Placental growth factor and Fms related tyrosine kinase-1 are hypomethylated in preeclampsia placentae.

Aim: This study aims to examine the DNA methylation (DNAm) and expression patterns of genes associated with placental angiogenesis in preeclampsia. Materials & methods: DNAm and expression were examined in normotensive (n = 100) and preeclampsia (n = 100) women using pyrosequencing and quantitative real-time PCR respectively. Results: Hypomethylation at several CpGs was observed in PlGF and FLT-1 in women with preeclampsia compared to normotensive controls. PlGF expression was lower in women with preeclampsia while FLT-1 expression was comparable. DNAm at various CpGs was negatively correlated with expression in both the genes and were associated with maternal blood pressure and birth outcomes. Conclusion: DNAm and expression of angiogenic factors in placentae are differentially regulated in preeclampsia and influence birth outcomes.

The REVAMP study: research exploring various aspects and mechanisms in preeclampsia: study protocol.

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.

Matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases -9 (MMP-9) are differentially expressed in different regions of normal and preeclampsia placentae.

Matrix metalloproteinases (MMPs) are involved in the extracellular matrix (ECM) remodeling during human placentation and parturition and have been shown to be associated with oxidative stress. Placental regional changes in oxygen availability and oxidative stress indices may influence regional differences in expression of MMPs. This study examines the protein and mRNA levels of MMP-2 and MMP-9 in different regions of the placenta in normotensive control (NC) women and women with preeclampsia (PE). Fifty-two NC women and 43 women with PE (18 delivered at term [T-PE] and 25 delivered preterm [PT-PE]) were recruited. Placental samples were taken from four regions: central basal (CM), central chorionic (CF), peripheral basal (PM), and peripheral chorionic (PF). MMP protein and mRNA levels were measured by ELISA and quantitative real time PCR, respectively. MMP-2 protein levels were higher in all the placental regions (P < 0.05) from PT-PE group as compared to the respective regions from the NC and T-PE groups. MMP-9 mRNA levels were higher in CM region as compared to CF and PM regions (P < 0.05) in the NC group and compared to CF and PF regions (P < 0.05) in the T-PE group. The MMP-9 mRNA levels were lower in the CF region in the PT-PE and T-PE groups (P < 0.05) as compared to the NC group. Elevated levels of MMP-2 protein levels were observed in all regions of PT-PE placenta possibly influencing the degradation of placental ECM. Lower mRNA expression of MMP-9 both in PT-PE and T-PE may contribute to a disturbed placental vascularization.

VEGF and VEGFR1 levels in different regions of the normal and preeclampsia placentae.

Altered placental angiogenesis is implicated in the pathophysiology of preeclampsia. We have earlier reported placental regional differences in oxidative stress markers and neurotrophins. Oxidative stress and neurotrophins are reported to regulate angiogenesis. This study aims to examine protein and mRNA levels of vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR1) in four regions [central maternal (CM), central fetal (CF), peripheral maternal (PM), and peripheral fetal (PF)] of the placenta in normotensive control (NC) women (n = 51) and women with preeclampsia (PE) (n = 43) [18 delivered at term (T-PE) and 25 delivered preterm (PT-PE)]. In all groups, CF region reported highest VEGF protein levels compared to all other regions. VEGF mRNA level was higher in CF region as compared to CM region in PE group (p < 0.05). VEGF levels were lower in all regions of PE, T-PE, and PT-PE groups (p < 0.05) as compared to their respective regions in NC group. VEGFR1 levels were lower in CF (p < 0.05) and PF (p < 0.01) regions as compared to CM region only in control. However, VEGFR1 levels were higher in CF (p < 0.05) and PF (p < 0.01) regions of PT-PE group as compared to control. VEGFR1 mRNA level was higher in PM region of PE group and T-PE group (p < 0.05 for both) as compared to control. VEGF levels in the PF region were positively associated with birth weight and placental weight. This study describes placental regional changes in angiogenic factors particularly highlighting increased VEGF in CF region possibly in response to hypoxic conditions prevailing in placenta.

Differential accumulation of vimentin fragments in preeclamptic placenta.

Preeclampsia is a pregnancy complication that is the result of abnormal placentation because of inadequate trophoblast invasion into spiral arteries that prevent normal blood flow to the placenta. We report the alteration in vimentin protein proteolysis in placenta of normotensive and preeclamptic women, which is known to have a role in many physiological functions other than its major function in the structural integrity of the cell. Placental proteome from normotensive (n = 25) and preeclamptic pregnancies (n = 25) showed eight differentially accumulated protein spots of vimentin (proteolytic fragments) by two-dimensional electrophoresis. Immunoblots of normotensive and preeclamptic placenta revealed a difference in proteolytic processing of vimentin. In particular, lower molecular weight vimentin fragments of 32 and 20 kDa were 3.3 and 2.6-fold (p < 0.0001) higher, respectively, in preeclampsia compared with normotensive placenta.

Hypermethylated CpG sites in the MTR gene promoter in preterm placenta.

AIM: Altered maternal one-carbon metabolism influences placental DNA methylation patterns and 'programs' the fetus for noncommunicable diseases in adult life. EXPERIMENTAL PROCEDURES: Levels of plasma folate, vitamin B12, homocysteine, mRNA and protein levels of MTHFR and MTR enzymes in placenta were compared among women delivering preterm (n = 83) and term (n = 75). MTR promoter CpG methylation was undertaken. RESULTS: MTHFR and MTR mRNA levels were higher while protein levels were lower, and MTR CpG sites were hypermethylated in the preterm group, as compared with the term group. Methylated CpG sites were negatively associated with maternal plasma vitamin B12 levels. CONCLUSION: Study suggests a dysregulation of enzyme genes in remethylation arm of the one-carbon metabolism in placenta of women delivering preterm.

Tubulointerstitial nephritis antigen-like 1 protein is downregulated in the placenta of pre-eclamptic women.

BACKGROUND: Tubulointerstitial nephritis antigen-like 1 protein (TINAGL1), is a matricellular protein, known to play role in cell adhesion and cell receptor interaction. Research related to TINAGL1 is limited to cell culture and animal models. Demonstration of TINAGL1 as a positive regulator of angiogenesis and its expression in the decidua of postimplantation mouse uterus, prompted us to validate its expression in human placenta during impaired angiogenesis in pre-eclamptic condition. METHODS: Placental tissue from normotensive (n = 25) and pre-eclamptic (n = 25) pregnancies were used to study the differentially expressed proteins by two-dimensional gel electrophoresis and TINAGL1 protein was validated with Western blotting. RESULTS: A total of 55 protein spots were differentially expressed (fold change >1.5, p < 0.05), of which 27 were upregulated and 28 were downregulated in the pre-eclamptic placenta. TINAGL1 was found to be downregulated in pre-eclamptic compared to normotensive pregnant women. CONCLUSION: This is the first study reporting TINAGL1 to be present in human placenta and differentially expressed in pre-eclamptic condition. The functional role of TINAGL1 in association to human pregnancy needs to be explored further.

Placental Proteomics Provides Insights into Pathophysiology of Pre-Eclampsia and Predicts Possible Markers in Plasma.

Pre-eclampsia is a hypertensive disorder characterized by the new onset of hypertension >140/90 mmHg and proteinuria after the 20th week of gestation. The disorder is multifactorial and originates with abnormal placentation. Comparison of the placental proteome of normotensive (n = 25) and pre-eclamptic (n = 25) patients by gel-free proteomic techniques identified a total of 2145 proteins in the placenta of which 180 were differentially expressed (>1.3 fold, p < 0.05). Gene ontology enrichment analysis of biological process suggested that the differentially expressed proteins belonged to various physiological processes such as angiogenesis, apoptosis, oxidative stress, hypoxia, and placental development, which are implicated in the pathophysiology of pre-eclampsia. Some of the differentially expressed proteins were monitored in the plasma by multiple reaction monitoring analysis, which showed an increase in apolipoproteins A-I and A-II in gestational weeks 26-30 (2-fold, p < 0.01), while haptoglobin and hemopexin decreased in gestational weeks 26-30 and week 40/at delivery (1.8 fold, p < 0.01) in pre-eclamptic patients. This study provides a proteomic insight into the pathophysiology of pre-eclampsia. Identified candidate proteins can be evaluated further for the development of potential biomarkers associated with pre-eclampsia pathogenesis.

Increased homocysteine levels exist in women with preeclampsia from early pregnancy.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Our results indicate that higher homocysteine levels exist in women with PE from early pregnancy and continue till delivery.

Reduced Maternal Erythrocyte Long Chain Polyunsaturated Fatty Acids Exist in Early Pregnancy in Preeclampsia.

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.

Regional differences in the placental levels of oxidative stress markers in pre-eclampsia.

OBJECTIVE: To examine placental malondialdehyde (MDA), catalase, and glutathione peroxidase (GPx) levels in four placental regions among women with and without pre-eclampsia. METHODS: A cross-sectional study was conducted among women aged 18-35 years with a singleton pregnancy in Pune, India, between May 3, 2013, and June 16, 2014. Three groups were enrolled: normotensive; pre-eclampsia, delivered at term; and pre-eclampsia, delivered preterm. Samples were collected from the central and peripheral placental regions (maternal and fetal sides) immediately after delivery. RESULTS: A total of 60 women were enrolled (35 normotensive; 11 with pre-eclampsia delivered at term; 14 with pre-eclampsia, delivered preterm). MDA levels were higher in all regions of the placenta among the pre-eclampsia versus normotensive groups (P<0.01). MDA levels were higher in the central maternal region than in the central fetal region in the preterm pre-eclampsia group (P=0.023). The MDA levels in the central maternal region were also higher in the preterm than in the term pre-eclampsia group (P=0.014). Catalase activity was lower in the peripheral maternal (P=0.036) and fetal (P=0.050) regions in the preterm pre-eclampsia group versus the normotensive group. The activity of GPx was higher in the peripheral maternal region than in the central fetal region in the normotensive group (P=0.033). CONCLUSION: Pre-eclampsia might be characterized by differential placental oxidative stress and antioxidant enzyme activity.

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

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.

Altered methylation and expression patterns of genes regulating placental angiogenesis in preterm pregnancy.

INTRODUCTION: Altered angiogenesis has been implicated in the pathogenesis of various pregnancy complications, particularly preeclampsia. At present, there is a lack of data on the possible role of angiogenesis and its molecular mechanism in preterm pregnancy. We have previously reported reduced placental global DNA methylation levels in preterm pregnancy. Now, we have extended the study to examine plasma levels of angiogenic factors from maternal and cord blood and correlate them with placental promoter CpG methylation and messenger RNA expression of these angiogenic genes in preterm pregnancies. METHODS: We recruited 99 women delivering at term and 90 women delivering preterm. Plasma levels of angiogenic factors, vascular endothelial growth factor (VEGF), placental growth factor (PlGF), fms-related tyrosine kinase 1 (FLT-1), and kinase insert domain receptor (KDR) were analyzed by enzyme-linked immunosorbent assay. Expression levels and promoter CpG methylation of angiogenic genes in placentae were determined by quantitative real-time polymerase chain reaction and by the Sequenom EpiTYPER technology, respectively. RESULTS: Maternal VEGF and PlGF levels (P < .01 for both) were lower but soluble FLT-1 (sFLT-1) levels and sFLT-1-PlGF ratio (P < .05 for both) were higher in the preterm group. Placental VEGF expression (P < .05) was lower, and CpG site 14 in the VEGF promoter was hypermethylated (P < .05) in the preterm group. The KDR expression (P < .05) was higher in women delivering preterm. CONCLUSIONS: Our study provides first evidence of differential placental CpG methylation patterns and expression of VEGF, FLT-1, and KDR genes in women delivering preterm. This may explain the possible mechanism for angiogenic imbalance in the pathophysiology of preterm pregnancy.

Differential regulation of brain-derived neurotrophic factor in term and preterm preeclampsia.

Our earlier studies in preeclampsia (PE) suggest a causal relationship between altered angiogenic factors and birth outcomes. Recent studies suggest that brain-derived neurotrophic factor (BDNF) can stimulate angiogenesis. The present study examines the levels of maternal and cord BDNF in women with PE (n = 106; full term [n = 60] and preterm [n = 46]) and normotensive women (n = 95; control) delivering at term. Maternal BDNF levels were lower (P < .05) in women with PE when compared to normotensive women. Cord BDNF levels were higher (P < .01) in women with PE delivering at term, while it was lower (P < .01) in women delivering preterm. Maternal BDNF levels were negatively associated with systolic and diastolic blood pressure (P < .01 for both). Our data for the first time suggest a possible role for BDNF in the pathophysiology of PE. Differential regulation of cord BDNF levels in preterm PE suggests a need to follow-up children to assess the neurodevelopmental effects in later life.

Differential expression of human placental neurotrophic factors in preterm and term deliveries.

Neurotrophic factors such as brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are involved in development of the placenta and fetal brain. A series of human and animal studies in our department have shown that micronutrients (folic acid, vitamin B12) and omega 3 fatty acids like DHA are all interlinked in the one carbon cycle. Any alterations in one carbon components will lead to changes in methylation patterns that further affect the gene expression at critical periods of development resulting in complications during pregnancy. This may further contribute to risk for neurodevelopmental disorders in children born preterm. Therefore this study for the first time examines the mRNA levels from preterm and term placentae. A total number of 38 women delivering preterm (<37 weeks gestation) and 37 women delivering at term (=>37 weeks gestation) were recruited. The mRNA levels of BDNF and NGF were analyzed by real time quantitative polymerase chain reaction. Our results indicate that BDNF and NGF mRNA levels were lower in preterm group as compared to term group. There was a positive association of placental BDNF and NGF mRNA levels with cord plasma BDNF and NGF levels. The differential expression of BDNF and NGF gene in preterm placentae may also alter the vascular development in preterm deliveries. Our data suggests that the reduced mRNA levels of BDNF and NGF may possibly be a result of altered epigenetic mechanisms and may have an implication for altered fetal programming in children born preterm.

Differential placental methylation and expression of VEGF, FLT-1 and KDR genes in human term and preterm preeclampsia.

BACKGROUND: Preeclampsia, a pregnancy complication of placental origin is associated with altered expression of angiogenic factors and their receptors. Recently, there is considerable interest in understanding the role of adverse intrauterine conditions in placental dysfunction and adverse pregnancy outcomes. Since we have observed changes in placental global DNA methylation levels in preeclampsia, this study was undertaken to examine gene promoter CpG methylation and expression of several angiogenic genes.We recruited 139 women comprising, 46 normotensive women with term delivery (≥37 weeks), 45 women with preeclampsia delivering preterm (<37 weeks) and 48 women with preeclampsia delivering at term. Expression levels and promoter CpG methylation of VEGF, FLT-1 and KDR genes in placentae from respective groups were determined by Taqman-based quantitative real time PCR and by the Sequenom® EpiTYPER™ technology respectively. RESULTS: We observed several differentially methylated CpG sites in the promoter regions of VEGF, FLT-1 and KDR between the normotensive and preeclampsia groups. We specifically observed hypomethylated CpGs in the promoter region and an increased expression of VEGF gene between term and preterm preeclampsia. However, mean promoter CpG methylation could not account for the higher expression of FLT-1 and KDR in preterm preeclampsia as compared to normotensive group. CONCLUSIONS: Our data indicates altered DNA methylation patterns in the VEGF, FLT-1 and KDR genes in preeclampsia as compared to the normotensive group, which could be involved in the pathophysiology of preeclampsia. Hypomethylation of VEGF promoter and consequent upregulation of VEGF mRNA levels could be a compensatory mechanism to restore normal angiogenesis and blood flow in preterm preeclampsia. This study suggests a role of altered DNA methylation in placental angiogenesis and in determining adverse pregnancy outcomes.

Dynamic proteome in enigmatic preeclampsia: an account of molecular mechanisms and biomarker discovery.

The coevolution of genomics and proteomics has led to advancements in the field of diagnosis and molecular mechanisms of disease. Proteomics is now stepping into the field of obstetrics, where early diagnosis of pregnancy complication such as preeclampsia (PE) is imperative. PE is a multifactorial disease characterized by hypertension with proteinuria, which is a leading cause of maternal and neonatal morbidity and mortality occurring in 5-7% of pregnancies worldwide. This review discusses the probable molecular mechanisms that lead to PE and summarizes the proteomics research carried out in understanding the pathogenicity of PE, and for identifying the candidate biomarker for diagnosis of the disease.

Matrix metalloproteinase-1 and -9 in human placenta during spontaneous vaginal delivery and caesarean sectioning in preterm pregnancy.

Preterm birth is a major public health problem in terms of loss of life, long-term and short term disabilities worldwide. The process of parturition (both term and preterm) involves intensive remodelling of the extracellular matrix (ECM) in the placenta and fetal membranes by matrix metalloproteinases (MMPs). Our previous studies show reduced docosahexaenoic acid (DHA) in women delivering preterm. Further omega 3 fatty acids are reported to regulate MMP levels. This study was undertaken to examine the placental levels of MMPs and their association with placental DHA levels in women delivering preterm. The levels of MMP-1 and MMP-9 in 74 women delivering preterm (52 by spontaneous vaginal delivery and 22 by caesarean sectioning) and 75 women delivering at term (59 by spontaneous vaginal delivery and 16 by caesarean sectioning) were determined by enzyme-linked immunosorbent assay (ELISA) and their association with placental DHA was studied. Placental MMP-1 levels were higher (p<0.05) in women delivering preterm (both by spontaneous vaginal delivery and caesarean sectioning) as compared to those delivering at term. In contrast, placental MMP-9 levels in preterm pregnancies was higher (p<0.05) in women with spontaneous vaginal delivery while lower (p<0.05) in women delivering by caesarean sectioning. Low placental DHA was associated with higher placental MMP-9 levels. Our study suggests a differential effect of mode of delivery on the levels of MMPs from placenta. Further this study suggests a negative association of DHA and the levels of MMP-9 in human placenta although the mechanisms need further study.

Altered metabolism of maternal micronutrients and omega 3 fatty acids epigenetically regulate matrix metalloproteinases in preterm pregnancy: a novel hypothesis.

Preterm birth is an important perinatal health problem. Several possible mechanisms have been proposed but it may be important to have a testable mechanistic hypothesis that can explain the possible common mechanism for preterm births around the globe. Altered metabolism of micronutrients, like folic acid, vitamin B(12), zinc and copper are known to be associated with adverse pregnancy outcomes such as preterm birth. We have recently reported that increased oxidative stress and reduced docosahexaenoic acid levels are associated with preterm delivery. Matrix metalloproteinases and their tissue inhibitors play vital roles in extracellular matrix remodelling/degradation during pregnancy. Expression and the activity of matrix metalloproteinases have been shown to be regulated by oxidative stress and hyperhomocysteinemia. We have recently reported gestation dependant changes in placental global methylation levels. Here, we propose a novel hypothesis that altered maternal micronutrients (folic acid, vitamin B(12)), omega 3 fatty acids, and consequent oxidative stress lead to altered epigenetic mechanisms resulting in altered expression of matrix metalloproteinases and their tissue inhibitors during pregnancy. This may have important implications in the epigenetic programming of adult diseases since preterm infants are known to be at increased risk for neurodevelopmental, metabolic and cardiovascular dysfunctions in later life.

Reduced levels of placental long chain polyunsaturated fatty acids in preterm deliveries.

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<0.01) in women delivering preterm. There was a positive association of placental DHA with placental weight (p=0.036) and nervonic acid with head circumference (p=0.040) in the preterm group. Altered placental LCPUFA status exists in Indian mothers delivering preterm, which may influence the birth outcome.