Exploring the latest science around DHA and pregnancy outcomes

By:  Talking Nutrition Editors

  • A pioneering new study establishes that supplementation with docosahexaenoic acid (DHA), an omega-3 fatty acid, during pregnancy at 1,000 mg per day significantly reduces the risk of early preterm birth (EPB), or birth < 34 weeks gestation.
  • This study represents a milestone in the scientific community’s understanding of the impact of DHA on pregnancy duration. The findings from this study should be utilized to shape clinical practice as well as national guidelines for DHA intake during pregnancy. 
  • We spoke with the lead researcher of the study, Dr. Susan E. Carlson, AJ Rice Professor of Nutrition and University Distinguished Professor at the University of Kansas Medical Center, to learn more about the key findings and the importance of this study.

Study examines impact of high vs. low dose of DHA on pregnancy duration

A recently published study sheds new light on the importance of DHA during pregnancy, highlighting that doses higher than what is found in many prenatal vitamin supplements can significantly decrease the rate of early preterm birth (EPB).1 The research was led by Susan E. Carlson, Ph.D., AJ Rice Professor of Nutrition and University Distinguished Professor at the University of Kansas Medical Center in the Department of Dietetics and Nutrition. The primary aim of the study, “Assessment of DHA on Reducing Early Preterm Birth” (ADORE), was to assess the impact of daily consumption of a prenatal supplement providing 1,000 mg of DHA compared to one providing 200 mg of DHA on the rate of EPB. 

A total of 1,100 pregnant women were enrolled and randomized to receive either the high dose or low dose of DHA. Eligible women were 12 to 20 weeks gestation when the intervention began. Participants received an algal source of DHA. 

In addition to assessing the impact of DHA dosing on EPB, the trial also evaluated maternal DHA status based on red blood cell phospholipid DHA as a secondary outcome. The study – a double-blind, randomized, superiority trial – was conducted at three academic medical centers in the US: University of Kansas, Ohio State University, and University of Cincinnati.

A high dose of DHA significantly reduced the rate of early preterm birth

Women who received the higher dose of DHA had a significantly reduced rate of EPB compared to women who received the lower dose of DHA; rates of EPB were 1.7% vs. 2.9% respectively, with a posterior probability of 0.91.  

An interplay between maternal DHA status and DHA dosing was also observed. “The trial found that a woman’s baseline DHA status, which is highly related to her DHA intake from diet or a prenatal supplement, made a difference. Women with low DHA status at enrollment and who were randomized to the high dose of DHA had half the incidence of EPB compared to those on the lower dose, 2% vs. 4.1%,” explains Dr. Carlson. The statistical analysis of these data results in a posterior probability of 0.93 that the higher dose was better for preventing EPB. The learning that a significant relationship exists between maternal DHA status and DHA dosing agrees with exploratory findings from another recent trial on DHA during pregnancy, the “Australian Omega-3 to Reduce the Incidence of Preterm Birth” (ORIP).2,3

In addition to the findings around DHA dosing and EPB, the research team also found an impact of the higher DHA dose on premature birth overall. Dr. Carlson explains: “Preterm birth <37 weeks was a secondary outcome. The higher dose of DHA reduced premature birth regardless of baseline DHA status (pp=0.95).”

The ADORE trial clarifies our understanding of the impact of DHA on pregnancy duration

Birth that occurs before 34 weeks of gestation is defined as early preterm birth (EPB). In the United States, EPB represent 2.75% of all births4 and 20% of preterm births.While the majority of all preterm births occur between 34 and 36.99 weeks gestation, EPB represents a significant medical and societal burden. These infants carry the highest risks of mortality, requiring costly in-hospital medical care, and experiencing long-term developmental challenges.6,7 Scientists have long been seeking to identify interventions that could reduce or prevent early birth. 

In 2018, a Cochrane Review concluded that EPB could be significantly reduced – nearly by half – when pregnant women received omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) including DHA through food or supplements, compared to women who did not receive any omega-3 LCPUFAs supplement.8 However, the Review included supplementation with eicosapentaenoic acid (EPA), another omega-3 LCPUFA, and it did not identify an optimal dose or type of omega-3 LCPUFAs for consumption.8 

Since many prenatal supplements already provide approximately 200 mg/day of DHA, Dr. Carlson and colleagues elected not to utilize a placebo when designing the study. Instead, they examined the effect of a high vs. low dose of DHA,1 an approach not taken by other studies.  

The ORIP and ADORE trials are the first to study EPB as a primary outcome and ADORE is the first study that compared a standard amount of DHA in many prenatal supplements to a higher dose,” states Dr. Carlson. Further, she explains “The amount commonly added to prenatal vitamins, 200 mg, has not been shown to prevent early preterm birth,”8 confirming the need to explore DHA dosing in a clinical trial.

What is the relevance of the ADORE trial findings?

Dr. Carlson provides insight into the significance of the trial’s findings. “The data are very clear that women are not getting enough DHA. We need to educate clinicians about the importance of DHA during pregnancy and provide them with the tools to recognize women who could benefit from a higher than standard dose.” The authors of the study encourage clinicians to consider testing DHA status in pregnant women, and for those with a low DHA status, advising high-dose DHA supplementation.

“The most important take-home message for clinicians who care for pregnant women is that DHA is important to prevent preterm birth and they should be encouraging women to take a prenatal supplement that provides adequate amounts of DHA.”

Given the significant impact observed, this work could have important relevance in areas of the world with fewer medical resources. In these areas, birth less than 37 weeks is a major cause of infant mortality.9 “The fact that a higher dose of DHA reduced preterm birth overall indicates that in populations with high rates of preterm births, higher doses of DHA supplementation should be considered,” suggests Dr. Carlson.

How can the ADORE trial inform clinical practice and future research?

While Dr. Carlson reflects on the importance of the learnings from the ADORE trial, she also acknowledges that the trial findings provide a call to action. “I’m passionate about the implementation of what we’ve learned,” she says. The ADORE trial, in combination with the recent Cochrane Review8 and the results of the exploratory analysis of the ORIP trial2,3 suggest a change is needed in both health policy and clinical practice. Available data should drive health agencies to set a recommended intake of DHA during pregnancy and can guide clinicians on DHA supplementation, especially for those women with low DHA status. 

Dr. Carlson is also looking to the future, to other areas of maternal nutrition where innovation is needed. She would like to see a study that aims to improve women’s DHA status before they become pregnant or very early in pregnancy. Dr. Carlson is also interested in improving education for pregnant women around the topic of prenatal nutrition, knowing that awareness is key to changing behavior.

Additionally, she is intrigued with the evidence that DHA and choline act synergistically during development, so that the sum of their effects is greater than the effect of each nutrient alone. She tells us “both choline and DHA are recognized as nutrients that need to be improved in the diets of most US women during pregnancy. Even though some prenatal supplements add choline, the amount is quite low.”

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Published on

09 July 2021

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References

  1. Carlson SE, Gajewski BJ, Valentine CJ, et al. Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial. EClinicalMedicine. 2021.
  2. Makrides M, Best K, Yelland L, et al. A Randomized Trial of Prenatal n-3 Fatty Acid Supplementation and Preterm Delivery. N Engl J Med. 2019;381(11):1035-1045.
  3. Simmonds LA, Sullivan TR, Skubisz M, et al. Omega-3 fatty acid supplementation in pregnancy-baseline omega-3 status and early preterm birth: exploratory analysis of a randomised controlled trial. Bjog. 2020;127(8):975-981.
  4. Martin JA HB, Osterman MJK, Driscoll AK. National Vital Statistics Reports. Births: Final Data for 2018. Vol 68, Number 13. 2019.
  5. Martin JA, Osterman MJK. Describing the Increase in Preterm Births in the United States, 2014-2016. NCHS Data Brief. 2018(312):1-8.
  6. Beam AL, Fried I, Palmer N, et al. Estimates of healthcare spending for preterm and low-birthweight infants in a commercially insured population: 2008-2016. J Perinatol. 2020;40(7):1091-1099.
  7. Kaempf J, Morris M, Steffen E, Wang L, Dunn M. Continued improvement in morbidity reduction in extremely premature infants. Arch Dis Child Fetal Neonatal Ed. 2020.
  8. Middleton P, Gomersall JC, Gould JF, Shepherd E, Olsen SF, Makrides M. Omega-3 fatty acid addition during pregnancy. Cochrane Database Syst Rev. 2018;11(11):Cd003402.
  9. Liu L, Oza S, Hogan D, et al. Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet. 2016;388(10063):3027-3035.

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