Dr. Mark Walker with a pregnant patient.Taking high doses of folic acid throughout pregnancy does not prevent preeclampsia in high-risk women, according to a large international clinical trial published in The BMJ. This refutes the findings of previous observational studies and is expected to change practice worldwide.

Preeclampsia, or high blood pressure during pregnancy, is the leading cause of pregnancy-related complications and death worldwide. It affects 10 million women around the world every year. The only cure is to deliver the baby, who is often born premature.

Folic acid is a vitamin that helps cells grow. All women are recommended to take a low dose (0.4 and 1.0 mg/day) throughout pregnancy. A high dose (4.0-5.0mg/day) is only recommended for women at high risk of neural tube birth defects, and should be stopped at the end of the first trimester. Despite this recommendation, studies have shown that many women around the world take high doses of folic acid (1.1-5.0 mg/day) during their entire pregnancy.

The study led by researchers at The Ottawa Hospital and the University of Ottawa was designed to test whether high dose folic acid could prevent preeclampsia, something that had been seen in observational and laboratory studies. 2,464 women at high risk of preeclampsia took either 4.0mg of folic acid or a placebo daily, starting between 8 and 16 weeks of gestation and stopping when their baby was born. Like all pregnant women, they were also advised to continue taking their prenatal vitamins (containing between 0.4-1.1 mg/day of folic acid) throughout their pregnancy. Preeclampsia affected 14.8 percent of the women in the high dose folic acid group and 13.5 percent in the placebo group, which was not a significant difference. There were no other significant health differences between the women or newborns in these the two groups.

 “People think folic acid is a harmless vitamin, so many pregnant women take it for longer and in higher doses than recommended,” said Dr. Mark Walker, Department Chief of Obstetrics, Gynecology and Newborn Care at The Ottawa Hospital and professor at the University of Ottawa and senior author on the paper.  “To avoid over-medication, doctors should clearly tell their patients when a high dose of folic acid is needed and when it should be stopped.”

The research team will also follow the babies born to these mothers over six years to see whether the higher doses of folic acid affects their health or neuro-cognitive development.

“Everyone who treats pregnant women has been waiting for an answer to this question,” said Dr. Wen, lead author of the study, and senior scientist at The Ottawa Hospital and professor at the University of Ottawa. “We have 70 different study sites in five countries around the world, from Jamaica to Australia, so our findings will have an impact on patient care not only in Canada, but around the world. We’re very grateful to everyone who made this study possible, especially the women who participated.” Dr. Shi Wu Wen

“The Ottawa Hospital is known around the world for leading international trials that answer important questions to improve health,” said Dr. Duncan Stewart, Executive-vice President of Research and senior scientist at The Ottawa Hospital and professor at the University of Ottawa. “This trial, which is the largest of its kind, is a flagship for our research institute.”

All research at The Ottawa Hospital is supported by generous donors who contribute to hospital priorities, including research to improve patient care.  This study was funded by the Canadian Institutes of Health Research.

Full reference: “Effect of high dose folic acid supplementation in pregnancy on preeclampsia (FACT): a double-bind, phase III, randomised controlled, international, multicentre trial.” Shi Wu Wen, Ruth Rennicks White, Natalie Rybak, Laura M Gaudet Stephen Robson, William Hague, Donnette Simms-Stewart, Guillermo Carroli, Graeme Smith, William D. Fraser, George Wells, Sandra T. Davidge, John Kingdom, Doug Coyle, Dean Fergusson, Daniel J Corsi, Josee Champagne, Elham Sabri, Tim Ramsay, Ben Willem J. Mol, Martijn A Oudijk, Mark C Walker, on behalf of the FACT Collaborating Group. The BMJ. September 12, 2018.

About The Ottawa Hospital: Inspired by research. Driven by compassion. The Ottawa Hospital is one of Canada’s largest learning and research hospitals with over 1,100 beds, approximately 12,000 staff and an annual budget of over $1.2 billion. Our focus on research and learning helps us develop new and innovative ways to treat patients and improve care. As a multi-campus hospital, affiliated with the University of Ottawa, we deliver specialized care to the Eastern Ontario region, but our techniques and research discoveries are adopted around the world. We engage the community at all levels to support our vision for better patient care. See www.ohri.ca for more information about research at The Ottawa Hospital.

About the University of Ottawa: —A crossroads of cultures and ideas

The University of Ottawa is home to over 50,000 students, faculty and staff, who live, work and study in both French and English. Our campus is a crossroads of cultures and ideas, where bold minds come together to inspire game-changing ideas. We are one of Canada’s top 10 research universities—our professors and researchers explore new approaches to today’s challenges. One of a handful of Canadian universities ranked among the top 200 in the world, we attract exceptional thinkers and welcome diverse perspectives from across the globe. www.uottawa.ca

Media Contact: Amelia Buchanan, Senior Communication Specialist, Ottawa Hospital Research Institute; ambuchanan@ohri.ca; Office: 613-798-5555 x 73687; Cell: 613-297-8315