Maternal Vitamin D Deficiency and Behavioral Issues in Offspring

Becky McCall

June 03, 2016

Maternal vitamin D deficiency in early pregnancy is associated with an increased risk of behavioral issues and attention-deficit/hyperactivity disorder (ADHD)–like symptoms in preschool children, according to new data from a birth cohort study in Greece.

But no association was found between maternal vitamin D deficiency and cognitive scores in the children at age 4, reported Vasiliki Daraki, MD, an endocrinologist from the University of Crete, Heraklion, Greece, who led the analysis, which was  a poster presented at the European Congress of Endocrinology 2016.

"Given the high prevalence of vitamin D deficiency among pregnant women, these findings could have important clinical and public-health implications," said Leda Chatzi, MD, coauthor of the poster and director of the Rhea mother-child pregnancy cohort, which was started in Crete in 2007.

Ironically, even in countries with abundant sunshine like Greece, vitamin D deficiency is a growing public-health issue, and there is no recommendation for pregnant women to take supplements. In fact, in this analysis, Dr Daraki and her colleagues showed that 60% of pregnant women were vitamin D deficient. "This is concerning, because the fetus is dependent on the supply of vitamin D from the mother," she said.

And "a recent study from Spain has also shown that vitamin D deficiency during the first trimester was associated with ADHD," Dr Daraki told Medscape Medical News.

First-Trimester Vitamin D Deficiency and Behavioral Problems

The Rhea longitudinal, prospective pregnancy cohort study aims to evaluate the nutritional, environmental, biological, and psychosocial exposures in the prenatal and early childhood periods of 1300 mothers and their children to the age of 7 years. This particular analysis was designed to investigate the associations between maternal 25-hydroxyvitamin D [25(OH) D] levels in early pregnancy with offspring neurodevelopment at 4 years of age.

A total of 471 mother-child pairs were included in the analysis. Maternal vitamin D status was measured by plasma concentration of 25(OH) D at the first prenatal visit (around 13 weeks). The levels were rated according to the 2011 Endocrine Society categories: sufficiency (> 75 nmol/L), insufficiency (52.5–72.5 nmol/L), or deficiency (< 50 nmol/L).

At 4 years of age, the children were evaluated for cognitive and motor functions using the McCarthy Scales of Children's Abilities (MSCA), and their emotional and behavioral development was assessed using two questionnaires: the Strengths and Difficulties Questionnaire (SDQ), and the Attention Deficit Hyperactivity Disorder (ADHD) Test. Multivariable linear regression analyses were used to estimate the effect of maternal vitamin D status on child neurodevelopment.

The analysis showed that maternal vitamin D levels lower than 50 nmol/L during the first trimester of pregnancy were associated with increased behavioral problems and ADHD-like symptoms among the offspring.

"The lower the mother's vitamin D levels, the higher the child's hyperactivity and inattention," reported Dr Daraki.

The most notable findings comprised a 2-point higher score in the SDQ scale of behavior problems (25-item scale; β-coef, 2.07) and a 5-point increase in score in the ADHD-like symptoms scale (36-item scale; β -coef, 5.36).

"This ADHD score is significant," remarked Dr Daraki.

The association of vitamin D deficiency in pregnancy with peer-group relationship problems was less pronounced, with only a 0.58-point increase in score.

"But in another analysis, when we examined mothers with even lower levels of deficiency, we did see a stronger relationship with peer-relation problems," she noted.

Cognitive function in the children was not found to be associated with vitamin D deficiency in pregnancy, however.

Maternal thyroid function in pregnancy or maternal obesity did not modify the observed associations.

"I think the role of vitamin D in the developing brain is in neuronal differentiation and axon development, and these are more important for behavioral problems than for cognition," Dr Daraki added.

In the future, she and her colleagues intend to measure the cognitive function and behavioral status at the age of 7 years and determine whether the results still hold at the later age.

Vitamin D Status in Early Pregnancy Important

"I think that we need to stay focused on vitamin D levels in early pregnancy, not late pregnancy. It is important that mothers who are deficient receive the right treatment. Unfortunately, because we have so much sunshine, most people think that in Greece we have adequate levels of vitamin D, but this isn't the case," Dr Daraki observed.

Asked to comment, Leonidas Duntas, MD, from the National and Kapodistrian University of Athens, Greece said this is an important study because vitamin D is increasingly being examined in light of its role in neuroendocrine connections.

"This study may hypothesize that a deficiency of vitamin D has an impact on immune regulation. It is very possible that this is the mechanism by which vitamin D deficiency leads to behavioral and attention-deficit problems," he said.

He added that it would be interesting to look at the children's weight gain, as well as cognitive outcomes and behavior as they get older.

"Furthermore, it would also be interesting to follow autoimmune parameters of the women, because there are indications that autoimmune disease might be involved in the increasing prevalence of autism and hyperactivity. Nutritional factors and the parathyroid hormone levels should also be taken into account," he concluded.

Dr Daraki, Dr Chatzi and Dr Duntas have declared no relevant financial relationships.

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Endocr Abstr. 2016;41:EP136. Abstract

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