Study questions maternal Vit D link to learning disorders

Sep 29,2021

New data suggests there is no association between prenatal vitamin D deficiency and offspring specific learning disorders, contrary to previous findings. Maternal vitamin D deficiency has been associated with unfavourable pregnancy outcomes, including gestational diabetes, impaired offspring bone development, prematurity, and subsequent risk of delayed cognitive impairment and neuropsychiatric disorders.

Studies have found that lower levels of prenatal vitamin D were associated with a higher risk offspring autism spectrum disorders, schizophrenia and attention deficit hyperactivity disorder (ADHD).

Yet previous studies have examined the association between prenatal vitamin D levels and diagnosed specific learning disorders - reading, writing, and arithmetic disorders - in offspring. Although the use of multiple micronutrient supplements during pregnancy has previously shown no beneficial effects on offspring cognitive outcomes.

To address the knowledge gap, researchers from the University of Turku, Finland, conducted a national nested case–control study that includes all singleton live births in Finland from 1996 to 2007. For this study, they included a subset of children born in 1996–1997 with diagnoses available from the Care Register for Health Care (CRHC) by the end of 2012.

They hypothesised that lower prenatal vitamin D levels would be associated with an increased risk of offspring learning disorders. This is the first study to examine the association between maternal vitamin D levels in prenatal sera and diagnosed specific learning disorders in offspring.

The study

The Finnish Maternity Cohort (FMC) includes two million maternal serum samples, which were collected mainly in the first trimesters of pregnancy from almost one million pregnancies.

The CRHC was used to identify all the cases, by detecting registered diagnoses of specific learning disorders by the end of 2012.

First, they examined maternal vitamin D as a continuous variable. Next, they categorised the maternal vitamin D levels into quintiles, with cut-off points that were based on the distribution of maternal vitamin D in the control group. Furthermore, maternal vitamin D was categorised based on clinical categories: (1) deficient (25(OH)D < 30 nmol/L), (2) insufficient (25(OH)D 30–49.9 nmol/L), and (3) sufficient levels of vitamin D (25(OH)D 50 nmol/L). The highest quintile and the sufficient category served as reference groups. They used the continuous measure of maternal vitamin D as the exposure variable in the sensitivity analyses of specific learning disorder subgroups and ADHD comorbidity. The associations between the covariates and (1) maternal 25(OH)D among controls and (2) specific learning disorders were tested with Student’s T- and F-tests for continuous covariate variables or Pearson chi-square tests for categorical variables. Covariates were included in the adjusted model if they were associated with both exposure and outcome at p < 0.1.A chi-square test was used to test the possible gender interaction for the association between continuous maternal vitamin D and specific learning disorders as well as the collinear association of maternal SES and smoking. They used conditional logistic regression for matched pairs to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Statistical significance was based on p < 0.05 in all other analyses except for the covariate testing.

No significant association

The researchers found no significant association between maternal vitamin D and offspring specific learning disorders. The findings do not support the hypothesis that prenatal vitamin D deficiency would be an etiological factor for specific learning disorders.

The authors conclude: "Previous studies have suggested prenatal vitamin D as an important factor for many developmental outcomes in offspring. Particularly, prenatal vitamin D deficiency has been associated with neuropsychiatric outcomes such as ASD, ADHD, and schizophrenia. However, this study found no association between prenatal vitamin D deficiency and offspring specific learning disorders."

The strengths of this study include the large, randomly selected samples from nationwide data sources and maternal serum samples during pregnancy, which were collected prospectively. Another strength is the use of a uniform diagnostic system (ICD). The specific learning disorder diagnoses from the CRHC are verified by a physician, in contrast to many other studies in which the diagnoses of specific learning disorders have relied on parent report.

However, the register-based diagnoses from specialised services also pose a limitation, as children with milder learning disorders are typically not referred to these services. Therefore, conclusions are limited to the more impending cases of specific learning disorders. Further, the associations were driven predominantly by the cases with multiple or mixed specific learning disorders, for example, reading disorder in combination with arithmetic disorder, and the cases with only reading disorders.

Research Background

The findings are in line with some previous studies that have examined maternal serum vitamin D and learning-related outcomes, such as academic achievement or IQ in school-aged children or adolescents. In contrast, an Australian study that examined language impairment in 5- and 10-year old children and a Danish study that looked at cognitive abilities in adolescents reported positive associations. The current authors suggest differing outcome variables and timing of the vitamin D measurement from maternal sera (early or late pregnancy, cord blood at birth) might explain the heterogeneous findings across studies.

Arrhenius, B.; Upadhyaya, S.; Hinkka-Yli-Salomäki, S.; Brown, A.S.; Cheslack-Postava, K.; Öhman, H.; Sourander, A. Prenatal Vitamin D Levels in Maternal Sera and Offspring Specific Learning Disorders. Nutrients 2021, 13, 3321.

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