Table 1.

Maternal seafood consumption in pregnancy and neurocognitive development in their children

Year Author Study Design Location Number of mother child pairs 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 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:
2007 Budtz-Jørgensen et al. Prospective Cohort Faroe Islands n=1,022 Moderate Risk of Bias	Verbal Boston Naming Test (BNT) WISC-R similarities; California Verbal Learning Test (CVLT) Motor Neuropsychological Examination System (NES2) Finger tapping (CATYSYS) CM=PY	Beneficial Greater seafood consumption was beneficial for motor function outcomes, both at 7 and 14 yr and spatial functioning at 14 yr, increasing from 0 to 4 oz/wk and from 4 to ≥12 oz/wk	14 yr 7 yr	Mean and SD of seafood consumption not reported. Greatest benefits ≥ 12 oz/wk Seafood consumption was distinguished from consumption of pilot whale meat and blubber that occurred in this cohort. Outcomes not categorized by white/oily or by species.	Geometric mean 4.27 pm (interquart range 2.6–7.7) (as reported in Grandjean et al., 1997) Most mercury exposure in this cohort originated from pilot whale. Greater seafood consumption was not associated with higher mercury levels (Grandjean et al., 1995).	Maternal seafood consumption was beneficially assoc. with offspring test scores, while mercury, mostly from pilot whale, was independently associated with adverse neurocognitive outcomes.
2008 Gale et al. Prospective Cohort United Kingdom n=217 Moderate Risk of Bias	Strengths and Difficulties Questionnaire (SDQ) Wechsler Abbreviated Scale of Intelligence (WISC) CM=Y	Beneficial Compared to mothers who ate no seafood, verbal IQ was higher among children: ≤ 4 oz/wk, 7.66 points (95% CI −.1 to 15.4); 4–8 oz/wk, 7.32 points (95% CI .26 to 14.4); ≥12 oz/wk, 8.07 points (95% CI .28 to 15.9). Children of mothers not eating oily seafood in early pregnancy had greater risk of hyperactivity: OR 2.94, (95% CI 1.28 to 6.7)	9 yr	Mean and SD of seafood consumption not reported. (range 0–≥12 oz/wk) Greatest benefit ≥12 oz/wk Outcomes not categorized by white/oily or by species for IQ but categorized as oily for hyperactivity.	Not reported	Greater seafood consumption was associated with greater verbal IQ in a dose response relationship. Children of mothers not eating oily seafood in early pregnancy had a nearly 3 times greater risk of hyperactivity.
2018 Golding et al. Prospective Cohort United Kingdom n=3840 Moderate Risk of Bias	Autism and autistic traits scale derived from Social and Communication Disorders Checklist (SCDC), Child Communication Checklist) 9 yr, Emotionality, Activity, Sociability temperament traits (EAS) temperament scale) 3 yr, repetitive behavior 5 yr. CM=Y	Beneficial When the mother ate no seafood, the adjusted odds ratio (AOR) for poor social cognition was 1.63 [95% CI 1.02, 2.62] per SD of mercury (p= 0.041). This result was significantly different from the association among the offspring of seafood eaters (AOR = 0.74 [95% CI 0.41, 1.35]).	9 yr	Not reported for this subgroup analysis. [Cohort characterized Hibbeln et al. 2007, Mean 8.3 SD 7.2 oz/wk) range (0 to 115 oz/wk) Outcomes not categorized by white/oily or by species.	Mean 0.60 (SD 0.26) hair ppm	Increasing exposure to mercury did not increase risk of autism or autistic traits so long as mother ate seafood. When mother did not eat seafood, there was increased risk of poor social cognition.
2017 Furlong et al. Prospective Cohort USA n=210 Moderate Risk of Bias	Wechsler Intelligence Scales-IV (WISC-IV) and Behavior rating inventory of executive functioning (BRIEF). CM=Y	Beneficial Children scored 7.71 higher points on the WISC perceptual reasoning factor of IQ p = 0.0422, 95%CI = 0.36, 15.06 (??=0.50, 95% CI 0.03, 0.97, SE = 3.752) per can of seafood (4 oz)/wk of maternal consumption.5	7–9 yr	Canned seafood consumption during pregnancy, per one can (4 oz/wk) Greatest benefit ≥ 8 oz/wk5 Outcomes not categorized by white/oily or by species.	Not reported	Canned seafood consumption was associated with improved perceptual reasoning component of IQ, but results may have been due to testing multiple outcomes.
2007 Hibbeln et al. Prospective Cohort United Kingdom n=8801	Denver Developmental Screening Test (DDST) Strength and Difficulties	Beneficial In 9 of 23 outcomes the greatest risk of low outcomes, e.g. Greater risk of low verbal IQ was among offspring of	DDST 6 mo 18 mo 30 mo 42 mo	Mean 8.3 oz/wk; (SD 7.2 oz/wk) Range 0 to 115 oz/wk Greatest benefit, i.e., least risk of low outcomes, was with consumption ≥12 pz/wk (range	Not reported in this subgroup analysis. [Characterized in Golding et al. (2017):	Children were more likely to have a variety of neurocognitive benefits, including improved verbal IQ,
Moderate Risk of Bias	Questionnaire (SDQ) Weschler Intelligence Scale for Children III UK (WISC-III UK) CM=Y	mothers consuming none vs. >12 oz/wk OR = 1·48, 95% CI 1·16–1·90 vs. > 0–12 oz/wk OR= 1·09, 95% CI 0·92–1·29; overall trend, p=0·004)	SDQ 7 yr WISC-III 8y	12–115 oz/wk) Outcomes not categorized by white/oily or by species.	Median=0.52 hair ppm, range 0.07– 3.55 ppm.	when their mothers ate >12 oz/wk as compared to those eating <12 oz/wk.
2018 Hibbeln et al. Prospective Cohort United Kingdom n=2224 Moderate Risk of Bias	15 scholastic achievement tests including, reading, spelling, phoneme awareness, mathematics and science. CM=PN	Null Each test score (except for arithmetic) was higher for children whose mothers ate seafood compared to children whose mothers ate no seafood, in unadjusted (but not in adjusted) analyses.	7 yr 8 yr 9 yr	Not reported for this subgroup analysis. [Cohort characterized Hibbeln et al. (2007), Mean 8.3 oz/wk (SD 7.2 oz/wk) range 0 to 115 oz/wk Outcomes not categorized by white/oily or by species.	Not reported for this subgroup analysis. [characterized in Golding et al. (2017) Median =0.52 hair ppm (range 0.07–3.55) ppm]	There was an indication of beneficial effects from seafood on scholastic tests but only in unadjusted analysis. There was no indication of any adverse effects of maternal mercury levels on scholastic abilities of the offspring whether the mother ate seafood or not.
2017 Golding et al. Prospective Cohort United Kingdom n=4134 Moderate Risk of Bias	Wechsler Intelligence Scale for Children (WISC-III UK) CM=Y	Beneficial Total IQ 9.5 points higher in the highest decile of mercury, as compared to the lowest decile, among seafood eating mothers. Among mothers not eating seafood, full-scale IQ trended to decrease (but not statistically significant) with higher mercury.	8 yr	Mean 8.3 oz/wk (SD 7.2) range (0 to 115] [Cohort characterized Hibbeln et al. 2007] Greatest benefit was assoc. with highest decile of mercury (0.94–3.55 ppm), among seafood consuming mothers. Among seafood-consuming mothers full-scale IQ increased +0.84 (IQ points): 95%CI +0.13, +1.56; with increasing mercury (per 1SD of mercury) p= 0.021) No differences found when comparing oily to white seafood.	Median =0.52 hair ppm Range: (0.07– 3.55 ppm) Mercury exposures did not differ comparing mothers who ate seafood to those who did not.	Among children of seafood eating mothers, those with the highest mercury levels (> 3.39 ppm) had 9.5 points higher IQ as compared to those wIth the lowest levels (<1.28 ppm) (table 2). Among offspring of seafood-consumers, increasing mercury, was assoc. with higher IQ in a dose response pattern that extended to the highest levels of mercury. In contrast, when women who did not eat seafood, mean IQ levels among offspring stayed roughly the same (although trended downward) as mercury increased. The maternal mercury levels were the essentially the same in both groups.
2012 Sagiv et al. Prospective Cohort USA n = 515 Moderate Risk of Bias	Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for ADHD Neurobehavioral Evaluation System 2 (NES2) Continuous performance test (CPT). CM=Y	Beneficial Higher seafood consumption (>8 vs. ≤8 oz/wk) was protective for adverse ADHD-related outcomes. Lower seafood consumption (≤8 vs. >8 oz/wk) was associated with greater risk of ADHD-diagnoses (e.g. impulsive/hyperactive [RR = 2.5; (95% CI,1.6– 5.0)].	8 yr	Mean 3.7oz/wk (3.9) Median 2.3 oz/wk (range 0.0–22.6) 52% of mothers consumed more than 8 oz/wk. Greatest benefit 8–22.6 oz/wk Outcomes not categorized by white/oily or by species.	Mean 0.45 hair ppm (range, 0.03–5.14 ppm) Protective associations between higher mercury and better CPT reaction times were found in girls (whose mother had <1 ppm).	Maternal seafood consumption > 8 oz/wk was associated with neurocognitive benefits for ADHD-related outcomes as compared to <8 oz/wk. Seafood was protective despite adverse effects of mercury, (comparing ≥ 1ppm to < 1ppm.
2013 Deroma et al. Prospective Cohort Northern Italy n=242 Serious Risk of Bias	Weschler Intelligence Scale for Children-III (Verbal and Full IQ, (WISC-III) CM=N	Null Neither maternal consumption of canned nor fresh seafood were significantly associated with full scale, verbal or performance IQ.	7.7 yr	Mean 3.2 oz/wk (SD and range not reported) Categorized by fresh or canned. Canned seafood trended toward negative associations with all the outcome variables but were not statistically significant in all adjusted analyses.	Mean 1.33 hair ppm, Median 0.93 ppm (range 0.06–8.03) (area contaminated by mercury spills)	Although maternal seafood and mercury were positively correlated, the effects of mercury and seafood on neurological outcomes trended in opposite directions (seafood beneficial, mercury adverse).
2016 Oken et al. Prospective Cohort USA n=1068 Moderate Risk of Bias	Kauffman Brief Intelligence Test (KBIT) WRAVMA drawing, WRAML design memory, WRAML picture memory, and WRAML summary score). CM=PY	Null Maternal seafood intake examined continuously and categorized as 0, 0–12, and ≥12 oz/wk.	7.7 yr	Mean 6.8 oz/wk SD 6.0 range (0–48 oz/wk) Not assoc. with benefit or harm Outcomes not categorized by white/oily or by species.	Erythrocyte mercury mean 4.0 (SD 3.6) ppb range (0, 38.2) ppb (not convertible to hair ppm)	This study reported no benefit from seafood or harm from mercury, up to 48 oz/wk and 38.2 ppb (erythrocyte) on an abbreviated test of IQ and other tests. Exceeding 12 oz/wk of seafood was not associated with harm, despite reported exposure to mercury.
2016 Steenweg-de Graaff Prospective Cohort n=3,802 Netherlands Serious Risk of Bias	Autistic Traits: The Social Responsiveness Scale (SRS) and Child Behavior Checklist, Pervasive Developmental Problems subscale (PDS); and Non-verbal IQ: 2 subtests of “Snijders-Oomen Niet-verbale Intelligentietest–Revisie” (SON-R 2½–7) CM=N	Null No relationship between maternal seafood consumption and SRC, PDS and non-verbal IQ scores (SON-R 2½–7).	6 yr	Median 2.65 oz/wk (range 0–21.2) Reported in Heppe et al 2011 (PMID: 21266095) Outcomes not categorized by white/oily or by species.	Not reported	Seafood consumption was measured against only non-verbal components of IQ, (verbal IQ not measured) with null results for performance components. Uncertain if critical confounding variables were assessed.
2018 Vejrup et al. Prospective Cohort Norway n=38,581 Moderate Risk of Bias	Speech and Language Assessment Scale (SLAS) Ages and Stages Questionnaire (ASQ), and Twenty Statements about Language-Related Difficulties (language 20). CM=Y	Beneficial Positive associations for mothers consuming > 14.1 oz/wk vs. 0–3.5 oz/wk for all child outcomes (SLAS, ASQ, language-20) in adjusted analyses.	5 yr	Median 7.6 oz/ wk (range 0–65 oz/wk). Greatest benefits (14.1–65 oz/wk) (mean not reported) Outcomes not categorized by white/oily or by species.	Mean 0.29 hair ppm (range 0–3.8 ppm), (n=2,239) Increased dietary mercury exposure was associated with improved SLAS scores when mothers had a seafood intake ≤14.1 oz/wk in the adjusted analysis. Mercury exposure was null, however, in the group >14.1 oz/wk (n=210).	Maternal seafood consumption was beneficially assoc. with offspring language and communication skills.
2016 Julvez et al. Prospective Cohort Spain n=1,892 (14 mo) n=1,589 (5 yr) Moderate Risk of Bias	Bailey Scales of Infant Development (BSID) McCarthy Scales of Children’s Abilities (MSCA) Childhood Asperger Syndrome Test (CAST) CM=PY	Beneficial Julvez et al. divided their cohort into quartiles for fatty seafood and quintiles for all seafood. The results for all seafood are in the 5th column. Offspring of mothers within the highest quartile for consumption of large fatty seafood (>10 oz/wk) had an adjusted increase of 2.29 points in McCarthy general cognitive score (95% CI: 0.42, 4.16). For MSCA outcomes, large fatty seafood (but not other subtypes), showed beneficial relationships across all quartiles. For CAST outcomes, large fatty seafood had beneficial relationships in quartile 4, lean seafood in quartiles, 2,3 and 5 and shellfish in quartile 3.	14 mo 5 yr	Mean 17.5 oz/wk Median 16.6 oz/wk Quintile means (all seafood) Q1, 6.9 oz/wk Q2, 11.9 oz/wk Q3, 16.2 oz/wk Q4, 21.2 oz/wk Q5, 30.2 oz/wk For all seafood, maximum benefits for BSID, CAST, MSCA total score, verbal and memory were in Q4 (mean 21.2 oz/wk); and MSCA executive function, and motor were in Q3/Q4 followed by an attenuation of a positive association in Q 5 (mean 30.2 oz/wk, but still trending beneficial).	(Mercury exposures were as reported in Llop et al., 2012) Definitions as provided by the authors: 1) large fatty seafood, (such as tuna, swordfish, albacore) 2) smaller fatty seafood, (such as mackerel, sardines, anchovies, salmon” and “tinned sardines/mackerel”) 3) lean seafood, (such as hake, sole, or bream”; and “tinned tuna,” which has similar levels of DHA and mercury as lean seafood) 4) shellfish, (“such as shrimp, prawns, lobster, or crab”; “clams, mussels, oysters”; and “squid, octopus, cuttlefish”)	Beneficial associations remained positive through >30.2 oz/wk of maternal seafood consumption for child neurodevelopment, among a population characterized by high seafood consumption. Intake of small fatty seafood was a predominant predictor of neurocognitive development at 14 mo. and lean and large fatty seafood were predominant predictors of neurocognitive benefits at 5 yrs. Lower risk of autism-spectrum traits were also observed with total, lean, and large fatty seafood consumption.
2008 Lederman et al. Prospective Cohort USA n=329 Moderate Risk of Bias	i) Psychomotor development index, (BSID-II) ii) Weschler Intelligence Scale for Children-III (Verbal and Full IQ, (WISC-III) CM=Y	i) Beneficial 8.7 point increase, any vs. no seafood ii) Beneficial 5.6 point increase, any vs. no seafood, on verbal and full IQ	i) 3yr ii) 4yr	Amounts not reported Groups were defined as any vs. no consumption Greatest benefit - any Outcomes not categorized by white/oily or by species.	All subjects Mean=0.64 ppm range (0.002–4.4) Seafood eaters Mean=0.72 ppm (range -unknown)	Maternal seafood consumption was beneficially assoc. with offspring psychomotor and IQ test scores despite the reported exposures to mercury. The IQ benefit was for verbal and full IQ but not for performance IQ. Conversely, when measured independent from seafood, mercury exposures were adversely associated with scores on the same tests.
2008 Mendez et al. Prospective Cohort Menorca, Spain n=392 Moderate Risk of Bias	McCarthy Scales of Children’s Abilities (MCSA) CM=PY	Beneficial Among children breast-fed for 6 mo., maternal seafood intakes of 8–12 oz/wk was associated with significantly higher scores of 5.9 to 8.6 points on MCSA subscales compared ≤ 4 oz/wk.	4 yr	Mean= 6.76 oz/wk (SD 6) (range not reported) Greatest benefits 8–12 oz/wk. No benefits or adverse effects for ≥12 oz /wk [Mean= 23.12 oz/wk (SD 15.44)] Outcomes differentiated by seafood and “other” seafood with lower DHA content (squid and shellfish).	Not reported	Beneficial effects of seafood consumption other than shellfish and squid were apparent among women breastfeeding <6 mo. These benefits were not seen >12 oz/wk but there were only 20 individuals in that category.
2001 Williams et al. Prospective Cohort United Kingdom n=435 Moderate Risk of Bias	High-grade stereopsis, (stereoscopic vision) CM= PY	Beneficial Children whose mothers ate oily seafood achieved high-grade stereopsis sooner than those whose mothers did not (adj OR: 1.57; 95% CI: 1.00, 2.45).	3.5 yr	Any seafood consumption (<2 oz/ wk or ≥2 oz/wk) (range not reported) Greatest benefit ≥2 oz/wk oily seafood Oily fish - beneficial White fish - null Shellfish - null	Not reported	Children whose mothers ate oily seafood were 57% more likely to achieve high-grade stereopsis by age 3.5 yr.
2008 Oken et al. Prospective Cohort USA n=341 Moderate Risk of Bias	Wide Range Assessment of Visual Motor Abilities (WRAVMA) Peabody Picture Vocabulary Test (PPVT) CM=PY	Beneficial WRAVMA drawing β=6.4, (95 % CI: 2.1, 10.7) WRAVMA total β=6.4, (95 % CI: 2.0, 10.8) >8 oz/wk vs. none PPVT-no association	3 yr	Mean 6.0 (5.6) oz/wk range, 0–30) oz/wk Canned tuna Beneficial outcomes seen at ≥8 oz/wk (range, >8–30 oz/wk) on the WRAVMA for canned tuna and for all seafood as follows: Compared to eating no canned tuna, mothers eating canned tuna ≥ 8 oz/wk had children with higher scores on the WRAVMA (total 5.6, 95% CI: 1.4, 9.8). Seafood ≥8 oz/wk of all seafood with mercury below the 90th percentile was beneficial on the WRAVMA. Outcome for ≥8 oz/wk with mercury above the 90th percentile trended somewhat less beneficial, but those results was not statistically significant. Outcomes comparing >8 oz/wk vs. <8 oz/wk of seafood other than canned tuna were null. Outcomes categorized by canned tuna, seafood other than canned tuna and all seafood.	Mean 0.53 hair ppm (SD, 0.47) range (0–2.3) ppm n=98	This study reported a beneficial effect from canned tuna on one test. It also attempted to measure beneficial effects from nutrients and adverse effects from mercury acting simultaneously for all seafood. Most of the results were not statistically significant, but trended toward greater than ≥ 8 oz/wk with less mercury being more beneficial than ≥ 8 oz/wk with more mercury and both being more beneficial than <8 oz/wk. None of the results <8 were statistically significant.
2008 Davidson et al. Prospective Cohort Republic of the Seychelles n=229 Moderate Risk of Bias	Bayley Scales Infant Development-II (BSID-II) Mental Developmental Index (MDI) Psychomotor Developmental Index (PDI) CM=PY	Null Maternal seafood not associated with 16 outcomes; higher mercury associated with adverse scores on one outcome (PDI), but not in models adjusting for dietary nutrient intakes.	5.9 mo 30 mo	Mean 36 oz/wk Outcomes not categorized by white/oily or by species.	Mean 5.7 ppm (SD 3.7) (range 0.2–8.5)	No beneficial or adverse effects from high levels of seafood consumption and high levels of mercury exposure (mean of 5.7 ppm is between 99.5th and 99.9th percentiles of U.S. exposure). It has been hypothesized that beneficial effects were not consistently seen in this study because the high consumption effectively saturated the participants so no further gains could be seen by the researchers.
2010 Lynch et al. Prospective Cohort Republic of the Seychelles n=229 Moderate Risk of Bias	Bayley Scales Infant Development-II (BSID-II) Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI) CM=PY	Beneficial A beneficial relationship was reported between docosahexaenoic acid (DHA) and the PDI outcome at 30 mo. modified by increasing mercury levels such that at 11 ppm exposure, the beneficial effect of DHA was eliminated. For MDI at 30 mo and PDI at 9 mo the relationship to DHA was similarly modified at 9 ppm, trending negative.	9 mo 30 mo	Mean 36 oz/wk Here, DHA was considered as a biomarker of seafood consumption. Outcomes not categorized by white/oily or by species.	Mean 5.7 ppm (SD 3.7) (range 0.2–8.5) (previously reported in Davidson et al. 2008)	DHA had beneficial effects on the BSID-II PDI that were reduced or eliminate at higher mercury exposures (past 11 ppm maternal hair). The change occurred at mercury exposure levels that were nearly twice the 99.9th percentiles of exposure for U.S. women of childbearing age.
2013 Valent et al. Prospective Cohort Italy n=606 Moderate Risk of Bias	Bailey Scale of Infant Development (BSID-III) including cognitive, language, motor, social-emotional, and adaptive functioning subscales CM=PN	Beneficial Positive associations between maternal seafood intake and social-emotional scores in a fully adjusted model that included mercury in cord blood (β = 1.84, p = 0.03).	18 mo	Mean 9.3 oz/wk (SD 6.8) (range 0–44 oz/wk). Greatest benefit up to 44 oz/wk Outcomes not categorized by white/oily or by species.	Arithmetic mean 1.061 ppm (SD 1.028) range (0.017–13.52) ppm	Maternal seafood intake beneficially associated with social-emotional scores but not with the others. No association between maternal hair mercury and any BSID-III scores.
2008 Oken et al Prospective Cohort Denmark n=25,446 Moderate Risk of Bias	Developmental milestone scores including motor social or cognitive development. CM=Y	Beneficial OR 1.29 (95% CI; 1.20, 1.38) comparing Highest quintile to (14 oz/wk, range 9.7–121) the lowest quartile (1.3 oz/wk, range: 0–2.6)	6 mo 18 mo	Mean = 6.6 oz/wk. (range: 0–121) Dose response benefits were continuous through to 121 oz/wk. For each additional 4 oz/ wk of seafood, the OR for higher development was 1.49 (95% CI: 1.33, 1.66) Outcomes not categorized by white/oily or by species.	Not reported	The magnitude of improvement in neurocognition was similar comparing breastfeeding >10 mo. to mothers consuming seafood >12 oz/wk. The highest quintile of seafood consumption in this cohort (mean of 14.5 oz/wk, range of 9.75 to 121 oz/wk) was associated with better attainment of developmental milestones at 18 months of age as compared to the lowest quintile of consumption (mean of 1.3 oz/wk, range of 0 – 2.6 oz/wk.
2019 Barbone Prospective Cohort Italy, Slovenia, Croatia, and Greece n=1086 Moderate Risk of Bias	Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). CM=Y	Beneficial Beneficial associations between increasing mercury in maternal hair and lower risk of suboptimal language scores (β=0.55; 95%CI: 0.05–1.05) and receptive communication scores (β=0.12; 95%CI: 0.02–0.22).	18 mo	All seafood 5.6 (SD 4.8) oz/wk (range not reported) Range not provided [if this is true]	Mean 0.997 ppm (SD 1.035) (range 0.017–13.52)	Although seafood consumption was measured, this study measured the associations between maternal mercury and neurocognition. Higher mercury was associated with better language and receptive communication scores in linear models across the range of mercury levels.
2004 Daniels et al. n=7,421 United Kingdom Prospective Cohort Moderate Risk Bias	MacArthur Communicative Development Inventory (MCDI) Denver Developmental Screening Test (DDST) CM=PY	Beneficial For children whose mothers consumed ≥18 oz/wk, the adjusted MCDI score was higher,72 (95% CI; 71–74), as compared to when mothers ate no seafood 68 (95% CI; 66 – 71). The DDST total was 2% higher among children whose mothers ate seafood 4.5–13.5 oz/wk as compared to none.	15 mo 18 mo	Greatest benefits at 4.5–13.5 oz/wk for vocab. comprehension (MCDI) and total DDSI, benefits continue through ≥18 oz/wk. Greatest benefit ≥18 oz/wk for social activity (MCDI) No difference when comparing outcomes to consumption of white seafood and to oily seafood	Total cord mercury (geometric mean ng/g 0.01 SD (0.4) (not convertible to hair ppm)	Maternal seafood consumption was beneficially assoc. with offspring test scores, despite quantified mercury exposure.
2016 Hu et al. Prospective Cohort China n=410 Moderate Risk of Bias	Gesell developmental schedules (GDS) CM=PY	Beneficial Greater seafood consumption was assoc. with better developmental quotient (DQ) scores of the adaptive domain (r=0.11, p =0.04). At the same time, a log-unit increase in umbilical blood mercury levels was associated with a 4.22-point (95 %CI 0.77 to 7.67) increase in the adaptive domain and a 4.06-point (95 %CI 0.51 to 7.62) increase in the social domain.	1 yr	Mean 3.5 oz/wk (est. from frequencies ≥ 4 oz/wk = 32.7% > 2 oz/wk < 4 oz/wk =39.5% ≤ 2 oz/wk = 27.8%) Greatest benefit unknown Outcomes not categorized by white/oily or by species.	Geomean 0.20 hair ppm (range <LOD-0.74) A-mean 0.23 hair ppm (SD 0.11)	Both maternal seafood consumption and maternal mercury were associated with neurocognitive benefits. The authors attributed the positive associations to the beneficial nutrients in seafood despite presence of mercury from seafood.
2005 Oken et al. Prospective Cohort US n=135 Moderate Risk of Bias	Visual recognition memory (VRM) CM=PY	Beneficial For each additional weekly seafood serving (4 oz), offspring VRM score was 4.0 points higher [95% CI), 1.3 to 6.7]	6 mo	Mean = 4.8 oz/wk (range, 0–22) Dose response benefits were continuous through to 22 oz/wk. Outcomes not categorized by white/oily or by species.	Mean 0.55 ppm, Range (0.02–2.38) Geometric mean 0.45 ppm with 10% of samples > 1.2 ppm	Maternal seafood consumption was beneficially assoc. higher with offspring test scores while mercury was independently associated with lower test scores. The gain per each additional serving of seafood was greater than the reduction per each additional serving from mercury.
2016 Xu et al. Prospective Cohort USA n=344 Moderate Risk of Bias	NICU Network Neurobehavioral Scale (NNNS), CM=PN	Beneficial Greater seafood consumption was associated with less need for special handling (β = −0.0027, SE = 0.0009, p = 0.002) and among girls, higher asymmetry scores (β=0.007, SE=0.003, p=0.02).	5 wk	Median: 1.3 oz/wk (total of 52 oz per woman during entire pregnancy (interquartile range: 6–17). Outcomes not categorized by white/oily or by species.	Geomean 0.18 hair ppm (95% CI; 0.16–0.21) (range 0.004–1.78) ppm Greater mercury associated with less need for special handing.	Mothers had very low levels of seafood consumption. Nonetheless, infants whose mothers consumed more seafood had better attention and needed less special handling. Seafood was not associated with harm, despite exposure to mercury.
2010 Suzuki et al. Prospective Cohort Japan n=498 Moderate Risk of Bias	Neonatal Behavioral Assessment Scale (NBAS) CM=PN	Beneficial Total seafood intake assoc. with beneficial motor scores R2=0.102, p<0.05, in one but not all adjusted models. (Continuous)	3 days	Mean 12.6 (SD 8.6) oz/wk Range (0.01–77.2) oz/wk Beneficial up to 77.2 oz/wk Outcomes not categorized by white/oily or by species.	Median 1.96 Mean 2.22 (SD 1.16) (range 0.29–9.35)	Maternal seafood consumption was associated with beneficial outcomes while mercury was independently associated with adverse outcomes. Per the authors, the data suggested that prenatal mercury adversely affects neonatal neurobehavioral function while maternal seafood intake appears to be beneficial.
2011 Davidson et al. Prospective Cohort Republic of the Seychelles n= 462 Moderate Risk of Bias	California Verbal Learning Test (CVLT), Wisconsin Card Sorting Test (WCST), the Woodcock-Johnson (W-J-II) Achievement Test, Subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB), and measures of problematic behaviors. CM=Y	Beneficial Increasing prenatal mercury was null for 21 endpoints but associated with better scores on four endpoints (higher W-J-II math calculation scores, reduced numbers of trials on the Intra-Extradimensional Shift Set of the CANTAB), fewer reports of substance use and incidents of and referrals for problematic behaviors in school. However, increasing prenatal mercury was adversely associated with one level of referrals to a school counselor.	17 yr	Mean 48 oz/wk (as previously reported. Shamlaye, et al. 1995) Outcomes not categorized by white/oily or by species.	Mean 6.9 ppm (SD 4.4) (range 0.54–22.74) Relationships to beneficial neurocognitive outcomes reported through the highest levels of mercury, in linear models.	Although seafood consumption was measured, the results were in terms of mercury associations with test scores. We include this study because it is the only study that reported outcomes out to 17 years of age. The oldest in other studies was nine years of age. Ocean seafood appeared to benefit neurocognitive development despite contributing an increasing exposure to mercury. Since mercury has no known benefit to neurocognitive development, the mercury in this study was likely to reflect the seafood consumed in this cohort.
2016 Llop et al. Prospective Cohort Spain n=1362 Moderate Risk of Bias	McCarthy Scales of Children’s Abilities (MSCA). CM=PY	Beneficial A doubling in mercury was associated with higher scores in most of the MSCA scales (β=1.29; 95% CI 0.28–2.31 general cognitive scale).	4–5 yr	Categories of seafood consumption oz/wk <12 12–20 >20–32 Greatest benefits >32	and corresponding Hair-Hg ppm 0.98 (0.24–1.2) 1.44 (1.32–1.56) 1.89 (1.76–1.98) 2.04 (1.9–2.2)	Statistically significant beneficial effects started to emerge at ≥ 12 oz/wk (MSCA verbal, numerical and memory), which was roughly at or above the EPA Reference Dose for mercury in this cohort.

¹RoB NOS scale. Summary and number of bias domains rated as 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) mercury in maternal blood (ug/L) = 3.59*[10] hair mercury (ppm). The cord blood mercury concentrations were standardized to maternal hair using data from Grandjean et al. (1992) [12]; cord blood mercury nmol/L = 5.0* mercury maternal hair (nmol/g) [12]

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

⁵data from corresponding author