Improving the survival, growth and developmental of low birth weight newborns through better nutrition

Lead Research Organisation: Liverpool School of Tropical Medicine

Abstract

Worldwide, deaths in the first month of life already account for nearly half of all child deaths. This proportion is set to rise as survival in older children is improving faster than in newborns. More than 9 in 10 newborn deaths occur in Africa and Asia and more than 8 in 10 of these deaths are in babies with low birthweight. The greatest risk is in very small babies (birthweight less than 1500g) where as many as 700 of every 1000 die. Small babies who survive often have poor longerterm growth and development posing highly significant consequences for families and societies.
Being small at birth is due mainly to being born too early (preterm), not growing well in the womb or a combination of both.
Unfortunately, we do not have effective interventions to prevent either of these problems. Therefore, these small babies are a growing challenge especially in poorer countries.
We know that nutrition and growth in early life are critically important for the development of the body organs, including the brain, and being able to fight-off the infections that cause many newborn deaths. Improved nutrition and optimal growth may also prevent diseases that are important in later life in poorer countries such as lung disease. However, achieving optimal nutrition in small babies remains a huge challenge especially as high quality, safe feeding through the veins, that bridges the gap between birth and full oral feeding, is rarely available in low-resource countries. In addition, the structure and function of the gut in preterm babies is immature and advancing oral feeds too quickly may cause life-threatening gut damage. The immature gut not only struggles to cope with milk feeds but also allows gut bacteria to cross into the body and cause infection. Small babies often need nursing in neonatal units (NNUs) for 4-6 weeks or more and this is exactly where their gut can be colonized with dangerous bacteria that are resistant to the available antibiotics.
There has been little research to tell us how best to feed small babies in NNUs in poorer countries. Even basic principles such as when to introduce feeds and how quickly feeds can be increased safely remain unclear. In addition, there are several promising interventions being developed in richer countries that may well be relevant, feasible and affordable in low-resource settings. These include using nutritional supplements of probiotics (safe, "healthy" bacteria) and components in breast milk ("lactoferrin") to prevent gut infections and boost the baby's immunity.
We will establish a core network of 6 NNUs (4 Nigeria/2 Kenya) linking African clinicians and researchers together and with international experts in newborn nutrition, gut health and longer-term lung and brain development. The network will build capacity in those NNUs with limited previous research experience and also engage researchers who are new to working in poorer countries.
Workshops in Nigeria and Kenya will allow the team to document current practices, share experience of practical feeding problems and review possible interventions for testing. Standard international criteria for the diagnosis of common problems (such as infection) will be adapted for use across the network and we will set-up a database to share essential clinical information. We will test novel methods to detect genes that make bacteria resistant to antibiotics and to measure key nutrients in small volume blood samples. We will also store samples for later research. We will ensure that we develop processes that are achievable even with low-resources so that they can be rolled-out to other NNUs to expand the network.
Our goal is to improve survival, growth and development in low birthweight babies through better nutrition. The network and processes that we will establish will enable us to design and implement the large-scale clinical trials that will be needed to advance care in these most vulnerable infants.

Technical Summary

We plan to establish a core network of 6 neonatal units (NNUs; 4 Nigeria/2 Kenya) to improve gut health and early nutrition in low birthweight (LBW) infants. LBW results from premature birth, intra-uterine growth retardation or both. Immature gut structure and function in preterm infants compromises nutrition, facilitates sepsis through bacterial translocation and risksnecrotising enterocolitis (NEC). Abnormal microbial colonization of the gut occurs during prolonged NNU admission including with anti-microbial resistant bacteria. Improved gut health and early nutrition would likely prevent sepsis and improve brain and other organ development.A weak evidence base contributes to the variation in practice regarding establishing feeds especially in vLBW infants
(<1500g). Nutritional interventions to improve gut health and reduce mortality that have become routine practice in many NNUs in richer countries may be practical, safe and affordable in low-resource settings. An example is probiotics that reduce all-cause mortality in vLBW infants (RR 0.72; 95% CI 0.57-0.92) and prevent NEC stage 2 or greater (0.57; 0.43-0.74). Our network will evaluate current evidence and document variation in feeding practices, adapt core outcome sets for common diseases, share anonymised clinical data and identify priorities for research. The dataset will collect information about maternal and early life variables as a basis for the assessment of long-term growth, respiratory and neurodevelopmental outcomes. We will pilot test volumetric absorptive microsampling technology combined with QPlex. Array for measuring inflammatory markers and micronutrients in small blood samples and high resolution melt based qPCR to describe acquisition of anti-microbial resistance genes in faecal flora. We will also bank samples for future analysis. We will engage other low-resource NNUs and develop processes that can be rolled-out to expand the network as a resource for multicentre clinical trials.

Publications

10 25 50
 
Title NeoNuNet case report forms and diagnostic methods forms 
Description The NeoNuNet members generated case report forms (CRFs) to collect demographic, clinical and outcome data for neonatal admissions and their mothers. We also generated CRFs to document the clinical signs and methods used to diagnose commomn diseases (sepsis, asphyxia, abdominal signs, respiratory problems) in low-resource units in the network. These CRFs are available on request and from our webpages. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2019 
Provided To Others? Yes  
Impact Making the resources that we have generated available has encouraged others to contact the Network including potential collaborators. 
URL http://www.lstmed.ac.uk/research/departments/clinical-sciences/neonatal-nutrition-network
 
Description NeoNuNet: collaboration with Newcastle University 
Organisation Newcastle University
Department Newcastle University Medical School
Country United Kingdom 
Sector Academic/University 
PI Contribution Established a link with clinical academics and researchers as collaborators/co-investigators. Engaged leading UK clinical academics in neonataology (Nick Embleton; Janet Berrington) in their first experience of research and neonatal practice in sub-Saharan Africa. New collaboration with Prof Georg Leitz for micronutrient analysis on blood samples from neonates in Nigeria and Kenya; on-going.
Collaborator Contribution Prof Nick Embleton participated in the NeoNUNet workshops in Nigeria (SKYPE) and Kenya and Liverpool in person. Dr. Janet Berrington attended the Liverpool workshop. State-of-the-art presentations in Neonatal nutrition and engaged in developing research proposals. Support for MSC and BSC proposals including hosting a short visit to Newcastle by a University of Liverpool BSc student.
Impact Research proposal developed and submitted to JGHT call 9 and Wellcome Trust Biomedical Resource and Technology grants; outcomes awaited. Contribution to research publications on-going.
Start Year 2018
 
Description NeoNuNet; collaboration with University of Liverpool Institute for Global Health 
Organisation University of Liverpool
Department Institute of Infection and Global Health
Country United Kingdom 
Sector Academic/University 
PI Contribution Engaged Dr. Melissa Gladstone (developmental outcomes) and Prof Janneke van de Wijgert (maternal vaginal flora). Dr. Gladstone attended the Nigeria workshop (by SKYPE) and both attended the Liverpool workshop.
Collaborator Contribution Dr. Gladstone: guidance on assessment of child development for future research proposals. Prof van de Wijgert: established feasibility and small collection of HVS from women delivering LBW infants as a basis for future research.
Impact Collection of HVS established in Nigeria and Kenya as a basis for future research
Start Year 2018
 
Description Diarrhoea and malnutrition; Utrecht Summer School 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Teaching workshop at the Utrecht Global Child Health Summer School on diarrhoea and malnutrition. About 30 junior clinicians and some academic staff attended. My teaching session was rated the second highest of the whole 5 day course. Teaching was rates as excellent Excellent by 77,8% students (average 40,7% excellent for other sessions).
Year(s) Of Engagement Activity 2018
 
Description Invited speaker; International Child Health Group Winter meeting 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited speaker for the RCPCH-affiliated ICHG Winter meeting held at Alder Hey Children's Hospitakl, Liverpool. Attended by 100+ child health professionsal and undergraduates. Presentation generated much debate and feedback was very positive. New contacts established with neonatal units in sSA.
Year(s) Of Engagement Activity 2018
 
Description NeoNuNet workshop, Maseno University, Western Kenya June 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Second NeoNuNet workshop to establish project in Kenya. Excellent attendance by clinical academics, health professionals of all cadres working with neonates and representatives of Kenyan Universities. Supported by kenya Paediatric Associations.
Year(s) Of Engagement Activity 2018
URL http://www.lstmed.ac.uk/research/departments/clinical-sciences/neonatal-nutrition-network
 
Description NeoNuNet workshop; Liverpool School of Tropical Medicine; November 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Third NeoNuNet workshop hosted at LSTM. Engaged with collaborators from UK (inc. Newcastle University), Nigeria and Kenya. Reviewed workshop activities and planned submission of research proposals. Engaes with BSC and MSC students top undertake linked projects.
Year(s) Of Engagement Activity 2018
URL http://www.lstmed.ac.uk/research/departments/clinical-sciences/neonatal-nutrition-network
 
Description NeoNuNet workshop; University College Hospital Ibadan, Nigeria March 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Launch event for the Neonatal Nutrition Network hosted by UCH/University oif Ibadan. Supported by the Nigeria National Neonatal Society (NISONM) and current President and Vice-President attended. Excellent attendance by all cadres of health profressionals in Nigeria working with neonates, national UNICEF representatives, UK and Kenyan collaborators. Highly successful launch event and generated new links with non-network neonatal units in Nigeria.
Year(s) Of Engagement Activity 2018
URL http://www.lstmed.ac.uk/research/departments/clinical-sciences/neonatal-nutrition-network