Differential effects of renin-angiotensine-aldosteron system inhibition, sympathoinhibition and low sodium diet on blood pressure in women with a history of preeclampsia: A double-blind, placebo-controlled cross-over trial (the PALM study).

Current guidelines lack sufficient evidence to recommend a specific blood pressure lowering strategy to prevent cardiovascular disease after preeclampsia. We conducted a double-blind cross-over trial to identify the most potent antihypertensive strategy: renin-angiotensin-aldosterone system (RAAS) inhibition (losartan), sympathoinhibition (moxonidine), low sodium diet and placebo (n = 10). Due to low inclusion rate our study stopped prematurely. Initiatory analyses showed no significant effect of antihypertensive strategy on office blood pressure and 24-hour blood pressure. However, nocturnal dipping was significantly higher on RAAS inhibition and low sodium diet compared to placebo and sympathoinhibition. Optimal cardiovascular prevention after preeclampsia should be further explored.

Maternal microbiome in preeclampsia pathophysiology and implications on offspring health.

Preeclampsia is a devastating hypertensive pregnancy disorder that currently affects 2%-8% of pregnancies worldwide. It is associated with maternal and fetal mortality and morbidity and adverse health outcomes both in mom and offspring beyond pregnancy. The pathophysiology is not completely understood, and there are no approved therapies to specifically treat for the disease, with only few therapies approved to manage symptoms. Recent advances suggest that aberrations in the composition of the microbiome may play a role in the pathogenesis of various diseases including preeclampsia. The maternal and uteroplacental environments greatly influence the long-term health outcomes of the offspring through developmental programming mechanisms. The current review summarizes recent developments on the role of the microbiome in adverse pregnancy outcomes with a focus on preeclampsia. It also discusses the potential role of the maternal microbiome in fetal programming; explores gut-targeted therapeutics advancement and their implications in the treatment of preeclampsia.

Effect of Ajwa Dates Consumption to Inhibit the Progression of Preeclampsia Threats on Mean Arterial Pressure and Roll-Over Test.

BACKGROUND: Preeclampsia is the major problem and the main leading cause of fetal and maternal mortality worldwide. The early prediction of preeclampsia in pregnant women is required to prevent the occurrence of preeclampsia. The mean arterial pressure (MAP) and roll-over test (ROT) are the combination of measurement which can be used to predict preeclampsia. On the contrary, Ajwa dates were reported to have an enormous activity which contributes to its role in improving health conditions. In this study, we aimed to evaluate the effect of daily consumption of seven Ajwa dates on prevention of preeclampsia, through MAP and ROT changes. METHODS: Forty pregnant women (n = 40) were randomly assigned into the control group (n = 10) and the intervention group which received a daily intake of Ajwa dates (n = 30). The MAP and ROT were assessed before and after the 8-week intervention period. RESULTS: The intervention group showed the significant reduction in MAP and ROT following the 8-week intervention period (p < 0.05). CONCLUSION: Daily consumption of seven Ajwa dates has a remarkable potential to decrease the MAP and ROT in pregnant women at risk of developing preeclampsia, and thus, it can contribute to prevent the development of preeclampsia.

Effect of maternal omega-3 fatty acids and vitamin E supplementation on placental apoptotic markers in rat model of early and late onset preeclampsia.

AIM: Disturbed placentation results in pregnancy complications like preeclampsia. Placental development is influenced by apoptosis during trophoblast differentiation and proliferation. Increased oxidative stress upregulates placental apoptosis. We have earlier reported increased oxidative stress, lower omega-3 fatty acids and vitamin E levels in women with preeclampsia. Current study examines effect of maternal omega-3 fatty acids and vitamin E supplementation on apoptotic markers across gestation in a rat model of preeclampsia. MAIN METHODS: Pregnant Wistar rats were randomly assigned to control; early onset preeclampsia (EOP); late onset preeclampsia (LOP); early onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (EOP + O + E) and late onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (LOP + O + E) groups. Animals (Control, EOP, EOP + O + E) were sacrificed at d14 and d20 of gestation while animals (LOP, LOP + O + E) were sacrificed at d20 to collect blood and placentae. Protein and mRNA levels of apoptotic markers were analyzed by ELISA and RT-PCR respectively. KEY FINDINGS: Protein levels of proapoptotic markers like Bcl-2 associated X-protein (BAX) (p < 0.05), caspase-8 and 3 (p < 0.01 for both) and malondialdehyde (p < 0.01) were higher only in the EOP group as compared to control. However, the antiapoptotic marker, B cell lymphoma 2 (Bcl-2) protein levels were lower in both the subtypes of preeclampsia (p < 0.01 for both). SIGNIFICANCE: Our findings suggest that supplementation was beneficial in reducing the caspase-8 and 3 in early onset preeclampsia but did not normalize BAX and Bcl-2 levels. This has implications for reducing placental apoptosis in preeclampsia.

Vegetable dietary pattern associated with low risk of preeclampsia possibly through reducing proteinuria.

BACKGROUND: Evidence on the potential roles that dietary patterns play in the risk of preeclampsia remains limited. OBJECTIVE: To examine the associations between dietary patterns during pregnancy and the risk of preeclampsia. STUDY DESIGN: We analyzed data from a cluster randomized controlled trial among 987 healthy pregnant women in three rural counties in northwestern China. Maternal diet during the whole pregnancy was assessed using a 107-item food frequency questionnaire with proportion size administered before delivery. Principal component factor analysis with varimax rotation was used to identify common dietary patterns. Preeclampsia was diagnosed by trained clinicians and recorded in delivery records. RESULTS: Nineteen participants (1.9%) were diagnosed with preeclampsia. Gestational hypertension and proteinuria were only weakly correlated with each other (Kappa = 0.06): 10.7% participants with gestational hypertension only, 8.8% with proteinuria only, 1.9% with both, and 78.6% with neither. Five common dietary patterns were identified: vegetable, meat, fruit, snack, and wheat staple patterns. After adjusting for calories, other dietary pattern scores and baseline blood pressure, a higher vegetable pattern scores was associated with lower risk of preeclampsia (P for trend = 0.041; the highest vs lowest quartile, adjusted relative risk = 0.20 [95% confidence interval, 0.04-0.98]). A similar association was also observed for the risk of proteinuria (P for trend = 0.015): the highest vs lowest quartiles of the vegetable pattern score, adjusted relative risk = 0.44 (95% confidence interval, 0.24-0.80). The other four pattern scores were not associated with preeclampsia. CONCLUSIONS: Adherence to vegetable dietary pattern may be associated with the lower risk of preeclampsia, possibly through reducing development of proteinuria. The original full study was registered at clinicaltrials.gov as NCT02537392.

Cuidado nutricional en la prevención de la preeclampsia: Una revisión sistemática / Nutritional care in theprevention of preeclampsia: A systematic review

Fundamentos: La preeclampsia (PE) es una de las principales causas de morbimortalidad materna en Colombia, por lo que se hace necesario indagar sobre el papel de la nutrición en la prevención de la PE a partir de los resultados y conclusiones de las publicaciones encontradas en la revisión. Métodos: Se realizó una revisión sistemática sobre la literatura existente en diferentes bases de datos como PubMed, Embase, Science Direct Freedom collection, Biblioteca Virtual de la Salud y Scielo, complementándose con una búsqueda de literatura gris. Se incluyeron datos de 28 estudios evaluados bajo las directrices Scottish Intercollegiate Guidelines Network (SIGN), en los que se abordaba aspectos nutricionales relacionados con la prevención de la PE. Resultados: Se encontró evidencia que respalda que la suplementación con vitamina D, calcio, ácido fólico, coenzima Q y L-Arginina cumplen un papel importante en la prevención de la PE, debido a su participación en diferentes procesos como el estrés oxidativo, la adecuada implantación de la placenta, entre otros. Conclusiones: El cuidado nutricional puede tener una posible relación en la prevención de la preeclampsia, sin embargo, se hace necesario realizar estudios complementarios que permitan confirmar la información existente desde el impacto de la nutrición

Background: The preeclampsia is one of the principal causes of morbidity and mortality in Colombian pregnant women, because of that it is necessary to investigate about the role of nutrition in the prevention of this disease base on results and conclusions of papers found on the systematic review done. Methods: A systematic review was performed on several different databases such as PubMed, Embase, Science Direct Freedom collection, BibliotecaVirtual de la Salud and Scielo, complemented with a search in gray literature. Data from different studies in which nutritional aspects related to PE prevention was collected. The quality of the articles was evaluated under the Scottish Intercollegiate Guidelines Network (SIGN) guidelines and finally a total of 28 articles were analyzed. Results: The evidence founded support the supplementation with vitamin D, calcium, folic acid, coenzyme Q and L-Arginine play an important role in the prevention of PE, since these participate in different process like the oxidative stress, the adequate implantation of the placenta, in other aspects. Conclusions: Care nutrition can have a possible relation in the prevention of preeclampsia, however, it is necessary to carryout complementary studies to confirm the existing information from the impact of nutrition

A randomised controlled trial of consumption of dark chocolate in pregnancy to reduce pre-eclampsia: Difficulties in recruitment, allocation and adherence.

In 2013-2014 we undertook a randomised controlled trial (RCT) to determine whether the daily ingestion of dark chocolate during pregnancy could reduce the incidence of pre-eclampsia in primigravidae. However, after two years we had not succeeded in recruiting more than 3.5% of the number of participants required to answer the research question, and the trial was halted. We also reviewed the literature on this topic and found it to be limited. We report here our findings and discuss the difficulties facing researchers in this area.

Vitamin D deficiency in mothers, neonates and children.

Vitamin D is produced in response to the exposure of skin to sunlight through UV-B synthesis. It can also be obtained from diet and dietary supplements. Vitamin D is essential for strong bones as it helps to absorb calcium from diet. Vitamin D deficiency mainly occurs if strict vegetarian diet is followed as mostly the source of vitamin D is animal based; therefore, exposure to sunlight is restricted or having dark skin color. Low vitamin D levels results in increased possibility of gestational diabetes among pregnant women, low birth weight and pre-eclampsia in infants, and mothers may suffer bone impairment, osteoporosis, hypocalcaemia, and hypertension. Vitamin D deficiency is directly linked with severe complication in mothers and neonates, causing rickets, poor fetal growth and infantile eczema in neonates. Higher prevalence rate of vitamin D deficiency has led professionals to emphasize on development of relevant precautionary measures.

Decreased Risk of Preeclampsia After the Introduction of Universal Voucher Scheme for Antenatal Care and Birth Services in the Republic of Korea.

Objectives A number of interventions to reduce disparities in maternal health have been introduced and implemented without concrete evidence to support them. In Korea, a universal voucher scheme for antenatal care and birth services was initiated in December 2008 to improve Korea's fertility rate. This study explores the risk of preeclampsia after the introduction of a universal voucher scheme. Methods Population-based cohort data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) covering 2002-2013 were analysed. A generalized linear mixed model (GLMM) was used to estimate the relationship between the risk of preeclampsia and voucher scheme introduction. Results The annual age-adjusted incidence of preeclampsia showed no significant unidirectional change during the study period. In the GLMM analysis, the introduction of a voucher scheme was associated with a reduced risk of preeclampsia, controlling for potential confounding factors. The interaction between household income level and voucher scheme was not significant. Conclusions for Practice This finding suggests that the introduction of a voucher scheme for mothers is related to a reduced risk of preeclampsia even under universal health coverage.

Changes in the renin-angiotensin-aldosterone system in response to dietary salt intake in normal and hypertensive pregnancy. A randomized trial.

It was hypothesized that primary renal sodium retention blunted the reactivity of the renin-angiotensin-aldosterone system to changes in salt intake in preeclampsia (PE). A randomized, cross-over, double-blinded, dietary intervention design was used to measure the effects of salt tablets or placebo during low-salt diet in PE patients (n = 7), healthy pregnant women (n = 15), and nonpregnant women (n = 13). High-salt intake decreased renin and angiotensin II concentrations significantly in healthy pregnant women (P < .03) and in nonpregnant women (P < .001), but not in PE (P = .58), while decreases in aldosterone and increases in brain natriuretic peptid (BNP) were similar in the groups. In PE patients, uterine and umbilical artery indices were not adversely changed during low-salt diet. Creatinine clearance was significantly lower in PE with no change by salt intake. PE patients displayed alterations of plasma renin and angiotensin II in response to changes in dietary salt intake compatible with a primary increase in renal sodium reabsorption in hypertensive pregnancies.

Effect of Docosahexaenoic Acid on Apoptosis and Proliferation in the Placenta: Preliminary Report.

INTRODUCTION: Observational studies confirm a higher incidence of preeclampsia in patients with low erythrocyte concentrations of omega-3 fatty acids. Observations point to an association of disorders of pregnancy, such as intrauterine growth restriction (IUGR) and preeclampsia, with excessive apoptosis. One potential mechanism of action of docosahexaenoic acid (DHA) promoting a reduction in the risk of pathological pregnancy may be by influencing these processes in the placenta. MATERIALS AND METHODS: We investigated 28 pregnant women supplemented with a fish oil product containing 300 mg DHA starting from pregnancy week 20 until delivery (DHA group). The control group consisted of 50 women who did not receive such supplementation (control group). We determined the expression of Ki-67 and p21 as markers of proliferation and caspase 3 activity as a marker of apoptosis and DHA levels in umbilical cord blood. RESULTS: Caspase 3 activity was significantly lower in the DHA group in comparison to the control group. Umbilical cord blood DHA concentration was higher in the DHA group. The expression of the proteins p21 and Ki-67 did not differ significantly between the groups. CONCLUSIONS: We observed an association between DHA supplementation and inhibition of placental apoptosis. We did not find an association between DHA and proliferation process in the placenta.

Plant-Based and Plant-Rich Diet Patterns during Gestation: Beneficial Effects and Possible Shortcomings.

Environmental and lifestyle factors are known to play an important role during gestation, determining newborns' health status and influencing their risk of being subject to certain noncommunicable diseases later in life. In particular, maternal nutritional patterns characterized by a low intake of plant-derived foods could increase the risk of gestation-related issues, such as preeclampsia and pregravid obesity, increase genotoxicant susceptibility, and contribute to the onset of pediatric diseases. In particular, the risk of pediatric wheeze, diabetes, neural tube defects, orofacial clefts, and some pediatric tumors seems to be reduced by maternal intake of adequate amounts of vegetables, fruits, and selected antioxidants. Nevertheless, plant-based diets, like any other diet, if improperly balanced, could be deficient in some specific nutrients that are particularly relevant during gestation, such as n-3 (ω-3) fatty acids, vitamin B-12, iron, zinc, and iodine, possibly affecting the offspring's health state. Here we review the scientific literature in this field, focusing specifically on observational studies in humans, and highlight protective effects elicited by maternal diets enriched in plant-derived foods and possible issues related to maternal plant-based diets.

Probiotics and pregnancy.

Complications of pregnancy are associated with adverse outcomes for mother and baby in the short and long term. The gut microbiome has been identified as a key factor for maintaining health outside of pregnancy and could contribute to pregnancy complications. In addition, the vaginal and the recently revealed placental microbiome are altered in pregnancy and may play a role in pregnancy complications. Probiotic supplementation could help to regulate the unbalanced microflora composition observed in obesity and diabetes. Here, the impact of probiotic supplementation during pregnancy and infancy is reviewed. There are indications for a protective role in preeclampsia, gestational diabetes mellitus, vaginal infections, maternal and infant weight gain and allergic diseases. Large, well-designed randomised controlled clinical trials along with metagenomic analysis are needed to establish the role of probiotics in adverse pregnancy and infancy outcomes.

Severe superimposed preeclampsia with obesity, diabetes and a mild imbalance of angiogenic factors.

Preeclampsia may be due to an excess of circulating anti-angiogenic growth factors derived from the placenta, but metabolic syndrome-like disorders may also set off a cascade of placental and systemic inflammation and oxidative stress. We present a case of severe superimposed preeclampsia with obesity, diabetes and a mild imbalance of angiogenic factors, in which diet therapy ameliorated the preeclamptic signs while improving the adiponectin level. A 41-year-old pregnant woman with obesity and diabetes was referred to our hospital because of severe proteinuria and hypertension at 22 weeks of gestation. After administration of insulin and hydralazine with diet therapy, her hypertension and proteinuria were ameliorated with a 15-kg weight loss. Her adiponectin level was low and her leptin level was high, but her angiogenic factor levels were within the normal ranges for pregnant women at admission. The diet therapy ameliorated her hypertension and proteinuria while improving her adiponectin level as she achieved weight loss. This case suggests that diet therapy for obese preeclampsia patients with a mild imbalance of anti-and pro-angiogenic factors may play an important role in managing preeclampsia. Measurements of maternal adipocytokines and angiogenic factors may be important to distinguish the main cause of preeclampsia, i.e., poor placentation or maternal constitutional factors, for managing preeclampsia in patients with obesity.

The role of calcium, magnesium, and zinc in pre-eclampsia.

Pre-eclampsia is the most common medical complication of pregnancy associated with increased maternal and infant mortality and morbidity. Its exact etiology is not known, although several evidences indicate that various elements might play an important role in pre-eclampsia. This study was carried out to analyze and to compare the concentration of calcium, magnesium, and zinc in the serum of women with pre-eclampsia and in normal pregnant women. Fifty clinically diagnosed patients with pre-eclampsia (25 with mild and 25 with severe pre-eclampsia) and 50 normal pregnant controls were enrolled in this study. The serum calcium, magnesium, and zinc levels were estimated with an atomic absorption spectrophotometer. The mean serum levels of calcium, magnesium, and zinc in normal pregnant group were 2.45 +/- 0.18 mmol/L, 0.79 +/- 0.13 mmol/L, and 15.64 +/- 2.4 micromol/L, respectively, while in mild pre-eclamptic group, these were 2.12 +/- 0.15 mmol/L, 0.67 +/- 0.14 mmol/L, and 12.72 +/- 1.7 micromol/L, respectively. Serum levels in severe pre-eclamptic group were 1.94 +/- 0.09 mmol/L, 0.62 +/- 0.11 mmol/L, and 12.04 +/- 1.4 micromol/L, respectively. These results indicate that reduction in serum levels of calcium, magnesium, and zinc during pregnancy might be possible contributors in etiology of pre-eclampsia, and supplementation of these elements to diet may be of value to prevent pre-eclampsia.

Effects of oral L-arginine supplementation on blood pressure and asymmetric dimethylarginine in stress-induced preeclamptic rats.

This study was carried out to elucidate the role of asymmetric dimethylarginine (ADMA) and nitric oxide (NO) in preeclampsia development, and to investigate the effect of L-arginine supplementation in rats. Preeclampsia was induced in pregnant rats using a stress model. L-arginine was administered orally and ADMA, urinary nitrate, and protein levels were measured on the 20th day of pregnancy. Compared with the group of rats that are normally pregnant, the levels of blood pressure (BP), protein excretion, and ADMA were significantly increased in preeclampsia which returned to normal levels following the supplementation of L-arginine. Both group of rats had similar urine nitrate levels. Arginine-ADMA-NO pathway is affected in preeclampsia. L-arginine supplementation decreased hypertension (HT), proteinuria, and ADMA levels indicating that taking L-arginine may be beneficial in preeclampsia treatment.

Effects of prolonged oral supplementation with l-arginine on blood pressure and nitric oxide synthesis in preeclampsia.

BACKGROUND: Several lines of evidence point to the dysfunction of the endothelial l-arginine-NO system in preeclampsia. We investigated the influence of dietary supplementation with l-arginine on blood pressure and biochemical measures of NO production in women with preeclampsia in prospective, randomized, placebo-controlled study. DESIGN: The 61 preeclamptic women on a standardized low nitrate diet received orally 3 g of l-arginine (n = 30) or placebo (n = 31) daily for 3 weeks as a supplement to standard therapy. The differences between the two groups in systolic (SBP), diastolic (DBP) and mean arterial blood pressures (MAP) as well as in plasma levels of selected aminoacids, plasma concentrations of nitrates/nitrites (NOx) and in 24-h urine NOx excretion were determined. RESULTS: After 3 weeks of treatment, values of SBP, DPB and MAP were significantly lower in the group taking l-arginine as compared with the placebo group (SBP: 134.2 +/- 2.9 vs. 143.1 +/- 2.8; DBP: 81.6 +/- 1.7 vs. 86.5 +/- 0.9; MAP: 101.8 +/- 1.5 vs. 108.0 +/- 1.2 mmHg, P < 0.01). Importantly, treatment with exogenous l-arginine significantly elevated 24-h urinary excretion of NOx and mean plasma levels of l-citrulline. Exogenous l-arginine did not influence plasma concentrations of l-arginine, l-ornithine and methylated arginines (ADMA, SDMA, L-NMMA). CONCLUSIONS: We conclude that in women with preeclampsia, prolonged dietary supplementation with l-arginine significantly decreased blood pressure through increased endothelial synthesis and/or bioavailability of NO. It is tempting to speculate that the supplementary treatment with l-arginine may represent a new, safe and efficient strategy to improve the function of the endothelium in preeclampsia.