Door closes on antioxidants for pregnancy complications?

By Stephen Daniells

- Last updated on GMT

Related tags Cent Oxidative stress Placebo group Vitamin c Folic acid

Another study has concluded that a combination of vitamins C and E
do not help reduce the risk of pregnancy complication
pre-eclampsia, but a leading charity has voiced hope that the door
is not closed and that research with these nutrients will continue.

Pre-eclampsia, affecting two to three per cent of all pregnancies, occurs when a mother's blood pressure rises to the hypertensive range, and excretion of protein in the urine becomes too high. It is estimated to be responsible for about 60000 deaths worldwide.

It is not known why some expectant mothers develop pre-eclampsia, although oxidative stress has been proposed to play a part. The role of antioxidants to reduce oxidative stress had been supported by a small clinical trial that linked vitamin C and E intake to fewer biomarkers for pre-eclampsia for predominantly low-risk participants.

The new placebo-controlled, randomized clinical trial, published in the new issue of The New England Journal of Medicine​ (Vol. 354, pp. 1796-1806), reports the effect of vitamin C (1000 mg) and vitamin E (d-alpha-tocopherol succinate, 400 IU), or placebo, for 1877 women during their first pregnancy from 14 to 22 weeks of gestation.

The Australian Collaborative Trial of Supplements (ACTS) found that there was no significant difference between placebo and supplemented groups in terms of the risk of pre-eclampsia, death or serious problems in the baby, or having a low birth weight child.

Of the 935 women receiving the vitamins, 56 women developed pre-eclampsia, equal to six per cent of the study population. Forty-seven women of the 942 in the placebo group developed pre-eclampsia, equal to five per cent.

It should be noted that, while the dosages of the vitamins was identical to those used in the recent London-based trial reported on-line in The Lancet (doi:10.1016/S0140-6736(06)68434-1), the incidence of pre-eclampsia was significantly lower in the ACTS study: 15 per cent of the supplemented group and 16 per cent of the placebo group were reported to have developed the condition in the London trial.

The London trial also reported that the antioxidant group gave birth to lower birthweight babies (28 per cent versus 24 per cent for the supplement and placebo groups, respectively). This was not found to be the case in the ACTS study with 8.7 per cent of babies born to vitamin-supplemented mothers being small, and 9.9 per cent of babies from the placebo mothers.

Interestingly, the ACTS researchers did report a benefit to a secondary study outcome: respiratory distress syndrome.

A significant limitation of this study is that most of the women studied already had dietary intakes of both vitamins above the recommended daily amounts before the trial began.

"Thus, the results cannot be generalized to women with low dietary intakes of antioxidants,"​ said lead author Alice Rumbold from the University of Adelaide, Women's and Children's Hospital.

Similar conclusions were reached by Marshall Lindheimer from the University of Chicago and Baha Sibai from the University of Cincinnati following publication of the London-based study. In an editorial in The Lancet, Lindheimer and Sibai pointed out that antioxidant supplements in areas of developing nations where nutrient deficiencies are rife, may produce different results.

Such views were echoed further by the US-based industry association, The National Nutritional Foods Association (NNFA). Dr. Daniel Fabricant, vice president of scientific affairs, said: "none of the women included in NEJM's study were Vitamin C and E deficient or in a state of sub-optimal vitamin status - a population that would stand to benefit the most from antioxidant supplementation during pregnancy.

NNFA contends that the study also lacked important information about sub-groups, such as smokers, and how antioxidant supplementation might have benefited them,"​ he said.

Mike Rich, chief executive of UK maternity charity, Action on Pre-eclampsia, which has been championing the research, told that he hoped the results did not close the door on research into the use of the antioxidants to reduce the risk of pre-eclampsia.

Rich explained that there is not real solution for women with pre-eclampsia, and there had been hope that the vitamins could help.

"One thing shown by the London study was that women did benefit from multivitamins and smaller doses. We hope that future research will focus on smaller doses,"​ said Rich.

It should also be stressed that expectant mothers, as well as all women of child-bearing age, should continue to eat folic acid-rich or fortified foods and/or take folic acid supplements to reduce the risk of neural tube defects.

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