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Psychiatry

Vitamin D, Birth Weight, and Schizophrenia Risk

Health at birth is important in neurodevelopment.

Last year around this time of waning UV light in the northern hemisphere, a study was published in the Archives of General Psychiatry that would warm the cockles of any sun-worshiping hearts:

"Neonatal Vitamin D Status and Risk of Schizophrenia: A Population-Based Case Control Study."

Thank you, Netherlands, a country that apparently keeps dried blood samples from all the babies born there. The researchers took 424 individuals with schizophrenia and 424 sex and age matched controls, and pulled their blood samples from the big bank of stored blood samples, and figured out each neonate's vitamin D levels.

Vitamin D is a big suspect in schizophrenia for the following reasons–vitamin D undoubtedly plays a role in the development of the brain. People born in winter and spring have higher risk for developing schizophrenia, and the farther you are born from the equator, the more likely your birth month will be a factor. Immigrants with dark skin who move to northern countries also have children with higher rates of schizophrenia. In addition, city kids are more likely to develop schizophrenia compared to country kids. This study is the first time researchers were able to go back and directly check the vitamin D levels from neonatal blood samples of people who later get schizophrenia.

The average level of vitamin D (measured as 25 (OH) vitamin D3) varied widely from winter to summer, with babies born in March (cases and controls) having the lowest levels, around 26 (which is defined as a deficient level), and babies born in August having an average level of nearly 50 (which is good level for summer). One caveat–the actual number may be misleading. The samples obviously might degrade over time, and these samples were up to 27 years old when tested. However, since there were matched controls of the same age for each patient, it was presumed that the degradation would be the same for both sets of data.

But now the key results–babies born with a vitamin D level of 46.5 had the lowest risk for schizophrenia (again, that might not be the actual level, measured so many years later). The babies within the lowest two quintiles (the lowest 40%) of vitamin D levels had significantly increased risk. Surprisingly, babies in the highest quintile, with the highest vitamin D levels, had higher risk too.

The researchers were able to go back and check for all sorts of variables which might confound things–UV light therapy at birth for high bilirubin might affect vitamin D levels, for example, admission to the neonatal intensive care unit, age, sex, etc. etc. and nothing seemed to change the overall U-shaped data curve, with the "sweet spot" between the 3rd and 4th quintiles of vitamin D levels.

Now the researchers wisely emphasized caution when considering these results–it's an observational study, and there can be plenty of confounders nobody thought of, and you simply cannot establish cause-effect relationships from an observational study. However, if was fantasize that the cause-effect relationship holds true, and low vitamin D levels in late pregnancy and at birth affects your brain development putting you at risk for schizophrenia later in life, the researchers suggest that mere vitamin D supplementation in dark-skinned immigrants in northern countries could reduce the incidence of schizophrenia in those populations by "a staggering 87%." There are a lot of "ifs" to consider here, but common sense wise and considering that we evolved on a planet with a sun and we make chemicals in our skin from sunlight that are important for neurodevelopment, it seems reasonable to suggest that our mothers-to-be not shy away from a very moderate amount of midday sun, if possible.

Another study from this same issue of the Archives is called "Birth Weight, Schizophrenia, and Adult Mental Disorder," where the researchers did pretty much what you might think, but on a very large scale. They followed 1.49 million single babies born in Sweden and Denmark between 1973 and 1986. Both countries have "comprehensive national registers of psychiatric treatment." In 2002 (Sweden) and 2005 (Denmark), these countries had 5,445 registered cases of schizophrenia and 57,455 cases of "any adult psychiatric disorder." (My first thought–5445 cases of schizophrenia seems low out of 1.49 million, and it is only 0.37 %. There should be around 14,900 cases as the worldwide prevalence is right around 0.5-1%)

The results: Birth weight of less than 2500 grams (5 pounds, 8 ounces) in these babies translates into a higher risk for schizophrenia, and the risk actually decreases (for schizophrenia) as the birth weights go up. The heavier the kiddos were, the lower the risk, all the way up to >4500g (that's 9 pounds, 15 ounces or higher). Low birth weight also translated into a higher risk for all mental disorders, including an aggregate "all diagnoses" group and for each subgroup of substance abuse, mood disorders (such as major depression and bipolar disorder), and anxiety disorders. And, indeed, in the subgroups, the higher the birth weight (all the way up to the megababy 10 pounder and above group), the lower the risk.

Interesting! Obviously, very low birth weight is associated with all sorts of issues–premature delivery, infection, brain hemorrhages–any or all of these could have stress on the baby's forming brain. It is interesting that the heavy babies had lower risk than the so-called normal weight babies. I actually would have expected another "U-shaped" curve here. Still, there could be huge confounders. High birth weights are associated with gestational diabetes, but I'm not sure how common that was in Sweden and Denmark back in the 70s and 80s, so maybe it wouldn't be as much of a factor as I would have thought.

One of those confounding factors could actually be vitamin D! This study showed maternal vitamin D intake associated with birth weight (low vitamin D = lower average birth weight), and it was postulated that adequate vitamin D intake protects moms from infections. This study is a little more interesting–white women with a vitamin D level from 60-80 had the lowest risk of having small for gestational age babies, but there was no relationship between vitamin D levels and birth weight in black women. The findings of this study showed that pregnant women who took 4000 IU vitamin D daily had a lower risk of preterm birth.

The lowdown, especially for mothers-to-be–don't get vitamin D deficient! And of course to make our quest for health all the more confusing, optimal vitamin D levels are likely dependent upon many things, such as the nutritional status of other complimentary vitamins and minerals, such as calcium, vitamin K2, and magnesium. Also, according to the folks at the Vitamin D Council, there is a 10-fold variation in the level of vitamin D compared to the oral supplement dose. That means it is really impossible to know your level without having your blood tested. Given there might be some minor risk of kidney stones or perhaps even cardiovascular complications at vitamin D levels higher than 50 (especially in concert with calcium supplementation), I like to recommend levels of between 35-50. Women seem to be able to tolerate somewhat higher levels, and theoretical cancer protection and the neonatal issues may suggest somewhat higher levels might be beneficial for women, but the data are preliminary.

Our skin shuts down vitamin D production when it gets feedback that we have too much, therefore, it is very difficult to overdose on vitamin D obtained from sunshine. Since there are few natural robust sources of vitamin D outside the sun-skin interaction, I like to err on the side of evolved preference, and suggest 10-20 minutes of midday sun 3-4 times a week during the late spring, summer, and early autumn months. I know a dermatologist would disagree with me, but I'm standing by my evolution-based common sense.

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Copyright Emily Deans, M.D.

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