Association of age at menarche with gestational hypertension and preeclampsia: A large prospective cohort in China.

This study explored the potential association between age at menarche and the risks of gestational hypertension and preeclampsia in Chinese women. Data were sourced from the China-US Collaborative Project for Neural Tube Defects Prevention, a large population-based cohort study. Our study consisted of 209 411 women pre-registered for pregnancy in two provinces in South China. Trained healthcare workers measured blood pressure at registration and recorded other pertinent health information. Using logistic regression, we assessed the correlations between age at menarche and the likelihood of developing gestational hypertension and preeclampsia, considering confounders such as maternal age, body mass index, ethnicity, parity, folic acid supplementation, education level, and occupation. The observed incidences for gestational hypertension and preeclampsia were 9.65% and 2.54%, respectively. The adjusted odds ratios (ORs) for gestational hypertension, based on age at menarche, were as follows: ≤13 years, 1.18 (95% confidence interval: 1.11-1.26); 14 years, 1.09 (1.04-1.15); 15 years, 1.11 (1.06-1.16); 16 years, 1.06 (1.01-1.12); and ≥17 years, 1.00 (reference; P for trend < .001). The correlation between age at menarche and preeclampsia varied across age groups, with the following respective ORs: 1.35 (1.20-1.52), 1.21 (1.09-1.34), 1.27 (1.15-1.39), 1.14 (1.03-1.26), and 1.00 (reference; P for trend < .001). This association appeared to be more pronounced in women with no folic acid supplementation and those with a lower education level. In conclusion, an earlier age at menarche seems to be linked to increased risks of gestational hypertension and preeclampsia.

The association between dietary mineral intake and the risk of preeclampsia in Chinese pregnant women: a matched case-control study.

Previous studies on the relationship between dietary minerals and preeclampsia (PE) have given inconsistent results. The aim of this study was to further clarify the relationship between dietary minerals intake and PE in Chinese pregnant women. In this study, 440 pairs of hospital-based preeclamptic and healthy women were matched 1:1. Dietary intake was obtained through a 78-item semi-quantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were plotted to evaluate the dose-response relationship between dietary minerals intake and PE. This study found significant inverse associations for dietary intake of calcium, magnesium, phosphorus, iron, copper, manganese and zinc and the risk of PE in both univariate and multivariate models (all P- trend < 0.05). After adjusting for possible confounders, compared with the lowest quartile, the odds ratio of the highest quartile was 0.74 (95% CI 0.56-0.98) for calcium, 0.63 (95% CI 0.42-0.93) for magnesium, 0.45 (95% CI 0.31-0.65) for phosphorus, 0.44 (95% CI 0.30-0.65) for iron, 0.72 (95% CI 0.53-0.97) for copper, 0.66 (95% CI 0.48-0.91) for manganese and 0.38 (95% CI 0.25-0.57) for zinc. In addition, a reverse J-shaped relationship between dietary minerals intake and PE risk was observed (P-overall association < 0.05). In Chinese pregnant women, a higher intake of dietary minerals, including calcium, magnesium, phosphorus, copper, iron, manganese, and zinc was associated with a lower odds of PE.

Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy.

BACKGROUND: Whether treatment of gestational diabetes before 20 weeks' gestation improves maternal and infant health is unclear. METHODS: We randomly assigned, in a 1:1 ratio, women between 4 weeks' and 19 weeks 6 days' gestation who had a risk factor for hyperglycemia and a diagnosis of gestational diabetes (World Health Organization 2013 criteria) to receive immediate treatment for gestational diabetes or deferred or no treatment, depending on the results of a repeat oral glucose-tolerance test [OGTT] at 24 to 28 weeks' gestation (control). The trial included three primary outcomes: a composite of adverse neonatal outcomes (birth at <37 weeks' gestation, birth trauma, birth weight of ≥4500 g, respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia), pregnancy-related hypertension (preeclampsia, eclampsia, or gestational hypertension), and neonatal lean body mass. RESULTS: A total of 802 women underwent randomization; 406 were assigned to the immediate-treatment group and 396 to the control group; follow-up data were available for 793 women (98.9%). An initial OGTT was performed at a mean (±SD) gestation of 15.6±2.5 weeks. An adverse neonatal outcome event occurred in 94 of 378 women (24.9%) in the immediate-treatment group and in 113 of 370 women (30.5%) in the control group (adjusted risk difference, -5.6 percentage points; 95% confidence interval [CI], -10.1 to -1.2). Pregnancy-related hypertension occurred in 40 of 378 women (10.6%) in the immediate-treatment group and in 37 of 372 women (9.9%) in the control group (adjusted risk difference, 0.7 percentage points; 95% CI, -1.6 to 2.9). The mean neonatal lean body mass was 2.86 kg in the immediate-treatment group and 2.91 kg in the control group (adjusted mean difference, -0.04 kg; 95% CI, -0.09 to 0.02). No between-group differences were observed with respect to serious adverse events associated with screening and treatment. CONCLUSIONS: Immediate treatment of gestational diabetes before 20 weeks' gestation led to a modestly lower incidence of a composite of adverse neonatal outcomes than no immediate treatment; no material differences were observed for pregnancy-related hypertension or neonatal lean body mass. (Funded by the National Health and Medical Research Council and others; TOBOGM Australian New Zealand Clinical Trials Registry number, ACTRN12616000924459.).

Mode of delivery and maternal vitamin D deficiency: an optimized intelligent Bayesian network algorithm analysis of a stratified randomized controlled field trial.

This study aimed to elucidate the algorithm of various influential factors relating to the association between 25-hydroxyvitamin D (25(OH)D) concentration at delivery and mode of delivery. The investigation constituted a secondary analysis using data collected as part of the Khuzestan Vitamin D Deficiency Screening Program in Pregnancy, which is a stratified randomized vitamin D supplementation-controlled trial comprising 1649 eligible pregnant women. The Bayesian Network (BN) method was utilized to determine the association algorithm between diverse influential factors associated with maternal vitamin D and mode of delivery. The optimized intelligent BN algorithm revealed that women presenting with moderate (35.67%; 95% CI: 33.36-37.96) and severe vitamin D deficiency (47.22%; 95% CI: 44.81-49.63) at delivery were more likely to undergo cesarean section than those presenting with normal concentrations of this nutritional hormone (18.62%; 95% CI: 16.74-20.5). The occurrence probabilities of preeclampsia in mothers with normal, moderate, and severe vitamin D deficiency at delivery were (1.5%; 95% CI: 0.92-2.09), (14.01%; 95% CI: 12.33-15.68), and (26.81%; 95% CI: 24.67-28.95), respectively. Additionally, mothers with moderate (11.81%; 95% CI: 10.25-13.36) and severe (27.86%; 95% CI: 25.69-30.02) vitamin D deficiency exhibited a higher probability of preterm delivery in comparison to those presenting with normal concentrations (1.12%; 95% CI: 0.62-1.63). This study demonstrated that the vitamin D status of pregnant women at delivery could directly affect the mode of delivery and indirectly through maternal complications, such as preeclampsia and preterm delivery, leading to a higher occurrence probability of cesarean section.

Perinatal Outcomes After Bariatric Surgery Compared With a Matched Control Group.

OBJECTIVE: To evaluate perinatal outcomes associated with pregnancy after bariatric surgery within a large integrated health care system using propensity score matching. METHODS: We conducted a retrospective cohort study that evaluated perinatal outcomes in pregnant patients after bariatric surgery from January 2012 through December 2018. History of bariatric surgery was identified by using International Classification of Diseases codes and a clinical database. Primary outcomes were preterm birth (PTB), gestational hypertension, preeclampsia, impaired glucose tolerance or gestational diabetes, a large-for-gestational-age (LGA) or small-for-gestational-age (SGA) neonates, and cesarean birth. Propensity scores were estimated by using logistic regression that accounted for age at delivery, prepregnancy body mass index, year of delivery, parity, neighborhood deprivation index, race and ethnicity, insurance status, initiation of prenatal visit in the first trimester, smoking during pregnancy, chronic hypertension, and preexisting diabetes. Five patients in the control group were matched to each patient in the case group on linear propensity score, and modified Poisson regression was used to adjust for covariates. Sensitivity analyses by timing and type of surgery were performed. RESULTS: We identified a case cohort of 1,591 pregnancies in patients after bariatric surgery and a matched cohort of 7,955 pregnancies in patients who had not undergone bariatric surgery. Demographic characteristics were similar in both groups. In multivariate models, pregnancy after bariatric surgery was associated with a decreased risk of preeclampsia (7.5% vs 10.2%, adjusted relative risk [aRR] 0.72, 95% CI 0.60-0.86), gestational diabetes or impaired fasting glucose (23.5% vs 35.0%, aRR 0.73, 95% CI 0.66-0.80), and LGA (10.6% vs 19.9%, aRR 0.56, 95% CI 0.48-0.65) and an increased risk of SGA (10.9% vs 6.6%, aRR 1.51, 95% CI 1.28-1.78). No significant differences were observed in PTB, gestational hypertension and cesarean delivery. CONCLUSION: Pregnancy after bariatric surgery in a racially and ethnically diverse cohort of patients is associated with decreased risk of preeclampsia, gestational diabetes or impaired fasting glucose, and LGA neonates; it is also associated with an increased risk of SGA neonates compared with pregnant patients in a matched control group.

Maternal folate status and placental vascular malperfusion: Findings from a high-risk US minority birth cohort.

INTRODUCTION: Maternal folate deficiency was associated with preeclampsia (PE) and PE was associated with placental maternal vascular malperfusion (MVM). However, no study has examined the association of maternal folate status with placental MVM. METHODS: We examined the association of maternal folate status and placental MVM in the Boston Birth Cohort. Primary exposure variables were maternal self-reported multivitamin supplement (<2, 3-5, >5 times/week) per trimester; and plasma folate levels (nmol/L) after birth. Primary outcome was presence/absence of placental MVM defined by the Amsterdam Placental Workshop Group standard classification. Covariates included demographics, chronic hypertension, clinically diagnosed PE, eclampsia and HELLP syndrome, gestational and pre-gestational diabetes, overweight/obesity, maternal cigarette smoking and alcohol use. Associations between folate and placental MVM were evaluated using multivariate logistic regressions. RESULTS: Of 3001 mothers in this study, 18.8% of mothers had PE, 37.5% had MVM. Mothers with the lowest self-reported frequency of folate intake had the highest risk of MVM (OR 1.45, 95% CI 1.03-2.05), after adjusting for the covariates. Consistently, among a subset of 939 mothers with plasma folate levels, folate insufficiency was associated with increased risk of MVM (OR 1.65, 95% CI 1.03-2.63), after adjusting for the covariables. As expected, mothers with low folate and placental MVM had highest rates of PE compared to those of high folate and no MVM (p < 0.001). DISCUSSION: In this high-risk birth cohort, low maternal folate status was associated with increased risk of placental MVM. Further investigation should explore the association between folate status, placental findings and the great obstetrical syndrome.

The association between maternal tea consumption and the risk of pregnancy induced hypertension: A retrospective cohort study in Lanzhou, China.

BACKGROUND: Existing evidence on the relationship between maternal tea consumption and pregnancy induced hypertension (PIH) is inconclusive. This study aimed to evaluate the association between maternal tea consumption and the risk of PIH. METHODS: This study analysed the data of women without chronic hypertension who participated in a retrospective birth cohort study conducted from 2010 to 2012 at the Gansu Provincial Maternity and Child Care Hospital in Lanzhou, China. Multivariable logistic regression models were used to estimate the association between tea consumption and the risk of PIH and its clinical subtypes by different tea exposure time windows. RESULTS: Among the 10,452 women included in this study, tea consumption during pregnancy was significantly associated with an increased risk of PIH (odds ratio [OR] = 1.44, 95 % confidence interval [CI]: 1.01, 2.05), gestational hypertension (OR = 1.86, 95 % CI: 1.07, 3.21), and early-onset preeclampsia (OR = 2.93, 95 % CI: 1.21, 7.09). This was especially the case with black tea (OR = 3.57, 95 % CI: 1.67, 7.62). CONCLUSIONS: Tea consumption during pregnancy might be associated with an increased risk of PIH, gestational hypertension, and early-onset preeclampsia. These findings have important implications for public health in reducing the PIH.

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.

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.

The association between dietary fatty acid intake and the risk of developing preeclampsia: a matched case-control study.

The association between dietary fat intake during pregnancy and the risk of developing preeclampsia has been examined in many epidemiological studies, but the results remain inconsistent. The aim of this study was to clarify this association in pregnant Chinese women. After conducting 1:1 matching, 440 pairs consisting of pregnant women with preeclampsia and hospital-based, healthy pregnant women matched by gestational week (± 1 week) and age (± 3 years) were recruited. A 79-item semi-quantitative food frequency questionnaire administered during face-to-face interviews was used to estimate the participants' dietary intake of fatty acids. We found that the intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were inversely associated with the risk of developing preeclampsia. Compared with the lowest quartile intake, the multivariate-adjusted odds ratios (95% confidence interval) of the highest quartile intake were 0.42 (0.26-0.68, p-trend < 0.001) for EPA, 0.52 (0.3-0.83, p-trend = 0.005) for DHA, and 0.41 (0.19-0.88, p-trend = 0.007) for AA. However, we did not observe any significant associations between the intake of total fatty acids, saturated fatty acids, and mono-unsaturated fatty acids and the risk of developing preeclampsia. Our results showed that the dietary intake of long-chain polyunsaturated fatty acids (i.e., EPA, DHA, and AA) may protect pregnant Chinese women against the development of preeclampsia.

Vitamin D insufficiency among Danish pregnant women-Prevalence and association with adverse obstetric outcomes and placental vitamin D metabolism.

INTRODUCTION: In pregnancy, vitamin D deficiency is associated with increased risk of fetal growth restriction and preeclampsia. The underlying mechanisms are not known, but placental dysfunction is believed to play a role. In a Danish population, where health authorities recommend a 10 µg/day vitamin D supplement during pregnancy, we explored current use of vitamin D supplements and vitamin D status. In term placentas, alterations in vitamin D metabolism and placental growth, evaluated by the key placental growth factor pregnancy-associated plasma protein-A (PAPP-A), and their relation to vitamin D insufficiency were investigated. MATERIAL AND METHODS: We included 225 randomly selected pregnant women attending a nuchal translucency scan at gestational weeks 11-14. Information on use of vitamin D supplements and body mass index (BMI) at inclusion was obtained using self-reported questionnaires. Plasma 25-hydroxyvitamin D was measured at inclusion and correlated with pregnancy outcomes and placental biology, as judged by expression of PAPP-A and enzymes involved in vitamin D metabolism (CYP24A1, CYP27B1) in term placentas. RESULTS: Vitamin D supplements were used by 92% of the women, but 42% were vitamin D insufficient (plasma 25-hydroxyvitamin D <75 nmol/L). Eleven women with singleton pregnancies developed fetal growth restriction or preeclampsia. In this small subset, first-trimester mean plasma 25-hydroxyvitamin D was lower in women who developed fetal growth restriction (43 ± 33nmol/L; n = 3; P = .006) and there was a tendency towards lower plasma 25-hydroxyvitamin D among women who developed preeclampsia (65 ± 19 nmol/L; n = 8; P = .08) in third trimester compared with uncomplicated pregnancies (79 ± 22 nmol/L; n = 187). In term placentas, PAPP-A expression was lower among participants with first-trimester vitamin D insufficiency (P = .009; n = 30) but no correlation was found between plasma 25-hydroxyvitamin D and mRNA expression of CYP24A1 (P = .67) and CYP27B1 (P = .34). BMI was negatively correlated with plasma 25-hydroxyvitamin D (P = .03) and positively correlated with placental mRNA expression of CYP24A1 (P = .003; n = 30). CONCLUSIONS: Despite high compliance with official guidelines regarding vitamin D supplements, vitamin D insufficiency was frequent and the findings indicate that vitamin D insufficiency may affect placental growth. High BMI was associated with vitamin D insufficiency and increased placental vitamin D turnover, but further investigations are needed.

The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: A randomized placebo-controlled study.

BACKGROUND: Low dietary calcium is associated with the hypertensive disorders of pregnancy, and evidence suggests that the risks associated with pre-eclampsia are reduced by calcium supplementation. In the general (non-pregnant) population, low dietary calcium intake is associated with hypertension with inconsistent evidence that calcium supplementation may reduce blood pressure. Women with pre-eclampsia are also at risk of hypertension later in life. An exploratory sub-study among early participants enrolled in the WHO long-term calcium supplementation in women at high risk of pre-eclampsia (CAP) study reported a trend to more blood pressure reduction with calcium in non-pregnant women with previous severe as opposed to non-severe pre-eclampsia. The current study reports the effects of low-dose calcium supplementation in non-pregnant women in the complete trial cohort. METHODS: The CAP Study was a multi-country randomized, double-blind placebo-controlled clinical trial to test the hypothesis that calcium deficiency may play a role in the genesis of pre-eclampsia in early pregnancy. From 2011 to 2016, non-pregnant women who had pre-eclampsia or eclampsia in their most recent pregnancy were randomized to receive either 500 mg/day elemental calcium or placebo. In this sub-study we compared the change in blood pressure from baseline to the 12-week visit between participants receiving calcium versus placebo for those not pregnant at the 12-week visit. RESULTS: Of 1355 women randomized, 810 attended a 12-week visit without being pregnant, of whom 791 had blood pressure measurements available for both baseline and 12-week visits. There was a greater reduction in blood pressure in the calcium group compared with the placebo group for systolic pressure (difference 3.1 mmHg, 95% CI 0.8 to 5.4) and mean arterial pressure (MAP) (difference 2.0 mmHg, 95% CI 0.1 to 3.8). The difference in diastolic blood pressure reduction (1.4 mmHg, 95% CI -0.5 to 3.3) was not statistically significant (p = 0.140). For women with previous pre-eclampsia with severe features (n = 447), there was significantly greater reduction in blood pressure in the calcium than the placebo group (difference for systolic 4.0, 95% CI 0.7 to 7.3; diastolic 3.0, 95% CI 0.5 to 5.5 and mean arterial pressure 3.3, 95% CI 0.8 to 5.9 mmHg). For women with previous pre-eclampsia without severe features (n = 344), there were no significant differences between calcium and placebo groups. ANOVA analysis found no statistically significant interaction between previous pre-eclampsia severity and treatment, for systolic (p = 0.372), diastolic (p = 0.063) or mean blood pressure (p = 0.103). CONCLUSIONS: Low-dose calcium supplementation significantly reduced systolic and mean arterial pressure in non-pregnant women with previous pre-eclampsia. We did not confirm a greater calcium effect in women with previous pre-eclampsia with severe versus non-severe features. The effect of low-dose calcium is of importance since even modest blood pressure reductions at a population level may have important benefits in terms of reduced major complications of hypertension. This study adds to the mounting evidence of health benefits which could be achieved for populations with low dietary calcium through strategies to increase calcium intake, particularly among women at high risk due to previous pre-eclampsia. CLINICAL TRIAL REGISTRATION: The trial was registered with the Pan-African Clinical Trials Registry, registration number PACTR201105000267371 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=267).

Pre-Pregnancy Obesity vs. Other Risk Factors in Probability Models of Preeclampsia and Gestational Hypertension.

In the face of the obesity epidemic around the world, attention should be focused on the role of maternal obesity in the development of pregnancy. The purpose of this analysis was to evaluate the prediction of preeclampsia (PE) and isolated gestational hypertension (GH) for a number of maternal factors, in order to investigate the importance of pre-pregnancy obesity (body mass index, BMI ≥ 30 kg/m2), compared to other risk factors (e.g., prior PE, pregnancy weight gain (GWG), infertility treatment, interpregnancy interval, family history, the lack of vitamin supplementation, urogenital infection, and socioeconomic factors). In total, 912 women without chronic diseases were examined in a Polish prospective cohort of women with a single pregnancy (recruited in 2015-2016). Separate analyses were performed for the women who developed GH (n = 113) vs. 775 women who remained normotensive, as well as for those who developed PE (n = 24) vs. 775 controls. The probability of each disease was assessed for the base prediction model (age + primiparity) and for the model extended by one (test) variable, using logistic regression. Three measures were used to assess the prediction: area under curve (AUC) of the base and extended model, integrated discrimination improvement (IDI) (the index shows the difference between the value of the mean change in the predicted probability between the group of sick and healthy women when a new factor is added to the model), and net reclassification improvement (NRI) (the index focuses on the reclassification table describing the number of women in whom an upward or downward shift in the disease probability value occurred after a new factor had been added, including results for healthy and sick women). In the GH prediction, AUC increased most strongly when we added BMI (kg/m2) as a continuous variable (AUC = 0.716, p < 0.001) to the base model. The highest IDI index was obtained for prior GH/PE (IDI = 0.068, p < 0.001). The addition of BMI as a continuous variable or BMI ≥ 25 kg/m2 improved the classification for healthy and sick women the most (NRI = 0.571, p < 0.001). In the PE prediction, AUC increased most strongly when we added BMI categories (AUC = 0.726, p < 0.001) to the base model. The highest IDI index was obtained for prior GH/PE (IDI = 0.050, p = 0.080). The addition of BMI categories improved the classification for healthy and sick women the most (NRI = 0.688; p = 0.001). After summing up the results of three indexes, the probability of hypertension in pregnancy was most strongly improved by BMI, including BMI ≥ 25 kg/m2 for the GH prediction, and BMI ≥ 30 kg/m2 for the PE prediction. Main conclusions: Pre-pregnancy BMI was the most likely factor to increase the probability of developing hypertension in pregnancy, compared to other risk factors. Hierarchies of PE and GH risk factors may suggest different (or common) mechanisms of their development.

The relationship among vitamin D, TLR4 pathway and preeclampsia.

Preeclampsia is a pregnancy-specific syndrome that has been the greatest cause of maternal and fetal morbidity and mortality. The impaired outcomes are related to maternal and the offspring healthy in the short and long-term. Although preeclampsia origins remain unclear, it is well known that there is impaired trophoblast invasion with culminant abnormal immune response. The early and late-onset preeclampsia have been studied, the subtypes have the same difference in the placentation and inflammatory features. Dietary compounds can stimulate or inhibit the activation of immune cells. Low vitamin D intake has been linked to impaired fetal development, intrauterine growth restriction, and preeclampsia. Vitamin D has been described as an anti-inflammatory effect. It can downregulate pro-inflammatory cytokines expression by the inhibition of the Nuclear Factor-ĸB pathway signaling cascade. High vitamin D levels could attenuate the immune response. On the other hand, vitamin D deficiency may contribute to increasing pro-inflammatory state. In preeclampsia, there is a reduced expression of vitamin D receptor and its metabolism is disrupted. In this review, we aimed to discuss the role of vitamin D as an anti-inflammatory agent in relation to the pro-inflammatory process of preeclampsia through the activation of the TLR4 pathway. Although there are limited studies showing the relation between vitamin D and lower risk of preeclampsia, the maternal status of vitamin D seems to influence the risk of PE development. Therefore, vitamin D supplementation in women may be a strategy to improve pregnancy outcomes.

Comparing levels of vitamin D, calcium and phosphorus in normotensive pregnant women and pregnant women with preeclampsia.

Vitamin D and calcium deficiency have been reported as one of the causes of preeclampsia. In this study, levels of vitamin D, calcium and phosphorus were evaluated in 51 normotensive pregnant women and 52 women with preeclampsia at the gestational age between 28 and 36 weeks in Tabriz. Logistic regression and general linear models were used for comparing levels and means of vitamin D, calcium and phosphorus between the two groups adjusting for education and Body Mass Index (BMI). The results showed that mean serum vitamin D (p = .73), calcium (p = .12) and phosphorus (p = .60) levels were not significantly different between the groups after adjusting for education and BMI. Based on this study, no relationship was observed between vitamin D deficiency and preeclampsia; however, it was seen that the hypocalcaemia could increase the risk of preeclampsia up to 8.5 times. Based on our results and the literature, it seems that further studies need to be done to provide more insights into this area.Impact statementWhat is already known on this subject? Preeclampsia is one of the three leading causes of maternal morbidity and mortality worldwide. Despite the importance of preeclampsia, the causes and methods of prevention of this disease are still unknown. Deficiency of vitamin D affects the calcium balance of mothers and fetuses and has also been reported as one of the causes of preeclampsia disease. Reducing serum calcium can lead to increased blood pressure in preeclamptic women. Changes in calcium metabolism during pregnancy could be one of the potential causes of preeclampsia. Although the association of vitamin D, calcium and phosphorus with preeclampsia have been discussed previously, the results are not consistent.What do the results of this study add? The results showed that mean serum vitamin D, calcium and phosphorus levels were not significantly different between the groups.What are the implications of these findings for clinical practice and/or future research? Based on this study, no relationship was observed between vitamin D deficiency and preeclampsia; however, it was seen that the hypocalcaemia could increase the risk of preeclampsia by up to 8.5 times. Based on our results and the literature, it seems that further studies need to be done to provide more insights into this area.

Evidence of an Association Between Vitamin D Deficiency and Preterm Birth and Preeclampsia: A Critical Review.

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.

Pregnancy Outcomes of Women Additionally Diagnosed as Gestational Diabetes by the International Association of the Diabetes and Pregnancy Study Groups Criteria.

BACKGROUND: We investigated the pregnancy outcomes in women who were diagnosed with gestational diabetes mellitus (GDM) by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria but not by the Carpenter-Coustan (CC) criteria. METHODS: A total of 8,735 Korean pregnant women were identified at two hospitals between 2014 and 2016. Among them, 2,038 women participated in the prospective cohort to investigate pregnancy outcomes. Diagnosis of GDM was made via two-step approach with 50-g glucose challenge test for screening followed by diagnostic 2-hour 75-g oral glucose tolerance test. Women were divided into three groups: non-GDM, GDM diagnosed exclusively by the IADPSG criteria, and GDM diagnosed by the CC criteria. RESULTS: The incidence of GDM was 2.1% according to the CC criteria, and 4.1% by the IADPSG criteria. Women diagnosed with GDM by the IADPSG criteria had a higher body mass index (22.0±3.1 kg/m² vs. 21.0±2.8 kg/m², P<0.001) and an increased risk of preeclampsia (odds ratio [OR], 6.90; 95% confidence interval [CI], 1.84 to 25.87; P=0.004) compared to non-GDM women. Compared to neonates of the non-GDM group, those of the IADPSG GDM group had an increased risk of being large for gestational age (OR, 2.39; 95% CI, 1.50 to 3.81; P<0.001), macrosomia (OR, 2.53; 95% CI, 1.26 to 5.10; P=0.009), and neonatal hypoglycemia (OR, 3.84; 95% CI, 1.01 to 14.74; P=0.049); they were also at an increased risk of requiring phototherapy (OR, 1.57; 95% CI, 1.07 to 2.31; P=0.022) compared to the non-GDM group. CONCLUSION: The IADPSG criteria increased the incidence of GDM by nearly three-fold, and women diagnosed with GDM by the IADPSG criteria had an increased risk of adverse pregnancy outcomes in Korea.

Shrunken pore syndrome, preeclampsia, and markers of NO metabolism in pregnant women during the first trimester.

Shrunken pore syndrome (SPS) is a condition that manifests itself as the decreased renal clearance of low-molecular-weight proteins but normal clearance of creatinine. Pregnant women with evidence of SPS during the first trimester have an increased risk of developing preeclampsia (PE). The nitric oxide (NO) metabolism markers arginine and ADMA, especially their ratio (Arg/ADMA), are recognized markers of endothelial dysfunction. The aim of this nested case-control study was to establish first-trimester reference intervals (RI) for markers of NO metabolism and to study these markers in women with evidence of SPS at the end of the first trimester. Seventy-four women were stratified in the first trimester according to evidence of SPS (SPS + or SPS-) and the occurrence of PE during subsequent pregnancy (PE + or PE-), as follows: SPS-/PE-, SPS+/PE-, SPS-/PE+, and SPS+/PE+. RIs were determined according to the CLSI EP28-A3c guidelines. Serum Arg and ADMA levels were analyzed. The Arg and ADMA concentrations did not differ among the four groups. However, women in the SPS+/PE + group had a significantly lower Arg/ADMA ratio than those in the other 3 groups (p = .02). In conclusion, we defined the first-trimester RI of Arg, ADMA and the Arg/ADMA ratio as markers of NO metabolism. Our results suggest that SPS in the first trimester predicts a pathophysiological hallmark of subsequent PE, i.e. lower NO production leading to increased vessel tone. Early identification of women at risk for later PE could lead to adaptive prophylactic interventions, such as supplementation with Arg or an NO-donor drug in order to mitigate the risk of developing PE.

Fat intake during pregnancy and risk of preeclampsia: a prospective cohort study in Denmark.

BACKGROUND: Previous studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), may decrease the risk of preeclampsia, but many suffer from important methodological limitations. METHODS: We prospectively examined the association between fat intake during pregnancy and preeclampsia and among 65,220 singleton pregnancies in the Danish National Birth Cohort (1996-2002). Women were asked to report their diet around gestation week 20 with a food frequency questionnaire. Preeclampsia diagnosis was obtained via linkage with the Danish National Patient Registry. We estimated relative risks (RR) and 95% confidence intervals (95% CI) of preeclampsia and severe preeclampsia according to fat intake using logistic regression models with generalized estimating equations to account for repeated pregnancies per woman while adjusting for potential confounders. RESULTS: We documented 1302 cases of preeclampsia, including 301 cases of severe preeclampsia. Intake of long-chain omega-3 fatty acids was associated to preeclampsia. Women in the top quintile of DHA intake had a lower risk of preeclampsia (RR 0.67 (0.51-0.89)) and severe preeclampsia (RR 0.46 (0.25-0.83)) than women in the bottom quintile. Women who met daily recommended intake of EPA+DHA according to the Dietary Guidelines for Americans (≥250 mg/day), had a lower risk of severe preeclampsia (RR 0.77 (0.60-0.99)), but not of preeclampsia (RR 0.93 (0.82-1.05)). Conversely, ALA intake was associated with higher risk of severe preeclampsia (RR 1.71 (1.07-2.75)). CONCLUSIONS: Higher intake of DHA is inversely related to preeclampsia and severe preeclampsia, whereas ALA increases the risk of severe preeclampsia among Danish women.

Population-based trends and risk factors of early- and late-onset preeclampsia in Taiwan 2001-2014.

BACKGROUND: Preeclampsia, a multisystem disorder in pregnancies complicates with maternal and fetal morbidity. Early- and late-onset preeclampsia, defined as preeclampsia developed before and after 34 weeks of gestation, respectively. The early-onset disease was less prevalent but associated with poorer outcomes. Moreover, the risk factors between early -and late- onset preeclampsia could be differed owing to the varied pathophysiology. In the study, we evaluated the incidences, trends, and risk factors of early- and late- onset preeclampsia in Taiwan. METHODS: This retrospective population-based cohort study included all ≧20 weeks singleton pregnancies resulting in live-born babies or stillbirths in Taiwan between January 1, 2001 and December 31, 2014 (n = 2,884,347). The data was collected electronically in Taiwanese Birth Register and National Health Insurance Research Database. The incidences and trends of early- and late-onset preeclampsia were assessed through Joinpoint analysis. Multivariate logistic regression was used to analyze the risk factors of both diseases. RESULTS: The age-adjusted overall preeclampsia rate was slightly increased from 1.1%(95%confidence interval [CI], 1.1-1.2) in 2001 to 1.3% (95%CI, 1.2-1.3) in 2012 with average annual percentage change (AAPC) 0.1%/year (95%CI, 0-0.2%). However, the incidence was remarkably increased from 1.3% (95%CI, 1.3-1.4) in 2012 to 1.7% (95%CI, 1.6-1.8) in 2014 with AAPC 1.3%/year (95%CI,0.3-2.5). Over the study period, the incidence trend in late-onset preeclampsia was steadily increasing from 0.7% (95%CI, 0.6-0.7) in 2001 to 0.9% (95%CI, 0.8-0.9) in 2014 with AAPC 0.2%/year (95%CI, 0.2-0.3) but in early-onset preeclampsia was predominantly increase from 0.5% (95%CI, 0.4-0.5) in 2012 to 0.8% (95%CI, 0.8-0.9) in 2014 with AAPC 2.3%/year (95%CI, 0.8-4.0). Advanced maternal age, primiparity, stroke, diabetes mellitus, chronic hypertension, and hyperthyroidism were risk factors of preeclampsia. Comparing early- and late-onset diseases, chronic hypertension (ratio of relative risk [RRR], 1.71; 95%CI, 1.55-1.88) and older age (RRR, 1.41; 95%CI 1.29-1.54) were more strongly associated with early-onset disease, whereas primiparity (RRR 0.71, 95%CI, 0.68-0.75) had stronger association with late-onset preeclampsia. CONCLUSIONS: The incidences of overall, and early- and late-onset preeclampsia were increasing in Taiwan from 2001 to 2014, predominantly for early-onset disease. Pregnant women with older age and chronic hypertension had significantly higher risk of early-onset preeclampsia.