Efeitos do cálcio em baixa e alta dosagem em gestantes com hipertensão gestacional: ensaio cliníco randomizado

Abstract

Background: Gestational hypertensive syndromes are considered one of the most important complications of the puerperal pregnancy cycle. The potential underlying mechanisms of these syndromes appear to be directly related to calcium concentration. Dietary calcium supplementation during pregnancy has been shown to reduce the incidence of complications of this syndrome such as pre-eclampsia, premature labor and low birth weight. The beneficial effects of this nutrient have been found in studies with both high doses and low doses. Conflicting results have been reported in the literature on safety in effective dosing and the impasse between the risks of over-supplementation. Despite the evidence indicating the potential effects of calcium, a small proportion of women receive prescriptions for the supplement during prenatal care in Brazilian public institutions, even though it is available in the public health system. Given the emerging dilemma regarding the dosage of calcium supplementation, this study assumes that the low dosage of calcium supplementation (500mg) will be equivalent to the positive effects of calcium supplementation 1500mg in reducing blood pressure levels and the proteinuria in pregnant women with gestational hypertension, as well as a reduction in the number of premature births and low birth weight. Identifying the effect of calcium can support a standardized clinical practice and the incentive for its prescription. Objective: The aims of this study is to investigate the effects of calcium supplementation in low and high doses on clinical parameters and predictive biomarkers of preeclampsia in pregnant women with gestational hypertension. Method: This is a randomized clinical trial with pregnant women diagnosed with gestational hypertension from the 20th week of gestation without associated proteinuria, randomly allocated into two groups: minimum intervention group (calcium 500mg/day) and maximum intervention group (calcium 1500mg/day). Every four weeks, clinical and laboratory parameters were assessed and information on birth was collected at the end of the study. Data were collected from June 2018 to July 2019. The primary outcome of the study was the reduction in blood pressure levels and the proteinuria and as secondary outcomes prematurity, low birth weight, birth, admission to a neonatal intensive care unit, cardiovascular risck and adherence to treatment. Results: in the period of data collection, 142 pregnant women were eligible for the research protocol. Of these, 18 refused to participate in the study, 49 were excluded for not meeting the inclusion criteria and 24 for other causes (ethnicity, fetal death, change of address), totaling 51 pregnant women at the end. When comparing the effect of calcium on intragroup biomarkers, it was possible to identify that in the group supplemented with 500mg/day, there was a significant reduction in systolic blood pressure (reduction of 7,33 mmHg), in proteinuria (reduction of 9,52 mg/dl), in the incidence of preeclampsia (protein/creatinine ratio) and an increase in microalbubinuria (increase of 4,2 mg/dl) with 04 weeks of supplement use. At the end of 08 weeks there was a reduction in the mean of proteinuria (reduction of 10,71mg/dl), urea (reduction of 12,8mg/dl) and C-reactive protein (reduction of 9,05 mg/dl) and a increase in triglycerides (increase of 63,67 mg/dl). On the other hand, from supplementation with 1500mg/day of calcium it was possible to observe a significant reduction in systolic blood pressure (reduction of 17,5 mmHg) and in HDL (reduction of 6,63 mg/dl) after 04 weeks of supplementation and at the end of 08 weeks a reduction in diastolic blood pressure (reduction of 8,8 mmHg), in urea (reduction of 5,8 mg/dl) and proteinuria (reduction 6,8 mg/dl) and C-reactive protein (reduction 6,91 mg/dl). In the analysis between the intervention groups it was possible to observe that at the end of 04 weeks there was a significant difference in the protein/creatinine ratio, being lower in the Ca 500mg/day group and in the PTH (pg/ml) being lower in the Ca 1500mg/day group. However, after 08 weeks of using the supplement, the differences were in the mean systolic, diastolic, urea, creatinine and LDL being lower in the 1500mg/day Ca group. Secondary neonatal outcomes between intervention groups after 8 weeks of supplementation were the same. No pregnant woman throughout the research protocol presented serious complications such as hypertensive peak, severe preeclampsia, Hellp (hemolysis, elevated liver enzymes and thrombocytopenia), renal failure, eclampsia or fetal death. Conclusion: calcium has a potential effect on the hemodynamic and metabolic processes of hypertensive pregnant women, varying according to the dosage ingested and the time of use. The effect of minimal supplementation on some analyzed parameters was equivalent to the effect of supplementation with high doses in the intragroup analysis, corroborating the initial hypothesis of the study. Better results were observed in the group with maximum supplementation, but positive effects were also found with a short time of use and low dosage without worse neonatal outcomes.