Richard J. Levine, M.D., John C. Hauth, M.D., Luis B. Curet, M.D., Baha M. Sibai, M.D., Patrick M. Catalano, M.D., Cynthia D. Morris, Ph.D., Rebecca DerSimonian, Sc.D., Joy R. Esterlitz, M.S., Elizabeth G. Raymond, M.D., Diane E. Bild, M.D., John D. Clemens, M.D., Jeffrey A. Cutler, M.D., Marian G. Ewell, Steven A. Friedman, Robert L. Goldenberg, Sig-Linda Jacobson, Gary M. Joffe, M.D, Mark A. Klebanoff, and Alice S. Petrulis, M.D.
Background Previous trials have suggested that calcium supplementationduring pregnancy may reduce the risk of preeclampsia. However,differences in study design and a low dietary calcium intakein the populations studied limit acceptance of the data.
Methods We randomly assigned 4589 healthy nulliparous womenwho were 13 to 21 weeks pregnant to receive daily treatmentwith either 2 g of elemental calcium or placebo for the remainderof their pregnancies. Surveillance for preeclampsia was conductedby personnel unaware of treatment-group assignments, using standardizedmeasurements of blood pressure and urinary protein excretionat uniformly scheduled prenatal visits, protocols for monitoringthese measurements during the hospitalization for delivery,and reviews of medical records of unscheduled outpatient visitsand all hospitalizations.
Results Calcium supplementation did not significantly reducethe incidence or severity of preeclampsia or delay its onset.Preeclampsia occurred in 158 of the 2295 women in the calciumgroup (6.9 percent) and 168 of the 2294 women in the placebogroup (7.3 percent) (relative risk, 0.94; 95 percent confidenceinterval, 0.76 to 1.16). There were no significant differencesbetween the two groups in the prevalence of pregnancy-associatedhypertension without preeclampsia (15.3 percent vs. 17.3 percent)or of all hypertensive disorders (22.2 percent vs. 24.6 percent).The mean systolic and diastolic blood pressures during pregnancywere similar in both groups. Calcium did not reduce the numbersof preterm deliveries, small-for-gestational-age births, orfetal and neonatal deaths; nor did it increase urolithiasisduring pregnancy.
Conclusions Calcium supplementation during pregnancy did notprevent preeclampsia, pregnancy-associated hypertension, oradverse perinatal outcomes in healthy nulliparous women. (NEngl J Med 1997;337:69 -76.)
Source Information
From the Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, Bethesda, Md. (R.J.L., R.D., E.G.R., J.D.C.); the Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham (J.C.H.); the Department of Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque (L.B.C.); the Department of Obstetrics and Gynecology, University of Tennessee College of Medicine, Memphis (B.M.S.); the Department of Obstetrics and Gynecology, MetroHealth Medical Center, Case Western Reserve University, Cleveland (P.M.C.); the Department of Medicine, Oregon Health Sciences University, Portland (C.D.M.); the Emmes Corporation, Potomac, Md. (J.R.E.); Family Health International, Research Triangle Park, N.C. (E.G.R.); and the Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Md. (D.E.B., J.A.C.). Other authors were Marian G. Ewell, Sc.D. (Emmes Corp., Potomac, Md.), Steven A. Friedman, M.D. (University of Tennessee College of Medicine, Memphis), Robert L. Goldenberg, M.D. (University of Alabama at Birmingham), Sig-Linda Jacobson, M.D. (Oregon Health Sciences University, Portland), Gary M. Joffe, M.D. (University of New Mexico Health Sciences Center, Albuquerque), Mark A. Klebanoff, M.D. (National Institute of Child Health and Human Development, Bethesda, Md.), and Alice S. Petrulis, M.D. (MetroHealth Medical Center, Cleveland).
Address reprint requests to Dr. Levine at the Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Bldg. 6100, Rm. 7B03, Bethesda, MD 20892-7510.
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