Vitamin D: fœtal and neonatal neuro-development

A window in Rajasthan

My two recent Blog posts were on the subjects of the high risk of post-operative complications in ethnic Black children, and the high risk of maternal complications in Black women, both taken from articles in the UK Guardian newspaper. 

Although sociological reasons were suggested in the newspaper articles, I was particularly concerned about the absence of consideration of the vitally important and well-recognised problem of serious vitamin D deficiency in these population groups. There might be some truth in the sociological factors, namely racism, but correction of these is difficult and a randomised controlled trial, if demanded, would be impossible. However correction of vitamin D deficiency could take place immediately, and a randomised controlled trial would be theoretically possible. However it would require major committment by the government public health bodies and funding would need to be found. In the present climate of ignoring vitamin D, both would be unlikely.

The second of these Blog posts, considering maternal risk, was published on June 21st. On the following day a reader, John Enebak, brought to my attention a medical-scientific paper published on-line only on June 19th 2024.

This was a research paper from a team of paediatricians working in Jodhpur, western Rajasthan, India, and it is published in Nutritional Neuroscience, an International Journal on Nutrition, Diet and Nervous System.

In the study 175 mother-child pairs were enrolled. In the third trimester of pregnancy the maternal blood level of vitamin D was measured in the usual way as 25(OH)D.

The maternal blood  level of vitamin D was found to have a significant positive relationship to the cognitive development of the infants as measured at 6 months of age (p=0.047).

Umbilical cord blood was measured immediately after birth. There was a high correlation between vitamin D levels in maternal blood 18.86 +/- 8.53ng/ml (47.15 +/- 21.33nmol/L ) and in cord blood 17.39 +/- 8.87 ng/ml (43.48 +/- 22.18nmol/L).

Cord blood vitamin D levels had a significant associatiion with socio-emotional development of the infants at 6 months (p=0.023) and at 9 months of age (p=0.01).

In this study we have good evidence of the importance of vitamin D during pregnancy to optimise neuro-development of the offspring.

More evidence

The sceptic might say "But this is not proof". I would counter this asking the sceptic of the definition of proof, to which there is most unlikely to be an answer. Very few people seem to know the meaning of "proof", which is the fulfillmentf of pre-determined criteria. "Proof" is often confused with "evidence", and the study above is most certainly evidence. "But it is only observation", might be the retort. 

But science is based on observation. Science is then like a revolving wheel, each revolution representing research producing more evidence. Evidence must be repeated, or supported by complementary evidence. Alternatively reproducible evidence that is in conflict with the hypothesis (the black swan in a world of white swans, after Karl Popper) should bring the line of research to an end.

Month of birth and subsequent Multiple Sclerosis

There is other evidence linking brain function to vitamin D. An example is a study of the results of 42,045 people with multiple sclerosis assembled from individual studies undertaken in Denmark, Sweden, Canada and the UK. It demonstrated that the number of sufferers born in the Spring was above the annual average and the number born in the Autumn was below the annual average. 

This suggests that summer gestation, maximising increased sun exposure and vitamin D production during the third trimester, gives to the offspring an advantage of brain integrity that persists into adult life, and conversely winter gestation gives a disadvantage.

Willer CJ, Dyment DA, Sadovnick AD, et al. Timing of birth and risk of multiple sclerosis: populationbased study. BMJ 2005; 330: 120-123.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC544426/

We can see the relationship between vitamin D blood levels (male and female) throught the year, and the timing of conception and subsequent delivery.

We can also see the risk of developing multiple sclerosis in relationship to month of birth, remembering the annual cycle of blood levels of vitamin D.

Spring birth after third trimester of pregnancy in the winter gives the greatest risk of multiple sclerosis.

We also know that multiple sclerosis is related to previous low intake of vitamin D.

Child Neurodevelopment : Study published in October 2023

Bruce Hollis has brought to my attention this study of the effect of vitamin D supplementation during pregnancy on subsequent neurodevopment of of offspring. The study was undertaken and the Medical University of Charleston, South Carolina, USA.

350 women were given a vitamin D supplement during pregnancy, randomised to receive either 400units (standard recommendation), 2,000units, or 4,000units each day. 172 consented to allow their offspring to participate in a follow-up study, and 156 were included in the final analysis.

Expressed as ng/ml, as in the paper

Figures:  Average blood vitamin D levels are shown for each group

Expressed as nmol/L

We can see the vitamin D characteristics in the Figures. In all randomised groups the initial blood vitamin D levels were less than 30ng/ml, 75nmol/L, and this is sub-optimal.

Maternal blood testing was repeated within one month of delivery. In all dose groups there was a significant increase in blood levels of vitamin D, the higher the dose, the greater the blood level achieved. 2,000 or 4,000units per day achieved a blood level of 40ng/ml, 100nmol/L and this is satisfactory.

Vitamin D supplements of 2,000 or 4,000 units per day during pregnancy achieved the first benefit of increasing blood levels, but th main purpose of the study was to look at possible benefits in respect of neurodevelopment of the offspring. This was assessed at between 3 and 5 years of age.

The method of assessment was the Brigance Screen II, a validated neurodevelopmental assessment tool. I must admit that I had no prior knowledge of this, but it is from a highly specialised area outside my clinical experience. 

I will not go into detail, but it is available in the original paper. Overall the study found evidence to support the important role that maternal vitamin D status during pregnancy influences child neurodevelopment. This was particularly noticable in respect of language development (also influenced by maternal educational level), in which vitamin D 2,000units per day was clearly superior to the "official" 400units per day, but in this study 4,000units per day showed no further advantage.

There was no analysis of vitamin D status in African American and Hispanic mothers.

https://www.mdpi.com/2072-6643/15/19/4250

Do no harm, but do your best

Medical practice is based on safety ("First do no harm") and also doing one's best to help a patient. "What can I do to help this pregnant mother-to-be to have a healthy baby?" One approach might be to detect and if necessary correct deficiency of the hormone cholecalciferol, that we know as vitamin D. The objective would be to use up-to-date information such as we have seen, to ensure that the maternal blood level of vitamin D is above 30ng/ml (75nmol/L), the maximum and safe level as judged by the valuable studies from India and the USA.  

Experience from the 2020 Covid-19 pandemic indicates that in respect of immunity and prevention of serious or fatal illness, a target blood level of vitamin D should be above 40ng/ml (100nmol/L).