Cross talk of vascular endothelial growth factor and neurotrophins in mammary gland development.

During the period of lactation, there is extensive growth and development of the mammary gland in order to fulfil the increased demands of milk for the growing infant. Angiogenesis plays a key role in alveolar development and facilitates optimal milk production. Vascular endothelial growth factor (VEGF) is one of the key growth factors regulating angiogenesis in mammary gland. Apart from VEGF, neurotrophins are also known to regulate angiogenesis through direct or indirect mechanisms. Few studies have demonstrated mRNA levels of neurotrophins and their receptors in mammary gland both in humans and rodents. A cross talk between VEGF and neurotrophins has been described in placental development. The enteric and central nervous system are not fully developed at birth, making it imperative to have appropriate levels of angiogenic factors and neurotrophins during postnatal period. The current review summarises studies which describe the role of neurotrophins and angiogenic factors in the mammary gland development.

Longitudinal Assessment of Oxidative Stress Markers in Women with Preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disorder and a major contributor to maternal and fetal morbidity and mortality. Role of oxidative stress in early pregnancy with the pathophysiology of the disorder is unclear. The current study aims to analyse maternal levels of oxidative stress markers (MDA and protein carbonyl) longitudinally across gestation and placental levels of oxidative stress markers (MDA, protein carbonyl and 8-oxo-2'-deoxyguanosine) in women with PE and compare them with non-PE women. 324 pregnant women (216 non-PE and 108 PE women) were longitudinally followed during pregnancy. Women with preeclampsia were stratified as early onset preeclampsia (EOP) and late onset preeclampsia (LOP) Maternal blood at four time points across gestation (11-14 weeks, 18-22 weeks, 26-28 weeks, and at delivery) and placenta were collected. Maternal and placental levels of oxidative stress markers were assessed using commercially available kits. Maternal plasma MDA and protein carbonyl levels were comparable between the PE and non-PE group at all timepoints across gestation. Maternal plasma MDA were significantly higher levels at 26-28 weeks in EOP women when compared to non-PE women (p < 0.05). Placental 8-oxo-dG levels were lower in the EOP group as compared to non-PE (p < 0.05). Elevated plasma MDA levels were positively associated with birth length at 18-22 weeks and 26-28 weeks in the PE group (p < 0.05 for both). Maternal plasma MDA levels were positively associated with systolic blood pressure at 18-22 weeks. Oxidative stress in early pregnancy is not associated with risk of PE.

Longitudinal profile of high-sensitivity C-reactive protein in women with pre-eclampsia.

PROBLEM: C-reactive protein (CRP) is a marker for inflammation and its role as a possible biomarker for an early prediction of pre-eclampsia (PE) is unclear. The present study investigates the levels of high-sensitivity CRP (hs-CRP) longitudinally across pregnancy in women with PE and compares them to women without PE (non-PE). METHOD OF STUDY: A total of 324 pregnant women [216 non-PE and 108 PE women] were included in this study. Maternal blood was taken at four different intervals (V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery). RESULTS: Maternal serum hs-CRP levels were higher at V1, V2, and V3 (p < .05 for all) in the PE group compared to the non-PE group. The hs-CRP levels were associated with maternal blood pressure throughout pregnancy. Maternal hs-CRP levels did not differ among early and late onset PE. Higher maternal hs-CRP levels were associated with the increased risk of PE in unadjusted model in early pregnancy. However, there was no significance after adjusting for confounding factors. CONCLUSIONS: Our findings suggest although the levels of hs-CRP were higher in PE in early pregnancy, they are not associated with an increased risk of PE.

Longitudinal Assessment of Calcium and Magnesium Levels in Women with Preeclampsia.

The present study reports the levels of maternal serum calcium and magnesium from early pregnancy until delivery, along with cord levels, in women who developed preeclampsia (PE) and compares them with those without PE. A total of 324 pregnant women (216 non-PE and 108 PE women) were included in this retrospective case-control study of prospectively collected data nested in an observational cohort study. Maternal blood was collected at 4 time points during pregnancy (V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery) and umbilical cord blood at delivery. Independent t tests were used to compare calcium, magnesium, and their ratio between two groups, and their associations with PE were studied using regression models. Calcium levels were similar between groups at all time points. Magnesium levels were lower (p = 0.021) at V2 in PE group as compared with non-PE group. Maternal calcium and magnesium levels were negatively associated, with blood pressure in early pregnancy. In fully adjusted logistic regression analysis, lower magnesium levels were associated with an increased risk of PE at V2 (OR 0.25 [95% CI 0.07, 0.94] p = 0.04). Lower magnesium in mid-pregnancy was associated with higher risk of PE. These changes were observed before the diagnosis of PE, thereby suggesting that they may have a role in the etiology of PE.

Association of maternal vitamin D status with the risk of preeclampsia.

The aim of this study was to examine serum vitamin D concentrations from early pregnancy until delivery in women who did and did not develop preeclampsia. This longitudinal study was carried out in Pune, India. A total of 1154 women with singleton pregnancies were recruited in early pregnancy from two hospitals. Blood samples were collected and stored at four time points across gestation: V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks and V4 = at delivery. 108 women who developed preeclampsia (PE) and 216 who did not develop PE (Non-PE) were randomly selected from the remainder. Serum 25-hydroxy vitamin D concentrations (25(OH)D) were estimated in their samples using commercially available ELISA kits. Independent t-tests were used to compare 25(OH)D between PE and non-PE groups. Logistic and linear regressions were used to examine associations of 25(OH)D with the risk of preeclampsia and birth outcomes, respectively, after adjusting for confounders. The mean (SD) 25(OH)D at V1 was 21.95 (19.64) in the Non-PE group and 17.76 (13.21) in the PE group. A decrease in the concentrations of vitamin D (ng ml-1) in mid-pregnancy (V2) and at delivery was associated with an increased risk of preeclampsia (0.31 [95% CI 0.11, 0.86], p = 0.024 and 0.24 [95% CI 0.08, 0.77], p = 0.016), respectively. Our finding of lower vitamin D concentrations in mid-pregnancy, before women developed clinical preeclampsia, suggests that vitamin D may have a role in its pathophysiology.

Gestational weight gain in the REVAMP pregnancy cohort in Western India: Comparison with international and national references.

Objective: To determine the trimester specific gestational weight gain (GWG) in a population of pregnant women from Western India and compare it with the Intergrowth-21st international and an Indian reference (GARBH-Ini cohort-Group for Advanced Research on BirtH outcomes). Study design: A prospective longitudinal observational study was undertaken in Pune, West India and data for gestational weight gain was collected [the REVAMP study (Research Exploring Various Aspects and Mechanisms in Preeclampsia)]. Generalized Additive Models for Location, Scale and Shape method (GAMLSS model) were used to create GWG centile curves according to gestational age, stratified by BMI at recruitment (n = 640) and compared with Intergrowth-21st reference and GARBH-Ini cohort. Multivariable regression analysis was used to evaluate the relationship between GWG and antenatal risk factors. Results: The median GWG was 1.68, 5.80, 7.06, and 11.56 kg at gestational ages 18, 26, 30, and 40 weeks, respectively. In our study, pregnant women gained less weight throughout pregnancy compared to Intergrowth-21st study, but more weight compared to the GARBH-Ini cohort centile curves in all the BMI categories. GWG in overweight/obese women (BMI ≥ 25) was significantly lower (<0.001) as compared to underweight (BMI < 18.5), or normal weight women (BMI ≥ 18.5 and <25). The median GWG at 40 weeks in underweight, normal and overweight/obese women was 13.18, 11.74, and 10.48 kg, respectively. Higher maternal BMI, older maternal age, higher parity and higher hemoglobin concentrations were associated with lower GWG, while taller maternal height was associated with greater GWG. Conclusion: GWG of Indian women is lower than the prescriptive standards of the Intergrowth charts.

Cognitive function and behavioral problems in children born to mothers with preeclampsia: an Indian study.

Studies from high-income countries report associations of preeclampsia (PE) with reduced cognitive function and adverse behavioural outcomes in children. We examined these associations in Indian children aged 5-7 years. Children of mothers with PE (n=74) and without PE (non-PE; n=234) were recruited at delivery at Bharati Hospital, Pune, India. The cognitive performance was assessed using 3 core tests from the Kaufman Assessment Battery and additional tests including Verbal fluency, Kohs block design, and Coding A (from Wechsler Intelligence Scale for Children). The parent-reported Strengths and Difficulties Questionnaire (SDQ) was used to assess children's behavioral characteristics. Scores were compared between children from PE and non-PE groups, and associations analyzed further using regression models, adjusted for potential confounders. After adjusting for age, sex, socio-economic status and maternal education, children of PE mothers had lower Kohs block design scores (adjusted odds ratio per score category 0.57, [95% CI 0.34-0.96] p=0.034; 0.62 [95%CI (0.36, 1.07), p=0.09 on further adjustment for birth weight and gestation) compared to children of mothers without PE. In the SDQ, there was a lower prevalence of abnormal 'conduct problem' scores in PE group than non-PE group (OR=0.33, 95% CI 0.13-0.83, p=0.018, in the fully adjusted model); there were no differences for other behavioral domains. This preliminary study in Indian children suggests that fetal exposure to maternal PE may have an adverse impact on visuo-spatial performance but does not adversely affect behavior. Further studies with larger sample sizes are essential to understand effects of maternal PE on cognitive/behavioral outcomes in children.

Associations of long-chain polyunsaturated fatty acid concentrations with birth outcome in term Indian mothers and their neonates.

The purpose of this study was to examine the maternal and cord long-chain polyunsaturated fatty acid (LCPUFA) concentrations and their associations with birth outcome in term deliveries. Pregnant women (n = 253) delivering at term were divided into two groups based on their babies' birth weights (1) normal birth weight (NBW), that is, ≥2.5 kg (n = 190) and (2) low-birth weight (LBW), that is, <2.5 kg (n = 63). Each group is further divided into two groups according to the baby's sex, that is, male NBW (M-NBW), female NBW (F-NBW), male LBW (M-LBW), and female LBW (F-LBW) groups. Maternal plasma docosahexaenoic acid and erythrocyte arachidonic acid (AA) levels were lower (P < 0.05 for both), while cord plasma docosahexaenoic acid and erythrocyte AA levels were higher (P < 0.05 for both) in LBW group when compared to the NBW group. Maternal erythrocyte AA levels were positively associated with birth weight (P = 0.001), while cord plasma docosahexaenoic acid levels were negatively (P = 0.05) associated with birth weight. Reduced maternal and increased cord LCPUFA levels exist in mothers delivering LBW babies, especially in mothers delivering female babies, indicative of sex-specific effects.

Long chain polyunsaturated fatty acids in mothers of preterm babies.

AIMS: to examine the levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in both plasma and erythrocytes of maternal and cord blood as well as in breast milk of mothers of preterm babies. METHODS: a total of 63 mothers of preterm babies were recruited from the Bharati Medical Hospital, Pune, India. RESULTS: plasma and erythrocyte DHA and AA levels were higher (P<0.001) in cord blood than in maternal blood. Maternal plasma DHA and AA were positively (P<0.01) associated with their respective maternal erythrocyte levels. There was a positive association (P<0.01) between maternal DHA (both plasma and erythrocyte) and cord DHA. Maternal plasma omega 3 and 6 fatty acids were positively (P<0.01) associated with their respective milk fatty acids. CONCLUSIONS: higher DHA and AA levels in cord blood compared to the mothers suggests a special mechanism to meet the increased demand of the fetus. Higher levels of milk DHA reflect the increased postnatal requirement of preterm babies suggesting a vital role for maternal milk. Lower maternal erythrocyte DHA concentrations in mothers delivering preterm as compared to term suggest that increased oxidative stress may be responsible for reduced DHA levels. This may alter the uterotonic factors like prostaglandins leading to premature triggering of labor.

Long chain polyunsaturated fatty acids in mothers and term babies.

AIM: To establish the levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in both plasma and erythrocytes of maternal and cord blood as well as in breast milk of mothers delivering babies at term. METHODS: A total of 148 mothers delivering babies at term were recruited from Bharati Medical Hospital, Pune, India. RESULTS: Levels of DHA and AA in both plasma and erythrocyte were higher in cord blood compared to levels in maternal blood (P<0.001). Maternal plasma and erythrocyte DHA levels had a positive association with the respective levels in cord blood (P<0.001). However, such an association was not seen for AA levels. Maternal plasma omega 3 and omega 6 fatty acids were positively associated with the respective milk fatty acids (P<0.01). CONCLUSIONS: Our results indicate that milk long-chain polyunsaturated fatty acids (LCPUFA) status reflects the concentrations of maternal LCPUFA in women delivering babies at term. Improving the maternal LCPUFA status throughout pregnancy and lactation may improve the milk LCPUFA status and ultimately benefit the infant.

Higher maternal plasma folate, vitamin B12 and homocysteine levels in women with preeclampsia.

Micronutrients like vitamin B12 and folate play an important role in nucleic acid metabolism, cell growth, and are important determinants of fetal growth. The present study examined the levels of maternal and cord plasma folate, vitamin B12, homocysteine, and their association with birth outcome in women with preeclampsia (PE). This study includes 450 normotensive control (NC) and 350 women with PE. PE women were further classified into women delivering at term (n = 224) and preterm (n = 126). Maternal and cord blood was collected at delivery. The levels of maternal vitamin B12 (p < 0.05), folate (p < 0.01), and homocysteine (p < 0.01) were higher in the PE group as compared to the NC group. Maternal folate levels were higher in both term and preterm groups, while vitamin B12 levels were higher only in the preterm group as compared to NC group. In contrast, homocysteine was higher only in the term PE group. Similar changes were also observed in the cord plasma. There was a positive association of maternal plasma homocysteine with systolic (r = 0.151, p = 0.000, n = 578) and diastolic blood pressure (r = 0.213, p = 0.000, n = 578) in the whole cohort. A negative association of maternal folate with systolic blood pressure (r = -0.105, p = 0.048, n = 352) while a positive association with baby weight in the NC group (r = 0.116, p = 0.029, n = 352). The present study suggests that maternal and cord micronutrient levels are altered in women with PE.

High maternal plasma antioxidant concentrations associated with preterm delivery.

BACKGROUND/AIMS: Our earlier study has shown that increased maternal oxidative stress and reduced antioxidants like vitamin E and C play an important role in fetal growth in preeclampsia. However, the role of antioxidants and their effects on gestation and birth outcome in normotensive pregnancies are not conclusive. The present study examined plasma malondialdehyde as a marker of oxidative stress and antioxidant concentrations (vitamins E and C) in maternal as well as in cord blood samples in normotensive women who delivered both preterm and at term. METHODS: 140 normotensive pregnant women were recruited at Bharati Medical Hospital, Pune, India, during the year 2007. Maternal and cord samples were examined for oxidative stress levels and vitamin C and E concentrations in women who delivered preterm (n=40) and at term (n=100). Mean values were compared with those of women delivering at term using the t test. RESULTS: Increased (p<0.05) oxidative stress was seen in preterm mothers as well as in cord samples. Preterm mothers had higher vitamin C concentrations (p<0.05), and these were positively associated with oxidative stress (p=0.02). Vitamin E levels were comparable between groups. CONCLUSIONS: Increased maternal circulating vitamin C concentrations and increased oxidative stress are associated with preterm delivery.

Fatty acids, antioxidants, and oxidative stress in pre-eclampsia.

OBJECTIVE: To investigate whether free radical-mediated membrane lipid peroxidation may be implicated in the pathogenesis of pre-eclampsia. METHODS: A prospective study using a sample of 55 healthy pregnant women and 60 pre-eclamptic women recruited at Bharati Medical Hospital, Pune, India. Maternal and cord samples were examined for (red blood cells and plasma) fatty acid profiles, antioxidants, and oxidative stress levels. Mean values were compared between case and control groups using the t test and Wilcoxon rank test. RESULTS: Pre-eclamptic women showed reduced total omega-3 fatty acids (P<0.05), increased omega-6:omega-3 ratio (P<0.05), higher oxidative stress (P<0.05), and lower antioxidant (P<0.05) levels. Similar trends were also observed in cord samples. CONCLUSION: Reduced antioxidants and increased oxidative stress leading to impaired essential polyunsaturated fatty acid levels may be a key factor in the development of pre-eclampsia.

Altered breast milk components in preeclampsia; An in-vitro proton NMR spectroscopy study.

OBJECTIVE: To investigate the metabolic profile of milk on day 3 and at the 6th month of lactation in mothers with preeclampsia (PE) and normotensive mothers. STUDY DESIGN: Women with PE (n=29) and control women (n=31) were recruited for this study. Milk was collected on day 3 and at the 6th month of lactation. Proton NMR spectroscopy was used to identify 25 milk metabolites (alpha-lactose, beta-lactose, oligosaccharides, myo-inositol, alanine, glutamate, glutamine, glycine, histidine, isoleucine, leucine, lysine, phenylalanine, tyrosine, valine, acetone, citrate, creatine, phosphocreatine, acetate, choline, lactate, lipid, phosphocholine and glycerophosphocholine). Principle component analysis (PCA) and Partial Least Square Discriminant Analysis (PLS-DA) were carried out to identify differences in milk metabolite composition between both the groups. RESULTS: The levels of milk metabolites varied between the control and PE groups. Alpha and beta-lactose, glycine, glycerophosphocholine (p<0.01 for all); glutamate, glutamine and phosphocholine levels (p<0.05 for all) were increased at the 6th month as compared to day 3 of lactation in the control group. However, in the PE group, only glycerophosphocholine level showed an increase (p<0.01) at the 6th month. The levels of acetate, acetone (p<0.05 for both) and creatine (p<0.01) decreased at the 6th month as compared to day 3 of lactation in both groups. However, the levels of oligosaccharides were similar between groups and also similar at day 3 and at the 6th month of lactation. CONCLUSION: Our data indicates differential levels of metabolites in the milk of women with PE. Future studies are required to investigate the associations between milk components and infant growth and development.

Differential oxidative stress levels in mothers with preeclampsia delivering male and female babies.

OBJECTIVES: Increased oxidative stress is known to be associated with pregnancy complications like preeclampsia (PE). We hypothesize that increased maternal oxidative stress may differentially affect/program the pregnancy outcome during early postnatal periods in male and female babies. MATERIALS AND METHODS: One-hundred three healthy pregnant women (gestation ≥ 37 weeks) were recruited for the normotensive control (NC) group and 57 women with term-preeclampsia (T-PE; gestation ≥ 37 weeks) and 28 women with preterm-preeclampsia (PT-PE; gestation <37 weeks) were also recruited. All infants were followed for anthropometric measurements until six months of age. RESULTS: Higher maternal plasma malondialdehyde (MDA) and erythrocyte superoxide dismutase and glutathione peroxidase (GPx) levels were observed in both T-PE and PT-PE groups. Higher maternal levels of MDA and GPx were seen in mothers delivering male babies in T-PE and PT-PE groups, respectively, as compared to mothers delivering female babies. Babies born to mothers with PT-PE showed poor growth and development on all the anthropometric parameters compared to those born to mothers with T-PE and NC. CONCLUSION: The altered levels of oxidative stress and antioxidant enzymes in mothers with PE delivering male babies suggest that they may be at higher risk for developing metabolic and neurodevelopmental disorders than female babies.

Preeclampsia alters milk neurotrophins and long chain polyunsaturated fatty acids.

OBJECTIVE: To examine the levels of breast milk neurotrophins 1.5, 3.5, and 6 months of lactation and long chain polyunsaturated fatty acids (LCPUFA) at day 3, 1.5, 2.5, 3.5 and 6 months of lactation in mothers with preeclampsia and compare them with normotensive women. Their associations with growth parameters in children are also examined. METHODS: Women with preeclampsia (n=101) and normotensive women (n=144) with singleton pregnancies were recruited for this study. Milk samples were collected and anthropometry was recorded at the first 6 months. The LCPUFA composition of milk samples was analyzed by using gas chromatography at all time points and neurotrophins were analyzed at 1.5, 3.5 and 6 months by Emax Immuno Assay System using Promega kits. RESULTS: Milk DHA levels were higher at day 3 (9.5%), and 1.5 (23%) and 3.5 (40%) months in mothers with preeclampsia as compared to controls. Milk nerve growth factor (NGF) levels were lower in preeclampsia group as compared to control group at 1.5 (20%) and 3.5 months (27.7%). Milk brain derived neurotrophic factor (BDNF) levels were lower at 1.5 months (10.5%) in the preeclampsia group as compared to control group. CONCLUSION: The present study suggests that there is a differential regulation of DHA and neurotrophins in breast milk in preeclampsia and are associated with growth parameters of children. Future studies should explore the associations between milk LCPUFA, neurotrophins with neurodevelopment in children.

Differential levels of long chain polyunsaturated fatty acids in women with preeclampsia delivering male and female babies.

Maternal long chain polyunsaturated fatty acids (LCPUFA) play a key role in fetal growth and development. This study for the first time examines the maternal and cord LCPUFA levels in preeclamptic mothers delivering male and female infants. In this study 122 normotensive control pregnant women (gestation≥37 weeks) and 90 women with preeclampsia were recruited. Results indicate lower maternal plasma docosahexaenoic acid (DHA) levels (p<0.05) in women with preeclampsia delivering male babies as compared to normotensive control women delivering male babies. Similarly, cord nervonic acid levels were lower (p<0.01) in women with preeclampsia delivering male babies as compared to normotensive control group. However, cord nervonic acid levels were comparable in women with preeclampsia and normotensive control women delivering female babies. This data suggests that male babies born to mothers with preeclampsia may be at an increased risk of developing neurodevelopmental disorders as compared to female babies. Future studies need to follow up both male and female children born to mothers with preeclampsia since altered levels of LCPUFA at birth may have differential implications for the growth and development.

Higher levels of brain derived neurotrophic factor but similar nerve growth factor in human milk in women with preeclampsia.

Children born to mothers with preeclampsia have consistently been suggested to be at risk for cognitive and behavioral disorders in later life. Breastfeeding is said to be associated with better neurodevelopment outcomes. Our earlier studies indicated higher levels of docosahexaenoic acid (DHA) in human milk in women with preeclampsia. DHA is known to regulate the expression of neurotrophins and together they play a vital role in neurodevelopment and cognitive performance. The present study examines the levels of maternal plasma and milk neurotrophins [(nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF)] in women with preeclampsia and compares them with normotensive women who served as controls. Singleton pregnant women diagnosed with preeclampsia (n=72) and controls (n=102) were recruited for this study from Bharati Hospital, Pune. Plasma and milk samples were analyzed for NGF and BDNF levels using the Emax Immuno Assay System using promega kits. Maternal plasma NGF and BDNF levels were lower (p<0.01 for both) in women with preeclampsia as compared to the control women. Milk NGF levels were similar while milk BDNF levels were higher (p<0.05) in the preeclampsia group as compared to controls. Plasma NGF levels were positively correlated with milk NGF levels in the control group. Our results indicate the differential regulation of milk NGF and BDNF levels in women with preeclampsia. The present study suggests a role for both NGF and BDNF in human milk for postnatal brain development. Further studies need to examine the associations of DHA and BDNF in human milk with cognition at later ages.

Maternal micronutrients and omega 3 fatty acids affect placental fatty acid desaturases and transport proteins in Wistar rats.

Adequate supply of LCPUFA from maternal plasma is crucial for fetal normal growth and development. The present study examines the effect of maternal micronutrients (folic acid and vitamin B12) and omega 3 fatty acids on placental mRNA levels of fatty acid desaturases (Δ5 and Δ6) and transport proteins. Pregnant female rats were divided into 6 groups at 2 levels of folic acid both in the presence and absence of vitamin B12. Both the vitamin B12 deficient groups were supplemented with omega 3 fatty acid. Maternal vitamin B12 deficiency reduced placental mRNA and protein levels of Δ5 desaturase, mRNA levels of FATP1 and FATP4 (p<0.05 for all) as compared to control while omega 3 fatty acid supplementation normalized the levels. Our data for the first time indicates that altered maternal micronutrients and omega 3 fatty acids play a key role in regulating fatty acid desaturase and transport protein expression in placenta.

Maternal micronutrients (folic acid and vitamin B(12)) and omega 3 fatty acids: implications for neurodevelopmental risk in the rat offspring.

Altered maternal micronutrients (folic acid, vitamin B(12)) are suggested to be at the heart of intra-uterine programming of adult diseases. We have recently described interactions of folic acid, vitamin B(12) and docosahexaenoic acid in one carbon metabolism that is considered to play a key role in regulation oxidative stress and chromatin methylation. However its impact on fetal oxidative stress and brain fatty acid levels has been relatively unexplored. The present study examined the effect of imbalance in maternal micronutrients (folic acid and vitamin B(12)) and maternal omega 3 fatty acid supplementation on oxidative stress parameters and brain fatty acids and in the offspring at birth. Pregnant female rats were divided into six groups at two levels of folic acid both in the presence and absence of vitamin B(12). Both the vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. Oxidative stress marker (malondialdehyde) and polyunsaturated fatty acid profiles in plasma and brain were analyzed in dam and offspring at d20. Our results for the first time indicate that imbalance in maternal micronutrients (excess maternal folic acid supplementation on a B(12) deficient diet) increases (p<0.01) oxidative stress in both mother and pups. This increased maternal oxidative stress resulted in lower (p<0.01) fetal brain DHA levels. Omega 3 fatty acid supplementation was able to restore (p<0.05) the levels of brain DHA in both the vitamin B(12) deficient groups. Our data has implications for implications for neurodevelopmental disorders since micronutrients and DHA are important modulators for neural functioning.