Table 1.
Literature review of maternal Vitamin B12, folate and/or multivitamin supplement and ADHD
| S. no. | Author/country/title | Diagnosis | Study design | Diagnostic criteria/data source | Period of supplementation | Dosage | Sample size/age | Covariates | Results |
|---|---|---|---|---|---|---|---|---|---|
| 1 | D’Souza et al. [31] (New Zealand) | ADHD symptoms | Prospective cohort (growing up in New Zealand) | Hyperactivity-inattention symptoms assessed by mother-report SDQ | Folic acid and multivitamin supplementation before pregnancy, during the first trimester, and after the first trimester assessed in late pregnancy | Not available | 6246/2 years | Mother’s ethnicity, mother’s education, mother’s age when pregnant, child’s gender, child’s gestational age, child’s birth weight, parity, planned pregnancy, mother in paid employment, area-level deprivation, and rurality |
Multivitamin was not associated with hyperactivity-inattention symptoms (OR 0.97, 95% CI 0.75–1.24) Compared to pre-conception and 1st trimester folic intake, both 1st trimester only (OR 0.98, 95% CI 0.74–1.31) and no intake (OR 0.88, 95% CI 0.57–1.34) were not associated with hyperactivity–inattention symptoms |
| 2 | Miyake et al. [33] (Japan) | ADHD symptoms |
Prospective cohort Kyushu Okinawa Maternal and Child Health Study (KOMCHS) |
Hyperactivity-inattention symptoms assessed by parent-report SDQ at age 5 years | Folate and other B-vitamin intake from food in the past month assessed by Diet history questionnaire (DHQ) at 5–39 weeks (no information of supplementation recorded) | Average consumption of food and beveragesa | 1199 3–16 years | Maternal age, gestation at baseline, region of residence, number of children, maternal and paternal education, household income, maternal depressive symptoms during pregnancy, maternal alcohol intake during pregnancy, maternal Vitamin B complex supplement use during pregnancy, maternal smoking during pregnancy, child’s birth weight, child’s sex, breastfeeding duration, and smoking in the household during the first year of life |
Vitamin B12 from food was not associated with hyperactivity–inattention problems, quartiles Q2 (OR 0.80, 95% CI 0.49–1.29), Q3 (OR 0.99, 95% CI 0.61–1.61) and Q4 (OR 0.81, 95% CI 0.50–1.32) Folate from food was not associated with hyperactivity–inattention problem, quartiles Q2 (OR 0.75, 95% CI 0.46–1.21), Q3 (OR 0.66, 95% CI 0.40–1.07) and Q4 (0.69, 95% CI 0.42–1.12) |
| 3 | Virk et al. [30] Denmark | Hyperkinetic disorder | Prospective cohort (Danish National Birth Cohort (DNBC)) | ICD-10 HKD diagnosis (F90.0–F90.9) at or after their fifth birthday, ADHD symptoms assessed by Parent-report SDQ for children at age 7 years | Folic acid and multivitamin supplementation from (4–8 weeks) assessed at 12 weeks | Not available | 35,059 Age:7 years | Maternal age, household SES, maternal smoking, alcohol consumption during pregnancy, maternal pre- pregnancy BMI, birth year, offspring’s sex |
Multivitamin intake was associated with lower risk for HKD diagnosis (aHR 0.70, 95% CI 0.52–0.96) and ADHD medication (aHR: 0.79, 95% CI 0.62–0.98) Folic acid intake was not associated with risk for HKD diagnosis (aHR 0.87, 95% CI 0.54–1.41) Multivitamin intake was not associated with parent report hyperactivity–inattention symptoms (aRR 0.90, 95% CI 0.76–1.06) however folic acid intake was associated with parent report hyperactivity–inattention symptoms (aRR 0.62, 95% CI 0.47–0.94) |
| 4 | Schlotz et al. [29] UK | ADHD symptoms | Prospective cohort | Mother-report SDQ at age 8 years |
Maternal red blood cell folate (RCF), measured at 14 weeks Total folate intake (TFI) from food and supplement assessed in early and late pregnancy assessed by Food frequency questionnaire (FFQ) at 14 weeks and during late pregnancy at 28 weeks |
Frequency of consumption of 100 foods or food groupsb |
139 Age:7.6–9.8 years |
Sex, mother’s tobacco or alcohol consumption during pregnancy, education, daily energy intake |
Lower maternal red cell folate concentration (RCF: beta β = − 0.24, 95% CI − 2.20, − 0.26) and total folate intake from food and supplements (TFI: beta β = − 0.24, 95% CI − 1.39, − 0.11) in early pregnancy were both associated with higher hyperactivity–inattention symptoms However, total folate intake from food and supplements in late pregnancy (TFI: beta β = 0.02, 95% CI − 0.80, 0.93) was not associated with hyperactivity–inattention symptoms |
| 5 | Julez et al. [32] Spain | ADHD symptoms | Prospective birth cohort from Menorca | ADHD-DSM-IV criteria-Psychologists and Teacher rated Cut-off 80th percentile | Folic acid and multivitamin supplementation assessed at the end of first trimester of pregnancy | Not available |
420 children Age: 4 years |
Parental social class and level of education, mother’s parity at child’s age four, mother’s marital status, tobacco smoking during pregnancy, maternal intake of supplementary calcium and iron at same time as study determinants, gestational age at interview, child’s gender, child’s duration of breast feeding, child’s age and school season during test assessment, evaluator (psychologist), child’s home location at age four |
Vitamin use without folic acid was not associated with ADHD (OR 0.26, 95% CI 0.05–1.31); Hyperactivity symptoms (OR 1.07, 95% CI 0.26–4.45) and Inattention symptoms (OR 0.24, 95% CI 0.05–1.33) Folic acid with or without other Vitamins was not associated with ADHD (OR 0.74, 95% CI 0.38–1.47). Hyperactivity symptoms (OR 1.44, 95% CI 0.68–3.03) but associated with inattention symptoms (OR 0.46, 95% CI 0.22–0.95) |
ADHD Attention-deficit/hyperactivity disorder, SDQ Strength and Difficulty Questionnaire, OR odds ratio, CI confidence Interval, KOMCHS Kyushu Okinawa Maternal and Child Health Study, DHQ Diet History Questionnaire, DNBC Danish National Birth Cohort, HKD hyperkinetic disorder, aHR adjusted hazard ratio, RCF red blood cell folate, TFI total folate intake, FFQ Food Frequency Questionnaire, DSM-IV Diagnostic and Statistical Manual of Mental Disorders, BMI body mass index, UK United Kingdom
aAverage consumption of eight categories of food ranging from “never” to “≥ 2 times/day” for foods and from “< 1 time/wk” to “≥ 6 times/day” for beverages. The relative portion size was compared with a standard portion size according to five categories: “50% smaller or less”, “20%–30% smaller”, “same”, “20–30% larger,” and “50% larger or more”
bAverage frequency of consumption of 100 foods or food groups in the preceding 3 months. The nutrient content of a standard portion of each food was multiplied by its reported frequency of use and supplement use was ascertained in detail, allowing calculation of average total intake of energy (kcal/day) and folate (TFI; µg/day)