Altered maternal micronutrients (folic acid, vitamin B₁₂) and omega 3 fatty acids through oxidative stress may reduce neurotrophic factors in preterm pregnancy

Abstract

Preterm pregnancies account for approximately 10% of the total pregnancies and are associated with low birth weight (LBW) babies. Recent studies have shown that LBW babies are at an increased risk of developing brain disorders such as cognitive dysfunction and psychiatric disorders. Maternal nutrition, particularly, micronutrients involved in one-carbon metabolism (folic acid, vitamin B(12), and docosahexaenoic acid (DHA)) have a major role during pregnancy for developing fetus and are important determinants of epigenesis. A series of our studies in pregnancy complications have well established the importance of omega 3 fatty acids especially DHA. DHA regulates levels of neurotrophins like brain-derived neurotrophic factor and nerve growth factor, which are required for normal neurological development. We have recently described that in one carbon metabolic pathway, membrane phospholipids are major methyl group acceptors and reduced DHA levels may result in diversion of methyl groups toward deoxyribonucleic acid (DNA) ultimately resulting in DNA methylation. In this review, we propose that altered maternal micronutrients (folic acid, vitamin B(12)), increased homocysteine, and oxidative stress levels that cause epigenetic modifications may be one of the mechanisms that contribute to preterm birth and poor fetal outcome, increasing risk for behavioural disorders in children.

Reduced maternal and cord nerve growth factor levels in preterm deliveries

“…In a recent review article we had proposed that an altered one‐carbon metabolism may cause epigenetic modifications of neurotrophins which may contribute to the risk of developing neurodevelopmental disorders in children born preterm (Dhobale and Joshi, 2011). Our data supports our hypothesis and suggests that increased oxidative and reduced levels of DHA in the mother as can reduce the levels of NGF in both mother and cord.…”

“…We have reported reduced levels of DHA in women delivering preterm babies. Based on these observations we have recently hypothesized that increased oxidative stress and decreased DHA may alter the levels and expression of neurotrophins in preterm deliveries (Dhobale and Joshi, 2011).…”

Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids

“…Facilitating the synthesis of BDNF in primary sensory neurons appears to be one of the mechanisms underlying the role of PGE 2 in the genesis of neuropathic pain, repair of damaged neurons, and neuronal regeneration. It was reported that altered maternal micronutrients (folic acid, vitamin B 12 ), increased homocysteine, and oxidative stress levels could cause epigenetic modifications that contributes to preterm birth and poor fetal outcome, increasing risk for behavioral disorders in children including autism [109,110]. In a recent study using bioinformatics approach we showed that lipoxin A 4 (LXA 4 ), a known anti-inflammatory bioactive metabolite derived from PUFAs, with a binding energy of À3.98 kcal/mol and dissociation constant of 1.2 mM showed the highest binding affinity for BDNF in comparison to other PUFAs and metabolites considered in the study.…”

Adult emotionality and neural plasticity as a function of adolescent nutrient supplementation in male rats

“…Like choline, omega-3 fatty acids also contribute to the integrity of neuronal plasma membranes, increase the expression of neurotropic factors [36], and alter DNA methylation patterns integral for gene expression [37]. The omega-3 fatty acid, docasahexaenoic acid (DHA), helps maintain ionic permeability of the membrane and thus synaptic function [36], and, consistent with the neuroprotective properties of omega-3 fatty acids, normalizes dysregulation of neurotrophic factors by traumatic brain injury [38].…”