INMA: “Higher ferritin levels during pregnancy may protect against ADHD symptoms during childhood”


A study based on the INMA cohort established in the regions of Gipuzkoa (Basque Country), Sabadell (Catalonia), and Valencia investigates the relation between maternal levels of ferritin during pregnancy and ADHD symptoms in their children at age 4 years.

Iron is an essential trace metal, which plays a central role in many brain functions and iron deficiency may contribute to behavioral and cognitive dysfunctions. Several epidemiological studies have reported an association between iron deficiency and low scores in tests assessing mental, social and motor development in infants, as well as a lower intelligence quotient, and poorer learning ability. In the human body, ferritin is the main protein involved in storage, transportation and release of iron in a controlled manner. Serum ferritin levels seem to be a reliable measure of iron stores in body tissues, including the brain.

Attention deficit/hyperactivity disorder (ADHD) is the most frequent childhood-onset neuropsychiatric condition, with an estimated worldwide prevalence of approximately 5% in school-aged children. Despite ADHD being the most studied neuropsychiatric condition in children  worldwide, the etiological factors are not well understood. Indeed, the disorder is likely to be due to a complex combination of environmental, genetic and biological factors. Scientific evidence supports the hypothesis that a lack of brain iron might contribute to the pathophysiology of ADHD.

The INMA study included 1,095 children with available data on maternal ferritin levels during pregnancy, ADHD symptoms data, and lifestyle information. Maternal blood samples were collected during early pregnancy (around 13 weeks of gestation) by venipuncture under fasting conditions and stored between −70 and −80 ◦C until analysis. Child ADHD symptoms at 4 years of age were assessed using the ADHD Rating Scale-IV completed by the child’s classroom teacher. The scale comprises 18 ADHD symptoms and is designed to evaluate inattention (9 symptoms) and hyperactivity/impulsivity (9 symptoms). Each symptom is rated using a 4-point scale: 0 = “not at all”, 1 = “just a little”, 2 = “pretty much” and 3 = “very much”. Scores were summed to provide  measures of inattention, hyperactivity/impulsivity and total ADHD symptoms.

The statistical analysis applied by the investigators revealed an inverse association between ferritin levels and inattention symptoms in boys (the more maternal ferritin, the less inattention symptoms). In contrast, no significant association was found between ferritin level and the rest of symptoms. Notably, this negative association was not observed in girls.

Findings show that maternal ferritin levels during pregnancy are independently associated with ADHD symptoms in 4-year-old children. More specifically, maternal ferritin levels seem to influence inattention symptoms in boys, whereas girls seem to be more protected. This study makes a new contribution to understanding the association between ferritin levels in mothers during pregnancy and ADHD symptoms in their children, including implications for clinical practice regarding prenatal iron supplementation. Therefore, authors plead for more research in order to clarify the mechanisms of action of iron and neurotransmitters in relation to cognitive function.

Reference: Santa-Marina L, Lertxundi N, Andiarena A, Irizar A, Sunyer J, Molinuevo A, Llop S, Julvez J, Beneito A, Ibarluzea J, Imaz L, Ferrin M. Maternal Ferritin Levels during Pregnancy and ADHD Symptoms in 4-Year-Old Children: Results from the INMA-INfancia y Medio Ambiente (Environment and Childhood) Prospective Birth Cohort Study. Int J Environ Res Public Health. 2020 Oct 22;17(21):7704.