Hypovitaminosis D in pregnant women and neonates is a current major concern in obstetrics and neonatology field.6 This study, as a part of the first cohort study in Indonesia about Vitamin D status and its impact on pregnancy and childhood in Indonesia.7 The first evidence related to vitamin D role on brain function was reported two decades ago through the discovery of vitamin D receptors (VDR) autoradiography in experimental animal brains and the discovery of 1,25-(OH)2-D/calcitriol in cerebrospinal fluid.14 In addition to that, VDRs are also widely distributed in mammalian brain and first expressed in brain development during the critical period of cell proliferation. These receptors could be found in certain brain regions, such as temporal lobes, cingulate, thalamus, cerebellum, amygdala and hippocampus areas.14,15 Calcitriol also works by affecting the production of cytokines and affecting neurotransmitters and synaptic plasticity, which play important roles in the learning process and neurocognitive development.15,16
Fetal brain development starts during early period of pregnancy. Some parts of the brain will develop rapidly in the last trimester, and the process of differentiation and synaptogenesis will develop up to post-natal period with the critical time in the first 1000 days of life.16 Thus, disruption in that period such as low maternal vitamin D level during pregnancy could lead to impaired fetal brain structure formation, such as brain ventricular enlargement and neocortex region thinning.4,17 Another concept suggests that vitamin D deficiency may weaken the integrity of perineuronal nets (PNNs), so that neural-circuit function will be disturbed and cognitive processes such as learning and memory will be impeded.18
The mean value of newborn vitamin D level from 116 subjects in this study was 16.2 ng/mL (8.0–35.4 ng/mL). As many as 12.9% of infants have vitamin D deficiency and 65.5% have insufficiency condition.5 A previous study on vitamin D level in the first trimester of pregnancy, which is a part of this cohort study, showed that the mean value of maternal 25 (OH) vitamin D level was 17.52 ng/mL.7 This result is similar to other previous studies6,8 which showed that newborn vitamin D level is lower (75–90%) than maternal vitamin D level. This could happen because the mother had to fulfill her own vitamin D requirement beside her fetal.19
Previous studies conducted to determine the correlation of vitamin D levels during early4, mid20, and late pregnancy, and/or cord blood at birth8 with child development had been carried out in several countries with various results.9 The previous part of this cohort study in Indonesia about associations between maternal vitamin D levels in early pregnancy (10–14 weeks gestation) with child development in the first year ages of life (3 months, 6 months, and 12 months), showed that ASQ scores in gross motor domains were significantly lower at 3 months of age, and did not have a significant difference for all developmental aspects at older ages (6 and 12 months).7,19
In this study, we examined cord blood vitamin D samples because maternal vitamin D could pass through the placenta and enter the fetal bloodstream, with the half-life around 2 months. Therefore, it could represent vitamin D level in the newborns.21,22 This study showed correlations between cord blood vitamin D levels and the developmental problem-solving domain at 12 and 24 months of age (r = 0.217 and r = 0.414), but no correlation with gross motor, fine motor, communication and personal social domains. Multiple linear regression analysis reinforces the state that a decrease in problem-solving scores is associated with a decrease in vitamin D levels. This could be explained by the extraskeletal effect of vitamin D on neuroplasticity15,16, which determined neurocognition aspect. Problem-solving domain can be a representative of neurocognition aspect. Adverse effects occuring in early life, such as hypovitaminosis D and inadequate stimulations, could cause neurocognition disturbance that can persist until later life. This was consistent with a recent meta-analysis study, regarding the association of maternal or newborn vitamin D levels with neurodevelopmental outcomes, which found that prenatal vitamin D levels had borderline positive associations with the infant cognitive development but no association with infant motor development.23
A cohort study in the United States assessing the relationship between cord blood vitamin D and developmental and cognitive achievement scores, showed that an increase in 5 nmol/L of vitamin D levels in the cord blood was associated with a very small increase in the Wechsler Intelligence Scale for Children (WISC) score at the age of seven years old.8,24 Other study in Australia stated that cord blood vitamin D level had a positive association with language development in children aged 18 months and 4 years old, although the association was weak.9 Thus, it could be concluded that vitamin D has an effect on child development, despite the weak association found on the currently available evidence.
The effort to increase infant vitamin D levels can be done in several ways. The provision of vitamin D supplementation in Indonesia is still difficult as a standard due to the high price. As an alternative, exposing 18.59% of body surface area to sunlight for 37.5 minutes per day especially between 10.00−13.00 is proven to be an effective method to meet daily vitamin D requirements, as reported by Judistiani et al.25
The limitation of this study was not report, several factors that could have affected vitamin D levels and neurodevelopmental status at the age of two year old, such as parenting style and complementary food given after the age of 6 months old. Future long-term cohort studies taking these factors into consideration or randomized clinical trial giving vitamin D supplementation is required.