Table 5.

Summary of the studies examining associations of maternal vitamin B12 status with offspring cognitive function

Author, Year, Sample size, Age, Country, Study design	Nutrient	Cognitive function	Results after adjustment for confounders	QS and RB
23WU BTF; 2012  N = 154  Age 18 Months  Canada  Prospective	Plasma vitamin B12 and holotranscobalamin concentrations assessed at 16 and 36 weeks gestation 7.8 % low B12 (<148 pmol/l)	Bayley Scales of Infant Development Receptive language, expressive language, cognitive skills, fine motor and gross motor	No association of B12 and holotranscobalamin with cognitive function Confounders adjusted for: The child’s sex, BF, ethnicity, MA, MIQ, maternal fatty acid level	13 Medium
25Bhate V; 2008  N = 108  Age 9 years  India  Prospective community based	Plasma Vitamin B12 concentrations assessed at 28 weeks gestation B12 status 2 groups Lowest <77 pmol/L Highest >224 pmol/L	Raven’s Coloured Progressive Matrices-Intelligence Visual recognition Colour Trial Test-sustained attention and executive function Digit-span test-short-term or working memory	Children in group 1 performed slowly in sustained attention (182 seconds Vs 159) and short-term memory (2.6 digits Vs 2.9) No association with other tests Confounders adjusted for: The child’s sex, age, education, weight and head circumference, B12 level, SES, education of the head of the family	14 Medium
26Veena SR; 2010  N = 536  Age 9-10 years  India  Prospective birth cohort	Plasma vitamin-B12 concentrations assessed at 30 ± 2 weeks gestation Low B12-(B12 < 150 pmol/L)-42 %	Kauffman Assessment Battery for Children-II-Learning, long-term retrieval, short-term memory and reasoning Wechsler Intelligence Scale for Children-III-attention and concentration Koh’s block design-visuo-spatial ability Verbal fluency	No association between B12 concentrations and cognitive function No difference in mean score between children of mothers with low and normal B12 status Confounders adjusted for: The child’s sex, GA, weight and head circumference at birth, parity, MA, maternal BMI, ME, PE, SES, religion, rural/urban residence, the child’s current age, education, head circumference, BMI and B12 concentrations	16 Medium
28Del Rio Garcia; 2009  N = 253  Age Infancy (1- 12 months)  Mexico  Prospective birth cohort	Daily dietary intake of vitamin B12 (first trimester FFQ) Deficient daily dietary intake (B 12 < 2.0 μg/day) – 21.3 %	Bayley Scales of Infant Development -II (Mental Development Index(MDI) and Psychomotor Development Index (PDI))	B12 intake deficiency-↓mental development (β = -1.6 points) Confounders adjusted for: BWT, BF, current age, energy intake at age 6 months, maternal BMI, pregnancy hypertension, ME, HE and MTHFR 1298A > C genotype	16 Medium
29Villamor E; 2012  N = 1210  Age 3 years  USA  Prospective pre-birth cohort	Average daily intake of vitamin B12 - 1st and 2nd trimester (FFQ + Supplements) Peri-conceptional B12 intake from supplements (LMP - 4Wks gestation)	Peabody Picture Vocabulary Test-Receptive Language Wide Range Assessment of Visual Motor Abilities-visual-motor; visual-spatial and fine motor	↑ B12 intake (2.6 μg/day) during 2nd trimester (not 1st trimester) -↓ (0.4 points) receptive language No association of peri-conceptional B12 intake with cognitive function Confounders adjusted for: MA, parity, ethnicity, MS, pre-pregnancy BMI, ME, PE, MIQ, energy, fish and iron intake, income, the child’s sex and English as primary language	15 Medium
30Boeke C; 2013  N = 895  Age 7 years  USA  Prospective pre-birth cohort	Average daily intake of B12 at 1st and 2nd trimester (FFQ + Supplements)	Peabody Picture Vocabulary Test-Receptive Language Wide Range Assessment of Memory and Learning-II edition, Design and Picture Memory subtests: visuo-spatial memory Kaufman Brief Intelligence Test-II edition Verbal and non-verbal intelligence	No association of B12 intake with cognitive function Confounders adjusted for: MA, parity, ethnicity, MS, ME, PE, MIQ, HE, intake of energy, fish and other methyl donors, the child’s sex and current age	16 Medium
37Bonilla C; 2012  N = 6259  Age 8 years  UK  Population based prospective birth cohort	Daily dietary vitamin B12 intake. (FFQ; 3rd trimester-32 weeks)	Wechsler Intelligence Scale for Children-III- Full-scale IQ	No association between maternal B12 intake and child’s IQ. Confounders adjusted for: The child’s sex, GA, BWT, BF, current age, MA, parity, ME, social class, MS, alcohol, maternal energy intake and infections in pregnancy, folate supplementation	14 Medium

QS quality score, RB risk of bias, LMP last menstrual period, BMI body mass index, FFQ food frequency questionnaire, BWT birthweight, SES socio-economic status, GA gestational age, MA maternal age, ME maternal education, PE paternal education, MIQ maternal intelligence, HE home environment, MS maternal smoking, BF breast-feeding, MTHFR methylenetetrahydrofolate reductase