Calcium supplementation for preventing pre-eclampsia/eclampsia
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Mdantsane eastern cape near east london south africa

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(near East London, South Africa)


Labour ward cecilia makiwane hospital

Labour ward, Cecilia Makiwane Hospital


Sa national enquiry into maternal deaths 2005 2007

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

Outline: Calcium and Pre-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


Hamlin rhj prevention of pre eclampsia lancet 1962 1 864 865

Hamlin RHJ. Prevention of pre-eclampsia. Lancet 1962;1:864-865


Eclampsia in addis ababa 1994 to 99

Eclampsia in Addis Ababa 1994 to ‘99

  • 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.

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


Mdantsane eastern cape near east london south africa

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


Calcium vs placebo proteinuria

Calcium vs Placebo: Proteinuria


Calcium vs placebo eclampsia

Calcium vs Placebo: Eclampsia


Calcium vs placebo maternal death

Calcium vs Placebo: Maternal Death


Calcium vs placebo maternal death severe morbidity

Calcium vs Placebo:Maternal death/ severe morbidity


Calcium vs placebo hellp syndrome

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)

→ ↓ 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

Hypothesis:


Future research the cap study

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

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 pre-pregnancy supplementation will reproduce the more dramatic epidemiological differences


Other benefits and risks of calcium supplementation

Other benefits and risks of calcium supplementation

  • 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

  • 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


Mdantsane eastern cape near east london south africa

REGION

CALCIUM (mg)

World

472

Developedcountries

860

Developingcountries

346

Africa

363

Latin America

499

Near East

498

Far East

352

Others

402

Daily provisional supply of calcium

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


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