Overall, birth defects and miscarriage are global problems, affecting up to 6% of babies
and up to 20% of known pregnancies
. A possible prevention, then, could help millions worldwide.
"Not only have we identified a cause of miscarriage, and of birth defects where the babies affected have heart and vertebral and kidney defects among others, but we've also discovered a prevention in the form of niacin, also known as vitamin B3," said Sally Dunwoodie, lead author of the study and a researcher at Sydney's Victor Chang Cardiac Research Institute.
Based on the findings, Dunwoodie suggests that pregnant women should take high doses of vitamin B3, also known as niacin, to prevent miscarriages and certain types of birth defects.
However, some experts urge caution: High-dose supplementation has not been proved effective -- or safe -- for pregnant women.
Essential nutrients during pregnancy?
Dunwoodie and her colleagues based their research on a New Jersey Medical School study
that found at least
a third of pregnant women have low levels of vitamin B3 during the first trimester, when a baby's organ development begins. The research also discovered that vitamin B3 levels were low in 60% of women by the third trimester.
The body needs B3 to make a protein known as nicotinamide adenine dinucleotide, or NAD. It is found in all living cells and is essential for them to make energy, repair genes and communicate with other cells.
But environmental pollutants and genetic mutations can disrupt a cell's ability to produce NAD, leading to lower levels than needed to function normally.
In the study, published Thursday
in the New England Journal of Medicine, Dunwoodie and her colleagues investigated the effects of a lack of vitamin B3 by sequencing the genomes of 13 families. Each of the families had children with birth abnormalities, affecting in particular the vertebrae, heart, kidney, anus, esophagus and trachea, or limbs.
The team detected gene mutations in some of the mothers associated with a deficiency of B3 and an inability to synthesize enough NAD.
The team followed this with experiments on mice engineered to have the same genetic defect.
With a regular diet, the pregnant mice had either miscarriages or pups with a range of severe birth defects.
However, once vitamin B3 was introduced into the diet of the pregnant mice, the miscarriages and birth defects ended, and all the pups were born healthy.
'Exciting' research for a rare disorder
"This is exciting and very encouraging research," said Dr. Lisa Waddell, deputy medical officer at the March of Dimes, which funds research and programs to end premature birth, birth defects and infant mortality.
Waddell, who was not involved in the study, warned that additional research in humans is needed before advising pregnant women to take B3 above and beyond the current US recommendation
of 18 milligrams a day.
Dr. Sarah Stock, senior clinical lecturer at the University of Edinburgh who also was not involved in the study, said it is "exciting" in that it increases our understanding of birth defects.
"However, it must be emphasized that this work was done in mice, and it is much too early to say if women should start taking extra vitamin B3," she said. More research is needed in humans, she agreed, and on what dose would be safe for women.
David Amor, a clinical geneticist and professor at the University of Melbourne, said "there is no reason to believe that dietary niacin deficiency is a major cause of birth defects in the general population."
Amor, who was not involved in the research, noted that the genetic condition studied by Dunwoodie and her colleagues is "likely to be very rare."
"A broader question is whether dietary niacin deficiency might play a role in birth defects, even in the absence of the genetic deficiency of NAD, and whether dietary supplementation of niacin might be of benefit to pregnant women in the general population," he said.
Michael Fenech of the Commonwealth Scientific and Industrial Research Organization, a government agency for scientific research in Australia, said the new research is "an important discovery." Fenech observed that high-dose niacin (140 milligrams a day), as recommended by the study authors for women with the identified gene mutation, is significantly higher than the recommended daily intake in the United States.
The study provides "no evidence" to support this recommendation, he said. "Furthermore, this dose may not be safe given that the tolerable upper intake level for niacin is only 35 milligrams a day for adults."
Stock noted that diet plays a vital role in a healthy pregnancy. "At the moment, all pregnant women and couples trying to become pregnant should try to follow recommendations to eat a balanced healthy diet."
Waddell added that doctors already recommend that pregnant women take a multivitamin containing B3.