RESUMO
BACKGROUND: In winter in Mongolia, 80% of adults have 25-hydroxyvitamin D (25(OH)D) concentrations <25â¯nmol/l (<10â¯ng/ml) and 99% have <50â¯nmol/l (<20â¯ng/ml). The vitamin D dose to avert deficiency during pregnancy in this population is unknown. METHODS: We conducted a randomized, controlled, double-blind trial of daily 600, 2000, or 4000â¯IU vitamin D3 for pregnant women in Mongolia (Clinicaltrials.gov #NCT02395081). We examined 25(OH)D concentrations at baseline (12-16â¯weeks' gestation), 36-40â¯weeks' gestation and in umbilical cord blood, using enzyme linked fluorescent assay. Sample size was determined to detect 0.4 standard deviation differences in 25(OH)D concentrations with 80% power. FINDINGS: 119 pregnant women were assigned 600â¯IU, 121 assigned 2000â¯IU and 120 assigned 4000â¯IU from February 2015 through December 2016. Eighty-eight percent of participants took ≥80% of assigned supplements. At baseline, 25(OH)D concentrations were similar across arms; overall mean⯱â¯standard deviation concentration was 19⯱â¯22â¯nmol/l; 91% wereâ¯<â¯50â¯nmol/l. At 36-40â¯weeks, 25(OH)D concentrations increased to 46⯱â¯21, 70⯱â¯23, and 81⯱â¯29â¯nmol/l for women assigned 600, 2000, and 4000â¯IU, respectively (pâ¯<â¯0.0001 across arms; pâ¯=â¯0.002 for 2000 vs. 4000â¯IU). Mean umbilical cord 25(OH)D concentrations differed by study arm (pâ¯<â¯0.0001 across arms; pâ¯<â¯0.0001 for 2000 vs. 4000â¯IU) and were proportional to maternal concentrations. There were no adverse events, including hypercalcemia, attributable to vitamin D supplementation. INTERPRETATION: Daily supplementation of 4000â¯IU during pregnancy is safe and achieved higher maternal and neonatal 25(OH)D concentrations than 2000â¯IU. Daily 600â¯IU supplements are insufficient to prevent vitamin D deficiency in Mongolia. FUND: Anonymous foundation and Brigham and Women's Hospital.
Assuntos
Sangue Fetal/química , Trimestres da Gravidez/sangue , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D/análogos & derivados , Adulto , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez/sangue , Terceiro Trimestre da Gravidez/sangue , Resultado do Tratamento , Vitamina D/administração & dosagem , Vitamina D/uso terapêutico , Adulto JovemRESUMO
Many studies of essential hypertension find evidence of insulin resistance in the same individuals, leading some to postulate a hypertensive role for insulin. However, the mechanisms by which insulin might exert a hypertensive effect are not fully resolved. An endogenous sodium pump inhibitor or digitalis-like factor (DLF) has been proposed as a hypertensive agent and its plasma concentrations are elevated in hypertension and in Type II diabetes, where insulin levels are elevated. Hence, we studied the effect of insulin on DLF using two approaches to achieve hyperinsulinemia. Normotensive men and women underwent a hyperinsulinemic, euglycemic clamp (40 mU/m2/min insulin, 40 mU = 1.6 x 10(-6) g) in which plasma insulin concentration was kept at high, but physiologic levels. Serum DLF (measured as inhibition of [Na,K]ATPase activity) and insulin levels were measured at baseline and every 30 min throughout the 2 hr clamp. Additionally, other subjects underwent an oral glucose tolerance test (OGTT) as a second means of increasing insulin levels. Insulin and DLF levels were measured prior to and hourly for 3 hours after receiving 100 gm of oral glucose. Serum DLF increased significantly during the clamp from a baseline of 4.6 +/- 0.81 to a peak of 8.7 +/- 1.2% inhibition (p=0.001). Comparison of the baseline and peak DLF levels with concomitant plasma insulin levels revealed a significant correlation (R=0.60, p=0.003). During the OGTT, DLF levels rose from a baseline of 2.4 +/- 1.0 to a peak level of 5.0 +/- 0.4%, p = 0.04. These results suggest that DLF, a factor that can cause vascular smooth muscle contraction and potentially influence blood pressure, is increased by hyperinsulinemia and provides a mechanism by which insulin may increase blood pressure.
Assuntos
Digitalis , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Hiperinsulinismo/etiologia , Plantas Medicinais , Plantas Tóxicas , Adolescente , Adulto , Glicemia , Jejum , Feminino , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/fisiopatologia , Insulina/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Primary hyperaldosteronism is an uncommon disorder, and there are few reports of its occurrence and management in pregnancy. CASE: Primary hyperaldosteronism was suspected before pregnancy in a 31-year-old women with refractory hypertension and hypokalemia. Pregnancy evaluation revealed suppressed renin levels and high aldosterone levels; computed tomography revealed a 1-cm mass in the left adrenal gland. The patient became pregnant before completion of evaluation and treatment. On high doses of nifedipine and nadolol, the first-trimester blood pressure was 130/98 mm Hg and remained high in the early second trimester. In view of the risks of poorly controlled hypertension, adrenalectomy was performed at 15 weeks' gestation, with rapid improvement in blood pressure and elimination of the patient's requirement for large doses of potassium daily. Antihypertensive medication was withdrawn, with maintenance of normal blood pressure until 36 weeks' gestation. At that time the blood pressure rose slightly but responded to bed rest. A healthy female infant was delivered at term by cesarean section. CONCLUSION: Previous reports of emergency preterm delivery and a case of neonatal mortality in the setting of hyperaldosteronism in pregnancy confirm the significant risks associated with this condition. In our patient, adrenalectomy in the early second trimester resulted in a rapid and sustained improvement in hypertension, reversal of hypokalemia and a good pregnancy outcome.
Assuntos
Glândulas Suprarrenais/fisiopatologia , Hiperaldosteronismo/diagnóstico , Complicações na Gravidez/diagnóstico , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/cirurgia , Adrenalectomia , Adulto , Aldosterona/sangue , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Terapia Combinada , Relação Dose-Resposta a Droga , Feminino , Humanos , Hiperaldosteronismo/fisiopatologia , Hiperaldosteronismo/terapia , Nadolol/uso terapêutico , Nifedipino/uso terapêutico , Potássio/sangue , Gravidez , Complicações na Gravidez/fisiopatologia , Complicações na Gravidez/terapia , Renina/sangue , Tomografia Computadorizada por Raios X , Vasodilatadores/uso terapêuticoRESUMO
BACKGROUND: Vitamin D has been added to milk in the United States since the 1930s to prevent rickets. We report the unusual occurrence of eight cases of vitamin D intoxication that appear to have been caused by excessive vitamin D fortification of dairy milk. METHODS: Medical records were reviewed and a dietary questionnaire was sent to eight patients who had unexplained hypervitaminosis D. Vitamin D analyses with high-performance liquid chromatography were performed on samples of the patients' serum, the dairy milk they drank, and the vitamin D concentrate added to the milk. RESULTS: All eight patients drank milk produced by a local dairy in amounts ranging from 1/2 to 3 cups (118 to 710 ml) daily. All had elevated serum 25-hydroxyvitamin D concentrations (mean [+/- SD], 731 +/- 434 nmol per liter [293 +/- 174 ng per milliliter]). Six of the eight patients had elevated serum vitamin D3 concentrations. Of the eight patients, seven had hypercalcemia and one had hypercalciuria but normocalcemia (mean serum calcium, 3.14 +/- 0.51 mmol per liter [12.6 +/- 2.1 mg per deciliter]). Analysis of the dairy's vitamin D-fortified milk revealed concentrations of vitamin D3 (cholecalciferol) that ranged from undetectable to as high as 232,565 IU per quart (245,840 IU per liter). An analysis of the concentrate that was used to fortify the milk, labeled as containing vitamin D2 (ergocalciferol), revealed that it contained vitamin D3. CONCLUSIONS: Hypervitaminosis D may result from drinking milk that is incorrectly and excessively fortified with vitamin D. Milk that is fortified with vitamin D must be carefully monitored.