The Influence of Vitamin D on Pregnancy and Outcomes: Current Knowledge and Future Perspectives.

INTRODUCTION: The purpose of the research was to explore the relationship between pathology and pregnancy outcomes with serum 25-hydroxycholecalciferol levels and vitamin D supplementation. METHODS: A literature search was performed for systematic literature reviews published between January 2018 and February 2023. Forty-two publications were selected for further analysis. RESULTS: This study demonstrates that elevated maternal serum 25(OH)D levels are associated with a decreased risk of preterm labour and various pregnancy-related health issues, highlighting the protective benefits of adequate vitamin D during pregnancy. CONCLUSION: Vitamin D supplementation during pregnancy at a dose of 2,000 IU or higher is preventive for pre-eclampsia, insulin resistance, and the development of bronchial asthma in early childhood. Vitamin D screening is indicated for all pregnant women. Dosages of vitamin D preparations should be determined individually, considering laboratory tests and risk factors.

Alterations in Antioxidant Micronutrient Concentrations in Placental Tissue, Maternal Blood and Urine and the Fetal Circulation in Pre-eclampsia.

Trace elements such as selenium and zinc are vital components of many enzymes, including endogenous antioxidants, and can interact with each other. Women with pre-eclampsia, the hypertensive disease of pregnancy, have been reported as having changes in some individual antioxidant trace elements during pregnancy, which are related to maternal and fetal mortality and morbidity. We hypothesised that examination of the three compartments of (a) maternal plasma and urine, (b) placental tissue and (c) fetal plasma in normotensive and hypertensive pregnant women would allow identification of biologically significant changes and interactions in selenium, zinc, manganese and copper. Furthermore, these would be related to changes in the angiogenic markers, placental growth factor (PlGF) and Soluble Fms-Like Tyrosine Kinase-1 (sFlt-1) concentrations. Venous plasma and urine were collected from healthy non-pregnant women (n = 30), normotensive pregnant controls (n = 60) and women with pre-eclampsia (n = 50) in the third trimester. Where possible, matched placental tissue samples and umbilical venous (fetal) plasma were also collected. Antioxidant micronutrient concentrations were measured by inductively coupled plasma mass-spectrometry. Urinary levels were normalised to creatinine concentration. Plasma active PlGF and sFlt-1 concentrations were measured by ELISA. Maternal plasma selenium, zinc and manganese were all lower in women with pre-eclampsia (p < 0.05), as were fetal plasma selenium and manganese (p < 0.05 for all); maternal urinary concentrations were lower for selenium and zinc (p < 0.05). Conversely, maternal and fetal plasma and urinary copper concentrations were higher in women with pre-eclampsia (p < 0.05). Differences in placental concentrations varied, with lower overall levels of selenium and zinc (p < 0.05) in women with pre-eclampsia. Maternal and fetal PlGF were lower and sFlt-1 higher in women with pre-eclampsia; maternal plasma zinc was positively correlated with maternal plasma sFlt-1 (p < 0.05). Because of perceptions that early- and late-onset pre-eclampsia have differing aetiologies, we subdivided maternal and fetal data accordingly. No major differences were observed, but fetal sample sizes were small following early-onset. Disruption in these antioxidant micronutrients may be responsible for some of the manifestations of pre-eclampsia, including contributing to an antiangiogenic state. The potential benefits of mineral supplementation, in women with deficient intakes, during pregnancy to reduce pre-eclampsia remain an important area for experimental and clinical research.

Iodine deficiency in pregnancy along a concentration gradient is associated with increased severity of preeclampsia in rural Eastern Cape, South Africa.

BACKGROUND: Preeclampsia is a leading cause of maternal mortality and morbidity in South Africa. Iodine deficiency in pregnancy, which is amenable to correction through iodine supplementation, has been reported to increase the risk of preeclampsia. However, the association of iodine nutrition status with preeclampsia in South Africa has not been studied. METHODS: We enrolled 51 randomly selected normotensive pregnant controls at term together with 51 consecutively selected cases of preeclampsia and 51 cases of severe preeclampsia/eclampsia, all in the third trimester, from Mthatha Regional and Nelson Mandela Academic Hospital in the Eastern Cape Province. Urinary iodine concentration (UIC), serum thyroid-stimulating hormone (TSH), triiodothyronine (FT3), thyroxine (FT4) and thyroglobulin (Tg) levels were compared between cases and controls. RESULTS: The respective chronological and gestational ages at enrolment for normotensive, preeclampsia and severe preeclampsia/eclampsia participants were: age 23, 24 and 19 years (p = 0.001), and gestational age 38, 34, and 35 weeks (p < 0.001). The median gravidity was 1 for all three groups. The median UIC, FT4, FT3 revealed a decreasing and Tg a rising trend with the severity of preeclampsia (p < 0.05). TSH had a non-significant rising trend (p > 0.05). The respective median values for normotensive, preeclampsia and severe preeclampsia/eclampsia participants were UIC 217.1, 127.7, and 98.8 µg/L; FT4 14.2, 13.7, and 12. pmol/L; FT3 4.8, 4.4, and 4.0 pmol//L; Tg 19.4, 21.4, and 32. Nine microgram per liter; TSH 2.3, 2.3, and 2.5 mIU/L. UIC < 100 µg/L, Tg > 16 µg/L and FT4 < 11.3 pmol/L were independent predictors of preeclampsia/eclampsia syndrome. CONCLUSION: Women with severe preeclampsia/eclampsia had significantly low UIC and high Tg, suggesting protracted inadequate iodine intake. Inadequate iodine intake during pregnancy severe enough to cause elevated Tg and FT4 deficiency was associated with an increased risk of severe preeclampsia/eclampsia.

Comprehensive fatty acid fractionation profilling in preeclampsia: a case control study with multivariable analysis.

BACKGROUND: Preeclampsia is a complication during pregnancy characterised by new-onset hypertension and proteinuria that develops after 20 weeks of gestation. Dyslipidemia in pregnancy is correlated with an increased risk of preeclampsia. However, the dynamic changes in lipid metabolic product, particularly fatty acid fraction, in preeclampsia maternal circulation, are not well understood. This study aimed to investigate fatty acid fraction in preeclampsia maternal blood compared with normotensive normal pregnancy. METHODS: A total of 34 women who developed preeclampsia and 32 women with normotensive normal pregnancy were included in our case-control study. Maternal blood samples were collected for serum fatty acid fractions analysis and other biochemical parameters. Serum fatty acid fractions included long-chain polyunsaturated fatty acid (LCPUFA), monounsaturated fatty acid (MUFA), saturated fatty acid, and total fatty acid, measured with gas chromatography-mass spectrometry (GC-MS). The mean difference of fatty acid level was analysed using parametric and non-parametric bivariate analysis based on normality distributed data, while the risk of preeclampsia based on fatty acid fraction was analysed using a logistic regression model. RESULTS: Women with preeclampsia have lower high-density lipoprotein (53.97 ± 12.82 mg/dL vs. 63.71 ± 15.20 mg/dL, p = 0.006), higher triglyceride (284.91 ± 97.68 mg/dL vs. 232.84 ± 73.69 mg/dL, p = 0.018) than that in the normotensive group. Higher palmitoleic acid was found in women with preeclampsia compared to normotensive normal pregnancy (422.94 ± 195.99 vs. 325.71 ± 111.03 µmol/L, p = 0.037). The binary logistic regression model showed that pregnant women who had total omega-3 levels within the reference values had a higher risk of suffering preeclampsia than those with the higher reference value (odds ratio OR (95% CI): 8,5 (1.51-48.07), p = 0.015). Pregnant women who have saturated fatty acid within reference values had a lower risk for suffering preeclampsia than those in upper reference value (OR (95% CI): 0.21 (0.52-0.88), p = 0.032). CONCLUSION: Overall, palmitoleic acid was higher in women with preeclampsia. Further analysis indicated that reference omega-3 in and high saturated fatty acid serum levels are characteristics of women with preeclampsia.

Could Vitamin D Be Effective in Prevention of Preeclampsia?

Prevention of preeclampsia (PE) remains one of the most significant problems in perinatal medicine. Due to the possible unpredictable course of hypertension in pregnancy, primarily PE and the high complication rate for the mother and fetus/newborn, it is urgent to offer pregnant women in high-risk groups effective methods of preventing the PE development or delaying its appearance. In addition, due to the association of PE with an increased risk of developing cardiovascular diseases (CVD) in later life, effective preeclampsia prevention could also be important in reducing their incidence. Ideal PE prophylaxis should target the pathogenetic changes leading to the development of PE and be safe for the mother and fetus, inexpensive and freely available. Currently, the only recognized method of PE prevention recommended by many institutions around the world is the use of a small dose of acetylsalicylic acid in pregnant women with risk factors. Unfortunately, some cases of PE are diagnosed in women without recognized risk factors and in those in whom prophylaxis with acetylsalicylic acid is not adequate. Hence, new drugs which would target pathogenetic elements in the development of preeclampsia are studied. Vitamin D (Vit D) seems to be a promising agent due to its beneficial effect on placental implantation, the immune system, and angiogenic factors. Studies published so far emphasize the relationship of its deficiency with the development of PE, but the data on the benefits of its supplementation to reduce the risk of PE are inconclusive. In the light of current research, the key issue is determining the protective concentration of Vit D in a pregnant woman. The study aims to present the possibility of using Vit D to prevent PE, emphasizing its impact on the pathogenetic elements of preeclampsia development.

Association of dietary calcium intake, total and ionized serum calcium levels with preeclampsia in Ethiopia.

BACKGROUND: Preeclampsia is a well-known cause of maternal mortality and morbidity in Ethiopia. The exact pathophysiology has not been fully understood. Calcium and magnesium deficiencies have been given emphasis to play roles in the pathophysiology. Although evidence is abundant, they are equivocal. The study aimed to see the association of dietary calcium intake, serum total calcium level and ionized calcium level with preeclampsia. It also evaluated the association between dietary calcium intake and serum calcium levels. MATERIALS AND METHODS: An unmatched case-control study was conducted in Gandhi Memorial, Tikur Anbessa, and Zewditu Memorial Hospitals, all in Addis Ababa, between October to December, 2019. Cases were 42 women with preeclampsia and controls were 42 normotensive women. The medical and obstetric history was gathered using a structured questionnaire and the dietary calcium intake information using a 24-h dietary recall. The serum levels of total serum calcium and ionized (free) calcium were measured using an inductively coupled mass spectrophotometer. Bivariate and multivariate logistic regression and Pearson correlation test were utilized during data analysis. RESULTS: In comparison with controls, women with preeclampsia had lower mean (± 1SD) levels of ionized calcium level (1.1 mmol/l ± 0.11), total serum calcium level (1.99 mmol/l ± 0.35) and lower median (IQR) dietary calcium intake (704 mg/24 h,458-1183). The odds of having preeclampsia was almost eight times greater in those participants with low serum ionized calcium level (OR 7.5, 95% CI 2.388-23.608) and three times higher in those with low total serum calcium level (OR 3.0, 95% CI 1.024-9.370). Low dietary calcium intake also showed statistically significant association with preeclampsia (OR 3.4, 95% CI 1.092 -10.723). Serum ionized calcium level and total serum calcium level showed positive correlation of moderate strength (p = 0.004, r = 0.307), but no correlation was found between dietary calcium intake with both forms of serum calcium levels. CONCLUSION: This study showed significant association between low dietary calcium intake and low serum calcium levels with preeclampsia, hence this can be used as a supportive local evidence for the current context-specific recommendation of calcium supplementation in societies with low-dietary calcium consumption in an attempt to prevent preeclampsia, therefore implementation study should be considered in Ethiopia to look for the feasibility of routine supplementation.

The plasma antioxidant vitamin status of the INTAPP cohort examined: The unsuspected importance of ß-carotene and γ-tocopherol in preeclampsia.

OBJECTIVE: Examine the levels of plasma antioxidant vitamins before and during a treatment with placebo or vitamin E + C supplement to prevent preeclampsia (PE). STUDY DESIGN: Per-protocol analysis of a subset group of pregnant women (n = 295) from the International Trial of Antioxidants for the Prevention of PE (INTAPP) randomized case-control study. Normotensive receiving placebo or vitamins (n = 115 and 87 respectively) were compared to gestational hypertension (GH) without proteinuria (n = 30 and 27) and PE (n = 21 and 15). Vitamin quantification was performed at 12-18, 24-26 and 32-34 weeks of gestation. MAIN OUTCOME MEASURES: Coenzyme (Co) Q10, ß-carotene and vitamins E (α and γ forms) plasma levels. RESULTS: Vitamin E + C supplementation was found to increase the α-tocopherol levels by 40% but was associated with a 57% decrease in the γ-tocopherol isoform for all study groups (p < 0.001). The ß -carotene was lower in the PE than in the normotensive and GH groups (p < 0.001) while the level of CoQ10 remained unaffected. CONCLUSIONS: A more personalized approach that target the suboptimal levels of specific antioxidants without disturbing the α/γ-tocopherol ratio could be a more successful approach to counteract oxidative stress in PE.

Effect of vitamin D3 supplementation during pregnancy on high risk factors - a randomized controlled trial.

OBJECTIVES: Vitamin D plays an important role in the release of the placenta and implantation, and low levels are a risk factor for pre-eclampsia. Studies have also shown that symptomatic treatment of vitamin D3 deficiency can effectively reduce the risk of pre-eclampsia. In this study, vitamin D3 supplementation was performed on the risk of pre-eclampsia to observe its effect. METHODS: From January 2016 to December 2018, 450 women with maternal treatment and delivery in our hospital underwent an open-label randomized study. The pregnant women were divided into low-dose, medium-dose, and high-dose groups. Compare the incidence of pre-eclampsia and the dose effect of vitamin D levels. RESULTS: In the maternal and perinatal periods of the 450 maternal women, the 25[OH] index of the three groups of pregnant women was significantly increased, while the high-dose increase index was more obvious. The relative risk reduction rate was significantly lower. Compared with the low-dose and middle-dose groups, the high-dose group had a significantly lower incidence of pre-eclampsia, while the IUGR index was lower, and other obstetric indicators were comparable. CONCLUSION: Vitamin D supplementation can effectively reduce the incidence of pre-eclampsia, while reducing the IUGR index, which has important value and significance in its clinical application.

Association between abnormal maternal serum levels of vitamin B12 and preeclampsia: a systematic review and meta-analysis.

CONTEXT: Some evidence has shown an association between maternal vitamin B12 levels and the development of preeclampsia in pregnant women, but the relationship between preeclampsia and vitamin B12 is not clear. OBJECTIVE: The aim of this systematic review was to compare serum vitamin B12 levels in women with preeclampsia with those in normotensive pregnant women. DATA SOURCES: The PubMed/MEDLINE, Scopus, and Web of Science databases were searched up to August 2019, along with the reference lists of included articles. STUDY SELECTION: The literature was searched for observational studies that investigated vitamin B12 levels in women with preeclampsia. DATA EXTRACTION: Data were extracted independently by 2 authors. Data were pooled using a random-effects model. RESULTS: Vitamin B12 levels in women with preeclampsia were significantly lower than those in healthy women (mean, -15.24 pg/mL; 95%CI, -27.52 to -2.954; P < 0.015), but heterogeneity between studies was high (I2 = 97.8%; P = 0.0103). Subgroup analyses based on folic acid supplementation, homocysteine concentrations, and gestational age at the time of sampling for vitamin B12 assessment did not identify the sources of heterogeneity. CONCLUSIONS: Women with preeclampsia had significantly lower vitamin B12 concentrations than normotensive pregnant women.

The bivariate NRIP1/ZEB2 RNA marker permits non-invasive presymptomatic screening of pre-eclampsia.

Using genome-wide transcriptome analysis by RNA sequencing of first trimester plasma RNA, we tested whether the identification of pregnancies at risk of developing pre-eclampsia with or without preterm birth or growth restriction is possible between weeks 9-14, prior to the appearance of clinical symptoms. We implemented a metaheuristic approach in the self-learning SVM algorithm for differential gene expression analysis of normal pregnancies (n = 108), affected pregnancies (n = 34) and non-pregnant controls (n = 19). Presymptomatic candidate markers for affected pregnancies were validated by RT-qPCR in first trimester samples (n = 34) from an independent cohort. PRKG1 was significantly downregulated in a subset of pregnancies with birth weights below the 10thpercentile as shared symptom. The NRIP1/ZEB2 ratio was found to be upregulated in pregnancies with pre-eclampsia or trisomy 21. Complementary quantitative analysis of both the linear and circular forms of NRIP1 permitted discrimination between pre-eclampsia and trisomy 21. Pre-eclamptic pregnancies showed an increase in linear NRIP1 compared to circular NRIP1, while trisomy 21 pregnancies did not.

Altered Bioavailability of Nitric Oxide and L-Arginine Is a Key Determinant of Endothelial Dysfunction in Preeclampsia.

BACKGROUND: Preeclampsia is a major cause of maternal and neonatal morbidity and mortality in sub-Saharan Africa. Evidence indicates that endothelial dysfunction is central to the pathogenesis of preeclampsia. This study assessed the level of the components of the arginine-nitric oxide pathway to evaluate endothelial dysfunction in normotensive pregnancies and pregnancies complicated with preeclampsia. METHODS: This case-control study was conducted among pregnant women who visited Comboni Hospital from January 2017 to May 2018. A total of 180 pregnant women comprising 88 preeclamptic women (PE) and 92 healthy normotensive pregnant women (NP) were recruited. Sociodemographic, clinical, and obstetric data were obtained using validated questionnaires. Blood pressure and anthropometrics were measured, and blood samples were collected for the estimation of nitric oxide (NO∙), L-arginine, asymmetric dimethylarginine (ADMA), and 3-nitrotyrosine using an enzyme-linked immunosorbent assay technique. RESULTS: The mean NO∙ (p = 0.010) and L-arginine/ADMA ratio (p < 0.0001) was significantly lower in PE compared to NP while mean L-arginine (p = 0.034), ADMA (p < 0.0001), and 3-nitrotyrosine (p < 0.0001) were significantly higher in PE than NP. ADMA showed a significant positive association with systolic blood pressure (ß = 0.454, p = 0.036) in severe PE. Women with PE had significant intrauterine growth restriction (p < 0.0001) and low birth weight infants (p < 0.0001) when compared to NP. CONCLUSION: Preeclampsia is associated with reduced NO∙ bioavailability, L-arginine/ADMA ratio, and elevated levels of ADMA and 3-nitrotyrosine. Measurements of the levels of these parameters can help in the early prediction of endothelial dysfunction in preeclampsia. Exogenous therapeutic supplementation with L-arginine during pregnancy to increase the L-arginine/ADMA ratio should be considered to improve endothelial function in preeclampsia and pregnant women at risk of developing preeclampsia.

Serum selenium levels of pre-eclamptic and normal pregnant women in Nigeria: A comparative study.

INTRODUCTION: Trace element selenium, an antioxidant, and peroxynitrite scavenger when incorporated into selenoproteins and enzymes reduce oxidative stress which is implicated in the aetiopathogenesis of pre-eclampsia. A paucity of information exists on the serum selenium levels among pre-eclamptic pregnant women in Nigeria, hence the need for this study. OBJECTIVE: To compare mean serum selenium levels and prevalence of selenium deficiency in preeclamptic pregnant women and their normotensive pregnant controls. MATERIALS AND METHODS: A comparative case-control study was carried out at the Department of Obstetrics and Gynaecology, Federal Medical Centre, Owerri, Imo state. Fifty-eight preeclamptic and equal normotensive pregnant controls were matched for age groups, gestational age groups, parity groups, and socio-economic status had their serum samples analyzed for selenium level using atomic absorption spectrophotometer (ASS). Data analysis was done using the statistical package for social sciences (SPSS) version 20.0. P-value of < 0.05 was considered to be statistically significant. RESULT: Mean serum selenium levels of the preeclamptic women(0.67±0.27µmol/l) was significantly (p<0.001) lower than that of the normotensive controls(1.20±0.46µmol/l). Selenium deficiency occurred significantly more in preeclamptic women (33(56.9%) than normotensive women (10(17.2%). Pearson's coefficient analysis showed negative correlation between serum selenium level with severity of systolic blood pressure (Correlation Coefficient (r) = -0.593), diastolic blood pressure(r = -0.519) and severity of preeclampsia(r = -0.598). CONCLUSION: Serum selenium levels of pre-eclamptic women were significantly lower compared to that of normotensive pregnant controls and selenium deficiency occurred significantly more among the preeclamptic pregnant women compared to the normotensive controls. Selenium level dynamics in pregnancy possibly could play a role in the incidence of pre-eclampsia among pregnant women.

Serum antioxidant micronutrient levels in pre-eclamptic pregnant women in Enugu, south-East Nigeria: a comparative cross-sectional analytical study.

BACKGROUND: Pre-eclampsia is a common obstetric complication of pregnancy in Nigeria, and oxidative stress has been implicated in its aetiopathogenesis. Despite this fact, there is a paucity of information regarding the serum antioxidant micronutrient status of pre-eclamptic Nigerian women. The objective of the was to determine the mean serum levels of some antioxidant trace elements (copper, zinc, selenium, magnesium, manganese) in pre-eclamptic pregnant women and compare with that of healthy pregnant women in Enugu, South-Eastern, Nigeria. METHODS: A cross-sectional analytical study was carried out at the Obstetrics and Gynaecology department of the University of Nigeria, Teaching Hospital Ituku-Ozalla, Enugu. Using atomic absorption spectrophotometry, the sera of 81 pregnant pre-eclamptic and 81 matched healthy pregnant controls were analyzed for the antioxidant micronutrients. Both descriptive and inferential analysis was performed using the statistical package for social sciences (SPSS) version 21.0 and a P value of < 0.05 was considered to be statistically significant. RESULTS: The mean serum levels of copper, selenium, and magnesium were found to be significantly lower in the pre-eclamptic pregnant group when compared to the healthy pregnant controls (p < 0.05). The mean serum levels of zinc and manganese did not differ between the two groups (p > 0.05). All the mean serum levels of micro-nutrients studied did not vary by category of pre-eclampsia (with or without severity findings) except manganese which was significantly lower in pre-eclamptic women without severity findings when compared to those with severity findings (p = 0.043). CONCLUSIONS: The serum levels of copper, selenium, and magnesium were significantly lower among pre-eclamptics when compared to their normal healthy controls. Low levels of selenium, copper, and magnesium may have contributed to the incidence of pre-eclampsia in our environment.

Vitamin-D dysregulation in early- and late-onset preeclampsia: A gestational-age matched study.

Vitamin D deficiency has been associated with preeclampsia, however, vitamin D supplementation studies have shown equivocal data on amelioration of this disease. We hypothesize that women with preeclampsia have an altered endogenous vitamin D homeostasis that counteracts the beneficial effects of vitamin D supplementation. Our study population consisted of 66 maternal/neonate dyads: 16 early-onset (<34 weeks) preeclampsia (EOP), 16 early-onset controls (EOC), 17 late-onset (≥34 weeks) preeclampsia (LOP), and 17 late-onset controls (LOC). Plasma levels of 25-OH-D and the bioactive metabolite 1α,25-(OH)2-D were studied by ELISA. Placental expression of vitamin D transporters (cubulin and megalin), metabolic genes (CYP2R1, CYP27B1, CYP24A1), and vitamin D binding protein (GC), were studied by real-time PCR, and the nuclear and cytosolic levels of the vitamin D receptor (VDR) protein were analyzed by immunoblotting. Maternal admission, maternal postpartum, and umbilical cord blood levels of 1α,25-(OH)2-D and placental nuclear vitamin D receptor protein levels, were significantly lower in EOP compared to EOC. In contrast LOP was characterized by lower 25-OH-D levels in maternal postpartum and cord blood, and decreased placental cubulin expression compared to LOC. Both EOP and LOP showed decreased placental expression of CYP2R1 and GC compared to controls. Multivariable linear regression analysis demonstrated that preeclampsia was a significant predictor of decreased 1α,25-(OH)2-D levels in early-onset subjects, while maternal BMI, but not preeclampsia, was the main predictor of decreased 25-OH-D in late-onset subjects. The highest positive correlation between the two vitamin D metabolites was observed in LOC umbilical cord blood. Finally, paired analysis of maternal metabolites before and after delivery indicated that women without preeclampsia had better maintenance of vitamin D levels. We conclude that EOP is characterized by decreased bioactivation of vitamin D and VDR in association with fetal growth restriction (FGR). In contrast, LOP is characterized by decreased 25-OH-D levels in association with decreased placental CYP2R1 and cubulin expression; and uncoupling of the 25-OH-D with the 1α,25-(OH)2-D metabolite.

Nephrotic syndrome due to preeclampsia before 20 weeks of gestation: a case report.

BACKGROUND: Preeclampsia (PE) refers to the development of hypertension and new-onset proteinuria or progressive organ damage (especially kidney) in a previously normotensive pregnant women after 20 weeks of gestation. Thus, new-onset nephrotic syndrome due to PE before 20 weeks of gestation seems to be rare, making its diagnosis difficult in this time period. CASE PRESENTATION: A 28-year-old woman presented with a new-onset nephrotic syndrome at 16 weeks of gestation. A high dose of oral glucocorticoids (prednisolone, 40 mg) was initiated for presumed glomerulonephritis since she presented with severe nephrotic syndrome before 20 weeks of gestation, however, the treatment was not effective. At 21 weeks of gestation, we confirmed that the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio was very high (sFlt-1, 13,400 pg/mL; PlGF, 21.9 pg/mL; serum sFlt-1/PlGF ratio 611.9). Therefore, we diagnosed nephrotic syndrome due to PE, and oral glucocorticoids were discontinued. After she underwent a cesarean section at 24 weeks & 3 days, we performed a kidney biopsy. Focal segmental sclerotic lesions with epithelial cell hyperplasia and foam cells in the tubular poles were seen on light microscopy. On immunofluorescence tests, C4d staining showed linear peripheral patterns in the glomeruli. Electron microscopy revealed diffuse subendothelial edema with focal foot process effacement. The histological diagnosis was severe glomerular endotheliosis with focal segmental glomerulosclerosis. Furthermore, the histology of placenta was consistent with PE. Eight months after delivery, her proteinuria disappeared completely. CONCLUSIONS: We not only confirmed an abnormal serum sFlt-1/PlGF ratio but also presented the histology compatible with pure PE in the kidney and placenta in a case of nephrotic syndrome before 20 weeks of gestation. The serum sFlt-1/PlGF ratio may be useful in determining the treatment strategy for atypical cases of pregnant women with nephrotic syndrome, particularly before 20 weeks of gestation.

Regulation of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia.

OBJECTIVE: To explore the regulatory effect of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia. PATIENTS AND METHODS: Altogether 100 patients with preeclampsia admitted to the Children & Women's Healthcare of Laiwu City were selected. They were divided into control group and experimental group according to different treatment methods. Among them, 51 patients in the control group were treated with magnesium sulfate combined with nifedipine, and 49 patients in the experimental group were treated with labetalol on the basis of the treatment in the control group. The therapeutic effects of the two methods were compared. The levels of the following factors in the two groups were compared: kallikrein expression, pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific ß1 glycoprotein (SPI), placental growth factor (PLGF), human placental prolactin (HPL), transforming growth factor ß1(TGF-ß1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin in serum and placenta tissues. RESULTS: After treatment, the blood pressure in the experimental group was lower than that in the control group (p<0.05). The expression of kallikrein in serum and placental tissue of the patients in the experimental group was higher than that of the patients in the control group (p<0.05); PAPP-A level was lower than that in the control group (p<0.05); TGF-ß1 level was higher than that in the control group (p<0.05); VCAM-1 and E-selectin were lower than those in the control group (p<0.05), and kallikrein and TGF-ß1 in serum and placenta in the non-occurrence group were higher than those in the occurrence group (p<0.05). The serum and placenta PAPP-A, VCAM-1, and E-selectin in the non-occurrence group were lower than those in the occurrence group (p<0.05). CONCLUSIONS: Magnesium sulfate combined with nifedipine and labetalol has good efficacy in the treatment of preeclampsia. They can promote the expression of endogenous kallikrein, reduce the level of pregnancy-related hypertension predictors, and weaken the infiltration ability of cytotrophoblasts.

Prevalence of vitamin D deficiency in Egyptian patients with pregnancy-induced hypertension.

Background Hypertensive disorders of pregnancy can cause severe maternal and fetal acute morbidity and mortality. Women with pre-eclampsia have been found to have alterations in calcium and vitamin D metabolism. There are conflicting results regarding the role of vitamin D deficiency in the development of pre-eclampsia. The aim was to compare 25 (OH) D level in patients with pre-eclampsia, eclampsia and normotensive pregnant women as well as to study the prevalence of Vitamin D deficiency among the 3 groups. Patients and methods Two hundred patients with pre-eclampsia, 100 with eclampsia and 200 normotensive pregnant controls were compared as regards vitamin D level. Results Mean 25(OH)D level was lower in the pre-eclampsia (14.8 ± 5.4 ng/mL) and in the eclampsia group (10.5 ± 1.6 ng/mL) than in the pregnant controls (19.5 ± 6.5 ng/mL) (P = 0.002). This difference was only significant between the eclampsia group and the pregnant controls (P = 0.02). All eclampsia cases had vitamin D insufficiency as compared to 17.5% in the pre-eclampsia group and 39.5% in the control group. Deficiency of vitamin D (<12 ng/mL) was 47.5% in the pre-eclampsia group, 80% in the eclampsia group and only 10.5% in the control group (P = 0.035). Conclusion Vitamin D deficiency is highly prevalent among Egyptian pregnant females. Our study supports the hypothesis that low vitamin D level can play a role in the development of pre-eclampsia and eclampsia. Thus, supplementation might prevent or delay the development of pre-eclampsia and eclampsia especially in patients at a high risk.

Serum calcium-magnesium ratio in women with pre-eclampsia at a tertiary hospital in Nigeria.

OBJECTIVE: To determine the serum calcium-magnesium ratio in pre-eclampsia and compare with normotensives. METHODS: A case-control study was conducted in a tertiary hospital between October 2017 and March 2018 among 81 pregnant women (27 cases and 54 controls matched for age, gestational age, and parity). An interviewer-administered questionnaire was used to obtain data on demography/clinical history. Venous blood was collected without stasis and sent for biochemical analysis. Statistical analysis used IBM SPSS 21.0. RESULTS: The levels of serum Ca2+ (7.73 + 1.24 vs 9.17 + 0.77; P<0.001), Ca2+ -Mg2+ ratio (3.36 + 0.60 vs 3.83 + 0.41; P=0.001), and Mg2+ (2.35 + 0.35 vs 2.41 + 0.16; P=0.469) were lower among cases. Serum Ca2+ level correlated negatively with systolic (r=0.45, P=0.05) and diastolic blood pressure (r=0.50, P=0.010) among the cases. Hypocalcemia was a risk factor (adjusted odds ratio [AOR] 7.63, 95% confidence interval [CI] 1.64-35.37) while social classes 2 and 3 were protective factors (AOR 0.01, 95% CI 0.00-0.46 and AOR 0.01, 95% CI 0.00-0.24, respectively) against pre-eclampsia. CONCLUSION: The result of this research supported the implication of micronutrients in pre-eclampsia and may help to understand the pathophysiological process of pre-eclampsia. It will also help to establish and enhance existing preventive strategies for the condition. The recommendation by WHO on calcium supplementation in pregnancy as a step in preventing the occurrence of pre-eclampsia should be practiced.

Homocysteine: Its Possible Emerging Role in At-Risk Population Groups.

Increased plasma homocysteine is a risk factor for several pathological disorders. The present review focused on the role of homocysteine (Hcy) in different population groups, especially in risk conditions (pregnancy, infancy, old age), and on its relevance as a marker or etiological factor of the diseases in these age groups, focusing on the nutritional treatment of elevated Hcy levels. In pregnancy, Hcy levels were investigated in relation to the increased risk of adverse pregnancy outcomes such as small size for gestational age at birth, preeclampsia, recurrent abortions, low birth weight, or intrauterine growth restriction. In pediatric populations, Hcy levels are important not only for cardiovascular disease, obesity, and renal disease, but the most interesting evidence concerns study of elevated levels of Hcy in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Finally, a focus on the principal pathologies of the elderly (cardiovascular and neurodegenerative disease, osteoporosis and physical function) is presented. The metabolism of Hcy is influenced by B vitamins, and Hcy-lowering vitamin treatments have been proposed. However, clinical trials have not reached a consensus about the effectiveness of vitamin supplementation on the reduction of Hcy levels and improvement of pathological condition, especially in elderly patients with overt pathologies, suggesting that other dietary and non-dietary factors are involved in high Hcy levels. The importance of novel experimental designs focusing on intra-individual variability as a complement to the typical case-control experimental designs and the study of interactions between different factors it should be emphasized.

A pilot study of alterations in oxidized angiotensinogen and antioxidants in pre-eclamptic pregnancy.

The oxidation status of angiotensinogen (AGT) may have a critical role in pre-eclampsia. We used a validated, quantitative, mass spectrometry-based method to measure the oxidized and total AGT levels in plasma of pre-eclamptic women (n = 17), normotensive-matched controls (n = 17), and healthy non-pregnant women (n = 10). Measurements of plasma glutathione peroxidase (GPx) activity and serum selenium concentrations were performed as markers of circulating antioxidant capacity. Higher proportions of oxidized AGT in plasma from pre-eclamptic women compared to matched normotensive pregnant controls (P = 0.006), whilst maintaining a similar total plasma AGT concentration were found. In the pre-eclamptic group, blood pressure were correlated with the proportion of oxidized AGT; no such correlation was seen in the normotensive pregnant women. Plasma GPx was inversely correlated with oxidized AGT, and there was an inverse association between serum selenium concentration and the proportion of oxidized AGT. This is the first time that oxidized AGT in human plasma has been linked directly to antioxidant status, providing a mechanism for the enhanced oxidative stress in pre-eclampsia. We now provide pathophysiological evidence that the conversion of the reduced form of AGT to its more active oxidized form is associated with inadequate antioxidant status and could indeed contribute to the hypertension of pre-eclampsia.