OBJECTIVES: To update a prior systematic review on the effects of omega-3 fatty acids (n-3 FA) on maternal and child health and to assess the evidence for their effects on, and associations with, additional outcomes.
DATA SOURCES: MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Centre for Agriculture and Biosciences (CAB) Abstracts from 2000 to August 2015; eligible studies from the original report; and relevant systematic reviews.
REVIEW METHODS: We included randomized controlled trials (RCTs) of any defined dose of n-3 FA (or combination) compared to placebo, any other n-3 FA, or alternative dose with an outcome of interest conducted in pregnant or breastfeeding women or neonates (preterm or term). We also included prospective observational studies that analyzed the association between baseline n-3 FA intake or biomarker level and followup outcomes. Postnatal interventions began within a week of birth for term infants and within a week of beginning enteral or oral feeding for preterm infants. Standard methods were used for data abstraction and analysis, according to the Evidence-based Practice Center Methods Guide.
RESULTS: We identified 4,275 potentially relevant titles from our searches, of which 95 RCTs and 48 observational studies met the inclusion criteria. Risk of bias was a concern with both RCTs and observational studies. Outcomes for which evidence was sufficient to draw a conclusion are summarized here with the Strength of Evidence (SoE). (Outcomes for which the evidence was insufficient to draw a conclusion are summarized in Appendix G of the report.).
Maternal Exposures and Outcomes: Gestational length and risk for preterm birth: Prenatal algal docosahexaenoic acid (DHA) or DHA-enriched fish oil supplementation had a small positive effect on length of gestation (moderate SoE), but no effect on risk for preterm birth (low SoE). Prenatal EPA (eicosapentaenoic acid) plus DHA-containing fish oil supplementation has no effect on length of gestation (low SoE). Supplementation with DHA, or EPA plus DHA-, or DHA-enriched fish oil does not decreaserisk for preterm birth (low SoE).
Birth weight and risk for low birth weight: Changes in maternal n-3 FA biomarkers were significantly associated with birth weight. Prenatal algal DHA or DHA-enriched fish oil supplementation had a positive effect on birth weight among healthy term infants (moderate SoE), but prenatal DHA supplementation had no effect on risk for low birth weight (low SoE). Prenatal EPA plus DHA or alpha-linolenic acid (ALA) supplementation had no effect on birth weight (low SoE).
Risk for peripartum depression: Maternal n-3 FA biomarkers had no association with risk for peripartum depression. Maternal DHA, EPA, or DHA-enriched fish oil supplementation had no effect on risk for peripartum depression (low SoE).
Risk for gestational hypertension/preeclampsia: Prenatal DHA supplementation among high-risk pregnant women had no effect on the risk for gestational hypertension or preeclampsia (moderate SoE). Prenatal supplementation of any n-3 FA in normal-risk women also had no significant effect on risk for gestational hypertension or preeclampsia (low SoE).
Fetal, Infant, and Child Exposures and Outcomes: Postnatal growth patterns: Maternal fish oil or DHA plus EPA supplementation had no effect on postnatal growth patterns (attainment of weight, length, and head circumference) when administered prenatally (moderate SoE) or both pre- and postnatally (low SoE). Fortification of infant formulas with DHA plus arachidonic acid (AA, an n-6 FA) had no effect on growth patterns of preterm or term infants (low SoE).
Visual acuity: Prenatal supplementation with DHA had no effect on development of visual acuity (low SoE). Supplementing or fortifying preterm infant formula with any n-3 FA had no significant effect on visual acuity assessed by visual evoked potentials (VEP) at 4 or 6 months corrected age (low SoE). Data conflicted on the effectiveness of supplementing infant formula for term infants with n-3 FA depending on when and how visual acuity was assessed (i.e. by VEP or by behavioral methods) and the type of essential FA provided (low SoE).
Neurological development: Prenatal or postnatal n-3 FA supplementation had no consistent effect on neurological development (low SoE).
Cognitive development: Prenatal DHA supplementation with AA or EPA had no effect on cognitive development (moderate SoE). Supplementing breastfeeding women with DHA plus EPA also had no effect on cognitive development in infants and children (low SoE). Supplementing or fortifying preterm infants' formula with DHA plus AA had a positive effect on infant cognition at some short-term followup times (moderate SoE). Supplementing or fortifying infant formula for term infants with any n-3 FA had no effect on cognitive development (low SoE). Evidence is insufficient to support any effect of n-3 FA infant supplementation on long-term cognitive outcomes.
Autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), and learning disorders: Maternal or infant n-3 FA supplementation had no effect on risk for autism spectrum disorders or ADHD (low SoE). No studies on other learning disorders were identified.
Atopic dermatitis (AD), allergies, and respiratory disorders: Pre- and postnatal (maternal and infant) n-3 FA supplementation had no consistent effect on the risk for AD/eczema, allergies, asthma, and other respiratory illnesses (moderate SoE). Biomarkers and intakes had no consistent association with the risk for AD, allergies, and respiratory disorders (low SoE).
Adverse events: Prenatal and infant supplementation with n-3 FA or fortification of foods with n-3 FA did not result in any serious or nonserious adverse events (moderate SoE); with the exception of an increased risk for mild gastrointestinal symptoms.
CONCLUSIONS: Most studies in this report examined the effects of fish oil (or other combinations of DHA and EPA) supplements on pregnant or breastfeeding women or the effects of infant formula fortified with DHA plus AA. As with the original report, with the exception of small increases in birth weight and length of gestation,n-3 FA supplementation or fortification has no consistent evidence of effects on peripartum maternal or infant health outcomes. No effects of n-3 FA were seen on gestational hypertension, peripartum depression, or postnatal growth. Apparent effects of n-3 FA supplementation were inconsistent across assessment methods and followup times for outcomes related to infant visual acuity, cognitive development and prevention of allergy and asthma. Future RCTs need to assess standardized preparations of n-3 and n-6 FA, using a select group of clinically important outcomes, on populations with baseline n-3 FA intakes typical of those of most western populations.
To update a prior systematic review on the effects of omega-3 fatty acids (n-3 FA) on maternal and child health and to assess the evidence for their effects on, and associations with, additional outcomes.
DATA SOURCES:
MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Centre for Agriculture and Biosciences (CAB) Abstracts from 2000 to August 2015; eligible studies from the original report; and relevant systematic reviews.
REVIEW METHODS:
We included randomized controlled trials (RCTs) of any defined dose of n-3 FA (or combination) compared to placebo, any other n-3 FA, or alternative dose with an outcome of interest conducted in pregnant or breastfeeding women or neonates (preterm or term). We also included prospective observational studies that analyzed the association between baseline n-3 FA intake or biomarker level and followup outcomes. Postnatal interventions began within a week of birth for term infants and within a week of beginning enteral or oral feeding for preterm infants. Standard methods were used for data abstraction and analysis, according to the Evidence-based Practice Center Methods Guide.
RESULTS:
We identified 4,275 potentially relevant titles from our searches, of which 95 RCTs and 48 observational studies met the inclusion criteria. Risk of bias was a concern with both RCTs and observational studies. Outcomes for which evidence was sufficient to draw a conclusion are summarized here with the Strength of Evidence (SoE). (Outcomes for which the evidence was insufficient to draw a conclusion are summarized in Appendix G of the report.). Maternal Exposures and Outcomes: Gestational length and risk for preterm birth: Prenatal algal docosahexaenoic acid (DHA) or DHA-enriched fish oil supplementation had a small positive effect on length of gestation (moderate SoE), but no effect on risk for preterm birth (low SoE). Prenatal EPA (eicosapentaenoic acid) plus DHA-containing fish oil supplementation has no effect on length of gestation (low SoE). Supplementation with DHA, or EPA plus DHA-, or DHA-enriched fish oil does not decreaserisk for preterm birth (low SoE). Birth weight and risk for low birth weight: Changes in maternal n-3 FA biomarkers were significantly associated with birth weight. Prenatal algal DHA or DHA-enriched fish oil supplementation had a positive effect on birth weight among healthy term infants (moderate SoE), but prenatal DHA supplementation had no effect on risk for low birth weight (low SoE). Prenatal EPA plus DHA or alpha-linolenic acid (ALA) supplementation had no effect on birth weight (low SoE). Risk for peripartum depression: Maternal n-3 FA biomarkers had no association with risk for peripartum depression. Maternal DHA, EPA, or DHA-enriched fish oil supplementation had no effect on risk for peripartum depression (low SoE). Risk for gestational hypertension/preeclampsia: Prenatal DHA supplementation among high-risk pregnant women had no effect on the risk for gestational hypertension or preeclampsia (moderate SoE). Prenatal supplementation of any n-3 FA in normal-risk women also had no significant effect on risk for gestational hypertension or preeclampsia (low SoE). Fetal, Infant, and Child Exposures and Outcomes: Postnatal growth patterns: Maternal fish oil or DHA plus EPA supplementation had no effect on postnatal growth patterns (attainment of weight, length, and head circumference) when administered prenatally (moderate SoE) or both pre- and postnatally (low SoE). Fortification of infant formulas with DHA plus arachidonic acid (AA, an n-6 FA) had no effect on growth patterns of preterm or term infants (low SoE). Visual acuity: Prenatal supplementation with DHA had no effect on development of visual acuity (low SoE). Supplementing or fortifying preterm infant formula with any n-3 FA had no significant effect on visual acuity assessed by visual evoked potentials (VEP) at 4 or 6 months corrected age (low SoE). Data conflicted on the effectiveness of supplementing infant formula for term infants with n-3 FA depending on when and how visual acuity was assessed (i.e. by VEP or by behavioral methods) and the type of essential FA provided (low SoE). Neurological development: Prenatal or postnatal n-3 FA supplementation had no consistent effect on neurological development (low SoE). Cognitive development: Prenatal DHA supplementation with AA or EPA had no effect on cognitive development (moderate SoE). Supplementing breastfeeding women with DHA plus EPA also had no effect on cognitive development in infants and children (low SoE). Supplementing or fortifying preterm infants' formula with DHA plus AA had a positive effect on infant cognition at some short-term followup times (moderate SoE). Supplementing or fortifying infant formula for term infants with any n-3 FA had no effect on cognitive development (low SoE). Evidence is insufficient to support any effect of n-3 FA infant supplementation on long-term cognitive outcomes. Autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), and learning disorders: Maternal or infant n-3 FA supplementation had no effect on risk for autism spectrum disorders or ADHD (low SoE). No studies on other learning disorders were identified. Atopic dermatitis (AD), allergies, and respiratory disorders: Pre- and postnatal (maternal and infant) n-3 FA supplementation had no consistent effect on the risk for AD/eczema, allergies, asthma, and other respiratory illnesses (moderate SoE). Biomarkers and intakes had no consistent association with the risk for AD, allergies, and respiratory disorders (low SoE). Adverse events: Prenatal and infant supplementation with n-3 FA or fortification of foods with n-3 FA did not result in any serious or nonserious adverse events (moderate SoE); with the exception of an increased risk for mild gastrointestinal symptoms.
CONCLUSIONS:
Most studies in this report examined the effects of fish oil (or other combinations of DHA and EPA) supplements on pregnant or breastfeeding women or the effects of infant formula fortified with DHA plus AA. As with the original report, with the exception of small increases in birth weight and length of gestation,n-3 FA supplementation or fortification has no consistent evidence of effects on peripartum maternal or infant health outcomes. No effects of n-3 FA were seen on gestational hypertension, peripartum depression, or postnatal growth. Apparent effects of n-3 FA supplementation were inconsistent across assessment methods and followup times for outcomes related to infant visual acuity, cognitive development and prevention of allergy and asthma. Future RCTs need to assess standardized preparations of n-3 and n-6 FA, using a select group of clinically important outcomes, on populations with baseline n-3 FA intakes typical of those of most western populations.
