Preeclampsia is a disorder of pregnancy that can strike without warning,
causing protein in the urine and high blood pressure. In turn,
preeclampsia may progress to eclampsia--hypertension and generalized
convulsions--which may be fatal.
The trial, reported in the July 10 New England Journal of Medicine, was
conducted by researchers at the National Institute of Child Health and
Human Development (NICHD) and several other academic and research
institutions. Funding was provided by the NICHD and by the National Heart,
Lung, and Blood Institute.
"Clearly, women need some calcium during pregnancy," said the study's
principal investigator, Richard J. Levine, MD, of the Division of
Epidemiology, Statistics, and Prevention Research at the NICHD. "But in
light of the results of our study, the high doses of calcium thought to
prevent preeclampsia at best provide no apparent benefit, and at worst,
could cause complications in certain high-risk women."
Preeclampsia is a potentially life-threatening complication of pregnancy
in which a woman may develop dangerously high blood pressure and begin
excreting protein in the urine. About 5 percent of first-time mothers and
1 to 2 percent of mothers having subsequent pregnancies develop the
condition. The authors note that preeclampsia is a leading cause of
maternal death. Even in cases where the condition does not progress to
eclampsia, the children born to mothers with preeclampsia may be small for
their gestational age or may be born prematurely. This may, in turn, place
them at risk for a variety of other complications of birth.
Although the high blood pressure accompanying preeclampsia can be treated
with blood pressure lowering drugs, the only curative treatment for the
overall condition is immediate delivery.
The results of numerous previous clinical trials and two meta-analyses
strongly suggested that calcium supplementation could greatly reduce the
risk of preeclampsia. In fact, a meta-analysis of 9 smaller trials
published last year and receiving widespread publicity concluded that
calcium supplementation could reduce the risk of preeclampsia by 62
Dr. Levine said that the current study, which found no reduction in
preeclampsia from calcium supplementation, enrolled a total of more than
twice the number of women than took part in all 9 trials in last year's
analysis. In addition, the women who took part in the current study took
as much or more calcium a day as did the women in the previous trials.
Dr. Levine added that the discrepancy between the current finding and the
earlier studies could be explained by a number of factors. For example,
many of the earlier studies did not have a placebo control group. In
addition, in contrast to the current study, two of the earlier studies
selected only women in whom test results indicated high risk for
preeclampsia. Moreover, the most recent meta-analysis also included a
study of women who experienced hypertension during pregnancy, but may not
have had preeclampsia.
For their study, Dr. Levine and his co-investigators recruited 4589
healthy first-time mothers who were from 13 to 21 weeks pregnant. Roughly
half (2295 women) were randomly assigned to take four calcium tablets per
day, with each tablet containing 500 mg. of calcium. The remainder (2294
women) were given a placebo containing no calcium. Both groups of women
were also given a multivitamin supplement containing 50 mg. of calcium.
Excluded from the study were women having conditions known to place them
at increased risk for preeclampsia: diabetes, pre-existing hypertension,
kidney disease, being pregnant with twins, and having previously had the
condition during an earlier pregnancy. Also excluded were women thought to
be at risk for developing kidney stones--a condition that potentially could
be worsened by high doses of calcium. This group included women who had
kidney disease, had high concentrations of blood calcium, had blood in the
urine, had previously had kidney stones, or had family members who had
Overall, compliance with the study's instructions was good, with women in
the calcium group taking the tablets 64 percent of the time and women in
the placebo group taking them 67 percent of the time. The women in the
calcium group consumed an average of about 2369 mg of calcium a day, and
the women in the placebo group averaged 982 mg of calcium a day. The
estimate of the women's calcium intake was derived from the foods they ate
as well as the pills they took.
The National Academy of Sciences' Recommended Daily Allowance for calcium
for pregnant women is 1200 mg a day. Dairy products and certain other
foods contain high amounts of calcium, with a cup of whole milk containing
291 mg., a cup of skim milk, 302 mg., a cup of shredded whole milk
mozzarella cheese, 579 mg., and a cup of tofu made with calcium sulfate,
At the study's conclusion, the researchers found no significant difference
in the occurrence of preeclampsia between the two groups, with about 6.9
percent of the calcium group and 7.3 percent of the placebo group
developing preeclampsia. Moreover, the calcium treatment did not appear to
reduce the severity of the disease or delay the amount of time it took a
woman to develop preeclampsia. Nor could the researchers find any
significant reduction in the risk of preeclampsia in women who had the
highest compliance rates for taking the tablets. Also, there was no benefit
of calcium supplementation in women who had the lowest calcium levels when
they entered the study, or in adolescents--the group thought to have the
greatest need for calcium during pregnancy.
Although the women taking high doses of calcium during the trial did not
experience any ill effects at the study's conclusion, Dr. Levine said it is
possible that some women taking large amounts of calcium could develop
kidney stones, particularly if they have a high concentration of calcium in
the blood, kidney disease, or a personal or family history of kidney
stones. In addition, high doses of calcium might suppress the function of
the parathyroid gland, placing the newborn at risk for low calcium levels.
"Our results do not support the use of calcium supplementation for the
prevention of preeclampsia in healthy, nulliparous women," the authors
Dr. Levine noted that because the study did not include women at high risk
for preeclampsia, it could not determine whether calcium supplementation
would prevent the development of preeclampsia in this group of women.
Other authors of the paper were John C. Hauth and Robert L. Goldenberg,
the University of Alabama at Birmingham; Luis B. Curet and Gary M. Joffe,
the University of New Mexico Health Sciences Center in Albuquerque; Baha
M. Sibai and Steven A. Friedman, the University of Tennessee College of
Medicine in Memphis; Patrick M. Catalano and Alice M Petrulis, Metrohealth
Medical Center, Case Western Reserve University in Cleveland, Ohio; Cynthia
D. Morris and Sig-Linda Jacobson, Oregon Health Sciences University, in
Portland; Joy R. Esterlitz and Marian G. Ewell, The Emmes Corporation,
Potomac, Maryland; Elizabeth G. Raymond, the NICHD and Family Health
International, Research Triangle Park, North Carolina; Diane E. Bild and
Jeffrey A. Cutler, the National Heart, Lung, and Blood Institute, NIH; and
Rebecca DerSimonian, John D. Clemens and Mark A. Klebanoff, NICHD.