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Calcium Supplementation and Prevention of Preeclampsia



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Am Fam Physician. 1998 Feb 15;57(4):791-7912.

Preeclampsia, usually defined as the onset of hypertension and proteinuria in the second half of pregnancy, occurs in about 5 percent of pregnancies. The pathophysiology of preeclampsia is not well understood, and the search for an effective preventive therapy has been unsuccessful. The results of several clinical trials and meta-analyses of these studies have suggested that calcium supplementation may help prevent preeclampsia. Levine and colleagues report on the results of the Calcium for Preeclampsia Prevention (CPEP) trial, a study sponsored by the National Institutes of Health and conducted at five medical centers.

The CPEP trial enrolled a cohort of 4,589 women. Almost 12,000 nulliparous women who were in their 11th to 21st week of pregnancy were screened for possible inclusion. Patients were excluded if they were receiving any prescribed medications, had an elevated baseline serum creatinine or calcium level or had a history of renal disease (including calculi) or hematuria.

Women who were initially determined to be eligible for the study were given a single-blind test of compliance for six to 14 days. Study subjects were considered compliant if they took at least 75 percent of placebo tablets. The patients were divided into two groups. Members of the treatment group were given tablets containing 500 mg of calcium carbonate and were asked to take two tablets with their morning and evening meals until delivery. The placebo group received tablets containing cornstarch and sugar and were given identical instructions. Follow-up visits were conducted every four weeks until the 29th week of pregnancy, every two weeks through the 35th week and weekly thereafter until delivery. Standardized measurements of blood pressure and urinary protein excretion were performed at each prenatal visit.

A total of 2,295 women received calcium and 2,294 received placebo. White, Hispanic and African-American women were equally represented in each group. Twelve percent of the patients from each group were current cigarette smokers. The number of prenatal visits, unscheduled outpatient visits and prenatal hospitalizations was the same in both groups. The average compliance with medication was 64 percent in the calcium group and 67 percent in the placebo group.

The incidence of preeclampsia was 6.9 percent in the calcium group and 7.3 percent in the placebo group. In women with preeclampsia, no difference in gestational age at the time of the diagnosis was noted between the calcium group and the placebo group. No statistically significant differences were apparent between the two groups in the incidence of pregnancy-associated hypertension without preeclampsia, pregnancy-associated proteinuria without hypertension and all other hypertensive disorders. The mean systolic blood pressure was slightly but not significantly lower in the calcium group than in the placebo group, although the calcium group had a slightly higher diastolic pressure.

The rate of obstetric complications, including cesarean section, placental abruption and urolithiasis, did not differ between the two groups. No significant difference was apparent between the calcium and placebo groups in the rate of preterm deliveries or perinatal deaths.

The authors conclude that prenatal supplementation with 2 g of calcium daily in nulliparous women does not reduce the incidence or severity of preeclampsia, nor does it delay the onset of preeclampsia. In addition, calcium does not reduce the incidence of pregnancy-associated hypertension. It also does not appear to affect the incidence of cesarean delivery, preterm delivery or perinatal death, as was suggested by previous studies.

Levine RJ, et al. Trial of calcium to prevent preeclampsia. N Eng J Med. 1997;337:69–76.


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