. 2016 Aug 12;16:220. doi: 10.1186/s12884-016-1011-z

Table 6.

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

Author, Year, Sample size, Age, Country, Study design	Nutrient	Cognitive function	Results after adjustment for confounders	QS and RB
³¹Wehby GL; 2008 N = 6774 Age 3 years USA Population based longitudinal	Prenatal iron supplements (3 months prior to pregnancy and/or during the following 3 months) 36.2 % used supplement	Denver developmental screening-language, personal-social, gross motor and fine motor	Iron use was associated with improved performance in personal-social development (OR = 0.5) but not with language and motor domains Confounders adjusted for: The child’s sex, age, ethnicity, MA, ME, MS, alcohol, drug abuse, income, maternal health status	11 High
³⁸Rioux FM; 2011 N = 63 Age 6 Months Canada Observational	Hb, serum ferritin at 28-32 weeks gestation 90 % mothers took iron supplements (27 mg of iron)	Brunet-Lezine Scale of Psychomotor Development of Early Childhood. Bayley Scales of Infant Development	No association between maternal gestational Iron status with mental and psychomotor development. Confounders adjusted for: ME, PE, MIQ, income, BF, GA, BWT, birth head circumference, infants’ current weight and Hb	16 Medium
³⁹Ferarouei. M; 2010 N = 9983 14 years N = 10474 16 years Finland Prospective Birth cohort study	Hb concentrations at 3rd 7th and 9th gestational months Anaemia	School performance 14 years- Self report 16 years- School report	↑maternal HB at 9 months-↑ total school performance score (β = 0.03) and theory score at 14 years and total score at 16 years Offspring of mothers with anaemia –low school scores (OR = -0.05 at 14 years and (OR = -0.06) at 16 years Confounders adjusted for: The child’s sex, BWT, pregnancy wanted or not, ME, social class, parity, marital status, MS, maternal mental health status	18 Low
⁴⁰Davidson PW; 2008 N = 229 Age 5, 9, 25and 30 months Republic of Seychelles Longitudinal cohort study	Iron- total body stores at 14-24 weeks of gestation assessed before the start of iron supplementation	Bayley Scales of Infant Development: Mental Development Index (MDI) and Psychomotor Development Index (PDI) (9 and 30 months) Infant cognition (Fagan Infantest-novelty preference) and Visual Expectation Paradigm –visual recognition memory (9 and 25 months) A-not-B and Delayed Spatial Alternation: inhibition, working memory, planning and attention (25 months)	No association between maternal iron stores and cognitive function at any age. Confounders adjusted for: The child’s sex, BWT, MA, SES, HE, MIQ and both parents living with the child (yes/no)	19 Low
⁴¹Lewis SJ; 2013 N = ~3,500 Age 8 years UK Population based prospective birth cohort	Hb concentrations Before 18 weeks Hb <11.0 g/dl -8 % After 28 weeks Hb <11.0 g/dl -30 %	Wechsler Intelligence Scale for Children-III- Full- scale IQ	No association between maternal Hb and child’s IQ Confounders adjusted for: GA, ME, the child’s genotype, iron supplementation, population stratification	15 Medium
⁴²Tran TD; 2013 N = 378 Age 6 months Vietnam Population based prospective cohort study	Iron deficiency anaemia (Hb <11.0 g/dl and serum ferritin <15 ng/ml) during 12-28 weeks of gestation-16 %	Bayley Scales of Infant and Toddler Development-III edition-cognitive score	Infants of anaemic mothers scored 11.6 points (0.77SD) lower in BSID cognitive scores compared to infants of non-anaemic mothers. Confounders adjusted for: parity, MA, ME, wealth index, the child’s birth and current weight, family support, BF.	18 Low
⁴³Zhou SJ; 2006 N = 302 Age 4 years; Australia Double blind randomized controlled trial	Iron supplements (20 mg/day) or placebo from 20 weeks gestation until delivery Compliance-86 %	Stanford Binet Intelligence Scale – IQ (verbal reasoning, visual reasoning, quantitative reasoning and short-term memory)	No difference between the children of supplement group and placebo group in the mean score of composite IQ or any subscales IQ or in the proportion of children whose IQ fell 1 or 2 SD below the mean. Confounders adjusted for: sex, birth order, gestational age, MA, ME, PE, HE, BF	20 Low
⁴⁴Li Q; 2009 N = 1305 Age 3, 6 and 12 months Double blind cluster randomized controlled trial China	3 intervention groups (All received folic acid) Folic acid alone 400 μg (n = 471)-control Iron 60 mg + folic acid 400 μg (n = 438) Multiple micronutrients ((b vitamins (1,2,3 6 AND 12), vitamin A, D, C, E and minerals (zinc, iodine, copper, selenium) + Iron 30 mg + 400 μg folic acid)) (n = 396) Daily supplementation from enrolment until delivery; inadequate information about compliance	Bayley Scales of Infant Development :Mental (MD) and Psychomotor development (PD)	No significant difference in infants MD and PD score at 3 and 6 months and PD score at 12 months between supplement groups Mean MD score among children of multiple micronutrient group increased by 1 to 1.22 points compared to children of folic acid alone, or folic acid + iron group at 12 months Confounders adjusted for: Infants age, sex, gestational age, apgar score, BWT, infant health, maternal age and BMI, parental education, occupation, SES, number of tablets consumed	19 Low

QS quality score, RB risk of bias, Hb haemoglobin, GA gestational age, MA maternal age, BWT birthweight, SES socio-economic status, ME maternal education, PE paternal education, MIQ maternal intelligence, HE home environment, MS maternal smoking, BF breast-feeding, BMI body mass index