Prenatal nutrition: of paramount importance

Professor Michael Crawford speechProfessor Michael Crawford’s speech at a House of Lords dinner on 21 September 2016 marked the 25th anniversary of the The Little Foundation for research into the cause and prevention of cerebral palsy (of which Professor Crawford was a founder member).

At the core of the speech was the scientifically-verified, hopefully world-changing fact that the prenatal nutrition of mothers is of paramount importance.

For your information and inspiration, here is the speech in full:

“The reason I am here is to tell you something of the scientific background and research we are doing, which could make cerebral palsy a thing of the past.

In 2010 Josette Sharon then CEO of UN World Food Programme commented in her report to the Board: “We now know more about nutrition. It is not just about providing a full cup for the child, it is what is in the cup that matters”. She went on to say “If a child under 2 years of age is malnourished, that child will be sentenced to a life of physical and mental limitations”.

The full weight of her remark is especially true of the prenatal period during which critical phases of brain development are accomplished. Derangement of development of any region of the brain during this period is lifelong. There is no catch-up later for missed or stunted development. Preterm delivery and low birthweight carry the highest risk of prenatal brain disorder and cerebral palsy.

In order for you to understand our work it is important to remind you that the brain is a fatty substance made with highly specialised essential fats which you have to obtain from the food you eat. These essential fats form the membranes which enable cell specialisation, and specifically in the brain provide the functional structures for signalling messages. The integrity of the membrane is also critical for the rapidly growing blood vessels in the brain. Leakage or rupture due to an inadequate composition can lead to inflammation, blockage of blood flow and regional cell death with scarring leading to CP.

To understand the nutritional requirements, you need to recall that the brain evolved in the sea 400-500 million years ago, where the nutrients used to make it were entirely of marine origin. A pretty obvious point. What is less well known is that our brains today are still made of the same sea-derived stuff. Hence the reason why Bertie Wooster was regularly at pains to point out that Jeeves was so intelligent because he virtually lived on fish!

There is robust evidence for the role of these essential fats for brain development, which was confirmed at a joint consultation of FAO and WHO, 2008-2010.

Our recent work is being conducted at Chelsea and Westminster Hospital, Imperial College, under the leadership of Professor Mark Johnson, head of Obstetrics and Gynaecology; Dr Enitan Ogundipe, who is in charge of neurodevelopmental assessment; Dr. Yiqun Wang, who is in charge of the lipid science; and the Little Foundation PhD student Anniebelle Sassine. Professor David Edwards and his team at St Thomas’s Hospital are responsible for the magnetic resonance images (MRI) of the brain around the time of birth which tell us if there is any abnormality, or if supplements have had an effect on the development of various regions of the brain before birth.

We set out to test the hypothesis that supplementing mothers with DHA from recruitment at their first antenatal clinic (12 weeks pma) might influence brain development as objectively assessed by birth outcome and MRI of the brain after birth. We measured the red cell DHA and other fatty acids at recruitment and at birth in the mother and newborn.

The first result has been accepted for publication. It provided a stunning and unexpected result. The red cell membrane is actually a piece of tissue and its composition reflects what the tissues make of the mother’s diet. It has a half-life of 120 days, hence its composition is a summation of several months beforehand. In a population of 296 mothers the red cell composition for a fatty acid – oleic acid –  predicted with a confidence of 93% preterm delivery at 34 weeks and a confidence of 85% at 30 weeks. Hence this marker is also predicting risk.

The MRI data which is in preparation for publication showed some effect of the supplement on head size and on differences in regions of the brain such as the cortex in the boys, but not the girls.

There are two important conclusions: first, because of the long half-life of the red cell, the fatty acid marker is telling us that it is the condition of the mother in the months leading up to conception which is of over-riding importance to the completion of the pregnancy to full term. It did not matter whether the mother took a supplement or not, nor her condition during the pregnancy – it was the condition of the mother in biological preparation for conception that matters most, with a stunning 93% confidence level.

That Nature prepares in advance for pregnancy should not be surprising. It is after all a general principle. You would not crouch at the Olympic starting grid next to Usain Bolt without preparation. You would not even get in your motor car to go on a long trip without checking your oil, water, petrol and tyres. Unfortunately, about half the pregnancies coming to our hospital, Chelsea and Westminster, are unplanned. Yet creating a new life, a new person, is truly the most important event in a lifetime.

Seafood for head and mindThe second conclusion comes from the nature of the oleic acid marker. A rise in membrane oleic acid is itself a marker for deficiency of membrane (tissue) DHA and several other essential fatty acids of dietary origin required by the brain. Because these are brain-specific, this result implies that global inadequacy of the stuff you need for brain development is linked to the highest known risk for developmental brain disorders.

The relatively weak response of the supplement in the MRI findings is consistent with the supreme importance of what happens before conception. Moreover an effect visible in the boys and not the girls is also consistent with an essential fat deficiency, as males are far more susceptible than females.

Confidence levels as high as 93% are very rare in biology and medicine. Hence we have a serious marker for risk. We now need to refine that marker not just to general risk but to specific risks such as autism, ADHD, learning and behavioural pathology and cerebral palsy. The specificity of the markers will point to cause, and hence prevention.

Tied to nutrition, we will also need to investigate the role of the immune system in exacerbating or repairing prenatal damage. We wish to study 1,000 pregnancies for the bulk of these neurodevelopmental disorders, and secondly, one of some 50,000 to nail cerebral palsy itself. Imperial College is especially suited for this study as we have five teaching hospitals linked to our science facility.

The deliverables will be a recipe to ensure the security of membrane integrity, lack of which is, we believe, the cause of disorder. Different recipes may well be required for the different disorders; however, it is worth remembering that the people who diagnose these conditions now refer to a spectrum, e.g. autistic spectrum disorders or ADHD spectrum, etc. Hence there will likely be a commonality.

This programme is not just of importance for cerebral palsy, it is also vital for understanding and dealing with the rise in mental ill health, now the most costly burden of ill-health in the UK and the West. In summary, in 2007 the DoH estimated mental ill health to cost £77 billion, a cost greater than heart disease and cancer combined. People said the high cost was just new diagnostics. Repeat in 2010 put the cost at £105 billion. The Wellcome Trust had it at £113 billion in 2013. Simon House here has done an analysis of the cost which is substantially greater, as violence was not included. A continued rise will result in an unthinkable outcome for humanity.

A previous Europe-wide study conducted by Dr. Martin Bax at Chelsea and Westminster Hospital examined MRI images of the brains of children with cerebral palsy. All cases of identifiable lesions in the brain were timed to well before the time of birth. This means they were not in the main due to obstetric mishap. As Professor Paul Polani at Guys had previously concluded, there was no specific genetic cause, and that means the cause was environmental – i.e. nutrition and/or infection.

Just as we learnt how to prevent neural tube defects with folic acid, it is now on the cards that we can similarly make CP and its allied neurodevelopmental disorders and mental ill-health things of the past, with a knock-on ability to enhance the health and abilities of future children. It is the future of our children that is at stake.”