Calcium supplementation for
preventing pre-eclampsia/eclampsia
Justus Hofmeyr, for the Calcium and Pre-eclampsia
(CAP) Study Group*
*Fernando Althabe, Sadiqua Allie, John Anthony, José
Belizán, Eduardo Bergel, Ana Pilar Betran, Eckhart
Buchmann, Sue Fawcus, Justus Hofmeyr, Anne
Horak, Stephen Munjanja, Adegboyega Oyebajo,
Diane Sawchuck, Mandisa Singata, Peter von
Dadelszen
• Effective Care Research Unit, University of the
Witwatersrand, Fort Hare and Eastern Cape
Department of Health
Mdantsane, Eastern Cape
(near East London, South Africa)
Labour ward, Cecilia Makiwane Hospital
SA National Enquiry into Maternal Deaths
2005-2007
1729
Population mortality estimates 150-580/100 000
34
622
383
223
108
Outline: Calcium and
Pre-eclampsia/eclampsia
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Epidemiology
Cochrane review of randomized trials
Implications for practice
Research agenda
Lancet. 1952 Jan 12;1(6698):64-8
Hamlin RHJ. Prevention of preeclampsia. Lancet 1962;1:864-865
Eclampsia in Addis Ababa 1994 to ‘99
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Tikur Anbessa and St Paul's Hospitals, Addis Ababa
Eclampsia 7.1/1000 deliveries
case fatality rate 13%.
? Change in diet
• Abate M, Lakew Z. Eclampsia a 5 years
retrospective review of 216 cases managed in two
teaching hospitals in Addis Ababa. Ethiop Med J.
2006 Jan;44(1):27-31.
Pre-eclampsia and dietary calcium
• Low incidence of pre-eclampsia noted in:
– Ethiopia (Hamlin 1962)
– Guatemala (Belizan 1980)
• Postulated due to high calcium diets
– Hamlin RHJ. Prevention of pre-eclampsia. Lancet
1962;1:864-5.
– Belizan JM, Villar J. The relationship between calcium intake
and edema, proteinuria, and hypertension-gestosis: an
hypothesis. American Journal of Clinical Nutrition
1980;33:2202-10.
Calcium to reduce pre-eclampsia:
Cochrane systematic review: 1998
• Large reduction in pre-eclampsia in several small
studies
• No significant effect in large US study (CPEP)
• ? Publication bias
• ? Different effects in populations with low and
adequate dietary calcium
Hofmeyr GJ, Atallah ÁN, Duley L. Calcium
supplementation during pregnancy for preventing
hypertensive disorders and related problems. Cochrane
Database of Systematic Reviews 1998
World Health organization randomized trial of
calcium supplementation among low calcium intake
women.
Villar J, Abdel-Aleem H, Merialdi M, Mathai M, Ali M, Zavaleta
N, Purwar M, Hofmeyr GJ, thi Nhu Ngoc N, Campódonico
L, Landoulsi S, Carroli G, Lindheimer M et al.
Am J Obstet Gynecol
2006;194: 639-649
↓
Revised Systematic
Review :
Hofmeyr GJ, Lawrie TA,
Atallah ÁN, Duley L.
Cochrane Database of
Syst Reviews 2010
Calcium vs Placebo: Pre-eclampsia
Calcium vs Placebo: Proteinuria
Calcium vs Placebo: Eclampsia
Calcium vs Placebo: Maternal Death
Calcium vs Placebo:
Maternal death/ severe morbidity
Calcium vs Placebo: HELLP syndrome
Hypothesis:
Calcium supplementation in 2nd half of pregnancy:
• ↓ blood pressure (↓ vascular tone)
• ↓ serious complications related to hypertension
• No effect on other organ dysfunction eg endothelial
• ↓ BP → ↓ early deliveries (induction/CS)
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→ ↓ low birthweight
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→ ↑ time to develop HELLP syndrome
• To prevent multisystem dysfunction may need adequate
calcium from before pregnancy
Hofmeyr GJ, Duley L, Atallah A. Dietary calcium supplementation for
prevention of pre-eclampsia and related problems: a systematic review
and commentary. BJOG. 2007; 114: 933-943
Future research: The CAP study
• The Calcium and Pre-eclampsia study
• Randomized trial: calcium 500mg daily vs placebo
commencing before conception till 20 weeks
• Participants: women with previous pre-eclampsia
who intend to conceive
• Routine calcium in second half of pregnancy
• If effective, next step trials of community level
calcium supplementation by food fortification
• ? Place of Vitamin D supplementation
• Further research on ideal dose
Calcium: summary of evidence
• Epidemiological association of dietary calcium with
huge discrepancies in rates of pre-eclampsia/
eclampsia
• Calcium supplementation in the second half of
pregnancy reduces
– pre-eclamsia (but not in largest trial)
– Severe morbidity (about 20%)
• This benefit is sufficient to justify programs to
supplement pregnant women with low calcium diets
• Ongoing research to determine whether prepregnancy supplementation will reproduce the more
dramatic epidemiological differences
Other benefits and risks of
calcium supplementation
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Reduced hypertension
Reduced osteoporosis
Reduced Urinary stones
Improved insulin sensitivity in type 2 diabetes
? Reduced colorectal cancer
? Increased risk of coronary artery disease if
excessive
• ?? Increased prostate cancer
Options for calcium supplementation
programs
• Individual supplementation during pregnancy
(limited to antenatal care attenders):
– Individuals with low calcium diet
– Populations with low calcium diet
– Women at high risk of pre-eclampsia (Nulliparous,
previous pre-eclampsia, risk factors, screening, etc)
– All pregnant women
• Population supplementation: fortification of staple
foods – Broad population coverage, except people
who grow their own food.
• Population dietary education
Daily provisional supply of calcium
per capita in developing and developed
countries (FAO, 1990)
REGION
World
Developed countries
Developing countries
Africa
Latin America
Near East
Far East
Others
CALCIUM (mg)
472
860
346
363
499
498
352
402