Table 2.

Seafood consumption during childhood and adolescence (up to 18 years of age) and neurocognitive development.

Year, Author Study Design Location Number children/adolescents Risk of Bias1	Neurocognitive outcomes Clinically meaningful?2	Beneficial/adverse/null and Size of effects (as compared to: e.g. no/highest seafood, or continuous)	Child’s age at consumption and at effect	Amount of seafood consumed -Mean+ SD (oz/wk) - (range) - Amount assoc. with largest beneficial or adverse effect - Outcomes categorized by seafood type? (e.g. oily/ white/species)	Mercury exposure (if provided, standardized to hair, ppm3)	Comments:
2009 Kim et al. Prosp. cohort Sweden n=9,448 Moderate Risk of Bias	Total school grades (sum of grades in 16 subjects, max of 320 total grades. CM=Y	Beneficial Mean of 225.5 total grades (SD 58.3) when consumption was > one meal/wk vs. Mean of 196.6 (SD 63.4) when consumption was <one meal/wk	15 – 16 yr	- > one meal/wk = >4 oz/wk4 Amounts measured. ≥4 oz/wk1 = 4 oz/wk ≤4 oz/wk Greatest benefit ≥ 4 oz/wk Outcomes not categorized by white/oily or by species.	Not reported	Seafood consumption of >one meal/wk at 15 yr. was associated with the higher academic grades at 16 yr.
2008 Åberg et al. Prosp Cohort Sweden n=4,792 Moderate Risk of Bias	Standardized intelligence tests for the Swedish Military. CM = Y	Beneficial Seafood consumption ≥4 oz/wk vs. <4 oz/wk was associated with higher combined intelligence per stanine (0.58 units; 95% CI 0.39, 0.76), verbal performance (0.45; 95% CI 0.27, 0.63) and visuospatial performance (0.50; 95% CI 0.31, 0.69).	15 – 18 yr.	Mean and SD not reported ≥4 oz/wk (20.2%) vs. 4 oz/wk (56.6%) vs. <4 oz/wk (22.7%) Greatest benefit at ≥ 4 oz/wk Outcomes not categorized by white/oily or by species.	Not reported	In this study of adolescent males there was a beneficial association between number of seafood meals per week at age 15 and intelligence test performance at age 18.
2017 Liu et al. Prospective Cohort China n=541 Moderate Risk of Bias	Wechsler Intelligence Scale for Children-Revised (WISC-R) CM=Y	Beneficial Improvement comparing ≥ 4 oz/wk vs. < 2 oz/wk Verbal IQ 4.75 pts improvement p< 0.002 Cohens d= 0.6 Performance IQ 3.39 pts improvement p<0.026 Cohens d= 0.416 Full scale improvement 4.80 pts, p<0.003 Cohens d=0.57	Seafood consumption at 9–11 yr. IQ at 12 yr.	Mean and SD not reported Greatest benefit at ≥ 4 oz/wk Outcomes not categorized by white/oily or by species.	Not reported	Greater seafood consumption was associated with higher IQ and fewer sleep disturbance problems. Effects of seafood on IQ appeared to be mediated by sleep quality. Children with fewer sleep disturbance problems were more likely to have higher cognitive function.
2004 Daniels et al. Prospective cohort UK n= 7421 Moderate Risk of Bias	MacArthur Communicative Development Inventory (MCDI) Denver Developmental Screening Test (DDST) CM=PN	Beneficial All mean MCDI scores were slightly higher among children who ate seafood at least once per week at 6 months and at 12 months of age. Relations between the infants’ seafood intake and DDST scores followed a similar pattern but were of smaller magnitude.	Consumption at 6 & 12 mo. Testing at 15 mo on the MCDI and at 18 mo on the DDST	. Comparison of rarely/ never to >1 meal (4 oz)/wk. Outcomes not categorized by white/oily or by species.	Not reported	Positive associations with seafood were consistent but small in magnitude.
Attention Deficit Hyperactivity Disorder (ADHD) outcomes
2017 Rios-Hernández Case control Madrid, Spain n=120 Moderate Risk of Bias	Diagnostic and Statistical Manual of Mental Disorders, (ADHD RS-IV) Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL)	Beneficial Fatty seafood consumption was significantly greater in healthy children than in children with ADHD. (tertiles of intakes) Highest (reference) Middle OR 1.84 (95 % CI 0.75–4.49) Lowest OR 2.50 (95 % CI 1.02–6.15) P for linear trend .046	Consumption and determining what was being consumed occurred among children who were 6–16 yr	Mean and SD not reported (amounts in each tertile not reported) Greatest benefit from fatty seafood ≥ 8–12 oz/wk Fatty seafood (blue fish) vs. white seafood.	Not reported	This study compared adherence to a “Mediterranean diet” that included fatty seafood by children diagnosed with ADHD to healthy children. Fatty seafood was the only food that appeared to be protective for ADHD within the Mediterranean dietary pattern. A source of uncertainty is that the findings may be due to differing dietary choices among children with ADHD rather than due to a cause of the ADHD.
2016 Zhou et al. Case control China n=592 Moderate Risk of Bias	Diagnostic and Statistical Manual of Mental Disorders, 4th ed., revised (DSM-IV-R). Criteria for ADHD CM=Y	Beneficial Highest tertial (Ref) 1.00 Mid. OR =1.6 (95 % CI 0.94–2.6) Low OR= 2.3 (95 % CI 1.36–3.70) p< 0.006	6–14 yr	Mean and SD not reported The “fish-white meat” dietary pattern was rich in shellfish, deep water seafood, white meat, freshwater seafood, organ meat and fungi and algae. Outcomes not categorized by white/oily or by species.	Not reported	This study compared dietary patterns of children with and without ADHD. The “fish-white meat” was the only dietary pattern assoc. with lower risk of AHDH. A source of uncertainty is that the findings may be due to dietary choices among children with ADHD rather than due to a cause of ADHD.
2014 Woo et al. Case control Korea n=192 Moderate Risk of Bias	Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) for ADHD CM=Y	Beneficial Children with the lowest adherence to a “traditional-healthy dietary pattern” that included seafood had greater risk of ADHD diagnosis OR= 3.2 (95% CI: −0.83–1.26) than children with the greatest adherence to the “traditional-healthy pattern.”	7–12 yr	Mean and SD not reported Outcomes were categorized by fatty (i.e., oily) fish and bone fish.	Not reported	Fatty and bone fish were predominant characteristics of the “traditional-healthy” dietary pattern. A source of uncertainty is that the findings may be due to differing dietary choices among children with ADHD rather than due a cause of ADHD.
2018 San Mauro Martin et al. Case control Spain n=89 Moderate Risk of Bias	Diagnostic and Statistical Manual of Mental Disorders, (ADHD RS-IV) CM=PN	Beneficial Lower adherence to a Mediterranean diet containing seafood was associated with a greater likelihood of an ADHD diagnosis. 95% of children without ADHD regularly consumed ≥8–12 oz/wk of seafood while 78% of children with ADHD regularly consumed >8–12 oz/wk of seafood (p=.003) Regular seafood consumption (≥8–12 /wk); Cases 78 % vs. controls 95% p< 0.003	9–10 yr	Mean and SD not reported ≥8–12 oz/wk vs. <8–12 oz/wk Greatest benefit ≥8–12 oz/wk Outcomes not categorized by white/oily or by species.	Not reported	Within the Mediterranean dietary pattern regular and greater seafood consumption appeared to be protective for ADHD. A source of uncertainty is that the findings may be due to differing dietary choices among children with ADHD rather than that due to a cause of ADHD.
2010 Hertz-Picciotto et al. Case Control USA n=452 Serious Risk of Bias	Risk of autism/autism spectrum disorder (AU/ASD) vs. Typical development (TD) vs. Delayed development CM = Y	Beneficial TD children were more likely to consume seafood (TD vs. AU/ASD) any seafood (76% vs. 43%) tuna (44% vs. 18 %) ocean (58% vs. 36%) freshwater (20% vs. 6%) all (p < 0.0001)	2–5y for both	Comparison of any seafood vs. no seafood, Not able to determine amounts Outcomes categorized by “any fish,” “ocean fish,” “tuna,” and “freshwater fish”.	TD= 0.17 SD 0.29 ppm AU/SUD = mean 0.14 SD 0.30 ppm p=ns	Sources of uncertainty included: Differences between groups were not controlled for confounders; and Findings may be due to differing dietary choices among children with AU/ASD rather than due to a cause of AU/ASD
Randomized controlled trials
2018 Øyen et al. RCT Norway n=232 Moderate Risk of Bias	Wechsler Preschool and Primary Scale of Intelligence, 3rd edition (WPPSI-III) and The 9-Hole Peg Test (9-HPT) CM=Y	Beneficial In the fully adjusted analysis, (including compliance, i.e., whether the children fully ate the meals provided to them), mean WPPSI-III total score improved more in the seafood (20.4, 95% CI 17.5–23.3) than in the meat group (15.2, 95% CI 12.4–18.0, p = 0.006) The seafood group gained 1.2 more IQ points per 3.5 oz of food eaten than the meat group (p < 0.0001)	FINS-KIDS study	Mean of 44.0 (SD 4.0) total study meals (5.4–8.5 oz/wk) were provided over 16 wks. 3 hot lunches/wk for 16 wk Each meal contained 1.8–2.8 oz fatty seafood (herring/mackerel) or meat (chicken/lamb/beef)	Reported in Kvestad et al. (2018) Seafood group Baseline: mean 0.373 (SD 0.211) ppm	WPPSI-III total scores and processing speeds over 16 wks, assigned to consume 3 fatty seafood lunches/wk as compared to 3 meat lunches/wk.
2018 Hysing et al. RCT Norway n=232 Moderate Risk of Bias	Strengths and Difficulties Questionnaire (SDQ) Sleep by parental questionnaire CM=N	Null No impact comparing assignment to seafood or meat lunches on SDQ scores or sleep.	4–6 yr	Children in the seafood group had an increase in exposure to mercury (change of +0.162, 95% CI 0.111, 0.213 ppm), whereas children in the meat group had decreased exposure to mercury (change of −0.053, 95% CI −0.103, −0.002 ppm).	Post: mean 0.529 (SD 0.259) ppm p<0.001 Meat group Baseline: Mean 0.374 (SD 0.198) ppm Post: Mean 0.315 (SD 0.182) ppm <0.001	No evidence of improvement in mental health measures on the SDQ or for sleep.
2018 Kvestad et al. RCT Norway n=232 Moderate Risk of Bbias	Wechsler Preschool and Primary Scale of Intelligence -III (WPPSI-III) CM=Y	Beneficial After adjusting for mercury levels, assignment to consume 3 fatty seafood meals/wk improved total scores 164.5 (95% CI; 160.9– 168.1) as compared to assignment to meat lunches. 159.0 (95% CI; 155.6, 162.4) p<0.008 There were no notable associations between mercury and the WPPSI-III raw scores at baseline or after 16 weeks of the fish/meat.				Fatty seafood lunches increased WPPSI-III total scores in comparison to meat lunches. The fatty lunches increased mercury exposures without harm being detected.
2017 Handeland et al. RCT Norway n=426 Moderate Risk of Bias	Attention performance (d2 test of attention) CM=PN	Beneficial Improvement in processing speed was significantly less in the meat (−11.8; 95% CI: −23.3, −0.4) and supplement (−13.4; 95% CI: −24.9, −1.8) group compared to the seafood group (reference). The supplement group showed less improvement in total performance (−10.4; 95% CI: −20.0, −0.7) compared to the food group (reference).	FINS-TEENS Study 14–15yr	Randomized to receive for 12 weeks: Fatty seafood; 9.6 oz/wk or Meat; 9.6 oz/wk or Capsules; 5.7 gm/wk of omega-3 HUFA (estimated to be the same amount of omega-3 highly unsaturated fatty acids (HUFAs) in the fatty seafood group)	Not reported	A small beneficial effect on attention from lunches of fatty seafood, compared to meat and supplements on processing speed. No evidence of improvement in mental health measures on the SDQ. But not sufficiently powered (by author report). A significant source of uncertainty is low dietary compliance. Children consuming at least half of the meals/capsules: 38% seafood, 56% meat, 87% capsules.
2017 Skotheim et al. RCT Norway n=425 Moderate Risk of Bias FINS-TEENS study	Strengths and Difficulties Questionnaire (SDQ) CM=N	Null No significant differences among the seafood, meat, and capsule groups. Per author report “The results should be seen as preliminary however as the dietary compliance in the seafood group was low and the analyses in the high score group (high SDQ) were under powered”.
2015 Sørensen et al. RCT Denmark n=726 Moderate Risk of Bias	Cognitive performance, the d2-test of attention and Danish standard tests in reading and math. CM=Y	Beneficial The intervention improved ‘school performance’ (p =0·015), ‘reading comprehension’ (p =0·043). The dose–response relationship suggested that approximately 20 % of the intervention effect on ‘school performance’ could be related to the increase in omega-3 fatty acid status. Difficult to determine if clinically meaningful, size of effect obscure.	10 yr	Seafood served 2x/wk, in school lunches 1 fatty and 2 lean seafood types/ 3 wk menu Among those eating seafood the median fish intake was 1.7 oz/wk (95 % CI 1.1, 12.2; P< 0·001) higher during the intervention period and the proportion of children eating seafood was higher in the intervention period than in the control period (91 v. 73%; P< 0·001), Outcomes not categorized by white/oily or by species.	Not reported	Effects not solely attributable to seafood intake. However, assoc. of increases in a biomarker of seafood intake (EPA+ DHA) with better cognitive performance give greater confidence in a contribution from seafood.

¹RoB NOS scale. Number of bias domains rated low/ moderate/serious

²Clinically meaningful (CM) Y= Yes, PY= Probably Yes, PY= Probably NO, N=NO, NI= not enough information

³Standardization from blood to hair mercury concentration as per the Net Effects Assessment 2014 (Table V3 p. 92) [10]

⁴one seafood meal is estimated to be 4 oz across all studies, unless otherwise defined by the study.