The effects of docosahexaenoic acid intake during pregnancy and lactation on infant growth and neurocognitive development and the associated effects of genetic variants of the FADS1 FADS2 gene cluster
Date
2014
Authors
Miller, Stacy Marie, author
Harris, Mary, advisor
Chicco, Adam, committee member
Baker, Susan, committee member
Frye, Melinda, committee member
Journal Title
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Abstract
Maternal docosahexaenoic acid (DHA) intake during pregnancy and/or lactation has been positively associated with infant growth and neurocognitive development. However, randomized controlled clinical trials (RCT) report mixed results. Several RCT that failed to demonstrate an effect of DHA supplementation have found correlations between DHA status and cognitive benefits, possibly due to a failure to account for total maternal DHA intake. The majority of studies to date investigating neurocognitive development have not examined the effect of supplementing women with DHA during both pregnancy and lactation and fail to determine the effects of maternal genetic variation on infant neurocognitive development. Single nucleotide polymorphisms (SNPs) within the fatty acid desaturase (FADS)1 FADS2 gene cluster encoding for Δ5- and Δ6-desaturase enzymes were previously reported to be associated with altered omega-3 (n-3) and omega-6 (n-6) fatty acid proportions of erythrocyte, plasma phospholipids and breastmilk, possibly effecting DHA transfer to the infant. This study was conducted to determine the relationship between DHA intake in women obtaining varying amounts of DHA daily during pregnancy and lactation and infant neurocognitive development in the first year of life and the association of maternal SNPs in the FADS1 FADS2 gene cluster. One hundred and fifteen pregnant women were randomized to receive purified tuna oil supplement containing 300 mg of DHA and 67 mg EPA per day or an identical placebo (Sunola oil) for the last trimester of pregnancy through the first 3 months of lactation in a double-blinded placebo controlled clinical trial. Two SNPs in the FADS1 FADS2 gene cluster, rs174575 and rs174561, were genotyped from maternal DNA and erythrocyte, plasma phospholipid and breastmilk fatty acids and daily DHA intake from food frequency questionnaires (FFQ) were analyzed. Neurocognitive development of the infants was measured using the Mental Development Index (MDI) of the Bayley Scales of Infant Development III (BSID-III) at 4 and 12 months of age. Gestational length in days was calculated based upon last menstrual period and birth date. Infant birth weights and lengths were obtained from pediatric medical records at delivery and at 2 months of age. Total daily DHA intake was estimated to range from 18 mg to 1.374 g per day calculated from all sources of DHA, including food and supplementation. Data was analyzed based on treatment group, placebo versus DHA, and by total daily DHA intake broken into three groups: low = 0-299 mg per day DHA, medium = 300-599 mg per day DHA, high = ≥600 mg per day DHA. DHA portion of 2 month breastmilk fatty acids directly correlated with daily DHA intake (r=0.37, p=0.0002). Erythrocyte and breastmilk DHA proportions significantly increased in women homozygous for the major allele (SNP rs174575, p=0.0002 and p=0.030, respectively; SNP rs174561, p=0.003 and p=0.040, respectively) in the high daily DHA intake compared to the low intake group. However, daily DHA intake had no effect significantly increasing DHA proportions in women homozygous for the minor alleles of both SNPs studied. Infants born to mothers in the high DHA intake group showed significantly higher scores on the 12 month cognitive scale of the MDI of the BSID-III (p=0.018), compared to the low intake group. No significant differences were seen between treatment groups or DHA intake groups on any of the 4 month infant cognitive testing. Genotype had no direct effect on BSID-III scores, however, ANCOVA for 12 month cognitive MDI subtest showed a statistically significant interaction between SNP rs174575 genotype and daily DHA intake group (p=0.023). Additionally, infants born to mothers in the DHA treatment group had an increase of 4.5 days in gestational age (p=0.048) and significantly lower incidence of preterm birth (5%; n=3) compared to infants born to mothers in the control group (18%; n=10; χ2=4.97, p=0.026). No significant differences were seen between treatment groups or DHA intake groups in infant growth measurements at birth or at 2 months of age, although 2 month breastmilk DHA proportion of fatty acids was negatively correlated with 2 month weight (r= -0.22, p=0.048). An intake of 600 mg of DHA per day or greater during the third trimester of gestation throughout the first three months of breastfeeding was associated with improved infant neurocognitive development. Genetic variants of the FADS1 FADS2 gene cluster influence erythrocyte and breastmilk fatty acids, and increased DHA intake does not effectively increase DHA proportions in minor allele carriers. Additionally, DHA supplementation increased gestational length and decreased preterm birth risk, however, did not affect infant birth weights. DHA supplementation during pregnancy and lactation could be beneficial for improving the neurocognitive development of infants, however, genetic variation may affect DHA transfer to the infant.
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Subject
Docosahexaenoic acid (DHA)
FADS1 FADS2 gene cluster
infant cognitive development
lactation
n-3 fatty acids
pregnancy