Calcium supplementation for preventing pre-eclampsia/eclampsia
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Calcium supplementation for preventing pre-eclampsia/eclampsiaJustus 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
Mdantsane, Eastern Cape pre-eclampsia/eclampsia(near East London, South Africa)

Sa national enquiry into maternal deaths 2005 2007
SA National Enquiry into Maternal Deaths 2005-2007 pre-eclampsia/eclampsia


Population mortality estimates 150-580/100 000






Outline calcium and pre eclampsia eclampsia
Outline: Calcium and pre-eclampsia/eclampsiaPre-eclampsia/eclampsia

  • Epidemiology

  • Cochrane review of randomized trials

  • Implications for practice

  • Research agenda

Lancet 1952 jan 12 1 6698 64 8
Lancet. 1952 Jan 12;1(6698):64-8 pre-eclampsia/eclampsia

Eclampsia in addis ababa 1994 to 99
Eclampsia in Addis Ababa 1994 to ‘99 1962;1:864-865

  • 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: 1962;1:864-865

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.

Pre-eclampsia and dietary calcium

Calcium to reduce pre eclampsia cochrane systematic review 1998
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: Pre-eclampsia supplementation among low calcium intake women.

Calcium vs placebo proteinuria
Calcium vs Placebo: supplementation among low calcium intake women. Proteinuria

Calcium vs placebo eclampsia
Calcium vs Placebo: supplementation among low calcium intake women. Eclampsia

Calcium vs placebo maternal death
Calcium vs Placebo: Maternal Death supplementation among low calcium intake women.

Calcium vs placebo maternal death severe morbidity
Calcium vs Placebo: supplementation among low calcium intake women. Maternal death/ severe morbidity

Calcium vs placebo hellp syndrome
Calcium vs Placebo: supplementation among low calcium intake women. HELLP syndrome


Calcium supplementation in 2 supplementation among low calcium intake women. nd 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)

→ ↓ low birthweight

→ ↑ 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
Future research: supplementation among low calcium intake women. 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
Calcium: summary of evidence supplementation among low calcium intake women.

  • 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 pre-pregnancy supplementation will reproduce the more dramatic epidemiological differences

Other benefits and risks of calcium supplementation
Other benefits and risks of calcium supplementation supplementation among low calcium intake women.

  • 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
Options for calcium supplementation programs supplementation among low calcium intake women.

  • 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

REGION supplementation among low calcium intake women.










Latin America


Near East


Far East




Daily provisional supply of calcium

per capita in developing and developed countries (FAO, 1990)