Calcium and Pre-Eclampsia (CAP) Study

Title: Long-term Calcium Supplementation in Women at High Risk of Pre-eclampsia: A Randomized, Placebo-controlled Trial. Calcium supplementation before and during pregnancy for preventing hypertensive disorders.

The Cap Study began in November 2011 and will end in October 2015.

Pricipal Investigator:

Dr Peter von Dadelszen, University of British Columbia, Vancouver, BC, Canada

Participating Sites:

  • Frere Maternity and Cecilia Makiwane Hospitals, East London, South Africa (Prof Justus Hofmeyr & Dr Mandisa Singata)
  • College of Health Sciences, Harare, Zimbabwe  (Prof Stephen Munjanja)
  • Mowbray Hospital, Cape Town, South Africa (Prof Sue Fawcus)
  • Chris Hani Baragwanath Hospital, Soweto, Johannesburg, South Africa (Dr Karlyn Frank, Dr Simpiwe Mose)
  • Stellenbosch University, Stellenbosch, Western Cape, South Africa (Prof David Hall)

Pre-eclampsia is more common in most low-income countries. Dietary calcium deficiency is one possible reason. Calcium supplementation (1-2g/day) in second half of pregnancy reduces hypertension and death/sever morbidity, but not proteinuria. One cause of pre-eclampsia is defective early placentation.

Randomised trial: calcium 500mg daily vs placebo commencing before inception to 20 weeks. All women receive routine calcium in second half of pregnancy.

Participants: women with previous pre-eclampsia who intend to conceive.

ECRU developed the Protocol. (In 2008 ECRU became an accredited World Health Organisation Collaboration Centre in Research Synthesis on Reproductive Health organisation.)

Funding: sub-grant from University of British Columbia, a grantee of the Bill and Melinda Gates Foundation.

Technical support: WHO.

If low-dose calcium supplementation before pregnancy reduces pre-eclampsia, this opens the possibility for food fortification to prevent pre-eclampsia at a population levl.

Our CAP study is the first ever randomized trial to study a pre-pregnancy intervention.

Background

The reduction in the diagnosis of pre-eclampsia with calcium supplementation might be the result of at least two different mechanisms: 1) calcium might alter the pathogenesis of endothelial damage and pre-eclampsia; or 2) calcium might prevent the manifestation of the disease by reducing BP (probably by a direct effect on vascular tone). As previous research in this field has all focused on calcium supplementation in the second half of pregnancy, it is important that the effect of calcium supplementation before and during early pregnancy be investigated. If effective, this would lay the groundwork for studies of food fortification to address the deficiency at a community level.

Goal 

The goal of this South African, Zimbabwean, and Arentinian RCT (in centres with known dietary calcium deficiency) to determine the effect of calcium supplementation before, and in the first half of, pregnancy on hypertension and other pregnancy outcomes.

Hypothesis

Calcium supplementation commenced before pregnancy will reduce the incidence of pre-eclampsia more effectively than does supplementation starting at 20 weeks’ gestation.

Methods

Study design
Randomised, double-blind placebo-controlled clinical trial.

Inclusion criteria
Women aged 18 to 45 years with a history of pre-eclampsia or eclampsia who plan to become pregnant.

Exclusion criteria

  • Age <18 years or >45 years
  • Chronic hypertension
  • Already pregnant
  • Taking calcium supplementation
  • History or symptoms of urolithiasis, renal disease, or parathyroid disease
  • Not in a sexual relationship
  • Using long-term contraception (eg hormonal, IUD, sterilization)
  • No informed consent.

Intervention

The study group will receive calcium supplementation with 500 mg elemental calcium daily from enrolment (before pregnancy) until 20 weeks' gestation.The control group will receive an identical placebo for the same duration. All women will receive unblinded calcium supplementation at 1000 mg from 20 weeks' gestation until delivery.

Outcomes

The primary outcome is Pre-eclampsia (diastolic blood pressure >90 mmHg on two occasions 4 hours apart, or >110 mmHg once, or systolic blood pressure >140 mmHg on two occasions 4 hours apart, or >160 mmHg once, after 20 weeks gestation in combination with proteinuria 2+ or more on urine dipstick, or >300mg/24 hours, or >500mg/L or urinary protein/creatinine ratio >0.034g/mmol, after 20 weeks' gestation).

Secondary outcomes related to concordance, maternal and neonatal well-being, and mode of delivery will be reported.

Sample size

To show a reduction in pre-eclampsia from 25% to 15% (with alpha-5%, beta=80%) will require 540 participants.

Analysis plan

Analysis will be by intention-to-treat.  The results will be reported according to CONSORT guidelines.  Categorical data will be presented as risk ratios with 95% confidence intervals.  Continuous data will be presented as mean differences with 95% confidence intervals.

International Conference of Midwives 2014: report from Catherine Parker

Posted on 12 Jun, 2014

The midwife is recognised as a responsible and accountable professional who works in partnership with women to give the necessary support, care and advice during pregnancy, labour and the post-partum period, to conduct births on the midwife's own responsibility and to provide care for the new born.

-Quote from ICM 2011-2014 Triennial report.

Ms. Catherine Parker, a midwife from Johannesburg, South Africa is an important stakeholder in the PRE-EMPT Calcium and Pre-eclampsia Study in South Africa. With sponsorship from the WHO and PRE-EMPT, Ms. Parker recently attended the International Confernence of Midwives 30th Triennal Congress in Prague, Poland.

Below is a summary of her report. For a full report with overviews of all the four days, please click here.

"This was my first ICM conference. Thanks to the very kind and generous donation by ECRU and UBC, I was afforded the life changing opportunity to be a full delegate at the 2014 Prague ICM conference where the State of the Worlds Midwifery 2014 was launched. Thank you to everyone for this gift. I cherish and honour it and am inspired to ensure change for the good for local and global midwifery.

The conference began on Saturday 31 May with a coming together of the largest group of midwives in history. The record was set under the auspices of, "The voices of Midwives", and this was prophetically challenging as the key message running through all the symposiums and workshops was that it was the midwives of the world who are able to make the most dramatic and effective change to the unacceptable levels of mortality and morbidity in maternal care.

One of the most impressive qualities of this conference was that for every conceivable problem, there was an individual or organisation that was working on and implementing a solution.

  • For the problem of shortages of staff there is training being offered and rolled out.
  • For the problem of lack of quality care there are or programmes aimed at measuring and implementing quality care.
  • For the problem of insufficient reproductive rights there are advocacy revolutions.
  • For the problem of professional isolation there is the solution of twinning.

Of all the issues South Africa faces, one of the most concerning is staff attrition. The burn out and lack of career advancement midwives experience, along with the compassion fatigue and poor social status of most public health midwives and nurses is something dear to my heart. Improving quality care and caring for the carers are two important keys to improving our chances of getting as close as possible to our MDG goals.  I am sure exposing more people to ICM congresses can have a huge impact on these negatives attributes of South African nurses. We can raise the standard, inspire, encourage, pamper, bless, educate, increase awareness, motivate, and impassion midwives by allowing more to be sent on these international congresses.  

The opening ceremony saw over 3800 midwives coming together from 126 different countries. A quote from this session that especially stood out for me as memorable was, "We must not allow our challenges to become our excuses.” This was the message from the Goodwill Ambassador, Her Excellency, the first Lady of Nigeria, Toyin Ojora-Saraki. Another overarching theme was that "Inequality matters". Regardless of which country you came from, you could tell a tale of unjust practices based on socio-economic discrepancies. We were all rallied to take up the charge against this scourge.

I have not done justice to the amazing experience I had sitting for four days under the inspiration of so many passionate women. My main take home message was that the goal is huge but achievable if we work together and continue to collaborate with different countries, organisations and individuals.

One final thought was that, while I met about 8 other South Africans I was saddened that many, many more South African midwives could not have had the same exhilarating and motivational boost personally and professionally. I am hoping to partner with the President of SOMSA to petition the SA Government for 100 midwives to attend the 2017 ICM Congress in Toronto. I am convinced that this could begin to alter the perceptions and attitudes of nurses and midwives. I am bursting with other ideas of reaching the tipping point of change.

Thank you once again to ECRU and UBC for this incredible opportunity. 

-Catherine Parker"

 

For more information on the Calcium and Pre-eclampsia (CAP) Study click below:

Get more information HERE

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