This important public health question was identified by the U.S. Departments of Agriculture (USDA) and Health and Human Services (HHS) to be examined by the 2020 Dietary Guidelines Advisory Committee. The 2020 Dietary Guidelines Advisory Committee, Pregnancy and Lactation Subcommittee conducted a systematic review to answer this question with support from the Nutrition Evidence Systematic Review (NESR) team. The goal of this systematic review was to examine the following question: What is the relationship between omega-3 fatty acid supplements consumed before and during pregnancy and lactation and developmental milestones, including neurocognitive development, in the child?
○. Limited evidence suggests that omega-3 fatty acid supplementation during pregnancy may result in favorable cognitive development in the child. (Grade: Limited). ○. Insufficient evidence is available to determine the relationship between omega-3 fatty acid supplementation during both pregnancy and lactation, or during pregnancy only, and language and social emotional development in the child. (Grade: Grade not assignable). ○. Insufficient evidence is available to determine the relationship between omega-3 fatty acid supplementation during pregnancy and motor and visual development, academic performance, and the risk of attention-deficit disorder, attention-deficit/hyperactivity disorder, and autism spectrum disorder in the child. (Grade: Grade not assignable). ○. No evidence is available to determine the relationship between omega-3 fatty acid supplementation during both pregnancy and lactation, or during pregnancy only, and anxiety or depression in the child. (Grade: Grade not assignable). ○. Insufficient evidence is available to determine the relationship between omega-3 fatty acid supplementation during both pregnancy and lactation and cognitive development in the child. (Grade: Grade not assignable). ○. No evidence is available to determine the relationship between omega-3 fatty acid supplementation during both pregnancy and lactation and visual development, academic performance, or the risk of attention-deficit disorder, attention-deficit/hyperactivity disorder, or autism spectrum disorder in the child. (Grade: Grade not assignable). ○. Insufficient evidence is available to determine the relationship between omega-3 fatty acid supplementation consumed during both pregnancy and lactation or during lactation alone, and cognitive, language, motor, and visual development in the child. (Grade: Grade not assignable). ○. No evidence is available to determine the relationship between omega-3 fatty acid supplementation consumed during both pregnancy and lactation or during lactation alone and academic performance, anxiety, depression, or the risk of attention-deficit disorder, attention-deficit/hyperactivity disorder, or autism spectrum disorder in the child. (Grade: Grade not assignable). ○. No evidence is available to determine the relationship between omega-3 fatty acid supplementation consumed during lactation and social-emotional development in the child. (Grade: Grade not assignable).
Literature search was conducted using 4 databases (PubMed, Cochrane, Embase, and CINAHL) to identify articles that evaluated an intervention or exposure of omega-3 fatty acid supplements consumed before and during pregnancy and/or lactation and the outcome of developmental milestones, including neurocognitive development, in the child. A manual search was also conducted to identify articles that may not have been included in the electronic databases searched. Articles were screened by two NESR analysts independently for inclusion based on pre-determined criteria. Data extraction and risk of bias assessment were conducted for each included study, and both were checked for accuracy. The Committee qualitatively synthesized the body of evidence to inform development of a conclusion statement(s), and graded the strength of evidence using pre-established criteria for risk of bias, consistency, directness, precision, and generalizability.
This systematic review included 31 articles from 14 randomized controlled trials (RCTs) and 1 prospective cohort study (PCS) published between 1980 and 2020. Studies included in this review assessed interventions/exposures during: ○. Pregnancy only: 11 RCTs (24 articles); 1 PCS (1 article). ○. Both pregnancy and lactation: 3 RCTs (6 articles). 11 of the 14 RCTs assessed cognitive development: ○. Eight RCTs delivered omega-3 fatty acid supplements during pregnancy alone. Of those 8 RCTs, 5 studies (11 articles) reported at least one statistically significant finding that supplementation resulted in favorable cognitive development in the child. One study reported at least one statistically significant finding that supplementation resulted in unfavorable measures of cognitive development in the child. All 8 studies reported at least one statistically non-significant result. Overall, results were inconsistent across different measures both within and between studies. ○. Three RCTs delivered omega-3 fatty acid supplements during both pregnancy and lactation. Of those 3 RCTs, 1 study reported at least one statistically significant finding that supplementation resulted in favorable cognitive development in the child. All 3 studies reported at least one statistically non-significant result. For language, motor, visual, and social-emotional development, findings were inconsistent and therefore a conclusion statement could not be drawn. Although all studies reported at least one statistically non-significant result, the number and direction of statistically significant findings varied across the body of evidence. Only 1 study examined academic performance; therefore, a conclusion could not be drawn. No evidence was available on omega-3 fatty acid supplementation and anxiety or depression. Only 1 study (2 articles) assessed the risk of attention-deficit disorder (ADD) or attention-deficit/hyperactivity disorder (ADHD); therefore a conclusion could not be drawn. Only 1 RCT and 1 PCS study assessed risk of autism spectrum disorder (ASD), and both had methodological limitations; therefore, the evidence was deemed insufficient to draw a conclusion. The ability to draw strong conclusions was limited by the following issues: ○. Wide variation in the developmental domains assessed, as well as in the measures used to evaluate child performance in each of those domains, which limited the ability to compare results across studies. ○. Potential risk of bias due to missing outcome data. Further, a lack of pre-registered data analysis plans potentially increased the risk of bias due to selectivity in results presented. ○. Findings were mixed both within and between studies, and these inconsistencies could not be explained by methodological differences. ○. Although some studies published results from multiple follow-up assessments, an insufficient number of studies were available to investigate the relationship between omega-3 fatty acid supplementation and developmental milestones in the child for many exposure-outcome pairs. Additionally, several studies did not provide evidence of sufficient sample size to detect effects, either because the study did not achieve the required sample size estimated by power calculations or because the study did not report a power calculation. This is particularly true for the long-term outcome assessments. ○. People with lower socioeconomic status, adolescents, and racially and ethnically diverse populations were underrepresented in the body of evidence. This systematic review included 8 articles from 4 RCTs published between 1980 and 2020. Studies included in this review assessed interventions/exposures during: ○. Both pregnancy and lactation: 3 RCTs (6 articles). ○. Lactation alone: 1 RCT (2 articles). All 4 RCTs assessed cognitive development: ○. Three RCTs provided omega-3 fatty acid supplements during both pregnancy and lactation. Of those 3 RCTs, 1 study reported at least one statistically significant finding that supplementation resulted in favorable cognitive development in the child. All 3 studies reported at least one statistically non-significant result. ○. One RCT provided omega-3 fatty acid supplements during lactation alone and showed a benefit of supplementation on one measure of cognitive development in the child. The study also reported statistically non-significant results on other measures of cognitive development. For language, motor, and social-emotional development, findings were inconsistent and therefore a conclusion statement could not be drawn. Although all studies reported at least one statistically non-significant result, the number and direction of statistically significant findings varied across the body of evidence. No evidence was available on omega-3 fatty acid supplementation and visual development, academic performance, anxiety, depression or the risk of ADD, ADHD, or ASD. The ability to draw strong conclusions was limited by the following issues: ○. Wide variation in the developmental domains assessed, as well as in the measures used to evaluate child performance in each of those domains, limited the ability to compare results across studies. ○. Missing outcome data raised concerns about risk of bias. Further, a lack of preregistered data analysis plans potentially increased the risk of bias due to selectivity in results presented. ○. Findings were mixed both within and between studies, and these inconsistencies could not be explained by methodological differences. ○. Although some studies published results from multiple follow-up assessments, an insufficient number of studies were available to investigate the relationship between omega-3 fatty acid supplementation and developmental milestones in the child for many exposure-outcome pairs. Additionally, multiple studies did not provide evidence of sufficient sample size to detect effects, either because the study did not achieve the required sample size estimated by power calculations or because the study did not report a power calculation. This is particularly true for the long-term outcome assessments. ○. People with lower socioeconomic status, adolescents, and racially and ethnically diverse populations were underrepresented in the body of evidence.
