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1.
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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2.
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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3.
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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4.
Association of vitamin D level and vitamin D deficiency with risk of preeclampsia: A systematic review and updated meta-analysis.
Akbari, S, Khodadadi, B, Ahmadi, SAY, Abbaszadeh, S, Shahsavar, F
Taiwanese journal of obstetrics & gynecology. 2018;(2):241-247
Abstract
OBJECTIVES Because of the immune modulatory effects of vitamin D3 in preeclampsia, we intend to have a systematic review and meta-analysis on association of both 25-hydroxy vitamin D (25-OHD) level (parametric approach) and 25-OHD deficiency (non-parametric approach) with preeclampsia. As well, for the parametric part, we used receiver operating characteristic (ROC) curve model. MATERIALS AND METHODS We used Web of Science, PubMed and Science Direct data bases through searching in titles. Google Scholar search engine was used in order to find missing papers. Finally 23 studies were imported. Both random and fixed models were reported. RESULTS Based on the forest plot, lower levels of 25-OHD were significantly associated with risk of preeclampsia (fixed and random P < 0.001). Based on the forest plot, vitamin D deficiency (25-OHD < 20 ng/ml) was significantly associated with risk of preeclampsia (fixed P < 0.0001; random P = 0.0029; fixed OR = 1.33; random OR = 1.54). Based on ROC curve results, we found 2 cutoffs of 10.60 and 20.05 ng/ml. CONCLUSION Women with vitamin D deficiency at cutoff 20 ng/ml are more at risk of preeclampsia. This association can be specific up to 90% at 10.60 ng/ml cutoff. Treatment of vitamin D deficiency is necessary before pregnancy.
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5.
Mechanisms of the effect of magnesium salts in preeclampsia.
Chiarello, DI, Marín, R, Proverbio, F, Coronado, P, Toledo, F, Salsoso, R, Gutiérrez, J, Sobrevia, L
Placenta. 2018;:134-139
Abstract
Preeclampsia is a heterogeneous pregnancy-specific syndrome associated with abnormal trophoblast invasion and endothelial dysfunction. Magnesium (Mg2+) level may be normal or decreased in women with preeclampsia. However, the use of Mg2+ salts, such as Mg2+ sulphate, are useful in reducing the pathophysiological consequences of preeclampsia with severe features and eclampsia. Although the mechanism of action of this Mg2+ salt is not well understood, the available evidence suggests a beneficial effect of Mg2+ for the mother and foetus. The mechanisms include a lower level of soluble fms-like tyrosine kinase 1 and endoglin, blockage of brain N-methyl-D-aspartate receptors, decreased inflammation mediators, activation of nitric oxide synthases, blockage of arginases, and reduced free radicals level. The maintenance of Mg2+ homeostasis in pregnancy is crucial for an appropriate pregnancy progression. Oral Mg2+ salts can be used for this purpose which could result in mitigating the deleterious consequences of this syndrome to the mother, foetus, and newborn.
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6.
Maternal serum and fetal cord-blood ischemia-modified albumin concentrations in normal pregnancy and preeclampsia: a systematic review and meta-analysis.
Seshadri Reddy, V, Duggina, P, Vedhantam, M, Manne, M, Varma, N, Nagaram, S
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. 2018;(24):3255-3266
Abstract
BACKGROUND/AIMS: A meta-analysis of maternal serum ischemia-modified albumin (IMA) and fetal cord-blood IMA concentrations in normal pregnancy (NP) compared to non-pregnant healthy controls (HC) and in preeclampsia (PE) compared with normal pregnant controls were studied. METHODS All major databases were searched for eligible studies. We included eight studies comparing serum IMA between NP and HC, 14 studies comparing serum IMA between PE and NP and five studies comparing cord-blood IMA between PE and NP groups. Meta-analyses on these included studies were performed using Review Manager 5.3. Pooled-overall effect size as standardized mean difference (SMD), publication bias, subgroup, and sensitivity analysis data were generated. RESULTS Random-effects meta-analysis indicated a significant increase in serum IMA in the NP group (SMD = 0.98, p = .01) and the PE group (SMD = 0.94, p < .0001) as compared with HC and NP groups, respectively. And, the cord-blood IMA has been found to be significantly increased in PE (SMD = 6.51, p < .0001) compared with the NP group. CONCLUSIONS This meta-analysis, the first of its kind showed that the increased serum IMA concentrations were indicative of increased oxidative stress in NP and PE. Measurement of maternal serum IMA and fetal cord-blood IMA concentrations were useful as simple, novel, and inexpensive markers of oxidative stress (OS) status in PE patients. Future large-scale studies are needed to explore IMA in relationship to the disease severity in PE.
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7.
Genetic and non-genetic risk factors for pre-eclampsia: umbrella review of systematic reviews and meta-analyses of observational studies.
Giannakou, K, Evangelou, E, Papatheodorou, SI
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2018;(6):720-730
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Abstract
OBJECTIVE To summarize evidence from the literature on genetic and non-genetic risk factors associated with pre-eclampsia (PE), assess the presence of statistical bias in the studies and identify risk factors for which there is robust evidence supporting their association with PE. METHODS PubMed and ISI Web of Science were searched from inception to October 2016, to identify systematic reviews and meta-analyses of observational studies examining associations between genetic or non-genetic risk factors and PE. For each meta-analysis, the summary-effect size was estimated using random-effects and fixed-effects models, along with 95% CIs and the 95% prediction interval. Between-study heterogeneity was expressed using the I2 statistic, and evidence of small-study effects (large studies had significantly more conservative results than smaller studies) and evidence of excess significance bias (too many studies with statistically significant results) were estimated. RESULTS Fifty-eight eligible meta-analyses were identified, which included 1466 primary studies and provided data on 130 comparisons of risk factors associated with PE, covering a wide range of comorbid diseases, genetic factors, exposure to environmental agents and biomarkers. Sixty-five (50%) associations had nominally statistically significant findings at P < 0.05, while 16 (12%) were significant at P < 10-6 . Sixty-five (50%) associations had large or very large heterogeneity. Evidence for small-study effects and excess significance bias was found in 10 (8%) and 26 (20%) associations, respectively. The only non-genetic risk factor with convincing evidence for an association with PE was oocyte donation vs spontaneous conception, which had a summary odds ratio of 4.33 (95% CI, 3.11-6.03), was supported by 2712 cases with small heterogeneity (I2 = 26%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger's test > 0.10) or excess of significance (P > 0.05). Of the statistically significant (P < 0.05) genetic risk factors for PE, only PAI-1 4G/5G (recessive model) polymorphism was supported by strong evidence for a contribution to the pathogenesis of PE. Eleven factors (serum iron level, pregnancy-associated plasma protein-A, chronic kidney disease, polycystic ovary syndrome, mental stress, bacterial and viral infections, cigarette smoking, oocyte donation vs assisted reproductive technology, obesity vs normal weight, severe obesity vs normal weight and primiparity) presented highly suggestive evidence for an association with PE. CONCLUSIONS A large proportion of meta-analyses of genetic and non-genetic risk factors for PE have caveats that threaten their validity. Oocyte donation vs spontaneous conception and PAI-1 4G/5G polymorphism (recessive model) showed the strongest consistent evidence for an association with risk for PE. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
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Resistant Hypertension in Pregnancy: How to Manage?
Bortolotto, MR, Francisco, RPV, Zugaib, M
Current hypertension reports. 2018;(8):63
Abstract
PURPOSE OF REVIEW The concept of resistant hypertension may be changed during pregnancy by the physiological hemodynamic changes and the particularities of therapy choices in this period. This review discusses the management of pregnant patients with preexisting resistant hypertension and also of those who develop severe hypertension in gestation and puerperium. RECENT FINDINGS The main cause of severe hypertension in pregnancy is preeclampsia, and differential diagnosis must be done with secondary or primary hypertension. Women with preexisting resistant hypertension may need pharmacological therapy adjustment. Several drugs can be used to treat severe hypertension, with exception of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists. The most used drugs are methyldopa, beta-blockers, and calcium channel antagonists. There is a general agreement that severe hypertension must be treated, but there are still debates over the goals of the treatment. Delivery is indicated in viable pregnancies in which blood pressure control is not achieved with three drugs in full doses. Resistant hypertension may arise in postpartum. The management of resistant hypertension in pregnancy must regard the possible etiology, the fetal well-being, and the mother's risk. Good care is mandatory to reduce maternal mortality risk.
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Nutraceutical Targeting of Placental Synthesis of Soluble Fms-Like Tyrosine Kinase- 1 (sFlt-1) as Strategy for Preventing and Controlling Pre-eclampsia.
Iloki-Assanga, S, McCarty, MF
Current pharmaceutical design. 2018;(20):2255-2263
Abstract
The primary driving force in preeclampsia (PE) appears to be excessive secretion of fms-like tyrosine kinase-1 (sFlt-1), a truncated decoy receptor for vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) that induces systemic endotheliopathy by depriving endothelial cells of the trophic support conferred by VEGF. Factors which boost placental sFlt-1 production in PE include hypoxia - reflecting improper placentation - oxidative stress, and deficient production of hydrogen sulfide (H2S). Nutraceutical measures which may address these issues include taurine and N-acetylcysteine - which may boost placental H2S production; spirulina and phase 2 inducers of heme oxygenase-1 such as lipoic acid - which may down-regulate placental NADPH oxidase activity; and citrulline, high-dose folate, and dietary nitrate - which by supporting placental nitric oxide production may aid proper placentation and hence prevent placental hypoxia. These agents may also help to alleviate the pathogenic impact of sFlt-1 excess. If the utility of such measures can be demonstrated in rodent models of PE, functional foods incorporating these nutraceuticals can be envisioned as aids to a healthful pregnancy. Moreover, rodent studies suggest that such prenatal supplementation may reduce risk for hypertension in adult offspring of the pregnancy. And, since women who develop PE are at markedly higher risk for cardiovascular disorders in their later life, continuing use of such supplementation - promoting effective NO and H2S bioactivity while aiding control of oxidative stress - may be advisable for the mothers.
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Autophagy regulation in preeclampsia: Pros and cons.
Nakashima, A, Aoki, A, Kusabiraki, T, Cheng, SB, Sharma, S, Saito, S
Journal of reproductive immunology. 2017;:17-23
Abstract
Autophagy is an evolutionarily conserved process in eukaryotes to maintain cellular homeostasis against stress. This process has two main functions: producing energy and quality control of intracellular proteins. During early pregnancy, extravillous trophoblasts (EVTs) invade the uterine myometrium and migrate along the lumina of spiral arterioles under hypoxic and low-nutrient conditions. Autophagy activation is observed in EVTs under these conditions, suggesting that EVTs use autophagy for adjusting to such harsh conditions. On the other hand, soluble endoglin, which is increased in sera in preeclamptic cases, inhibits autophagy in vitro, resulting in suppression of EVT functions, invasion and vascular remodeling. In addition, p62/SQSTM1, a substrate degraded by autophagy, accumulates in EVTs in preeclamptic placental biopsy samples, exhibiting impaired autophagy in vivo. There are, however, some opposing reports in which autophagy activation, an increase of autophagy vacuoles or LC3 dots, was more frequently observed in preeclamptic or FGR placentas than in normal pregnancy. Thus, changes in autophagy status are seen in preeclamptic placentas, but the mechanism by which autophagy modulates biological changes in the placentas is still unknown. Recently, there is increasing evidence that autophagy is involved in maintaining pregnancy. This review introduces the role of autophagy for maintaining pregnancy and its correlation with preeclampsia.