Little Brains, Big Impact: Innovations in Early Neurodevelopment

A WRH research group led by Dr. Fernandes that operates within our Global Health theme.

Research in Neurodevelopment

Studying the brain growth and development of healthy and at-risk children worldwide

Why this Project is important?

The first 1000 days of life, from conception to age 2, are foundational to brain development.

During this period, the developing brain is highly sensitive to environmental influences, both positive and adverse, with multi-system and enduring effects through the lifecourse. This period is also a critical window of opportunity to promote generational physical and mental health in the context of global maternal and child health.

Globally one in three children is at risk of not achieving their full developmental potential by age 5. This is due to the lack of screening resources. many children do not receive the interventions they require within the first 1000 days (golden window) of brain development because they are identified too late in life.

Video: Eugenics: Sciences greatest scandal

Prof Stephen Kennedy and Dr Michelle Fernandes from the Nuffield Department of Women's and Reproductive Health feature in the documentary: “Eugenics: Science's Greatest Scandal”

International Impact

Global uptake: The INTER-NDA toolkit has been applied in multiple research projects in over 20 countries. It's also been applied as ab outcome measure evaluating community-based cognitive and nutritional interventions to promote and rescue neurodevelopment in vulnerable children in the contexts of malnutrition, socio-adversity and the zika epidemic

Capacity development: over 350 international assessors have been trained and standardised in the implementation of the INTER-NDA. Together with regional collaborators, Dr Fernandes and colleagues have formalised capacity development units in the Caribbean and have provided capacity development support to regional collaborators South India, Nigeria and Slovakia.

Translational research: Feasibility studies examining the toolkit’s use within the NHS for the developmental screening of babies born preterm have been completed in Oxford and Southampton. The INTER-NDA is listed as a key resource for neonatal neurodevelopmental follow-up by the British Association of Perinatal Medicine.

To date, the INTER-NDA has been used in research, programmatic and clinical evaluations in over 40,000 children from 26 countries.-Michelle Fernandes

a "whole child approach" to developmental assessment

In addition to the INTER-NDA toolkit, the INTERGROWTH-21^st Project team have out together a comprehensive neurodevelopment package of tools for the assessment of children aged 22 to 30 months.

Neurodevelopment outcomes measured and their tools:

Cognition, fine and gross motor, language, positive and negative behaviour - Toolkit manual
Vision - The Cardiff tests manual
Auditory - Cortical auditory evoked response potentials using EEG recording system manual
Sleep, physical activity and circadian rhythms - Actigraphy manual

innovation

The INTER-NDA toolkit is a major innovation in the field of global child health because:

The INTER-NDA was created specifically to meet the gaps in current early childhood development assessments. It is a comprehensive, international, mixed-methodology assessment measuring the six key early childhood development domains: cognition, language, gross motor skills, fine motor skills, positive behaviour and negative behaviour.

Its norms are the first international early childhood development standards, constructed using the WHO’s prospective, prescriptive methodology from the INTERGROWTH-21st Project’s cohort of low-risk children from Brazil, India, Italy, Kenya and the UK who demonstrated similar socio-environmental, growth and health characteristics, from early fetal life to age 2.

The INTER-NDA’s application in INTERGROWTH-21st showed that children across diverse geographies, populations and cultures achieve very similar neurodevelopmental outcomes at age 2 if their basic health, nutritional and socio-environmental needs during early life are met. The result stimulated important debate about the scientific and ethical rationale behind racially-adjusted norms.

INTER-NDA toolkit

Between 2012 and 2020, the Early Brain Science team of the Oxford Maternal and Perinatal Health Institute, led by Dr Michelle Fernandes, developed the INTERGROWTH-21^st Neurodevelopmental Assessment (INTER-NDA) and an accompanying toolkit for its rapid dissemination across international settings.

The toolkit consists of:

1) A novel, standardised, assessment (the INTER-NDA) of early child development (ECD); specifically designed for non-specialist assessors to use internationally (www.inter-nda.com).

2) The first international, prescriptive ECD standards constructed according to WHO guidelines.

3) A bespoke, international educational programme (consisting of training, standardisation and cultural customisation modules available as face-to-face and virtual sessions) to build local capacity in ECD surveillance using the INTER-NDA.

4) An automated, web-based calculator for the estimation and interpretation of END risk on the INTER-NDA. Results are available in <60 seconds in PDF format.

5) A checklist to guide the INTER-NDA’s implementation in research, clinical practice, and health programmes.

The INTER-NDA can be found freely online.

first fetal atlas

Using results from the INTERGROWTH project, Prof. Ana Namburete and her team have constructed the first digital atlas showing the dynamics of normative maturation of each hemisphere of the fetal brain between 14 and 31 weeks' gestation- a critical period of human development.

The atlas was produced using over 2,500 3-dimensional ultrasound brain scans that were aquired serially during pregnancy from 2,194 fetuses.

This study is unique because, for the first time, an international dataset of 3D US scans, collected using standardised methods and equipment, has been analysed with advanced artificial intelligence (AI) and image processing tools to construct a map showing how the fetal brain matures as pregnancy advances.

UPDATE: our ongoing work in early brain sciences

Mechanistic research: We undertake mechanistic research, employing multi-modal techniques to study early brain structure and function including neuropsychometric, neuroimaging, neurophysiological, epidemiological and multi-omics approaches to understand trajectories of typical & atypical brain development from early fetal life to age 2 years. We have identified five phenotypes of fetal growth associated with differential high and low risk neurodevelopmental profiles during infancy and childhood.
Extension of toolkits to neonates and infants: We focus on the construction, validation and dissemination of novel methods to rapidly & sensitively identify children with developmental delay at key points of contact with healthcare services i.e. birth, 1 and 2 years. Specifically, we ensure that these tools are designed to enable their international uptake and scalability, and that they do not require specialist professionals or infrastructure for their use. We have extended the INTER-NDA’s approach to children aged 1 year, by constructing and validating the Oxford Neurodevelopmental Assessment. We are currently validating a novel neonatal neurobehavioural assessment for children aged 0-6 weeks.

Useful links

Global Health theme

Nuffield Department of Women's and Reproductive Health manages over 30 research groups that fall within either Global Health, Cancer, Maternal & Fetal Health; Big data; and Reproductive Medicine & Genetics.

Global Health theme

Intergrowth 21st

An International Fetal and Newborn Growth Consortium dedicated to improving perinatal health through the development of new fetal and newborn growth standards, providing tools for the continuity of care from conception to 5 years of age.

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Maternal and fetal health theme

Our Maternal & Fetal Health research covers the following research groups: Lactation, Intelligent Imaging in Fetal Health, the Clinical Research Group, Oxford Labour Monitoring, Placental Imaging and Pre-eclampsia

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