Pre-conceptual and prenatal supplementary folic acid and multivitamin intake, behavioral problems, and hyperkinetic disorders: A study based on the Danish National Birth Cohort (DNBC)

Abstract

OBJECTIVE: To evaluate whether early folic acid or multivitamin supplementation during pregnancy prevents diagnosis of hyperkinetic disorders (HKD), treatment for attention deficit hyperactivity disorder (ADHD) and ADHD-like behaviors reported by parents participating in the DNBC for children at age 7. METHODS: HKD diagnosis and ADHD medication use data was obtained from the Danish National Hospital, Central Psychiatric and Pharmaceutical registers. We estimated hazard ratios (HRs) for HKD diagnosis and ADHD medication use and risk ratios (RRs) for parent reported ADHD behavior collected with the Strength and Difficulties Questionnaire (SDQ), comparing children whose mothers took folic acid or multivitamin supplements early in pregnancy defined as starting peri-conceptionally (4-weeks prior to their last menstrual period (LMP)) through 8-weeks after their LMP (−4 to 8 weeks), to children whose mothers indicated no supplement use for the same entire period. RESULTS: We identified 384 children (1.1%) with a hospital diagnosis for HKD and 642 children (1.8%) treated with ADHD medication. We found no association between risk of HKD diagnosis or intake of ADHD medication and early maternal folic acid use. However, early multivitamin use was associated with an approximately 30% reduction in risk for HKD diagnosis (aHR: 0.70, 95% CI: 0.52–0.96) and 21% reduction in treatment with ADHD medication (aHR: 0.79, 95% CI: 0.62–0.98). We also observed a reduced risk in parent reported ADHD behaviors but these results were attenuated after adjustment. CONCLUSION: Our data suggest that multivitamin use in early pregnancy may reduce risk for HKD diagnosis and treatment for ADHD in the offspring.

Preconception and Prenatal Nutrition and Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis

“…Three studies examined maternal folic acid supplementation in relation to offspring ADHD risk or symptoms [63,64,65,66,67], with most reporting null findings. Specifically, maternal folic acid-specific supplementation before and in early pregnancy was not associated with clinical diagnosis of hyperkinetic disorders or ADHD medication use in a large study of 35,059 children in the DNBC [65], although it was associated with a lower risk of hyperactivity-inattention problems as measured by the Strength and Difficulties Questionnaire (SDQ) among a subgroup of children followed to age seven. Similarly, maternal intake of any folic acid supplementation before or in early pregnancy was not associated with the risk of the hyperactivity-inattention problem among 6247 children in the Growing Up in New Zealand Study [63] and 420 children in the Menorca cohort in Spain [66].…”

“…Among the studies previously mentioned, three also assessed the association between maternal multivitamin intake and child ADHD risk [63,65,66]. Overall, the findings are inconsistent.…”

“…Overall, the findings are inconsistent. Maternal multivitamin intake was associated with a lower risk of hyperkinetic disorders and ADHD medication in the DNBC [65], but it was not associated with the hyperactivity-inattention problems in the Growing up in New Zealand Study [63]. Maternal intake of multivitamins containing no folic acid was associated with a non-significant reduction in risk of the hyperactivity-inattention problem in the Spanish Menorca cohort (OR = 0.24, 95% CI: 0.05, 1.31) [66].…”

Significant Effects of Maternal Diet During Pregnancy on the Murine Fetal Brain Transcriptome and Offspring Behavior

“…With respect to the finding of hyperactivity/increased locomotion in powdered-chow exposed offspring, human studies evaluating the impact of vitamin and micronutrient deficiencies on offspring attention deficit hyperactivity disorder (ADHD) risk have reported mixed results (Li et al, 2019). For example, maternal multivitamin and folate intake were associated with a lower risk of ADHD diagnosis and medication use in the Danish National Birth Cohort, but not in a New Zealand birth cohort (Virk et al, 2018;D'Souza et al, 2019). Deficiencies in B vitamins and Vitamin D have also been linked to increased ADHD risk in children (Morales et al, 2015;Altun et al, 2018;Fasihpour et al, 2019;Kotsi et al, 2019), although some studies have failed to find these associations (Gustafsson et al, 2015).…”

Can broad-spectrum multinutrients treat symptoms of antenatal depression and anxiety and improve infant development? Study protocol of a double blind, randomized, controlled trial (the ‘NUTRIMUM’ trial)

“…While there is limited evidence for the association between maternal diet and beneficial outcomes for offspring, the observational study, KOMCHS in Japan showed that behavioural problems in childhood were less likely in children whose mothers consumed a diet high in vegetables, fruit and vitamin C during pregnancy [ 60 ] and used supplements of folate, vitamin B2 and vitamin B6 [ 61 ]. A Danish cohort study (DNBC) reported the risk for hyperkinetic disorders and treatment for ADHD to be lower in children whose mothers used multivitamins early in pregnancy compared to those who consumed folic acid only [ 62 ]. There have been limited studies to date examining the impact of diet and dietary supplementation on infants whose mothers experienced mental health difficulties during the antenatal period.…”