Iron deficiency and common neurodevelopmental disorders—A scoping review

Abstract

Background A wealth of human and experimental studies document a causal and aggravating role of iron deficiency in neurodevelopmental disorders. While pre-, peri-, and early postnatal iron deficiency sets the stage for the risk of developing neurodevelopmental disorders, iron deficiency acquired at later ages aggravates pre-existing neurodevelopmental disorders. Yet, the association of iron deficiency and neurodevelopmental disorders in childhood and adolescence has not yet been explored comprehensively. In this scoping review, we investigate 1) the association of iron deficiency in children and adolescents with the most frequent neurodevelopmental disorders, ADHD, ASD, and FASD, and 2) whether iron supplementation improves outcomes in these disorders. Method Scoping review of studies published between 1994 and 2021 using “iron deficiency / iron deficiency anemia” AND “ADHD” OR “autism” OR “FASD” in four biomedical databases. The main inclusion criterion was that articles needed to have quantitative determination of iron status at any postnatal age with primary iron markers such as serum ferritin being reported in association with ADHD, ASD, or FASD. Results For ADHD, 22/30 studies and 4/4 systematic reviews showed an association of ADHD occurrence or severity with iron deficiency; 6/6 treatment studies including 2 randomized controlled trials demonstrated positive effects of iron supplementation. For ASD, 3/6 studies showed an association with iron deficiency, while 3/6 and 1/1 systematic literature review did not; 4 studies showed a variety of prevalence rates of iron deficiency in ASD populations; 1 randomized controlled trial found no positive effect of iron supplementation on behavioural symptoms of ASD. For FASD, 2/2 studies showed an association of iron deficiency with growth retardation in infants and children with prenatal alcohol exposure. Conclusion Evidence in favor of screening for iron deficiency and using iron supplementation for pediatric neurodevelopmental disorders comes primarily from ADHD studies and needs to be further investigated for ASD and FASD. Further analysis of study methodologies employed and populations investigated is needed to compare studies against each other and further substantiate the evidence created.

Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial

“… 39 Studies exploring relationships between infant and childhood iron deficiency and neurodevelopmental disorders such as autism spectrum disorder and attention deficit hyperactivity disorder have largely been correlative and have found inconsistent evidence of association. 40 Therefore, it will be valuable to follow the cohort to determine whether children born to women receiving ferric carboxymaltose have improved developmental trajectories and altered risk of neurodevelopmental disorders.…”

The Nutritional Online sUrvey for pRegnancy Induced Sickness & Hyperemesis (NOURISH) study: results from the first trimester

“…47 This is relevant to HG, as research has linked HG to adverse child neurological outcomes, 23,48 which has been hypothesised to be due to nutritional factors. However, it is not known whether this is due to basic malnutrition caused by a basic lack of energy (calorie intake) or if it is more specifically linked to particular micronutrients of concern, known to be linked to child cognitive and neurodevelopment (e.g., iodine, iron [49][50][51][52] ). Better characterisation of nutritional intake throughout pregnancy, linked to long-term follow-up of offspring, would allow this to be further explored and reduce reliance on retrospective studies, which may be subject to bias.…”

The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder

“…A scoping review reported that three studies found statistical evidence for an association between iron deficiency and ASD severity, while three studies did not. Further contradictory results were reported in studies investigating the prevalence of iron deficiency and iron deficiency anemia [ 207 ]. A study demonstrated that hemoglobin levels were significantly lower in ASD patients with intellectual disabilities and severe ASD [ 208 ].…”