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Maternal Omega-3 Nutrition, Placental Transfer and Fetal Brain Development in Gestational Diabetes and Preeclampsia.
Devarshi, PP, Grant, RW, Ikonte, CJ, Hazels Mitmesser, S
Nutrients. 2019;(5)
Abstract
Omega-3 fatty acids, particularly docosahexaenoic fatty acid (DHA), are widely recognized to impact fetal and infant neurodevelopment. The impact of DHA on brain development, and its inefficient synthesis from the essential alpha-linolenic acid (ALA), has led to recommended DHA intakes of 250-375 mg eicosapentaenoic acid + DHA/day for pregnant and lactating women by the Dietary Guidelines for Americans. Despite these recommendations, the intake of omega-3s in women of child-bearing age in the US remains very low. The low maternal status of DHA prior to pregnancy could impair fetal neurodevelopment. This review focuses on maternal omega-3 status in conditions of gestational diabetes mellitus (GDM) and preeclampsia, and the subsequent impact on placental transfer and cord blood concentration of omega-3s. Both GDM and preeclampsia are associated with altered maternal omega-3 status, altered placental omega-3 metabolism, reduced cord blood omega-3 levels and have an impact on neurodevelopment in the infant and on brain health later in life. These findings indicate lower DHA exposure of the developing baby may be driven by lower placental transfer in both conditions. Thus, determining approaches which facilitate increased delivery of DHA during pregnancy and early development might positively impact brain development in infants born to mothers with these diseases.
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Effect of vitamin D3 supplementation in pregnancy on risk of pre-eclampsia - Randomized controlled trial.
Ali, AM, Alobaid, A, Malhis, TN, Khattab, AF
Clinical nutrition (Edinburgh, Scotland). 2019;(2):557-563
Abstract
BACKGROUND Vitamin D plays pivotal role in decidualization and implantation of the placenta. Recent researches have shown that low level of vitamin D3 "25-hydroxyvitamin D (25[OH]D)" in serum is a risk factor for pre-eclampsia. Latest evidence supports role of vitamin D3 deficiency treatment in reducing the risk of pre-eclampsia. The aim of this study is to determine the effect of antenatal supplementation of vitamin D3 on the risk of pre-eclampsia and to explore the dose effect in attaining the vitamin D3 normal level. METHOD An open labelled randomized controlled study was conducted on 179 pregnant women presenting in King Fahad Medical City antenatal clinic from Oct 2012-Oct 2015. Patients with age less than 20 years or more than 40 years, pregnancy with fetal anomalies, history of hypertension, pre-eclampsia, recurrent miscarriage, chronic renal or hepatic disease and malignancy were excluded from the study. Serum 25[OH]D was analysed during the first trimester (between 6 and 12 weeks of pregnancy). Patients with vitamin D3 deficiency (serum levels <25 nmol/L) were included in the study and randomized for vitamin D3 supplementation 400 IU (Group 1) versus 4000 IU (Group 2). Both groups were compared for the prevalence of pre-eclampsia and dose effect on vitamin D level. RESULTS Of 179 gravidae enrolled, 164 completed the trial. Mean maternal 25[OH]D was significantly increased in group 2 from 16.3 ± 5 nmol/mL to 72.3 ± 30.9 nmol/mL compared with group 1 from 17.5 ± 6.7 nmol/mL to 35.3 ± 20.7 nmol/mL (p > 0.0001). The relative risk reduction (RRR) for attaining ≥75 nmol/L before delivery was significantly higher (RRR 93.2 [CI 79-98] when treated with 4000 IU. The total incidence of pre-eclampsia in the study population was 4.3%. In comparison to group 1, the group 2 reported fewer pre-eclampsia events during the study period (8.6% versus 1.2%; p < 0.05). The total number of IUGRs was lesser in the group 2 (9.6%) versus group 1 (22.2%); p = 0.027. However, other obstetric outcomes were comparable between both groups. CONCLUSION Vitamin D supplementation in the deficient group reduces the risk of pre-eclampsia and IUGR in a dose dependant manner. However larger clinical trials are essential to investigate optimum dosage of vitamin D3 in this group.
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Effect of preeclampsia on human milk cytokine levels.
Freitas, NA, Santiago, LTC, Kurokawa, CS, Meira Junior, JD, Corrente, JE, Rugolo, LMSS
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(13):2209-2213
Abstract
INTRODUCTION Preeclampsia (PE) is a systemic inflammatory disease, and its effect on human milk immune components is poorly understood. OBJECTIVE To investigate whether PE affects human milk cytokine levels. METHODS This was a prospective observational study involving mothers diagnosed with PE and with singleton pregnancy with no fetal malformation. The following cases were excluded: diabetes, chorioamnionitis, use of illicit drugs and alcohol, mastitis and congenital infection. In total, 228 mothers were studied and divided into two groups matched by gestational age: PE (n = 114) and normotensive (control, n = 114). Colostrum was collected from 24-72 hours postpartum, and mature milk was collected at the end of the first month. Cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12, and TNF-α) were measured using flow cytometry. A generalized linear model with a gamma distribution was used to analyze the differences between groups versus time interaction. RESULTS The mean gestational age was 36 weeks. Increased IL-1 and IL-6 levels and reduced IL-12 levels in the colostrum were detected in PE, while in the mature milk, the IL-6 and IL-8 levels were lower than those of the control group. CONCLUSIONS PE is associated with increased levels of inflammatory cytokines in colostrum and decreased levels in mature milk.
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Calcium supplementation commencing before or early in pregnancy, for preventing hypertensive disorders of pregnancy.
Hofmeyr, GJ, Manyame, S, Medley, N, Williams, MJ
The Cochrane database of systematic reviews. 2019;(9):CD011192
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Abstract
BACKGROUND The hypertensive disorders of pregnancy include pre-eclampsia, gestational hypertension, chronic hypertension, and undefined hypertension. Pre-eclampsia is considerably more prevalent in low-income than in high-income countries. One possible explanation for this discrepancy is dietary differences, particularly calcium deficiency. Calcium supplementation in the second half of pregnancy reduces the serious consequences of pre-eclampsia, but has limited effect on the overall risk of pre-eclampsia. It is important to establish whether calcium supplementation before, and in early pregnancy (before 20 weeks' gestation) has added benefit. Such evidence could count towards justification of population-level interventions to improve dietary calcium intake, including fortification of staple foods with calcium, especially in contexts where dietary calcium intake is known to be inadequate. This is an update of a review first published in 2017. OBJECTIVES To determine the effect of calcium supplementation, given before or early in pregnancy and for at least the first half of pregnancy, on pre-eclampsia and other hypertensive disorders, maternal morbidity and mortality, and fetal and neonatal outcomes. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Trials Register (31 July 2018), PubMed (13 July 2018), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP; 31 July 2018), and reference lists of retrieved studies. SELECTION CRITERIA Eligible studies were randomised controlled trials (RCT) of calcium supplementation, including women not yet pregnant, or women in early pregnancy. Cluster-RCTs, quasi-RCTs, and trials published as abstracts were eligible, but we did not identify any. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. They assessed the quality of the evidence for key outcomes using the GRADE approach. MAIN RESULTS Calcium versus placeboWe included one study (1355 women), which took place across multiple hospital sites in Argentina, South Africa, and Zimbabwe. Most analyses were conducted only on 633 women from this group who were known to have conceived, or on 579 who reached 20 weeks' gestation; the trial was at moderate risk of bias due to high attrition rates pre-conception. Non-pregnant women with previous pre-eclampsia received either calcium 500 mg daily or placebo, from enrolment until 20 weeks' gestation. All participants received calcium 1.5 g daily from 20 weeks until birth.Primary outcomes: calcium supplementation commencing before conception may make little or no difference to the risk of pre-eclampsia (69/296 versus 82/283, risk ratio (RR) 0.80, 95% confidence interval (CI) 0.61 to 1.06; low-quality evidence). For pre-eclampsia or pregnancy loss or stillbirth (or both) at any gestational age, calcium may slightly reduce the risk of this composite outcome, however the 95% CI met the line of no effect (RR 0.82, 95% CI 0.66 to 1.00; low-quality evidence). Supplementation may make little or no difference to the severe maternal morbidity and mortality index (RR 0.93, 95% CI 0.68 to 1.26; low-quality evidence), pregnancy loss or stillbirth at any gestational age (RR 0.83, 95% CI 0.61 to 1,14; low-quality evidence), or caesarean section (RR 1.11, 95% CI 0.96 to 1,28; low-quality evidence).Calcium supplementation may make little or no difference to the following secondary outcomes: birthweight < 2500 g (RR 1.00, 95% CI 0.76 to 1.30; low-quality evidence), preterm birth < 37 weeks (RR 0.90, 95% CI 0.74 to 1.10), early preterm birth < 32 weeks (RR 0.79, 95% CI 0.56 to 1.12), and pregnancy loss, stillbirth or neonatal death before discharge (RR 0.82, 95% CI 0.61 to 1.10; low-quality evidence), no conception, gestational hypertension, gestational proteinuria, severe gestational hypertension, severe pre-eclampsia, severe pre-eclamptic complications index. There was no clear evidence on whether or not calcium might make a difference to perinatal death, or neonatal intensive care unit admission for > 24h, or both (RR 1.11, 95% CI 0.77 to 1.60; low-quality evidence).It is unclear what impact calcium supplementation has on Apgar score < 7 at five minutes (RR 0.43, 95% CI 0.15 to 1.21; very low-quality evidence), stillbirth, early onset pre-eclampsia, eclampsia, placental abruption, intensive care unit admission > 24 hours, maternal death, hospital stay > 7 days from birth, and pregnancy loss before 20 weeks' gestation. AUTHORS' CONCLUSIONS The single included study suggested that calcium supplementation before and early in pregnancy may reduce the risk of women experiencing the composite outcome pre-eclampsia or pregnancy loss at any gestational age, but the results are inconclusive for all other outcomes for women and babies. Therefore, current evidence neither supports nor refutes the routine use of calcium supplementation before conception and in early pregnancy.To determine the overall benefit of calcium supplementation commenced before or in early pregnancy, the effects found in the study of calcium supplementation limited to the first half of pregnancy need to be added to the known benefits of calcium supplementation in the second half of pregnancy.Further research is needed to confirm whether initiating calcium supplementation pre- or in early pregnancy is associated with a reduction in adverse pregnancy outcomes for mother and baby. Research could also address the acceptability of the intervention to women, which was not covered by this review update.
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Abnormal expression and clinical significance of 25-hydroxyvitamin D and sFlt-1 in patients with preeclampsia.
Chen, X, Xi, X, Cui, F, Wen, M, Hong, A, Hu, Z, Ni, J
The Journal of international medical research. 2019;(10):4673-4682
Abstract
OBJECTIVE To determine the association between levels of serum 25-hydroxyvitamin D (25[OH]D) and soluble fms-like tyrosine kinase 1 (sFlt-1) in patients with preeclampsia. METHODS Clinical and demographic data were collected from patients with preeclampsia and healthy pregnant controls. Serum 25(OH)D and sFlt-1 levels were evaluated by enzyme-linked immunosorbent assay and their correlations were determined using Spearman’s rank correlation coefficient. Associations between serum 25(OH)D and sFlt-1 levels and disease severity and clinical parameters were evaluated. RESULTS Significantly lower serum 25(OH)D and higher sFlt-1 levels were observed in patients with preeclampsia (n = 100) versus controls (n = 100), and 25(OH)D was inversely correlated with sFlt-1 in patients with preeclampsia. Serum 25(OH)D levels were reduced, while sFlt-1 concentration was increased in patients with severe versus mild preeclampsia. Serum 25(OH)D levels were reduced in late-onset versus early-onset severe preeclampsia. Patients with preeclampsia who had lower serum 25(OH)D or elevated sFlt-1 levels showed significantly higher blood pressure indexes versus those with higher 25(OH)D or lower sFlt-1. CONCLUSIONS Low serum 25(OH)D and high sFlt-1 may be candidate biomarkers for preeclampsia diagnosis and prognosis.
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Risk of Ischemic Placental Disease in Relation to Family History of Preeclampsia.
Ananth, CV, Jablonski, K, Myatt, L, Roberts, JM, Tita, ATN, Leveno, KJ, Reddy, UM, Varner, MW, Thorp, JM, Mercer, BM, et al
American journal of perinatology. 2019;(6):624-631
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OBJECTIVE To assess the risk of ischemic placental disease (IPD) including preeclampsia, small for gestational age (SGA), and abruption, in relation to preeclampsia in maternal grandmother, mother, and sister(s). STUDY DESIGN We performed a secondary analysis of data from a randomized trial of vitamins C and E for preeclampsia prevention. Data on family history of preeclampsia were based on recall by the proband. The associations between family history of preeclampsia and the odds of IPD were evaluated from alternating logistic regressions. RESULTS Of the 9,686 women who delivered nonmalformed, singleton live births, 17.1% had IPD. Probands provided data on preeclampsia in 55.5% (n = 5,374) on all three family members, 26.5% (n = 2,562) in mother and sister(s) only, and 11.6% (n = 1,125) in sister(s) only. The pairwise odds ratio (pOR) of IPD was 1.16 (95% confidence interval [CI]: 1.00-1.36) if one or more of the female relatives had preeclampsia. The pORs of preeclampsia were 1.54 (95% CI: 1.12-2.13) and 1.35 (95% CI: 1.03-1.77) if the proband's mother or sister(s) had a preeclamptic pregnancy, respectively, but no associations were seen for SGA infant or abruption. CONCLUSION This study suggests that IPD may share a predisposition with preeclampsia, suggesting a familial inheritance.
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Evidence of an Association Between Vitamin D Deficiency and Preterm Birth and Preeclampsia: A Critical Review.
Woo, J, Giurgescu, C, Wagner, CL
Journal of midwifery & women's health. 2019;(5):613-629
Abstract
Vitamin D deficiency has been associated with adverse pregnancy and birth outcomes such as increased risk for preterm birth and preeclampsia. This state of the science review analyzed recently published meta-analyses and relevant studies that have evaluated the association between vitamin D deficiency and preeclampsia or preterm birth. The results suggest that a positive association between vitamin D deficiency and preterm birth exists. However, the findings of the relationship between vitamin D deficiency and preeclampsia were inconclusive, possibly because of the need for supplementation to occur prior to placentation. This may be because of a lack of studies with ethnic minority populations, who are more likely to experience vitamin D deficiency, and inadequate supplementation doses used for treatment of vitamin D deficiency. Health care providers should screen pregnant women at risk for vitamin D deficiency and supplement women accordingly based on their vitamin D status. Lastly, well-designed and standardized clinical trials need to include large cohorts of minority pregnant women to establish the impact of vitamin D supplementation on improving preterm birth and preeclampsia risk in pregnancy.
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Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial.
Wen, SW, White, RR, Rybak, N, Gaudet, LM, Robson, S, Hague, W, Simms-Stewart, D, Carroli, G, Smith, G, Fraser, WD, et al
BMJ (Clinical research ed.). 2018;:k3478
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OBJECTIVE To determine the efficacy of high dose folic acid supplementation for prevention of pre-eclampsia in women with at least one risk factor: pre-existing hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia in a previous pregnancy, or body mass index ≥35. DESIGN Randomised, phase III, double blinded international, multicentre clinical trial. SETTING 70 obstetrical centres in five countries (Argentina, Australia, Canada, Jamaica, and UK). PARTICIPANTS 2464 pregnant women with at least one high risk factor for pre-eclampsia were randomised between 2011 and 2015 (1144 to the folic acid group and 1157 to the placebo group); 2301 were included in the intention to treat analyses. INTERVENTION Eligible women were randomised to receive either daily high dose folic acid (four 1.0 mg oral tablets) or placebo from eight weeks of gestation to the end of week 16 of gestation until delivery. Clinicians, participants, adjudicators, and study staff were masked to study treatment allocation. MAIN OUTCOME MEASURE The primary outcome was pre-eclampsia, defined as hypertension presenting after 20 weeks' gestation with major proteinuria or HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). RESULTS Pre-eclampsia occurred in 169/1144 (14.8%) women in the folic acid group and 156/1157 (13.5%) in the placebo group (relative risk 1.10, 95% confidence interval 0.90 to 1.34; P=0.37). There was no evidence of differences between the groups for any other adverse maternal or neonatal outcomes. CONCLUSION Supplementation with 4.0 mg/day folic acid beyond the first trimester does not prevent pre-eclampsia in women at high risk for this condition. TRIAL REGISTRATION Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.
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Nutritional approach to preeclampsia prevention.
Achamrah, N, Ditisheim, A
Current opinion in clinical nutrition and metabolic care. 2018;(3):168-173
Abstract
PURPOSE OF REVIEW Although not fully understood, the physiopathology of preeclampsia is thought to involve an abnormal placentation, diffuse endothelial cell dysfunction and increased systemic inflammation. As micronutrients play a key role in placental endothelial function, oxidative stress and expression of angiogenic factors, periconceptional micronutrient supplementation has been proposed to reduce the risk of preeclampsia. However, recent studies reported conflicting results. RECENT FINDINGS Calcium intake (>1 g/day) may reduce the risk of preeclampsia in women with low-calcium diet. Data from recently updated Cochrane reviews did not support routine supplementation of vitamins C, E or D for either the prevention or treatment of preeclampsia. Evidences are also poor to support zinc or folic acid supplementation for preeclampsia prevention. Dark chocolate, flavonoid-rich food, and long-chain polyunsaturated fatty acids might also be candidates for prevention of preeclampsia. SUMMARY Through antioxidant, anti-inflammatory or vasoactive proprieties, micronutrients are good candidates for preeclampsia prevention. Calcium supplementation is recommended to prevent preeclampsia in women with low-calcium intake. Despite positive clinical and in-vitro data, strong evidence to support periconceptional supplementation of other micronutrients for preeclampsia risk-reduction is still lacking. Further studies are also needed to evaluate the benefit of nutritional supplementation such as chocolate and long-chain polyunsaturated fatty acids.
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Preeclampsia and gestational weight gain in the Norwegian Fit for Delivery trial.
Hillesund, ER, Seland, S, Bere, E, Sagedal, LR, Torstveit, MK, Lohne-Seiler, H, Vistad, I, Øverby, NC
BMC research notes. 2018;(1):282
Abstract
OBJECTIVE Excessive gestational weight gain is linked to risk of preeclampsia, but it is not clear whether the association is causal. The purpose of this paper was to examine gestational weight gain in the Norwegian Fit for Delivery study among women who developed preeclampsia compared to those who did not, and to further explore associations between weight gain and preeclampsia by including data on body composition (bioimpedance) assessed in the last trimester of pregnancy. RESULTS A total of 550 women were eligible for the study. Women who developed preeclampsia gained more weight than women who did not (difference 3.7 kg, p = 0.004), with a 3.5 kg difference in total body water observed in week 36 (p = 0.040). Adjusted for age, education, pre-pregnancy body mass index (BMI), randomization, and fat mass, a one kg increase in GWG was associated with 1.3 times higher odds of preeclampsia (OR: 1.31, 95% CI 1.15-1.49, p < 0.001). An independent inverse association between fat mass in week 36 and odds of preeclampsia was observed (OR: 0.79, 95% CI 0.68-0.92, p = 0.002). Given the observed difference in total body water, these findings point to excess fluid as the component driving the association between gestational weight gain and preeclampsia in the present study. Trial registration The NFFD trial has the Clinical Trials registration: clinicaltrial.gov NCT0100168.