeds
and summary measure of type of feed up to development of NEC

14. Daily feeding data: Time of first feed , Type, Volume
You will be familiar with this simple way of capturing this data through the daily feeding data form
A drop down menu for the name of formula , and the volume ml given to a baby in 24 hours

15. Summary Population-based data
Integrating clinical and research processes
UKNC-NEC study – a stepping stone for future collaborative studies
In summary, collaborative efforts in collecting high quality routine data can provide population-based data , which can be used for research purposes as well as your day-to day clinical uses. Integrating both clinical and research processes.
Many of you have embraced the uKNC NEC studyd and seen it as an opportunity for it to be a stepping stone for future collaborative studies.
we have been approached by neonatal surgeons and neonatologists to address surgical related issues
We are currently collaborating with the East of England network to evaluate the effect of a care bundle designed to reduce NEC. The routine electronic data is being used for analysis and data agreement studies are being conducted
We look forward future collaborations.

16. Acknowledgements- THANK YOU
Supervisors: Professors Neena Modi and Kate Costeloe
UKNC–NEC Study Group: All neonatal units contributing data
NDAU Team
NDAU Steering Board
Jane Abbott (BLISS) Jacquie Kemp
Prof. Peter Brocklehurst Prof. Azeem Majeed
Prof. Kate Costeloe Prof. Neena Modi
Prof. Liz Draper Prof. Andrew Wilkinson