linoleic-acid and Pre-Eclampsia

Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia, and may help to prevent preterm birth. This is an update of a review last published in 2014.. To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes.. We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (18 September 2017), and reference lists of retrieved studies.. We included randomised controlled trials (RCTs), including cluster-randomised trials, comparing high-dose calcium supplementation (at least 1 g daily of calcium) during pregnancy with placebo. For low-dose calcium we included quasi-randomised trials, trials without placebo, trials with cointerventions and dose comparison trials.. Two researchers independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two researchers assessed the evidence using the GRADE approach.. We included 27 studies (18,064 women). We assessed the included studies as being at low risk of bias, although bias was frequently difficult to assess due to poor reporting and inadequate information on methods.High-dose calcium supplementation (≥ 1 g/day) versus placeboFourteen studies examined this comparison, however one study contributed no data. The 13 studies contributed data from 15,730 women to our meta-analyses. The average risk of high blood pressure (BP) was reduced with calcium supplementation compared with placebo (12 trials, 15,470 women: risk ratio (RR) 0.65, 95% confidence interval (CI) 0.53 to 0.81; I² = 74%). There was also a reduction in the risk of pre-eclampsia associated with calcium supplementation (13 trials, 15,730 women: average RR 0.45, 95% CI 0.31 to 0.65; I² = 70%; low-quality evidence). This effect was clear for women with low calcium diets (eight trials, 10,678 women: average RR 0.36, 95% CI 0.20 to 0.65; I² = 76%) but not those with adequate calcium diets. The effect appeared to be greater for women at higher risk of pre-eclampsia, though this may be due to small-study effects (five trials, 587 women: average RR 0.22, 95% CI 0.12 to 0.42). These data should be interpreted with caution because of the possibility of small-study effects or publication bias. In the largest trial, the reduction in pre-eclampsia was modest (8%) and the CI included the possibility of no effect.The composite outcome maternal death or serious morbidity was reduced with calcium supplementation (four trials, 9732 women; RR 0.80, 95% CI 0.66 to 0.98). Maternal deaths were no different (one trial of 8312 women: one death in the calcium group versus six in the placebo group). There was an anomalous increase in the risk of HELLP syndrome in the calcium group (two trials, 12,901 women: RR 2.67, 95% CI 1.05 to 6.82, high-quality evidence), however, the absolute number of events was low (16 versus six).The average risk of preterm birth was reduced in the calcium supplementation group (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97; I² = 60%; low-quality evidence); this reduction was greatest amongst women at higher risk of developing pre-eclampsia (four trials, 568 women: average RR 0.45, 95% CI 0.24 to 0.83; I² = 60%). Again, these data should be interpreted with caution because of the possibility of small-study effects or publication bias. There was no clear effect on admission to neonatal intensive care. There was also no clear effect on the risk o. High-dose calcium supplementation (≥ 1 g/day) may reduce the risk of pre-eclampsia and preterm birth, particularly for women with low calcium diets (low-quality evidence). The treatment effect may be overestimated due to small-study effects or publication bias. It reduces the occurrence of the composite outcome 'maternal death or serious morbidity', but not stillbirth or neonatal high care admission. There was an increased risk of HELLP syndrome with calcium supplementation, which was small in absolute numbers.The limited evidence on low-dose calcium supplementation suggests a reduction in pre-eclampsia, hypertension and admission to neonatal high care, but needs to be confirmed by larger, high-quality trials.

Topics: Calcium; Dietary Supplements; Female; Humans; Hypertension; Linoleic Acid; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Premature Birth; Randomized Controlled Trials as Topic; Vitamin D; Vitamins

To determine the effect of low doses of linoleic acid and calcium on prostaglandin (PG) levels and the efficacy of this treatment in the prevention of preeclampsia.. In a randomized, double-blind, placebo-controlled study we treated 86 primigravidas with risk factors for preeclampsia (high biopsychosocial risk [above 3 points], positive roll-over test, and high mean blood pressure [above 85 mmHg)] with daily doses of either 450 mg linoleic acid and 600 mg calcium (n=43) or 450 mg starch and 600 mg lactose placebo (n=43) during the third trimester of pregnancy.. Four women in the experimental group (9.3%) developed preeclampsia compared with 16 (37.2%) controls (relative risk 0.25, 95% confidence interval 0.09, 0.69, P < .001). The median serum levels of PGE2 after 4 weeks of treatment increased by 106% in the experimental group (P=.03) and decreased by 33% in the control group (P=.02). The median ratio between thromboxane B2 and PGE2 decreased by 40% in the experimental group (P=.02) and increased by 18% in the control group (P=.14). No significant differences were observed in the median ratio between thromboxane B2 and 6-keto PGF1alpha in either group. No serious maternal or neonatal side effects of treatment occurred in either group.. The administration of low daily doses of linoleic acid and calcium during the third trimester of pregnancy reduced the incidence of preeclampsia significantly in women at high risk, possibly by correcting the PGE2 levels.

Topics: Calcium; Dietary Supplements; Dinoprostone; Double-Blind Method; Female; Humans; Linoleic Acid; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Prostaglandins; Socioeconomic Factors; Thromboxane B2

Topics: Calcium, Dietary; Dietary Supplements; Female; Humans; Linoleic Acid; Pre-Eclampsia; Pregnancy

Fatty acids (FA), especially arachidonic (AA, 20:4ω6) and docosahexaenoic (DHA, 22:6ω3) acids are critical for the health and development of infants. Colostrum FA composition has been examined in 101 lactating Tunisian women delivering prematurely using gas chromatography. Among polyunsaturated FA, linoleic acid predominated whereas each of the other polyunsaturated FA accounted for 1% or less of total FA. Colostrum AA and DHA contents were lower in women aged above 34 years compared to those less than 34 years. Preeclampsia was associated with lower DHA (0.40±0.22 vs. 0.53±0.27; p=0.018), but higher AA (1.14±0.44 vs. 0.93±0.30; p<0.006) and AA:DHA ratio (4.31±4.04 vs. 2.29±2.79; p<0.001). In multivariate analysis, colostrum DHA correlated with plasma DHA (β, 0.417; p=0.002), maternal age (β, -0.290; p=0.028) and preeclampsia (β, -0.270; p=0.042). Preterm colostrum FA profile in Tunisian women is comparable to those of other populations. Colostrum AA and DHA levels are altered in aged and pre-eclamptic women.

Topics: Adult; Arachidonic Acid; Chromatography, Gas; Colostrum; Docosahexaenoic Acids; Fatty Acids; Fatty Acids, Unsaturated; Female; Gestational Age; Humans; Infant, Premature; Linoleic Acid; Pre-Eclampsia; Pregnancy; Risk Factors; Tunisia; Young Adult

Preeclampsia is the main complication of pregnancy in developing countries. Calcium starting at 14 weeks of pregnancy is indicated to prevent the disease. Recent advances in prevention of preeclampsia endorse the addition of conjugated linoleic acid.. To estimate the protective effect from calcium alone, compared to calcium plus conjugated linoleic acid in nulliparous women at risk of preeclampsia.. A case-control design nested in the cohort of nulliparous women attending antenatal care from 2010 to 2014. The clinical histories of 387 cases of preeclampsia were compared with 1,054 normotensive controls. The exposure was prescriptions for calcium alone, the first period, or calcium plus conjugated linoleic acid, the second period, from 12 to 16 weeks of gestational age to labor. Confounding variables were controlled, allowing only nulliparous women into the study and stratifying by age, education and ethnic group.. The average age was 26.4 yrs old (range= 13-45), 85% from mixed ethnic backgrounds and with high school education. There were no differences between women who received calcium carbonate and those who did not (OR= 0.96; 95% CI= 0.73-1.27). The group of adolescents (13 to 18 years old) in the calcium plus conjugated linoleic acid was protected for preeclampsia (OR= 0.00; 95% CI= 0.00-0.44) independent of the confounder variables.. 1. Calcium supplementation during pregnancy did not have preventive effects on preeclampsia. 2. Calcium plus Conjugated Linoleic acid provided to adolescents was observed to have preventive effect on Preeclampsia.. La preeclampsia es la principal causa de mortalidad materna y bajo peso al nacer en países en vías de desarrollo. Empezar la suplementación de calcio en la semana 14 de gestación es indicada para prevenir la enfermedad. Recientes avances en prevención de preeclampsia han sugerido la suplementación de calcio y la combinación de calcio con ácido linoleico conjugado.. Estimar el efecto protector de la suplementación de calcio (CC), comparado con la suplementación de calcio más ácido linoleico conjugado (CC+ALC) en mujeres embarazadas primigravidas con relación al desarrollo de preeclampsia.. Se realizó un estudio de casos y controles anidado en una cohorte retrospectiva de mujeres embarazadas primigravidas que asistieron al programa de control prenatal entre el año 2010 hasta el años 2014. La historia clínica de 387 casos de preeclampsia fueron comparadas con 1,054 controles en pacientes embarazadas primigestantes, normotensas. Las gestantes expuestas fueron consideradas como aquellas gestantes que recibieron solo calcio, en el primer periodo de evaluación, o calcio más ácido linoleico conjugado, segundo periodo de evaluación, desde las semanas 12 a la 16 del embarazo. Los posibles factores de confusión se controlaron admitiendo solo las primigestantes y estratificando, por edad, educación y grupo étnico de la paciente.. La edad promedio de las pacientes fue de 26.4 años (rango 13-45), 85% con etnia mestiza y educación secundaria completa. La exposición a CC+ALC tuvo un efecto protector en las adolescentes (13 a 18 años) (OR= 0.00, IC 95%= 0.00-0.44;. 1. La suplementación de solo calcio durante el embarazo no tuvo efecto preventivo para la preeclampsia, 2. La suplementación con calcio y ácido linoleico conjugado previno la aparición de preeclampsia en adolescentes.

Topics: Adolescent; Adult; Age Factors; Calcium Carbonate; Case-Control Studies; Cohort Studies; Drug Therapy, Combination; Female; Humans; Linoleic Acid; Middle Aged; Parity; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Second; Young Adult

Neutrophils infiltrate systemic vasculature of women with preeclampsia, so we tested the hypothesis that factors in plasma of preeclamptic women activate endothelial cells to produce IL-8 resulting in transendothelial migration of neutrophils. Neutrophil migration was studied using the Transwell system. An endothelial cell line was grown to confluence on the inserts and treated with 10% plasma from normal nonpregnant (NNP), normal pregnant (NP) and preeclamptic (PE) women or with an oxidizing solution containing linoleic acid (OxLA). Compared to medium control, NNP plasma or NP plasma, PE plasma significantly stimulated IL-8 and neutrophil migration which was inhibited by vitamins E and C or IL-8 neutralizing antibody. Compared to medium control or LA, OxLA stimulated IL-8 and neutrophil migration which was inhibited by vitamins E and C or IL-8 antibody.. Factors present in plasma of preeclamptic women stimulate transendothelial migration of neutrophils which is due to induction of oxidative stress and production of IL-8.

Topics: Adult; Antioxidants; Ascorbic Acid; Cell Line; Cell Migration Assays, Leukocyte; Cell Movement; Coculture Techniques; Endothelial Cells; Female; Humans; Interleukin-8; Linoleic Acid; Neutrophils; Oxidation-Reduction; Oxidative Stress; Pre-Eclampsia; Pregnancy; Vitamin E

Pregnant women with the vascular complication of preeclampsia show altered lipid metabolism characterized by elevated circulating triglycerides and nonesterified free fatty acids. We have compared the effect of maternal plasma from women with and without preeclampsia on cultured vascular endothelial cells and determined whether these plasma-induced changes were reproduced with free fatty acid solutions of palmitic, oleic and linoleic acid, representative of circulating levels reported in preeclampsia.. Lipid accumulation was quantified by oil-red O staining, apoptosis by terminal dUTP nick-end labelling (TUNEL) and the measurement of mitochondrial redox capacity, and membrane potential recorded using MTT reduction and JC-1 accumulation for human umbilical vein endothelial cells (HUVECs) exposed to plasma and free fatty acids.. Lipid droplet accumulation was significantly increased in cultured HUVECs conditioned with maternal plasma from pregnancies with preeclampsia compared with normal uncomplicated controls. This increase was replicated following exposure to free fatty acids at the combined concentrations defined in preeclampsia. Plasma from these women also caused a significant decrease in mitochondrial dehydrogenase activity, a marked reduction in mitochondrial membrane potential and an increase in apoptosis compared with normal pregnancy. Again these effects were reproduced using free fatty acids in combination at the levels previously associated with preeclampsia.. These findings support the concept of a circulating pathogenic factor for preeclampsia and highlight the possibility that this factor is not a single compound but perhaps the combined elevation of the free fatty acids palmitic, oleic and linoleic acid in the maternal circulation.

Topics: Apoptosis; Case-Control Studies; Cells, Cultured; Endothelial Cells; Fatty Acids, Nonesterified; Female; Humans; Linoleic Acid; Lipid Metabolism; Membrane Potential, Mitochondrial; Oleic Acid; Oxidation-Reduction; Palmitic Acid; Pre-Eclampsia; Pregnancy

Preeclampsia has many characteristics similar to the metabolic syndrome. One of these is aberrant lipid metabolism. We studied free fatty acid (FFA) profiles at baseline and after oral glucose load in 21 preeclamptic and 11 normotensive pregnant women. Insulin sensitivity was measured by intravenous glucose tolerance test. We found that serum total FFA concentrations at baseline were 67% higher in preeclamptic than in normotensive pregnancies (P=0.0002). The difference between the two groups was largest in the concentrations of oleic (75%), linoleic (129%) and arachidonic (315%) acids. Oral intake of glucose suppressed total FFA in preeclamptic women by 40% (95% CI 32.1-46.1%, P<0.0001) but only 24% in control women (95% CI 0.01-42.0%, P=0.045). Insulin sensitivity, which in preeclamptic women was 37% lower (P=0.009), was unrelated to total or any individual FFA concentration. We concluded that preeclamptic women have higher circulating FFA concentrations, which despite insulin resistance are suppressed by oral glucose loading.

Topics: Arachidonic Acid; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Linoleic Acid; Oleic Acid; Pre-Eclampsia; Pregnancy

Preeclampsia is associated with oxidative stress, elevated plasma levels of linoleic acid (LA), and increased vascular smooth muscle expression of the inflammatory chemokine, interleukin-8 (IL-8). We hypothesized that increased levels of LA under conditions of oxidative stress would increased production of IL-8 by vascular smooth muscle cells because LA is the dietary precursor to arachidonic acid (AA) and its metabolites that mediate inflammation. We also hypothesized that oleic acid (OA), which is not metabolized to AA metabolites, would not increase IL-8 under conditions of oxidative stress.. To test this hypothesis, we cultured placental arterial smooth muscle (PASM) cells with an oxidizing solution enriched with LA (OxLA) or OA (OxOA). Media concentrations were analyzed for IL-8 and AA metabolites. Inhibitors were used to block the lipoxygenase and cyclooxygenase pathways.. Exposure of cells to OxLA, but not to OxOA, significantly increased production of IL-8. OxLA also significantly increased production of AA metabolites. Nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway, blocked IL-8 and leukotriene B4 (LTB4) production induced by OxLA, whereas indomethacin, an inhibitor of the cyclooxygenase pathway, blocked IL-8, prostaglandin E2 (PGE2), and thromboxane B2 (TXB2) production. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated gene expression in PASM cells for representative lipoxygenase (LTB4) and cyclooxygenase (thromboxane) metabolite receptors.. PASM cells produced IL-8 in response to LA, but not OA, under conditions of oxidative stress. The IL-8 response was mediated by AA metabolites.

Topics: Arachidonic Acid; Cells, Cultured; Female; Gene Expression; Humans; Interleukin-8; Leukotriene B4; Linoleic Acid; Lipoxygenase; Muscle, Smooth, Vascular; Oleic Acid; Oxidative Stress; Pre-Eclampsia; Pregnancy; Prostaglandin-Endoperoxide Synthases; Reverse Transcriptase Polymerase Chain Reaction; Thromboxane B2; Up-Regulation

The activities of placental superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but not catalase, are lower than normal in preeclampsia, which could contribute to the uncontrolled placental production of lipid peroxides and thromboxane (TX). Oxidative stress, hyperlipidemia and increased iron levels in the maternal compartment in preeclampsia could be responsible for these placental changes by causing oxidative stress in the placenta.. We tested this possibility in vitro by exposing a trophoblast-like cell line, ED27, to a combination of linoleic acid (LA, 90 microM) and an oxidizing solution composed of hypoxanthine, xanthine oxidase and ferrous sulfate (OxLA) for 6 days. For these studies, the cells were treated with dexamethasone (10-8 M) for the first 72 hr. This was done to differentiate the cells into a phenotype more like syncytiotrophoblast cells as evidenced by production of beta-human chorionic gonadotropin (beta-hCG).. After 6 days of exposure to OxLA, the activities of SOD and GSH-Px were significantly decreased as compared to exposure to LA alone. In contrast, catalase activity was increased by OxLA. The OxLA-induced decreases in SOD and GSH-Px activities were attenuated by deferoxamine, an iron chelator, suggesting a role for Fe2+ in the decreased activities. Compared to LA, OxLA significantly increased TX secretion and lipid peroxidation in cells and media at 2, 4 and 6 days. Deferoxamine inhibited the OxLA-induced increase in lipid peroxidation, but not the increase in TX. Isolation of trophoblast cells and villous core tissue from term placentas verified that antioxidant enzyme activity was localized primarily to the trophoblast cell compartment lending validity to the in vitro findings.. These data mimic the changes in placental SOD, GSH-Px, catalase, TX and lipid peroxidation that occur in preeclampsia suggesting that maternal hyperlipidemia and increased iron levels may be responsible for placental oxidative stress and abnormalities in antioxidants and thromboxane.

Topics: Adult; Analysis of Variance; Catalase; Cell Line; Chorionic Gonadotropin; Deferoxamine; Female; Ferrous Compounds; Glutathione Peroxidase; Humans; Iron Chelating Agents; Linoleic Acid; Lipid Peroxidation; Oxidative Stress; Pre-Eclampsia; Pregnancy; Superoxide Dismutase; Thromboxane B2; Trophoblasts; Xanthine Oxidase

Recently, we showed that levels of circulating free fatty acids are increased in women who later develop pre-eclampsia long before the clinical onset of the disease. Among the serum free fatty acids, oleic-, linoleic-, and palmitic acid were found to be increased by 37, 25 and 25%, respectively. In the present study we asked if these free fatty acids can interfere with endothelial cell functions. Cultured endothelial cells were exposed to linoleic-, oleic- and palmitic acid in concentrations ranging from 0.016 to 0.133 mumol ml-1, resulting in molar ratios of free fatty acids to albumin of 0.2-1.6. We found that among these fatty acids, linoleic acid reduced the thrombin-stimulated prostacyclin release by 30-60%, oleic acid by 10-30%, whereas palmitic acid had no effect. Endothelial cells incubated in presence of linoleic acid showed a concentration-dependent reduction in prostacyclin release in response to thrombin, and cells incubated with linoleic acid for up to 28 h, showed a reduced thrombin-induced prostacyclin release at every time point. Endothelial level of cGMP mainly reflected the synthesis of endothelium-derived relaxing factor/nitrogen monoxide (EDRF/NO), since blocking of the endogenous production of EDRF/NO with N-omega-nitro-L-arginine, resulted in about 90% reduction in cGMP-content of the endothelial cells. Incubation with linoleic acid reduced the endothelial cGMP level by 70%. Linoleic acid reduced the endothelial cells ability to inhibit platelet aggregation by 10-45%, (p = 0.0019). It was concluded that linoleic acid impedes the ability of the endothelial cells to produce prostacyclin and cGMP, and to inhibit platelet aggregation.

Topics: Cells, Cultured; Cyclic GMP; Endothelium, Vascular; Epoprostenol; Fatty Acids, Nonesterified; Female; Humans; Linoleic Acid; Linoleic Acids; Nitric Oxide; Oleic Acid; Oleic Acids; Palmitic Acid; Palmitic Acids; Platelet Aggregation; Pre-Eclampsia; Pregnancy

The biochemical essential fatty acid (EFA) status of neonates born after normal and hypertensive pregnancies (PIH) and that of their mothers was assessed by measuring the fatty acid composition of phospholipids (PL), triglycerides (TG) and cholesterol esters (CE) of umbilical cord serum and maternal serum, respectively. Relative contents of linoleic acid of serum PL and CE were significantly lower in mothers with PIH compared to normal pregnancies. Most other (n-6) polyenes in PL tended to be higher under hypertensive conditions. Total maternal (n-3) polyenes of serum PL were significantly higher in PIH, mainly due to clupanodonic acid, 22:5 (n-3), and cervonic acid, 22:6 (n-3). Total maternal (n-7) and (n-9) fatty acids were also significantly higher in PIH (PL and CE). The results indicate that PIH is associated with a relative increased unsaturation of maternal serum PL, which might facilitate the placental transfer of long-chain, polyunsaturated fatty acids. As a result, the neonatal EFA status after PIH only slightly differs from normal.

Topics: Cholesterol Esters; Fatty Acids; Fatty Acids, Essential; Female; Fetal Blood; Humans; Infant, Newborn; Linoleic Acid; Linoleic Acids; Maternal-Fetal Exchange; Phospholipids; Postpartum Period; Pre-Eclampsia; Pregnancy; Triglycerides

Fatty acid patterns were determined for maternal and cord sera from normal and preeclamptic pregnancies using gas liquid chromatography. Ten normal and 11 preeclamptic maternal sera were used; 6 preeclamptic and 6 normal cord sera were measured. Fatty acid patterns were measured in the nonesterified fatty acids (NEFA), the triglycerides (TG), the cholesterol esters (CE), and the phospholipids (PL). Preeclampsia showed significant differences in the essential fatty acid patterns in the maternal and cord sera compared to normal pregnancy. Oleic acid, an early indicator of essential fatty acid deficiency, made up a significantly greater proportion of preeclamptic cord blood NEFA, TG, and PL than in normal cord blood. Abnormalities in essential fatty acid patterns may be associated with decreased prostacyclin production and dysmaturity which may be seen with preeclampsia.

Topics: Arachidonic Acid; Arachidonic Acids; Cholesterol Esters; Fatty Acids, Essential; Fatty Acids, Nonesterified; Female; Humans; Linoleic Acid; Linoleic Acids; Maternal-Fetal Exchange; Oleic Acid; Oleic Acids; Phospholipids; Pre-Eclampsia; Pregnancy; Triglycerides

As a part of a larger study, 15 healthy primigravidas were studied from 28 weeks gestation until 3 days after deliver. In 6 of these women pre-eclampsia (PET) developed; the remaining 9 subjects, who were age matched had normal pregnancies. Plasma phospholipid-esterified 18:2(9,11):18:2(9,12)fatty acids were measured by high performance liquid chromatography (HPLC). The ratio of 18:2(9,11):18:2(9,12)linoleic acid was significantly higher in the PET group than in the normotensive group at 28 weeks' gestation--that is before the onset of symptoms and signs of PET. The ratio remained significantly higher in the PET group than in the normotensive group until deliver, except at 30 weeks when the difference between the ratios just failed to reach statistical significance. It is suggested that measurement of the ratio of 18:2(9,11) to 18:2(9,12)linoleic acid in plasma phospholipids may be useful as a predictor of the likely development of PET.

Topics: Chromatography, High Pressure Liquid; Female; Humans; Isomerism; Linoleic Acid; Linoleic Acids; Phospholipids; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Prognosis