Low DHA and EPA a ‘strong risk factor’ for preterm birth: Danish data

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Pregnant women with low plasma levels of long chain omega-3 fatty acids in their first and second trimesters may be at a significantly higher risk of early preterm birth, new research suggests.

The data, published in EBioMedicine, suggests that that low blood concentrations of certain long chain fatty acids - specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) - may be a ‘strong risk factor’ for preterm birth.

Preterm birth is a major cause of neonatal death and is linked to a raft of health issues during development and later life including cognitive deficiencies and cardiometabolic problems.

The team, led by Sjurdur Olsen from Harvard Chan School and Statens Serum Institut in Copenhagen, noted that for decades it has been suggested that higher intakes of EPA and DHA,  can reduce the risk of preterm birth. But, while some studies have supported this theory, research findings have been inconsistent.

The new study is the first study to examine whether low plasma concentrations of long chain omega-3 fatty acids in early and mid-pregnancy is associated with increased risk of subsequent early preterm birth.

“Our findings of a relatively strong association between plasma concentrations of total EPA and DHA in pregnancy and risk of early spontaneous preterm birth may suggest that that body levels of these fatty acids are causally implicated in the physiologic processes leading up to premature labour and delivery,” said the authors.

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The findings also suggest that plasma measurements of EPA and DHA in pregnancy could be used to identify women at risk of early preterm birth, they concluded.

"At a time when many pregnant women are hearing messages encouraging them to avoid intake of fish altogether due to mercury content, our results support the importance of ensuring adequate intake of long chain omega-3 fatty acids in pregnancy,” said Olsen.

Danish data

Olsen and her team looked at data from the Danish National Birth Cohort, a nationwide study that follows 96,000 children in Denmark through questionnaires and registry linkages.

In a case-controlled study they analysed blood samples from 376 women who gave birth very prematurely (prior to 34 weeks of gestation) between 1996 and 2003 and 348 women who had a full-term birth. All women had given blood samples during their first and second trimesters of pregnancy.

Analysis of the blood samples showed that women with the lowest levels of EPA+DHA (with EPA+DHA levels of 1.6% or less) had a 10 times higher risk of early preterm birth when compared with women in the three highest groups (with EPA+DHA levels of 1.8% or higher).

When the team further split up the data and looked just at women who had been consistently in the lowest group for DHA and EPA concentration in both the first and second trimester, the team found that those women were associated with 48 times more risk of early preterm birth than those in the higher groups.

Analysis also showed a threshold effect for EPA+DHA concentrations somewhere between 2.0% and 2.5%, said Olsen and colleagues - who noted a ‘sharp increase’ in risk at low levels which then flattens rapidly out at higher levels.

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Implications

The authors said that their findings suggest that for pregnant women with low levels of EPA+DHA, eating more fish or taking a fish oil supplement could potentially lower the risk of preterm birth.

"Early preterm birth has immense health, economic, and emotional costs,” said study co-author Andrew Thorne-Lyman. “Our findings are consistent with the results of most randomised trials of long chain omega-3 fatty acid supplements in pregnancy and support the importance of ensuring adequate intake of these nutrients during pregnancy, either through fish intake or supplements, to help prevent early preterm birth."

“Extending pregnancy even by a few days could be of significant clinical value in foetuses in danger of being delivered prior to 34 weeks,” the team noted.

However, the team cautioned that broad generalisations about the findings may be limited due to the fact that it was conducted in Denmark, where preterm birth rates are low.

As such, the study needs to be replicated in other populations, they added.

"An effect of this magnitude is rare, but the precision of the estimate is tight, which supports the reliability these findings,” commented co-author Jeremy Furtado, senior research scientist at Harvard Chan School. “It will be important to replicate these findings in other populations, but the results of this study certainly suggest that assessment of plasma EPA+DHA status in women has the potential to be used in the future to help predict women's risk."

Source: EBioMedicine

Published online, ahead of print, doi:10.1016/j.ebiom.2018.07.009

“Plasma Concentrations of Long Chain N-3 Fatty Acids in Early and Mid-Pregnancy and Risk of Early Preterm Birth”

Authors: S Olsen, et al