Calcium supplementation for preventing pre-eclampsia/eclampsia Justus Hofmeyr, for the Calcium and Pre-eclampsia (CAP) Study Group* *Fernando Althabe, Sadiqua Allie, John Anthony, Jos

1
Calcium supplementation for preventing
pre-eclampsia/eclampsiaJustus Hofmeyr, for the
Calcium and Pre-eclampsia (CAP) Study
GroupFernando 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

2
Mdantsane, Eastern Cape(near East London, South
Africa)
3
Labour ward, Cecilia Makiwane Hospital
4
SA National Enquiry into Maternal Deaths 2005-2007
1729
Population mortality estimates 150-580/100 000
34
622
383
223
108
5
Outline Calcium and Pre-eclampsia/eclampsia

• Epidemiology
• Cochrane review of randomized trials
• Implications for practice
• Research agenda

6
Lancet. 1952 Jan 121(6698)64-8
7
(No Transcript)
8
Hamlin RHJ. Prevention of pre-eclampsia. Lancet
19621864-865
9
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 Jan44(1)27-31.

10
(No Transcript)
11
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
  19621864-5.
• Belizan JM, Villar J. The relationship between
  calcium intake and edema, proteinuria, and
  hypertension-gestosis an hypothesis. American
  Journal of Clinical Nutrition 1980332202-10.

12
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

13

• 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
• 2006194 639-649
• ?
• Revised Systematic
• Review
• Hofmeyr GJ, Lawrie TA,
• Atallah ÁN, Duley L.
• Cochrane Database of
• Syst Reviews 2010

14
Calcium vs Placebo Pre-eclampsia
15
Calcium vs Placebo Proteinuria
16
Calcium vs Placebo Eclampsia
17
Calcium vs Placebo Maternal Death
18
Calcium vs PlaceboMaternal death/ severe
morbidity
19
Calcium vs Placebo HELLP syndrome
20
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

21
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

22
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

23
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

24
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

25
(No Transcript)
26
Daily provisional supply of calcium per capita
in developing and developed countries (FAO,
1990)