Context:

The likely significance of omega-3 fatty acids for child and maternal health is therefore suggested by the observations that: the human brain and retina each contain considerable omega-3 fatty acid content; the child delivered at term receives and important supply of omega-3 fatty acids especially in the third trimester of pregnancy; and, due to a shortened gestational period, the child delivered prematurely receives less exposure to omega-3 fatty acid content than does the term child. This evidence is systematically reviewed there.

Objectives:

The purpose of this study was to conduct a systematic review of the scientific-medical literature to identify, appraise and synthesize the evidence of omega-3 fatty acids in child and maternal health. Evidence was sought to investigate a series of questions regarding the influence of the omega-3 fatty acid intake (supplemented during pregnancy) on the duration of gestation, incidence of preeclampsia, eclapmsia or gestational hypertension (GHT), and incidence of infants small for gestational age (SGA), as well as the association between the maternal biomarkers during pregnancy and the pregnancy outcomes outlined above. The influence of the omega-3 fatty acid intake (supplemented or breast milk) on the developmental outcomes in preterm and term infants, such was growth, neurocognitive development and visual function, were also investigated, as well as the association between the maternal, fetal or child's biomarkers and these clinical outcomes. The impact of effect modifiers was also examined, as well as the safety profile. The results will be sued to inform a research agenda.

Data Sources:

A comprehensive search for citations was conducted using five electronic databases (MEDLINE®, PreMEDLINE®, EMBASE, Cochrane Central Register of Controlled Trials, and CAB Health). Searches were not restricted by language of publication, publication type, or study design, except with respect to the MeSH term “dietary fats,” which was limited by study design to increase its specificity. Search elements included scientific terms (with acronyms), generic and trade names relating to the exposure and its sources (e.g., preterm, term, child development, etc). Additional published or unpublished literature was sought through manual searches of references lists of included studies and key review articles, and from the files of content experts.

Study Selection:

Studies were considered relevant if they described live human populations of healthy preterm (<37 weeks of GA), term (>37 weeks of GA) infants of healthy pregnant women, investigated the use of any supplements (formula, diet, etc.) known to contain omega-3 fatty acids and/or human milk, and utilizing pertinent pregnancy and child developmental outcomes (e.g., growth, neurocognitive, visual). Studies examining the questions concerning the efficacy had to employ a controlled research design (i.e., RCTs), whereas, any type of design other than case-series or case-study was permitted to address the possible association between the content of biomarkers and the clinical outcomes. Three levels of screening for relevance, and two reviewers per level, were employed. Disagreements were resolved by consensus and, if necessary, third-party intervention.

Data Extraction:

All data were extracted by one reviewer, then verified by a second one. Data included the characteristics of the report, study population, intervention/exposure and comparator(s), cointerventions, discontinuations (with reasons), and outcomes (i.e., clinical, biomarkers, safety). Study quality (internal validity) and study applicability (external validity) were appraised.

Data Synthesis:

Question-specific qualitative synthesis of the evidence was derived. Meta-analysis was conducted with data concerning the supplemental influence on incidence of premature deliveries, GHT, birth weight, incidence of IUGR, growth patterns, (i.e., weight, length and head circumference) in term and preterm infants, neurological and cognitive development in term infants, and visual function in both term and preterm infants. One hundred and seventeen reports, describing 89 studies, were deemed relevant for the systematic review, with many studies described in more that one question.

Conclusions:

Studies investigating the influence of omega-3 fatty acids on child and maternal health revealed the absence of a notable safety profile (i.e., moderate-to-severe AEs). Pregnancy outcomes were either unaffected by omega-3 fatty acid supplementation, or the results were inconclusive. Results suggested the absence of effects with respect to the impact of supplementation on the incidence of GHT, preeclampsia or eclampsia, as well as on infants being born SGA. However, regarding evaluations of the duration of gestation, some discrepancies were observed, although most of the studies failed to detect a statistically significant effect. Biomarker data failed to clarify patterns in pregnancy outcome data.

Results concerning the impact of the intake of omega-3 fatty acids on the development of infants are primarily, although not uniformly, inconclusive. The inconsistencies in study results may be attributable to numerous factors.

In addition, making clear sense of the absolute or relative effects of individual omega-3 fatty acids, or even omega-3 fatty acid combinations, on child outcomes is complicated or precluded by the following problem. Studies typically employed interventions that involved various cointerventional or background constituents (e.g., omega-6 fatty acids), yet whose metabolic interactions with the omega-3 fatty acid(s) were not taken into account in interpreting the results. The dynamic interplay among these fatty acid contents (e.g., competition for enzymes), and how this interplay may influence outcomes, may differ in important ways depending on whether DHA or olive oil is added to the combination of cointerventional or background constituents, particularly in the maternal population. This strategy prevented the isolation of the exact effects relating to the omega-3 fatty acid content. It is thus very difficult to reliably ascribe definite child outcome-related benefits, or the absence thereof, to specific omega-3 fatty acids. Biomarker data failed to clarify patterns in child outcome data.

Future research should likely consider investigating the impact of specific omega-6/omega-3 fatty acid intake ratios, in no small part to control for the possible metabolic interactions involving these types of fatty acids. To produce results that are applicable to the North American population, populations consuming high omega-6/omega-3 fatty acid intake ratios should likely be randomized into trials also exhibiting better control of confounding variables than was observed, especially in the present collection of studies of child outcomes.