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The Effect of Calcium Supplementation on Body Weight Before and During Pregnancy in Women Enrolled in the WHO Calcium and Preeclampsia Trial.
Cormick, G, Betrán, AP, Harbron, J, Seuc, A, White, C, Roberts, JM, Belizán, JM, Hofmeyr, GJ
Food and nutrition bulletin. 2020;(3):332-342
Abstract
INTRODUCTION Obesity is a major and challenging public health problem. The aim of this substudy is to evaluate the effect of calcium supplementation on body weight in women recruited in the Calcium and Preeclampsia trial. METHODS Women were recruited before pregnancy and randomized to receive a calcium supplement containing 500 mg of elemental calcium or placebo until 20 weeks' gestation; all women received 1.5 g from 20 weeks until delivery. RESULTS A total of 630 women conceived during the study, 322 allocated to calcium and 308 to placebo. Among these, 230 allocated to calcium and 227 allocated to placebo had information on body weight at baseline and at 8 weeks' gestation. During the study period, women allocated to calcium had a mean weight increase of 1.1 (SD ±5.5) kg, whereas those allocated to placebo had a mean increase of 1.5 (SD ±6.1) kg, a mean difference of 0.4 kg (95% -0.4 (-1.4 to 0.6); P = .408). Women classified as obese at the start of the trial had a lower body weight gain at 8 weeks' gestation (1.0 kg; 95% CI: -3.2 to 1.2; P = .330) and at 32 weeks' gestation (2.1 kg; 95% CI: 5.6-1.3; P = .225) if they received calcium as compared to placebo. However, none of these differences were statistically significant. CONCLUSION The smaller increase in body weight found in women supplemented with 500 mg elemental calcium daily is quantitatively consistent with previous studies. However, in this study, the difference was not statistically significant.
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Effect of vitamin D3 supplementation in pregnancy on risk of pre-eclampsia - Randomized controlled trial.
Ali, AM, Alobaid, A, Malhis, TN, Khattab, AF
Clinical nutrition (Edinburgh, Scotland). 2019;(2):557-563
Abstract
BACKGROUND Vitamin D plays pivotal role in decidualization and implantation of the placenta. Recent researches have shown that low level of vitamin D3 "25-hydroxyvitamin D (25[OH]D)" in serum is a risk factor for pre-eclampsia. Latest evidence supports role of vitamin D3 deficiency treatment in reducing the risk of pre-eclampsia. The aim of this study is to determine the effect of antenatal supplementation of vitamin D3 on the risk of pre-eclampsia and to explore the dose effect in attaining the vitamin D3 normal level. METHOD An open labelled randomized controlled study was conducted on 179 pregnant women presenting in King Fahad Medical City antenatal clinic from Oct 2012-Oct 2015. Patients with age less than 20 years or more than 40 years, pregnancy with fetal anomalies, history of hypertension, pre-eclampsia, recurrent miscarriage, chronic renal or hepatic disease and malignancy were excluded from the study. Serum 25[OH]D was analysed during the first trimester (between 6 and 12 weeks of pregnancy). Patients with vitamin D3 deficiency (serum levels <25 nmol/L) were included in the study and randomized for vitamin D3 supplementation 400 IU (Group 1) versus 4000 IU (Group 2). Both groups were compared for the prevalence of pre-eclampsia and dose effect on vitamin D level. RESULTS Of 179 gravidae enrolled, 164 completed the trial. Mean maternal 25[OH]D was significantly increased in group 2 from 16.3 ± 5 nmol/mL to 72.3 ± 30.9 nmol/mL compared with group 1 from 17.5 ± 6.7 nmol/mL to 35.3 ± 20.7 nmol/mL (p > 0.0001). The relative risk reduction (RRR) for attaining ≥75 nmol/L before delivery was significantly higher (RRR 93.2 [CI 79-98] when treated with 4000 IU. The total incidence of pre-eclampsia in the study population was 4.3%. In comparison to group 1, the group 2 reported fewer pre-eclampsia events during the study period (8.6% versus 1.2%; p < 0.05). The total number of IUGRs was lesser in the group 2 (9.6%) versus group 1 (22.2%); p = 0.027. However, other obstetric outcomes were comparable between both groups. CONCLUSION Vitamin D supplementation in the deficient group reduces the risk of pre-eclampsia and IUGR in a dose dependant manner. However larger clinical trials are essential to investigate optimum dosage of vitamin D3 in this group.
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Adverse Maternal and Neonatal Outcomes in Indicated Compared with Spontaneous Preterm Birth in Healthy Nulliparas: A Secondary Analysis of a Randomized Trial.
Tita, AT, Doherty, L, Roberts, JM, Myatt, L, Leveno, KJ, Varner, MW, Wapner, RJ, Thorp, JM, Mercer, BM, Peaceman, A, et al
American journal of perinatology. 2018;(7):624-631
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OBJECTIVE To compare the risks of adverse maternal and neonatal outcomes associated with spontaneous (SPTB) versus indicated preterm births (IPTB). METHODS A secondary analysis of a multicenter trial of vitamin C and E supplementation in healthy low-risk nulliparous women. Outcomes were compared between women with SPTB (due to spontaneous membrane rupture or labor) and those with IPTB (due to medical or obstetric complications). A primary maternal composite outcome included: death, pulmonary edema, blood transfusion, adult respiratory distress syndrome (RDS), cerebrovascular accident, acute tubular necrosis, disseminated intravascular coagulopathy, or liver rupture. A neonatal composite outcome included: neonatal death, RDS, grades III or IV intraventricular hemorrhage (IVH), sepsis, necrotizing enterocolitis (NEC), or retinopathy of prematurity. RESULTS Of 9,867 women, 10.4% (N = 1,038) were PTBs; 32.7% (n = 340) IPTBs and 67.3% (n = 698) SPTBs. Compared with SPTB, the composite maternal outcome was more frequent in IPTB-4.4% versus 0.9% (adjusted odds ratio [aOR], 4.0; 95% confidence interval [CI], 1.4-11.8), as were blood transfusion and prolonged hospital stay (3.2 and 3.7 times, respectively). The frequency of composite neonatal outcome was higher in IPTBs (aOR, 1.8; 95% CI, 1.1-3.0), as were RDS (1.7 times), small for gestational age (SGA) < 5th percentile (7.9 times), and neonatal intensive care unit (NICU) admission (1.8 times). CONCLUSION Adverse maternal and neonatal outcomes were significantly more likely with IPTB than with SPTB.
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Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial.
Wen, SW, White, RR, Rybak, N, Gaudet, LM, Robson, S, Hague, W, Simms-Stewart, D, Carroli, G, Smith, G, Fraser, WD, et al
BMJ (Clinical research ed.). 2018;:k3478
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OBJECTIVE To determine the efficacy of high dose folic acid supplementation for prevention of pre-eclampsia in women with at least one risk factor: pre-existing hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia in a previous pregnancy, or body mass index ≥35. DESIGN Randomised, phase III, double blinded international, multicentre clinical trial. SETTING 70 obstetrical centres in five countries (Argentina, Australia, Canada, Jamaica, and UK). PARTICIPANTS 2464 pregnant women with at least one high risk factor for pre-eclampsia were randomised between 2011 and 2015 (1144 to the folic acid group and 1157 to the placebo group); 2301 were included in the intention to treat analyses. INTERVENTION Eligible women were randomised to receive either daily high dose folic acid (four 1.0 mg oral tablets) or placebo from eight weeks of gestation to the end of week 16 of gestation until delivery. Clinicians, participants, adjudicators, and study staff were masked to study treatment allocation. MAIN OUTCOME MEASURE The primary outcome was pre-eclampsia, defined as hypertension presenting after 20 weeks' gestation with major proteinuria or HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). RESULTS Pre-eclampsia occurred in 169/1144 (14.8%) women in the folic acid group and 156/1157 (13.5%) in the placebo group (relative risk 1.10, 95% confidence interval 0.90 to 1.34; P=0.37). There was no evidence of differences between the groups for any other adverse maternal or neonatal outcomes. CONCLUSION Supplementation with 4.0 mg/day folic acid beyond the first trimester does not prevent pre-eclampsia in women at high risk for this condition. TRIAL REGISTRATION Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.
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Prediabetes in pregnancy, can early intervention improve outcomes? A feasibility study for a parallel randomised clinical trial.
Hughes, RCE, Rowan, J, Williman, J
BMJ open. 2018;(3):e018493
Abstract
OBJECTIVE Measurement of glycated haemoglobin (HbA1c) in early pregnancy is routine in New Zealand to identify women with diabetes and prediabetes. However, the benefit of early intervention in women with prediabetes is inconclusive. Our aim was to test the feasibility of a two-arm parallel randomised controlled trial of standard care versus early intervention in pregnancies complicated by prediabetes. SETTING Two tertiary referral centres in New Zealand. PARTICIPANTS Women <14 weeks' gestation and HbA1c ≥5.9%-6.4% (41-46 mmol/mol) measured at booking, without pre-existing diabetes. INTERVENTIONS Randomisation was done by remote web-based allocation into one of two groups. Women in the early intervention group attended an antenatal diabetes clinic, commenced daily home blood glucose monitoring, and medication was prescribed if lifestyle measures failed to maintain target blood glucose levels. Controls received lifestyle education, continued standard care with their midwife and/or obstetrician, and were asked to perform a 75 g oral glucose tolerance test at 24 weeks' gestation with a referral to clinic if this test was positive. Both groups received lifestyle questionnaires at recruitment and in late pregnancy. OUTCOME MEASURES Recruitment rate, adherence to protocol and validation of potential primary outcomes. RESULTS Recruitment rates were lower than expected, especially in Māori and Pacific women. Non-adherence to allocated treatment protocol was significant, 42% (95% CI 24% to 61%) in the early intervention group and 30% (95% CI 16% to 51%) in controls. Caesarean section and pre-eclampsia were signalled as potential primary outcomes, due to both the high observed incidence in the control group and ease of measurement. CONCLUSIONS For a future definitive trial, extending the gestation of eligibility and stepped-wedge cluster randomisation may overcome the identified feasibility issues. Consistent with published observational data, pre-eclampsia and emergency caesarean section could be included as primary outcome measures, both of which have a significant impact on maternal and neonatal morbidity and healthcare costs. TRIAL REGISTRATION NUMBER ACTRN12615000904572; Pre-results.
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Celastrol synergizes with oral nifedipine to attenuate hypertension in preeclampsia: a randomized, placebo-controlled, and double blinded trial.
Xiao, S, Zhang, M, Liang, Y, Wang, D
Journal of the American Society of Hypertension : JASH. 2017;(9):598-603
Abstract
Preeclampsia, a disease mainly manifesting as serious hypertension during pregnancy, affects expectant mothers around the globe. Celastrol, a naturally existing triterpenoid, is known to exhibit beneficial effects attenuating cardiovascular symptoms including hypertension. We here assessed the treatment outcome against preeclampsia with a combined use of celastrol and nifedipine. A total of 626 patients with preeclampsia were enrolled, screened, and assigned by random to groups receiving either nifedipine + placebo or nifedipine + celastrol orally. Time required to control hypertension as well as time before another hypertensive crisis were defined as primary end points. Secondary end points include the number of dosages required to control hypertension, as well as maternal and neonatal adverse effects. The time to control hypertension showed a marked reduction in nifedipine + celastrol group, while time before a new hypertensive crisis was significantly lengthened with the treatment, compared with the nifedipine + placebo group. The number of dosages required to control hypertension was also lower in the nifedipine + celastrol group. The two treatment groups were not statistically different regarding adverse effects, either maternal or neonatal. Results from the current study provide evidence for the potential role of celastrol serving as an effective and safe adjuvant to oral nifedipine against hypertension in patients with preeclampsia.
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Simulation Study Assessing Healthcare Provider's Knowledge of Pre-Eclampsia and Eclampsia in a Tertiary Referral Center.
Hilton, G, Daniels, K, Carvalho, B
Simulation in healthcare : journal of the Society for Simulation in Healthcare. 2016;(1):25-31
Abstract
INTRODUCTION The aim of the study was to assess knowledge of labor and delivery healthcare providers at a tertiary referral center in the management of pre-eclampsia and eclampsia. METHODS Thirteen multidisciplinary teams participated in this institutional review board-exempt study. Each group encountered the same scenario that involved a pre-eclamptic parturient who progressed to eclampsia. The participants were unaware of the scenario topic before the drill and that key interventions would be recorded and timed. Seven of 13 groups were randomized to have a cognitive aid available. RESULTS Twelve of 13 groups attempted to lower the blood pressure; however, only 7 of 12 groups used the correct first-line antihypertensive medication as per the American College of Obstetricians and Gynecologists' guidelines. All groups requested and administered the correct bolus dose of magnesium (4-6 g intravenously). Only 2 of 13 groups took appropriate action to lower the blood pressure to a "safe range" before induction of general anesthesia, and 4 of the 13 anesthesiologists made drug modifications for induction of anesthesia. None of the 7 groups randomized to have a cognitive aid used it. CONCLUSIONS Our results show widespread magnesium sulfate utilization; however, the use of antihypertensive medication is not universally administered in compliance with current guidelines. The importance of blood pressure management to reduce maternal morbidity and mortality in the setting of pre-eclampsia needs to be emphasized. Interestingly, availability of a cognitive aid did not ensure its utilization in this scenario. Findings suggest that for cognitive aids to be effectively used, it is essential that staff has been trained and become familiar with them before an emergent event.
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A comparison between the two methods of magnesium sulfate administration for duration of 12 versus 24 h after delivery in patients with severe preeclampsia.
Kashanian, M, Koohpayehzadeh, J, Sheikhansari, N, Bararpour, F, Sahraian, G, Asadolla, S
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2016;(14):2282-7
Abstract
OBJECTIVES To compare between the two methods of magnesium sulfate administration for duration of 12 versus 24 h after delivery in patients with severe preeclampsia. METHOD The study was performed as a randomized clinical trial on 182 cases of severe preeclampsia. In one group, Mg sulfate (MgSO4) was prescribed for 12 h after delivery and, in the other group, it was prescribed for 24 h after delivery. Both groups were compared for occurrence of convulsion and other adverse effects. RESULTS The women of the two groups did not have significant difference according to age, BMI, parity and gravidity, gestational age at the time of delivery. Also, systolic blood pressure, diastolic blood pressure, antihypertensive use, previous diabetes and renal disorders, gestational diabetes, and proteinuria were similar in both groups before treatment. One woman had convulsion in the 12-h group and MgSO4 was continued for 24 h in this case. Blood pressure, urine volume, and laboratory indexes did not show significant differences between the two groups before and after treatment. Also, adverse effects were similar in both groups. Pain of the injection site was less in the 12-h group (p = 0.048). CONCLUSION Administration of MgSO4 for a duration of 12 h after delivery should be considered somehow as effective as 24 h prescription for preventing convulsion after delivery.
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Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in high-risk pregnant women: a pilot randomized controlled trial.
Costantine, MM, Cleary, K, Hebert, MF, Ahmed, MS, Brown, LM, Ren, Z, Easterling, TR, Haas, DM, Haneline, LS, Caritis, SN, et al
American journal of obstetrics and gynecology. 2016;(6):720.e1-720.e17
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BACKGROUND Preeclampsia complicates approximately 3-5% of pregnancies and remains a major cause of maternal and neonatal morbidity and mortality. It shares pathogenic similarities with adult cardiovascular disease as well as many risk factors. Pravastatin, a hydrophilic, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor, has been shown in preclinical studies to reverse various pathophysiological pathways associated with preeclampsia, providing biological plausibility for its use for preeclampsia prevention. However, human trials are lacking. OBJECTIVE As an initial step in evaluating the utility of pravastatin in preventing preeclampsia and after consultation with the US Food and Drug Administration, we undertook a pilot randomized controlled trial with the objective to determine pravastatin safety and pharmacokinetic parameters when used in pregnant women at high risk of preeclampsia. STUDY DESIGN We conducted a pilot, multicenter, double-blind, placebo-controlled, randomized trial of women with singleton, nonanomalous pregnancies at high risk for preeclampsia. Women between 12(0/7) and 16(6/7) weeks' gestation were assigned to daily pravastatin 10 mg or placebo orally until delivery. Primary outcomes were maternal-fetal safety and pharmacokinetic parameters of pravastatin during pregnancy. Secondary outcomes included rates of preeclampsia and preterm delivery, gestational age at delivery, birthweight, and maternal and cord blood lipid profile (clinicaltrials.gov identifier NCT01717586). RESULTS Ten women assigned to pravastatin and 10 to placebo completed the trial. There were no differences between the 2 groups in rates of study drug side effects, congenital anomalies, or other adverse or serious adverse events. There was no maternal, fetal, or neonatal death. Pravastatin renal clearance was significantly higher in pregnancy compared with postpartum. Four subjects in the placebo group developed preeclampsia compared with none in the pravastatin group. Although pravastatin reduced maternal cholesterol concentrations, umbilical cord cholesterol concentrations and infant birthweight were not different between the groups. The majority of umbilical cord and maternal pravastatin plasma concentrations at the time of delivery were below the lower limit of quantification of the assay. Pravastatin use was associated with a more favorable pregnancy angiogenic profile. CONCLUSION This study provides preliminary safety and pharmacokinetic data regarding the use of pravastatin for preventing preeclampsia in high-risk pregnant women. Although the data are preliminary, no identifiable safety risks were associated with pravastatin use in this cohort. This favorable risk-benefit analysis justifies using pravastatin in a larger clinical trial with dose escalation.
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The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: An exploratory, randomized placebo controlled study.
Hofmeyr, GJ, Seuc, AH, Betrán, AP, Purnat, TD, Ciganda, A, Munjanja, SP, Manyame, S, Singata, M, Fawcus, S, Frank, K, et al
Pregnancy hypertension. 2015;(4):273-9
Abstract
BACKGROUND Epidemiological findings suggest that the link between poverty and pre-eclampsia might be dietary calcium deficiency. Calcium supplementation has been associated with a modest reduction in pre-eclampsia, and also in blood pressure (BP). METHODS This exploratory sub-study of the WHO Calcium and Pre-eclampsia (CAP) trial aims to determine the effect of 500mg/day elemental calcium on the blood pressure of non-pregnant women with previous pre-eclampsia. Non-pregnant women with at least one subsequent follow-up trial visit at approximately 12 or 24weeks after randomization were included. RESULTS Of 836 women randomized by 9 September 2014, 1st visit data were available in 367 women of whom 217 had previously had severe pre-eclampsia, 2nd visit data were available in 201 women. There was an overall trend to reduced BP in the calcium supplementation group (1-2.5mmHg) although differences were small and not statistically significant. In the subgroup with previous severe pre-eclampsia, the mean diastolic BP change in the calcium group (-2.6mmHg) was statistically larger than in the placebo group (+0.8mmHg), (mean difference -3.4, 95% CI -0.4 to -6.4; p=0.025). The effect of calcium on diastolic BP at 12weeks was greater than in those with non-severe pre-eclampsia (p=0.020, ANOVA analysis). CONCLUSIONS There is an overall trend to reduced BP but only statistically significant in the diastolic BP of women with previous severe pre-eclampsia. This is consistent with our hypothesis that this group is more sensitive to calcium supplementation, however results need to be interpreted with caution.