Scientific Documents

DHA and support of the cognitive development of the unborn child and breastfed infant - Scientific substantiation of a health claim related to DHA and support of the cognitive development of the unborn child and breastfed infant pursuant to Article 14 of Regulation (EC) No 1924/2006 [1]

Summary (90 KB)

Opinion (152 KB)

Summary

Following an application from Merck Selbstmedikation GmbH submitted pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to DHA and support of the cognitive development of the unborn child and breastfed infant.

The scope of the application was proposed to fall under a health claim referring to children’s development and health.

The food constituent that is the subject of the proposed claim is docosahexaenoic acid derived from tuna oil and presented in soft gel capsules which contain >200 mg DHA, >50 mg eicosapentaenoic acid (EPA) and between 11.4 and 14.4 mg d-α-tocopherol. The food supplement is intended for pregnant and lactating women.
DHA is a well characterised fatty acid the absorption of which is well documented. DHA can be quantified in foods by established methods. The Panel considers that the food constituent, DHA, for which the claim is made is sufficiently characterised.

The claimed effect is that DHA provided via the mother contributes to the child’s cognitive development. The target population for the claimed effect is unborn children and breastfed infants. The target population for the supplementation with DHA is pregnant and lactating women.

The Panel considers that normal cognitive development is beneficial for children’s development and health.

The applicant identified a total of 48 publications to support the health claim (25 human intervention and observational studies, three meta-analyses of human intervention studies, five systematic reviews, four other review publications, three guidelines/consensus opinions and eight mechanistic human studies). Sixteen publications, including one unpublished follow-up study, on 15 randomised controlled trials (RCT), one non-randomised controlled trial and four observational studies were considered as pertinent by the applicant to substantiate the proposed claim.
The Panel considers that for the substantiation of the claim under consideration only human intervention or observational studies reporting effects on cognitive function development in offspring of mothers who were exposed to defined intakes of DHA either through supplementation or diet during pregnancy and/or lactation can provide the necessary evidence.
Five RCT of DHA supplementation in pregnant or lactating women which include endpoints related to cognitive function assessment and two observational cohort studies on the effects of maternal DHA status at birth or maternal oily fish consumption during pregnancy on children’s intelligence, fine motor ability, communication and social development up to the age of seven years are considered as pertinent to the claim under consideration.

DHA supplementation during pregnancy
Two RCT have assessed the effect of supplementation of women with DHA during pregnancy. In the first study 29 pregnant women consumed either 200 mg DHA/day or a placebo. A two-step problem solving test was performed at the age of nine months in the infants of both groups of mothers as well as the Fagan Test of Infant Intelligence (FTII). No significant effect on performance in problem solving tasks but a significantly higher combined total intention score and total intentional solution score were found in infants of mothers supplemented during pregnancy compared to the placebo group. There were no significant differences between the groups in the five outcome variables of the FTII. The Panel notes the small sample size of this study and that the statistical significance in some outcome measurements appears only in regression analysis. In the second study 98 pregnant women received either fish-oil capsules (2.2 g DHA, 1.1 g EPA/day) or olive oil capsules. Their children were tested at the age of 2.5 years among others for development, receptive language, and behaviour. Compared to the olive oil group children from the fish-oil group attained a significantly higher score for eye hand coordination. There was no difference between the groups for other subscales of development, receptive language and for the different items of the Child Behaviour Checklist. There was a significant positive correlation between the eye and hand coordination score and n‑3 PUFA composition of cord blood erythrocytes. The Panel considers this study not to be informative for the proposed claim under the proposed conditions, because of the high DHA dose applied. Further, the Panel notes that the high DHA dose in the mother did not promote cognitive development of their infants.

DHA supplementation during lactation
Two RCT have assessed the effect of supplementation of breastfeeding women with DHA. In the first study 52 mothers of term infants were randomised to either of five doses of a DHA-rich algal oil (0, 0.2 g, 0.4 g, 0.9 g, 1.3 g DHA) to be taken daily from day five after delivery for 12 weeks. Infant red blood cell (RBC) DHA at 12 weeks and home stimulation were the only independent factors associated with Bayley’s mental development index (MDI) at one year of age, whilst at two years gender and social score of the spouse were the only significant predictors of Bayley’s MDI. In a second study 114 breastfeeding mothers were assigned to capsules with high-DHA algal oil (200 mg DHA/day) and 113 mothers to capsules with DHA-free vegetable oil for four months after delivery. There were no significant differences between groups in the Gesell Gross Motor Inventory, Clinical Adaptive Test (CAT) or Clinical Linguistic and Auditory Milestone Scale (CLAMS) developmental quotient at either 12 or 30 months and in the Bayley MDI at 30 months of age, but the Bayley Psychomotor Development Index (PDI) was higher in the children of the DHA group. No significant correlation could be found between infant plasma phospholipids DHA content at either four or eight months of age and any measure of neurodevelopment. Unpublished data on neuropsychological functions (gross and fine motor, executive, perceptual, visual, verbal) and a sustained attention subtest of the Leiter International Performance Scale at five years of age in 71 children from the DHA and 70 children from the control group showed better performance of children from the DHA group in one sustained attention subtest. The Panel considers that a positive association of one out of many neurodevelopmental indices with maternal DHA supplementation is insufficient to conclude on the overall effect on cognitive development. The significance of the results of the follow-up at the age of five years is questionable due to considerable attrition of both the DHA and the control group.

In another study 341 pregnant women consumed either 10 mL of cod liver oil (1183 mg DHA, 803 mg EPA) or corn oil (4747 mg linoleic acid, LA; 92 mg α-linolenic acid, ALA) from 18 weeks of gestation until three months after delivery. Children in the cod liver oil group had significantly higher scores on the Mental Processing Composite at age four years than children from the corn oil group. There was no correlation between umbilical plasma phospholipids n-3 LCPUFA and intelligence scores, but both docosapentaenoic acid (DPA) and DHA content of infants’ plasma phospholipids at age four weeks and maternal EPA and DHA intake during pregnancy were positively correlated with individual intelligence scores. In a recent follow-up study 82 children from the cod liver oil group and 61 children from the corn oil group were tested with the Kaufman Assessment Battery for Children (K-ABC) at 7 years of age. No significant differences were found between children from the two different supplement groups. The Panel notes that the results obtained in too small groups of subjects at the age of 7 years did not establish a positive relationship between a high maternal DHA supplementation during both pregnancy and lactation and cognitive development.

In the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) children were tested with an abbreviated form of the Wechsler Intelligence Scale for Children III at the age of eight years and the results were related to seafood consumption by the mothers during pregnancy. The odds ratio for a suboptimal outcome of the verbal IQ was 1.48 for no seafood consumption by the mother compared to high seafood consumption. Moreover, there was a significant trend for suboptimal results also for the fullscale IQ. The Panel considers that the available data do not permit an estimation of maternal DHA consumption and, therefore, cannot contribute to establish a relationship between maternal DHA supplementation and cognitive development of the child.
The Panel concludes that there is insufficient evidence to establish a cause and effect relationship between the consumption of supplementary DHA during pregnancy and lactation and cognitive development in unborn children or breastfed infants.