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Table 5 Summary of the studies examining associations of maternal vitamin B12 status with offspring cognitive function

From: Association between maternal nutritional status in pregnancy and offspring cognitive function during childhood and adolescence; a systematic review

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
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
 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
 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)
 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
 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
 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
 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
  1. 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