Nisha Wadhwani - Academia.edu (original) (raw)

Papers by Nisha Wadhwani

Research paper thumbnail of Cognitive function and behavioral problems in children born to mothers with preeclampsia: an Indian study

Research paper thumbnail of Maternal vitamin D deficiency influences long-chain polyunsaturated fatty acids and pregnancy outcome in association with alterations in one-carbon metabolism

Research paper thumbnail of Maternal Fats and Pregnancy Complications: Implications for Long-term Health

Prostaglandins, Leukotrienes and Essential Fatty Acids

Research paper thumbnail of The REVAMP study: research exploring various aspects and mechanisms in preeclampsia: study protocol

BMC Pregnancy and Childbirth

Background: Preeclampsia is a major cause of maternal, fetal and neonatal morbidity and mortality... more Background: Preeclampsia is a major cause of maternal, fetal and neonatal morbidity and mortality, particularly in developing countries. Considering the burden of preeclampsia and its associated complications, it is important to understand the underlying risk factors and mechanisms involved in its etiology. There is considerable interest in the potential for dietary long chain polyunsaturated fatty acids (LCPUFA) as a therapeutic intervention to prevent preeclampsia, as they are involved in angiogenesis, oxidative stress, and inflammatory pathways. Methods: The REVAMP study (Research Exploring Various Aspects and Mechanisms in Preeclampsia) follows a cohort of pregnant women from early pregnancy until delivery to examine longitudinally the associations of maternal LCPUFA with clinical outcome in preeclampsia. A multisite centre for advanced research was established and pregnant women coming to Bharati hospital and Gupte hospital, Pune, India for their first antenatal visit are recruited and followed up at 11-14 weeks, 18-22 weeks, 26-28 weeks, and at delivery. Their personal, obstetric, clinical, and family history are recorded. Anthropometric measures (height, weight), food frequency questionnaire (FFQ), physical activity, socioeconomic status, fetal ultrasonography, and color Doppler measures are recorded at different time points across gestation. Maternal blood at all time points, cord blood, and placenta at delivery are collected, processed and stored at − 80°C. The children's anthropometry is assessed serially up to the age of 2 years, when their neurodevelopmental scores will be assessed. Discussion: This study will help in early identification of pregnant women who are at risk of developing preeclampsia. The prospective design of the study for the first time will establish the role of LCPUFA in understanding the underlying biochemical and molecular mechanisms involved in preeclampsia and their association with developmental programming in children.

Research paper thumbnail of Maternal vitamin D deficiency increases the thromboxane/prostacyclin ratio through alterations in the one‐carbon cycle in Wistar rats

Research paper thumbnail of Maternal long chain polyunsaturated fatty acid status and pregnancy complications

Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA)

Maternal nutrition plays a crucial role in influencing fetal growth and birth outcome. Any nutrit... more Maternal nutrition plays a crucial role in influencing fetal growth and birth outcome. Any nutritional insult starting several weeks before pregnancy and during critical periods of gestation is known to influence fetal development and increase the risk for diseases during later life. Literature suggests that chronic adult diseases may have their origin during early life - a concept referred to as Developmental Origins of Health and Disease (DOHaD) which states that adverse exposures early in life "program" risks for later chronic disorders. Long chain polyunsaturated fatty acids (LCPUFA), mainly omega-6 and omega-3 fatty acids are known to have an effect on fetal programming. The placental supply of optimal levels of LCPUFA to the fetus during early life is extremely important for the normal growth and development of both placenta and fetus. Any alteration in placental development will result in adverse pregnancy outcome such as gestational diabetes mellitus (GDM), preeclampsia, and intrauterine growth restriction (IUGR). A disturbed materno-fetal LCPUFA supply is known to be linked with each of these pathologies. Further, a disturbed LCPUFA metabolism is reported to be associated with a number of metabolic disorders. It is likely that LCPUFA supplementation during early pregnancy may be beneficial in improving the health of the mother, improving birth outcome and thereby reducing the risk of diseases in later life.

Research paper thumbnail of Altered metabolic homeostasis between vitamin D and long chain polyunsaturated fatty acids in preeclampsia

Medical Hypotheses, 2017

Sub-optimal maternal nutrition may result in pregnancy complications like preeclampsia. Preeclamp... more Sub-optimal maternal nutrition may result in pregnancy complications like preeclampsia. Preeclampsia is known to be of placental origin and a major cause of maternal morbidity and mortality worldwide. Our earlier studies suggest that altered metabolism of folic acid, vitamin B12 and long chain polyunsaturated fatty acid (LCPUFAs) in the one carbon cycle increases homocysteine levels in preeclampsia. Recent reports indicate that vitamin D deficiency may also have a role in preeclampsia, although the mechanisms are unclear. A disturbed one carbon cycle can influence methylation patterns of various genes involved in placental development. Altered expression of cystathionine beta synthase (CBS) gene can result in hyperhomocystenemia. Higher homocysteine levels are known to increase reactive oxygen species (ROS) production which in turn leads to increased expression of phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2). Higher expression of PLA2 and COX-2 can influence the release of arachidonic acid (AA) from membrane phospholipid and result in increased conversion to thromboxane. Vitamin D [1,25(OH)2D3] is known to induce the CBS gene expression while it can suppress the oxidative stress-induced COX-2 up-regulation and thromboxane production. Based on this, we propose a novel hypothesis that a disturbed vitamin D and LCPUFA metabolism influence the regulation of the one carbon cycle which will trigger inflammation through oxidative stress in preeclampsia. This may lead to altered feto-placental growth and development in preeclampsia.

Research paper thumbnail of Altered development and function of the placental regions in preeclampsia and its association with long-chain polyunsaturated fatty acids

Wiley Interdisciplinary Reviews: Developmental Biology, 2016

The placenta is an essential organ formed during pregnancy that mainly transfers nutrients from t... more The placenta is an essential organ formed during pregnancy that mainly transfers nutrients from the mother to the fetus. Nutrients taken up by the placenta are required for its own growth and development and to optimize fetal growth. Hence, placental function is an important determinant of pregnancy outcome. Among various nutrients, fatty acids, especially long-chain polyunsaturated fatty acids (LCPUFAs), including omega 3 and omega 6 fatty acids, are essential for placental development from the time of implantation. Studies have associated these LCPUFAs with placental development through their roles in regulating oxidative stress, angiogenesis, and inflammation, which may in turn influence their transfer to the fetus. The placenta has a heterogeneous morphology with variable regional vasculature, oxidative stress, and LCPUFA levels in healthy pregnancies depending upon the location within the placenta. However, these regional structural and functional parameters are found to be disturbed in pathological conditions, such as preeclampsia (PE), thereby affecting pregnancy outcome. Hence, the alterations in LCPUFA metabolism and transport in different regions of the PE placenta as compared with normal placenta could potentially be contributing to the pathological features of PE. The regional variations in development and function of the placenta and its possible association with placental LCPUFA metabolism and transport in normal and PE pregnancies are discussed in this review. WIREs Dev Biol 2016, 5:582-597. doi: 10.1002/wdev.238 For further resources related to this article, please visit the WIREs website.

Research paper thumbnail of Placental DHA and mRNA Levels of PPARγ, LXRα and their Relationship to Birth Weight

Journal of Clinical Lipidology, 2016

A very large number of fatty acids play wide range of physiological roles in cellular growth and ... more A very large number of fatty acids play wide range of physiological roles in cellular growth and function in placental as well as fetal growth. However, docosahexaenoic acid (DHA), in addition to its critical role in cellular membranes, is known to act as a ligand for several nuclear receptors and regulates the activity of transcription factor families like peroxisome proliferator-activated receptor, liver X receptor (LXR), retinoid X receptor (RXR), and sterol regulatory element binding protein (SREBP). These transcription factors and DHA are known to regulate the placental and fetal growth and development. The objective of the present study was to examine the fatty acids and transcription factors in the placenta of women delivering low birth weight (LBW) babies. The present study examines the fatty acid and mRNA levels of various transcription factors in the placentae of women delivering normal birth weight (NBW) (n = 38) and women delivering LBW (n = 36). Placental fatty acids were analyzed using gas chromatography. Placental mRNA levels of PPARα, PPARγ, SREBP-1c, LXRα, RXRα, and RXRγ were examined using quantitative real time PCR. Placental DHA levels and mRNA levels of placental PPARγ and LXRα were lower (P < .05 for all) in women delivering LBW babies. There was a positive association of placental PPARγ mRNA levels and placental DHA levels with baby weight (P < .05 for both). Our data suggest that lower placental DHA and transcription factors may have a vital role in the etiology of LBW babies.

Research paper thumbnail of Reduced Maternal Erythrocyte Long Chain Polyunsaturated Fatty Acids Exist in Early Pregnancy in Preeclampsia

Lipids, 2015

The present prospective study examines proportions of maternal erythrocyte fatty acids across ges... more The present prospective study examines proportions of maternal erythrocyte fatty acids across gestation and their association with cord erythrocyte fatty acids in normotensive control (NC) and preeclamptic pregnancies. We hypothesize that maternal fatty acid status in early pregnancy influences fetal fatty acid stores in preeclampsia. 137 NC women and 58 women with preeclampsia were included in this study. Maternal blood was collected at 3 time points during pregnancy (16-20th weeks, 26-30th weeks and at delivery). Cord blood was collected at delivery. Fatty acids were analyzed using gas chromatography. The proportions of maternal erythrocyte α-linolenic acid, docosahexaenoic acid, nervonic acid, and monounsaturated fatty acids (MUFA) (p < 0.05 for all) were lower while total n-6 fatty acids were higher (p < 0.05) at 16-20th weeks of gestation in preeclampsia as compared with NC. Cord 18:3n-3, 22:6n-3, 24:1n-9, MUFA, and total n-3 fatty acids (p < 0.05 for all) were also lower in preeclampsia as compared with NC. A positive association was observed between maternal erythrocyte 22:6n-3 and 24:1n-9 at 16-20th weeks with the same fatty acids in cord erythrocytes (p < 0.05 for both) in preeclampsia. Our study for the first time indicates alteration in maternal erythrocyte fatty acids at 16th weeks of gestation which is further reflected in cord erythrocytes at delivery in preeclampsia.

Research paper thumbnail of Role of Maternal Long-Chain Polyunsaturated Fatty Acids in Placental Development and Function

Impact of Maternal Nutrition, 2015

ABSTRACT

Research paper thumbnail of Increased homocysteine levels exist in women with preeclampsia from early pregnancy

The Journal of Maternal-Fetal & Neonatal Medicine, 2015

The present prospective study examines the levels of maternal plasma folate, vitamin B12 and homo... more The present prospective study examines the levels of maternal plasma folate, vitamin B12 and homocysteine in normotensive control (NC) women and women with preeclampsia (PE) from early pregnancy till delivery. The present study includes 126 NC and 62 PE women. Maternal blood was collected at 3 time points during pregnancy (T1 = 16th-20th weeks, T2 = 26th-30th weeks and T3 = at delivery). Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay technology. Maternal plasma folate levels were similar between NC and PE women at all the time points across gestation. Maternal plasma vitamin B12 levels were significantly higher in PE (p < 0.05) as compared with NC at T2. Maternal plasma homocysteine levels were higher in PE as compared with NC at all the time points, i.e. T1, T2 (p < 0.05 for both) and T3 (p < 0.01). Our results indicate that higher homocysteine levels exist in women with PE from early pregnancy and continue till delivery.

Research paper thumbnail of Maternal vitamin B12 deficiency leads to altered expression of maternal fatty acid desaturases

Research paper thumbnail of Reduced levels of placental long chain polyunsaturated fatty acids in preterm deliveries

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2011

Reports suggest that the placenta in preterm birth may provide clues to predicting the risk of in... more Reports suggest that the placenta in preterm birth may provide clues to predicting the risk of individuals developing chronic diseases in later life. Placental delivery of long chain polyunsaturated fatty acids (LCPUFA) (constituents of the cell membrane and precursors of prostaglandins) is essential for the optimal development of the central nervous system of the fetus. The present study examines the levels of LCPUFA and their association with placental weight and birth outcome in 58 women delivering preterm and 44 women delivering at term. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels were lower (p o 0.01) in women delivering preterm. There was a positive association of placental DHA with placental weight (p ¼0.036) and nervonic acid with head circumference (p ¼ 0.040) in the preterm group. Altered placental LCPUFA status exists in Indian mothers delivering preterm, which may influence the birth outcome.

Research paper thumbnail of Altered maternal proportions of long chain polyunsaturated fatty acids and their transport leads to disturbed fetal stores in preeclampsia

Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA), 2014

Our previous cross-sectional studies have shown altered proportions of long chain polyunsaturated... more Our previous cross-sectional studies have shown altered proportions of long chain polyunsaturated fatty acids (LCPUFA) in preeclampsia (PE) at the end of pregnancy when the pathology has already progressed. The present longitudinal study for the first time reports fatty acid proportions from 16th week of gestation till delivery and placental transport in PE. This is a hospital based study where women were recruited in early pregnancy. Maternal blood was collected at 3 time points i.e. T1¼ 16-20th week, T2 ¼26-30th week and T3¼ at delivery. Cord blood and placenta were collected at delivery. This study reports data on 140 normotensive control (NC) and 54 PE women. In PE we report lower proportions of DHA in maternal plasma at T1, cord plasma and placenta (po0.05 for all). The mRNA levels of placental Δ5 desaturase, fatty acid transport proteins-1,-4, were lower (p o0.05 for all) in PE. There was also a positive association between cord and maternal plasma DHA and total omega-3 fatty acids at T1. This study demonstrates that women with PE have lower fatty acids stores at 16-20th week of gestation and lower placental synthesis and transport. It is likely that supplementation of omega-3 fatty acids during the 16-20th week of gestation may help in improving fatty acid status in infants born to mothers with PE.

Research paper thumbnail of Effect of maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids on liver fatty acid desaturases and transport proteins in Wistar rats

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2012

Research paper thumbnail of Maternal micronutrients and omega 3 fatty acids affect placental fatty acid desaturases and transport proteins in Wistar rats

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2013

Adequate supply of LCPUFA from maternal plasma is crucial for fetal normal growth and development... more 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 B 12) and omega 3 fatty acids on placental mRNA levels of fatty acid desaturases (D5 and D6) 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 B 12. Both the vitamin B 12 deficient groups were supplemented with omega 3 fatty acid. Maternal vitamin B 12 deficiency reduced placental mRNA and protein levels of D5 desaturase, mRNA levels of FATP1 and FATP4 (po0.05 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.

Research paper thumbnail of A prospective study of maternal fatty acids, micronutrients and homocysteine and their association with birth outcome

Maternal & Child Nutrition, 2013

Our earlier studies both in animals and in humans have indicated that micronutrients (folic acid,... more Our earlier studies both in animals and in humans have indicated that micronutrients (folic acid, vitamin B12) and long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), are interlinked in the one-carbon cycle, which plays an important role in fetal 'programming' of adult diseases. The present study examines the levels of maternal and cord plasma fatty acids, maternal folate, vitamin B12 and homocysteine in healthy mothers at various time points during pregnancy and also examine an association between them. A longitudinal study of 106 normal pregnant women was carried out, and maternal blood was collected at three time points, viz., T1 = 16-20th week, T2 = 26-30th week and T3 = at delivery. Cord blood was collected at delivery. Fatty acids were estimated using a gas chromatograph. Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay (CMIA) technology. Maternal plasma folate (P < 0.05), vitamin B12 (P < 0.01) and DHA (P < 0.05) levels were lowest, while maternal homocysteine levels were highest (P < 0.01) at T3. There was a negative association between maternal DHA and homocysteine at T2 (P < 0.05) and T3 (P < 0.01). There was a positive association between plasma DHA in maternal blood at T3 and cord blood. Furthermore, there was a positive association between maternal folate and vitamin B12 at T3 and baby weight, whereas maternal homocysteine at T1 were inversely associated with baby weight at delivery. Our study provides evidence for the associations of folic acid, vitamin B12, homocysteine with DHA and baby weight, suggesting that a balanced dietary supplementation of folate-vitamin B12-DHA during pregnancy may be beneficial.

Research paper thumbnail of Exploring the role of LC-PUFA metabolism in pregnancy complications

Prostaglandins, Leukotrienes and Essential Fatty Acids

Research paper thumbnail of Cognitive function and behavioral problems in children born to mothers with preeclampsia: an Indian study

Research paper thumbnail of Maternal vitamin D deficiency influences long-chain polyunsaturated fatty acids and pregnancy outcome in association with alterations in one-carbon metabolism

Research paper thumbnail of Maternal Fats and Pregnancy Complications: Implications for Long-term Health

Prostaglandins, Leukotrienes and Essential Fatty Acids

Research paper thumbnail of The REVAMP study: research exploring various aspects and mechanisms in preeclampsia: study protocol

BMC Pregnancy and Childbirth

Background: Preeclampsia is a major cause of maternal, fetal and neonatal morbidity and mortality... more Background: Preeclampsia is a major cause of maternal, fetal and neonatal morbidity and mortality, particularly in developing countries. Considering the burden of preeclampsia and its associated complications, it is important to understand the underlying risk factors and mechanisms involved in its etiology. There is considerable interest in the potential for dietary long chain polyunsaturated fatty acids (LCPUFA) as a therapeutic intervention to prevent preeclampsia, as they are involved in angiogenesis, oxidative stress, and inflammatory pathways. Methods: The REVAMP study (Research Exploring Various Aspects and Mechanisms in Preeclampsia) follows a cohort of pregnant women from early pregnancy until delivery to examine longitudinally the associations of maternal LCPUFA with clinical outcome in preeclampsia. A multisite centre for advanced research was established and pregnant women coming to Bharati hospital and Gupte hospital, Pune, India for their first antenatal visit are recruited and followed up at 11-14 weeks, 18-22 weeks, 26-28 weeks, and at delivery. Their personal, obstetric, clinical, and family history are recorded. Anthropometric measures (height, weight), food frequency questionnaire (FFQ), physical activity, socioeconomic status, fetal ultrasonography, and color Doppler measures are recorded at different time points across gestation. Maternal blood at all time points, cord blood, and placenta at delivery are collected, processed and stored at − 80°C. The children's anthropometry is assessed serially up to the age of 2 years, when their neurodevelopmental scores will be assessed. Discussion: This study will help in early identification of pregnant women who are at risk of developing preeclampsia. The prospective design of the study for the first time will establish the role of LCPUFA in understanding the underlying biochemical and molecular mechanisms involved in preeclampsia and their association with developmental programming in children.

Research paper thumbnail of Maternal vitamin D deficiency increases the thromboxane/prostacyclin ratio through alterations in the one‐carbon cycle in Wistar rats

Research paper thumbnail of Maternal long chain polyunsaturated fatty acid status and pregnancy complications

Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA)

Maternal nutrition plays a crucial role in influencing fetal growth and birth outcome. Any nutrit... more Maternal nutrition plays a crucial role in influencing fetal growth and birth outcome. Any nutritional insult starting several weeks before pregnancy and during critical periods of gestation is known to influence fetal development and increase the risk for diseases during later life. Literature suggests that chronic adult diseases may have their origin during early life - a concept referred to as Developmental Origins of Health and Disease (DOHaD) which states that adverse exposures early in life "program" risks for later chronic disorders. Long chain polyunsaturated fatty acids (LCPUFA), mainly omega-6 and omega-3 fatty acids are known to have an effect on fetal programming. The placental supply of optimal levels of LCPUFA to the fetus during early life is extremely important for the normal growth and development of both placenta and fetus. Any alteration in placental development will result in adverse pregnancy outcome such as gestational diabetes mellitus (GDM), preeclampsia, and intrauterine growth restriction (IUGR). A disturbed materno-fetal LCPUFA supply is known to be linked with each of these pathologies. Further, a disturbed LCPUFA metabolism is reported to be associated with a number of metabolic disorders. It is likely that LCPUFA supplementation during early pregnancy may be beneficial in improving the health of the mother, improving birth outcome and thereby reducing the risk of diseases in later life.

Research paper thumbnail of Altered metabolic homeostasis between vitamin D and long chain polyunsaturated fatty acids in preeclampsia

Medical Hypotheses, 2017

Sub-optimal maternal nutrition may result in pregnancy complications like preeclampsia. Preeclamp... more Sub-optimal maternal nutrition may result in pregnancy complications like preeclampsia. Preeclampsia is known to be of placental origin and a major cause of maternal morbidity and mortality worldwide. Our earlier studies suggest that altered metabolism of folic acid, vitamin B12 and long chain polyunsaturated fatty acid (LCPUFAs) in the one carbon cycle increases homocysteine levels in preeclampsia. Recent reports indicate that vitamin D deficiency may also have a role in preeclampsia, although the mechanisms are unclear. A disturbed one carbon cycle can influence methylation patterns of various genes involved in placental development. Altered expression of cystathionine beta synthase (CBS) gene can result in hyperhomocystenemia. Higher homocysteine levels are known to increase reactive oxygen species (ROS) production which in turn leads to increased expression of phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2). Higher expression of PLA2 and COX-2 can influence the release of arachidonic acid (AA) from membrane phospholipid and result in increased conversion to thromboxane. Vitamin D [1,25(OH)2D3] is known to induce the CBS gene expression while it can suppress the oxidative stress-induced COX-2 up-regulation and thromboxane production. Based on this, we propose a novel hypothesis that a disturbed vitamin D and LCPUFA metabolism influence the regulation of the one carbon cycle which will trigger inflammation through oxidative stress in preeclampsia. This may lead to altered feto-placental growth and development in preeclampsia.

Research paper thumbnail of Altered development and function of the placental regions in preeclampsia and its association with long-chain polyunsaturated fatty acids

Wiley Interdisciplinary Reviews: Developmental Biology, 2016

The placenta is an essential organ formed during pregnancy that mainly transfers nutrients from t... more The placenta is an essential organ formed during pregnancy that mainly transfers nutrients from the mother to the fetus. Nutrients taken up by the placenta are required for its own growth and development and to optimize fetal growth. Hence, placental function is an important determinant of pregnancy outcome. Among various nutrients, fatty acids, especially long-chain polyunsaturated fatty acids (LCPUFAs), including omega 3 and omega 6 fatty acids, are essential for placental development from the time of implantation. Studies have associated these LCPUFAs with placental development through their roles in regulating oxidative stress, angiogenesis, and inflammation, which may in turn influence their transfer to the fetus. The placenta has a heterogeneous morphology with variable regional vasculature, oxidative stress, and LCPUFA levels in healthy pregnancies depending upon the location within the placenta. However, these regional structural and functional parameters are found to be disturbed in pathological conditions, such as preeclampsia (PE), thereby affecting pregnancy outcome. Hence, the alterations in LCPUFA metabolism and transport in different regions of the PE placenta as compared with normal placenta could potentially be contributing to the pathological features of PE. The regional variations in development and function of the placenta and its possible association with placental LCPUFA metabolism and transport in normal and PE pregnancies are discussed in this review. WIREs Dev Biol 2016, 5:582-597. doi: 10.1002/wdev.238 For further resources related to this article, please visit the WIREs website.

Research paper thumbnail of Placental DHA and mRNA Levels of PPARγ, LXRα and their Relationship to Birth Weight

Journal of Clinical Lipidology, 2016

A very large number of fatty acids play wide range of physiological roles in cellular growth and ... more A very large number of fatty acids play wide range of physiological roles in cellular growth and function in placental as well as fetal growth. However, docosahexaenoic acid (DHA), in addition to its critical role in cellular membranes, is known to act as a ligand for several nuclear receptors and regulates the activity of transcription factor families like peroxisome proliferator-activated receptor, liver X receptor (LXR), retinoid X receptor (RXR), and sterol regulatory element binding protein (SREBP). These transcription factors and DHA are known to regulate the placental and fetal growth and development. The objective of the present study was to examine the fatty acids and transcription factors in the placenta of women delivering low birth weight (LBW) babies. The present study examines the fatty acid and mRNA levels of various transcription factors in the placentae of women delivering normal birth weight (NBW) (n = 38) and women delivering LBW (n = 36). Placental fatty acids were analyzed using gas chromatography. Placental mRNA levels of PPARα, PPARγ, SREBP-1c, LXRα, RXRα, and RXRγ were examined using quantitative real time PCR. Placental DHA levels and mRNA levels of placental PPARγ and LXRα were lower (P < .05 for all) in women delivering LBW babies. There was a positive association of placental PPARγ mRNA levels and placental DHA levels with baby weight (P < .05 for both). Our data suggest that lower placental DHA and transcription factors may have a vital role in the etiology of LBW babies.

Research paper thumbnail of Reduced Maternal Erythrocyte Long Chain Polyunsaturated Fatty Acids Exist in Early Pregnancy in Preeclampsia

Lipids, 2015

The present prospective study examines proportions of maternal erythrocyte fatty acids across ges... more The present prospective study examines proportions of maternal erythrocyte fatty acids across gestation and their association with cord erythrocyte fatty acids in normotensive control (NC) and preeclamptic pregnancies. We hypothesize that maternal fatty acid status in early pregnancy influences fetal fatty acid stores in preeclampsia. 137 NC women and 58 women with preeclampsia were included in this study. Maternal blood was collected at 3 time points during pregnancy (16-20th weeks, 26-30th weeks and at delivery). Cord blood was collected at delivery. Fatty acids were analyzed using gas chromatography. The proportions of maternal erythrocyte α-linolenic acid, docosahexaenoic acid, nervonic acid, and monounsaturated fatty acids (MUFA) (p < 0.05 for all) were lower while total n-6 fatty acids were higher (p < 0.05) at 16-20th weeks of gestation in preeclampsia as compared with NC. Cord 18:3n-3, 22:6n-3, 24:1n-9, MUFA, and total n-3 fatty acids (p < 0.05 for all) were also lower in preeclampsia as compared with NC. A positive association was observed between maternal erythrocyte 22:6n-3 and 24:1n-9 at 16-20th weeks with the same fatty acids in cord erythrocytes (p < 0.05 for both) in preeclampsia. Our study for the first time indicates alteration in maternal erythrocyte fatty acids at 16th weeks of gestation which is further reflected in cord erythrocytes at delivery in preeclampsia.

Research paper thumbnail of Role of Maternal Long-Chain Polyunsaturated Fatty Acids in Placental Development and Function

Impact of Maternal Nutrition, 2015

ABSTRACT

Research paper thumbnail of Increased homocysteine levels exist in women with preeclampsia from early pregnancy

The Journal of Maternal-Fetal & Neonatal Medicine, 2015

The present prospective study examines the levels of maternal plasma folate, vitamin B12 and homo... more The present prospective study examines the levels of maternal plasma folate, vitamin B12 and homocysteine in normotensive control (NC) women and women with preeclampsia (PE) from early pregnancy till delivery. The present study includes 126 NC and 62 PE women. Maternal blood was collected at 3 time points during pregnancy (T1 = 16th-20th weeks, T2 = 26th-30th weeks and T3 = at delivery). Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay technology. Maternal plasma folate levels were similar between NC and PE women at all the time points across gestation. Maternal plasma vitamin B12 levels were significantly higher in PE (p < 0.05) as compared with NC at T2. Maternal plasma homocysteine levels were higher in PE as compared with NC at all the time points, i.e. T1, T2 (p < 0.05 for both) and T3 (p < 0.01). Our results indicate that higher homocysteine levels exist in women with PE from early pregnancy and continue till delivery.

Research paper thumbnail of Maternal vitamin B12 deficiency leads to altered expression of maternal fatty acid desaturases

Research paper thumbnail of Reduced levels of placental long chain polyunsaturated fatty acids in preterm deliveries

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2011

Reports suggest that the placenta in preterm birth may provide clues to predicting the risk of in... more Reports suggest that the placenta in preterm birth may provide clues to predicting the risk of individuals developing chronic diseases in later life. Placental delivery of long chain polyunsaturated fatty acids (LCPUFA) (constituents of the cell membrane and precursors of prostaglandins) is essential for the optimal development of the central nervous system of the fetus. The present study examines the levels of LCPUFA and their association with placental weight and birth outcome in 58 women delivering preterm and 44 women delivering at term. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels were lower (p o 0.01) in women delivering preterm. There was a positive association of placental DHA with placental weight (p ¼0.036) and nervonic acid with head circumference (p ¼ 0.040) in the preterm group. Altered placental LCPUFA status exists in Indian mothers delivering preterm, which may influence the birth outcome.

Research paper thumbnail of Altered maternal proportions of long chain polyunsaturated fatty acids and their transport leads to disturbed fetal stores in preeclampsia

Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA), 2014

Our previous cross-sectional studies have shown altered proportions of long chain polyunsaturated... more Our previous cross-sectional studies have shown altered proportions of long chain polyunsaturated fatty acids (LCPUFA) in preeclampsia (PE) at the end of pregnancy when the pathology has already progressed. The present longitudinal study for the first time reports fatty acid proportions from 16th week of gestation till delivery and placental transport in PE. This is a hospital based study where women were recruited in early pregnancy. Maternal blood was collected at 3 time points i.e. T1¼ 16-20th week, T2 ¼26-30th week and T3¼ at delivery. Cord blood and placenta were collected at delivery. This study reports data on 140 normotensive control (NC) and 54 PE women. In PE we report lower proportions of DHA in maternal plasma at T1, cord plasma and placenta (po0.05 for all). The mRNA levels of placental Δ5 desaturase, fatty acid transport proteins-1,-4, were lower (p o0.05 for all) in PE. There was also a positive association between cord and maternal plasma DHA and total omega-3 fatty acids at T1. This study demonstrates that women with PE have lower fatty acids stores at 16-20th week of gestation and lower placental synthesis and transport. It is likely that supplementation of omega-3 fatty acids during the 16-20th week of gestation may help in improving fatty acid status in infants born to mothers with PE.

Research paper thumbnail of Effect of maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids on liver fatty acid desaturases and transport proteins in Wistar rats

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2012

Research paper thumbnail of Maternal micronutrients and omega 3 fatty acids affect placental fatty acid desaturases and transport proteins in Wistar rats

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2013

Adequate supply of LCPUFA from maternal plasma is crucial for fetal normal growth and development... more 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 B 12) and omega 3 fatty acids on placental mRNA levels of fatty acid desaturases (D5 and D6) 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 B 12. Both the vitamin B 12 deficient groups were supplemented with omega 3 fatty acid. Maternal vitamin B 12 deficiency reduced placental mRNA and protein levels of D5 desaturase, mRNA levels of FATP1 and FATP4 (po0.05 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.

Research paper thumbnail of A prospective study of maternal fatty acids, micronutrients and homocysteine and their association with birth outcome

Maternal & Child Nutrition, 2013

Our earlier studies both in animals and in humans have indicated that micronutrients (folic acid,... more Our earlier studies both in animals and in humans have indicated that micronutrients (folic acid, vitamin B12) and long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), are interlinked in the one-carbon cycle, which plays an important role in fetal 'programming' of adult diseases. The present study examines the levels of maternal and cord plasma fatty acids, maternal folate, vitamin B12 and homocysteine in healthy mothers at various time points during pregnancy and also examine an association between them. A longitudinal study of 106 normal pregnant women was carried out, and maternal blood was collected at three time points, viz., T1 = 16-20th week, T2 = 26-30th week and T3 = at delivery. Cord blood was collected at delivery. Fatty acids were estimated using a gas chromatograph. Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay (CMIA) technology. Maternal plasma folate (P < 0.05), vitamin B12 (P < 0.01) and DHA (P < 0.05) levels were lowest, while maternal homocysteine levels were highest (P < 0.01) at T3. There was a negative association between maternal DHA and homocysteine at T2 (P < 0.05) and T3 (P < 0.01). There was a positive association between plasma DHA in maternal blood at T3 and cord blood. Furthermore, there was a positive association between maternal folate and vitamin B12 at T3 and baby weight, whereas maternal homocysteine at T1 were inversely associated with baby weight at delivery. Our study provides evidence for the associations of folic acid, vitamin B12, homocysteine with DHA and baby weight, suggesting that a balanced dietary supplementation of folate-vitamin B12-DHA during pregnancy may be beneficial.

Research paper thumbnail of Exploring the role of LC-PUFA metabolism in pregnancy complications

Prostaglandins, Leukotrienes and Essential Fatty Acids