Neonatal Research

For years we have heard about the mediterranean diet and the anomalous finding that despite relatively high dietary fat intake the people living in Greece, Italy, Southern France (in particular) have very low frequency of vascular disease. This has been ascribed to the particular characteristics of the ‘mediterranean diet’ with its high intake of olive oil, especially extra-virgin olive oil, which is rich in polyphenols and monounsaturated fat, and mixed nuts which are rich in polyphenols, monounsaturated fat, and polyunsaturated fat, including alpha-linolenic acid.

A recently published article in the PNEJM actually performed the first big prospective randomized trial of primary prevention of vascular disease in high risk men and women, over 55 for men, over 60 for women, with other risk factors or type 2 diabetes. The intervention was dietary advice to eat a mediterranean diet with extra extra-virgin olive oil (1 litre a week!) or extra mixed nuts (30 g a day).

They stopped the trial early as there were much more composite endpoints (myocardial infarction, stroke or cardiovascular death) in the controls.

The diet included advice to use extra-virgin olive oil as the only dietary oil (including for cooking) and at least 7 glasses of wine a week.

I think I am part way there….

Annie keeps telling me I should write something about Maggie. I can do no better than to redirect anyone who wants a more honest evaluation of her legacy than all the hagiography in the press over the last few days to this article http://www.salon.com/2013/04/09/the_woman_who_wrecked_great_britain/.

I will quote one sentence ‘Margaret Thatcher was a zealot, a friend to the worst mass murderers of the 1980s, a force for antisocial cruelty, and her violent means of ending the great British experiment in social democracy made the country a more brutal, less equal country’. Farewell Maggie.

A report from Mount Sinai hospital in Toronto of an innovative program to integrate parents much more into the day to day care of babies in the NICU. (O’Brien K, Bracht M, Macdonell K, McBride T, Robson K, O’Leary L, Christie K, Galarza M, Dicky T, Levin A et al: A pilot cohort analytic study of family integrated care in a canadian neonatal intensive care unit. BMC Pregnancy and Childbirth 2013, 13(Suppl 1):S12.) Free access to full text.This is a pilot study performed as a prospective case-control design. Babies who were no longer ventilated, but could be stable on CPAP, and had more than 50% of their feeds enterally were eligible if a parent was available to spend at least 8 hours a day in the NICU.

There was a fairly intensive educational intervention, and the parents took over a lot of the things that are currently usually done by the nurses, for 8 hours a day between the hours of 7 am and 8 pm.

‘Parents were also expected to provide care for their infant(s), especially in the areas of feeding, bathing, dressing, holding, and providing skin-to-skin care, perform basic charting, and maintain a record of their own learning regarding their proficiency in providing care for their infant(s) in the NICU. Nurses remained responsible for more technical aspects of the infant’s care, such as insertion of nasogastric catheters, placement of CPAP prongs, oral suctioning, and adjustment of oxygen concentrations.’

The primary outcome of this pilot was to a measure of growth, the change in the z score between enrollment and 21 days. It was a little better in the Family Integrated Care Infants, but not significantly. Among the other outcomes they examined, there were many more mothers breastfeeding at discharge, and perhaps fewer nosocomial infections, less retinopathy and fewer reports of adverse incidents.

Now this isn’t the most rigorous design, but I think it was appropriate for this pilot project, and it certainly suggests that integrating families more into the care of their babies may have substantial benefits on short term outcomes.

I asked Katharina Staub, a parent representative who is founder and president of the Canadian Premature Babies Foundation to comment:

As a parent of premature twins born at 27 weeks in 2008, I can only applaud this type of approach to the care of premature infants.

Having spoken to one of the mothers who participated in this initial study, it was clear that her participation in the study made for a very positive experience in the NICU. Her anxiety was reduced because of her extensive involvement in the daily care of her baby.

For parents it is empowering to be supported by the staff in the training of how to take care of your baby in the NICU. It gives you confidence to be part of the healing of their child.

What most parents view as normal with a full term child, the act of parenting, feeding, caring for the infant is not so easy in the NICU. This type of care gives a great basis for bonding with your child. It will be interesting to see the results of the Canada wide study that has started in 16 centres.

Katharina Staub Canadian Premature Babies Foundation.

This is a great TEDx talk from a girl from Kenya who…. well read the description on the Guardian page and watch the talk. Very inspiring tale, (after the nauseating start).

No I am not perseverating; this post is about something not solely neonatal, but very important to clinical research. Recently a psychology investigator became intrigued that many studies of functional MRI produced extremely high correlation coefficients, that is, the relation between brain activity in the region of interest and the task the subjects were set (such as choosing something) was very frequently enormously high.

The relevance to neonatology is of course that fMRI is increasingly used to show how different premie brains are to the rest of humanity.

So this investigator examined how the data being produced were being analyzed (Vul E, Harris C, Winkielman P, Pashler H: Puzzlingly high correlations in fMRI studies of emotion, personality, and social cognition. Perspectives on psychological science 2009, 4(3):274-290). It turns out that many studies look at brain activity in a particular 3-dimensional place ‘a voxel’ (volumetric pixel) and look at how it changes with a particular task compared to baseline. All well and good, except that depending on the resolution of the study here may be as many as 500,000 voxels to look at.

What many studies have done is to look initially at all of the voxels, then to select only those that have a greater than average change in activity. After that they produce a correlation coefficient based solely on those voxels that showed a positive correlation, the data from the others being deleted. The authors of this investigation realized that this could artificially inflate, or even produce, significant correlations when there were not real correlations. They went as far as to artificially produce a completely random data set and then did exactly the same thing to that data set as other investigators do to real fMRI data. Not too surprisingly they showed that selecting significant data, and then analyzing only those data that you have already decided are significant, is extremely biased, and can produce significant results from random data.

This has been followed by a really interesting study (Bennett CM, Baird AA, Miller MB, Wolford GL: Neural correlates of interspecies perspective taking in the post-mortem atlantic salmon: an argument for proper multiple comparisons correction. Journal of Serendipitous and Unexpected Results 2011, 1:1-5). The authors took a dead salmon. They then performed fMRI of the salmon and… well I will let the authors explain ‘The [dead] salmon was shown a series of photographs depicting human individuals in social situations with a specified emotional valence, either socially inclusive or socially exclusive. The salmon was asked to determine which emotion the individual in the photo must have been experiencing.’ They then repeated the fMRI, they analyzed the result using standard methods, which showed that the dead salmon was very sensitive to human social stress. Now I must admit that, although the study was published in a peer reviewed journal (the journal of serendipitous and unexpected results jsur.org) this is the only paper that this journal has ever published, even though their website suggests that they have been preparing their first issue for about 3 years now.

What this means is that the fMRI results as analyzed in a large number of papers is questionable. Even if the data are reliable, the analysis can produce highly significant results if they are analyzed inappropriately. fMRI has been used in follow up studies in several studies of preterm infants, I don’t know if these inappropriate techniques of analysis were implicated, partly because as the authors of the first study note, the description of the methods is often very sketchy, so you wouldn’t necessarily realize what had been done. The other thing that it might mean is that the next time you eat salmon, it may understand how you feel, especially if it is sushi…

Troger B, Muller T, Faust K, Bendiks M, Bohlmann MK, Thonnissen S, Herting E, Gopel W, Hartel C: Intrauterine Growth Restriction and the Innate Immune System in Preterm Infants of </=32 Weeks Gestation. Neonatology 2012, 103(3):199-204. Infants born with IUGR often have low white blood cell counts, and neutrophil counts, in addition, this study seems to show that there are functional immune deficits also, interleukin levels were lower in the IUGR babies when their blood cell cultures were stimulated, than preterm infants who had normal growth.

An issue of Early Human Development with a section about ‘Psychosocial development of adolescent preterm children’, which includes a review by Saroj Saigal on Quality of life of former premature infants during adolescence and beyond. Early Hum Dev 2013, 89(4):209-213. As you would expect it is excellent. Also if you are at all unsure of the concept of Executive Function, there is a very high quality review from Peter Anderson’s group in Melbourne (Burnett AC, Scratch SE, Anderson PJ: Executive function outcome in preterm adolescents. Early Hum Dev 2013, 89(4):215-220.) This is the group that has done more than any other to study this issue in former preterm infants, and they explain the concepts as well as reviewing the data.

Harvey ME, Nongena P, Gonzalez-Cinca N, Edwards AD, et al: Parents’ experiences of information and communication in the neonatal unit about brain imaging and neurological prognosis: a qualitative study. Acta Paediatrica 2013, 102(4):360-365. Preterm babies (and others in the NICU) often get head ultrasounds, and brain MRI as  a routine. You may remember that Annie and I wrote a commentary recently which bemoaned the fact that no-one had bothered to ask parents is they thought this was a good idea. Well it looks like the group of David Edwards in London is doing that. This nice qualitative study explored the experiences of parents around receiving information about brain imaging. Parents found themselves to be passive recipients of information. I don’t see in this article any questioning of the usefulness of brain imaging for parents, but that may be coming.