The women of the Faroe Islands, rugged specks in the remote North Atlantic, eat a lot of fish. And government records show that they have a much lower rate of premature births than in the rest of the Kingdom of Denmark — one of the lowest in the world.
Dr. Sjurdur F. Olsen, a leading researcher on how a mother's diet affects her child's health, put those puzzle pieces together more than three decades ago, and published the hypothesis that the omega-3 fatty acids in cold-water fish could help prevent preterm births.
Studies exploring that link have brought mixed results, but now, his team's new paper in the journal EBioMedicine strengthens it and moves it earlier: It finds that Danish women with the lowest levels of the fatty acids EPA and DHA in their blood in the first two trimesters of pregnancy were at much higher risk for giving birth prematurely.
"Early preterm birth occurs 10 times more frequently in that group compared to those with higher levels of these fatty acids in their plasma," says Olsen, head of the Centre for Fetal Programming at Statens Serum Institut in Denmark and an adjunct professor of nutrition at the Harvard Chan School of Public Health.
Health authorities already recommend that pregnant women eat fish, but avoid those high in mercury, including swordfish, tuna and shark.
The EBioMedicine study is the first "to show definitely that extremely low levels of the type of fatty acids that are in fish are very highly correlated with very early preterm births," says Dr. Kelle H. Moley, chief scientific officer at the March of Dimes, which helped fund Olsen's work.
Past studies had given omega-3 supplements to women late in pregnancy to try to prevent preterm birth. "What this paper really suggests," she says, "is that probably even pre-conceptually, you need to have a certain level of fish in your diet that is going to raise your blood levels of these important omega-3 fatty acids in the first and second trimesters. And that is not what anyone has been looking at."
The study used rich Danish government records — the Danish National Birth Cohort — and blood samples to compare two groups of more than 300 women each: mothers who gave birth before 34 weeks of pregnancy and mothers who carried their babies to full-term, typically 40 weeks.
It found a steep rise in risk for preterm birth in the two-fifths of women with the lowest levels of fatty acids — concentration lower than 2 percent in their blood.
It's not clear exactly how that concentration translates to how much fish a woman consumes, Olsen says, and because testing for omega-3 levels is expensive and the findings still new, he doesn't expect obstetricians to start routine testing at this point.
But he does expect the findings to spur more research, particularly on how much fish a woman needs to eat to lower her risk of preterm birth, and when she needs to eat it.
And he points out that three lines of evidence are now converging: randomized trials that found increased intake of omega-3 supplements can delay preterm delivery; observational diet studies showing a link between self-reported low intake of fish in pregnancy and risk of preterm birth; and now this new study, a "biomarker study" showing that women who have low levels of fatty acids in their blood are at higher risk for preterm birth.
"Those are three quite different ways of studying the same issue," he says, and taken together, they add weight to the notion that if you're a woman whose diet is low on omega-3s, "increasing your intake will lower your risk of preterm birth."
Among the study's caveats: It looked only at Danish women, and must be replicated in other populations. But Moley from the March of Dimes points out that Danish women tend to eat more fish than American women, so the effects could be even more dramatic here because the omega-3 levels may be lower.
Many prenatal vitamins now include omega-3s, Moley says, and many doctors already recommend that women start them before getting pregnant, "but I think in extremely vulnerable populations of women that have high rates of preterm births, it is probably even more important to start that earlier."
Omega-3s could end up like folic acid, she says, widely advertised so women are aware of their benefits even before pregnancy.
How, exactly, low levels of fatty acids could lead to premature birth is not clear, but one leading theory is that the low levels create problems with immune function that throw off the tricky dance between the mother's body and the fetus. There could be genetic elements as well; recent research has looked at how genes linked to fatty acid metabolism may affect how long a woman's pregnancy lasts.
Dr. Thomas McElrath, director of the preterm birth clinic at Brigham and Women’s Hospital in Boston, says that for years, the link between omega-3s and preterm birth has been elusive, with some studies confirming it and others not.
"It's always been just sort of beyond reach in terms of becoming something that may be more tangible in clinical practice," he says.
The new study adds important information, he says, because "it suggests that really, what we may be looking at is that women who have a deficiency, if not an extreme deficiency, in fatty acids in their diet may be the ones who are the most vulnerable — but that there is a certain level beyond which it really doesn't matter if you have more, or much more. It's not going to create a difference in the risk profile."
So that threshhold effect could explain why some previous studies have found no effect of omega-3s, he says.
Ultimately, McElrath says, for sweeping changes in clinical practice — for obstetricians to routinely recommend omega-3 supplements, for example — it generally takes a "gold-standard" randomized trial rather than an "observational" study like this one.
"It's still early days," he says. And he's cautious about recommending supplements because they may contain impurities. As for simply recommending safe types of fish to patients, McElrath already does that in prenatal visits — but it can be a challenge.
"About a third of the patients will say right off, 'Nope, stop. Stop right now,' " he says. "'I just don't eat fish. I just don't like fish. And I'm feeling nauseous, and I just don't even want to talk about fish right now.' "