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

Abstract

Ferritin status during prenatal brain development may influence the risk of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood. We investigated the association of maternal ferritin in pregnancy and ADHD-like symptoms in offspring. A total of 1095 mother-child pairs from three birth cohorts of the INMA Project (Spain) were studied. Maternal plasma ferritin in pregnancy was measured at 11.57 weeks of gestation. Children′s ADHD-like symptoms at ages 4–5 years were assessed using the ADHD Rating Scale-IV. The count model of the zero-inflated Poisson regression model showed a significant inverse association between ferritin (continuous variable) and inattention, β = −0.19 (−0.32, −0.07), for boys. Comparing ferritin level by tertiles, significant differences were observed between the first tertile ([1.98, 20.92]) and the second ([20.92, 38.79]) and third tertiles ([38.79, 216.5]) (mg/L).The number of symptoms was lower for those in the third tertile, β = −0.3 (−0.55, −0.5), and for those in the second one, β = −0.37 (−0.6, −0.14). The model stratification by sex also showed this inverse association for boys only, β = −0.21 (−0.34, −0.08). No associations were found between ferritin level and hyperactivity or total ADHD symptoms. High ferritin levels during pregnancy show a protective association with child inattentive-type ADHD symptoms.

Maternal Iron Status in Pregnancy and Child Health Outcomes after Birth: A Systematic Review and Meta-Analysis

“…Of these, 142 papers were fully read and led to the identification of 41 studies meeting the inclusion criteria. Scanning reference lists led to the inclusion of three more studies, resulting in a total of 44 studies [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ] ( Figure 1 ).…”

“…Maternal measurements were timed throughout pregnancy, with most of them occurring during the third trimester or at birth. Of the 10 studies that examined the first trimester of pregnancy, reflecting the period of organogenesis, only four explored outcomes beyond infancy [ 53 , 58 , 60 , 64 ]. One found impaired memory in 5-year-old children of mothers with anorexia nervosa and low ferritin levels [ 53 ].…”

Motor Developmental Outcomes in Children Exposed to Maternal Diabetes during Pregnancy: A Systematic Review and Meta-Analysis

“…Maternal obesity was a confounder in this meta-analysis as the majority of studies did not adjust findings by BMI, or other major confounders such as glycaemic control or gestational morbidities. Only one study adjusted data for weight gain during pregnancy [ 30 ], two studies adjusted data for birth weight and gestational age [ 15 , 19 ], and three studies adjusted for education level [ 12 , 20 , 28 ], thus, reported motor scores can be considered as independent of those confounders.…”

“…This may relate to the fact that GDM often involves a less severe form of hyperglycaemia of shorter duration. We noted that two studies were limited to women with pre-existing diabetes and had the largest difference in motor scores between groups [ 12 , 32 ], whereas studies limited to GDM [ 28 , 30 ] had the lowest difference between groups. In the study by Torres-Espinola et al [ 30 ], children born to diabetic mothers had the lowest motor skill at 18 months, but this difference was lost in adjusted models.…”

“…There is also evidence that maternal diabetes can have deleterious effects on the developing foetus, as well conditions such as maternal hyperglycaemia, ketonaemia, and recurrent changes in glucose status [ 7 , 10 ]. Iron deficiency is also associated with diabetes [ 11 ] and can also adversely affect neurodevelopment in humans [ 12 ]. During pregnancy, a hyperglycaemic environment of the intrauterine life negatively impacts foetal neural development [ 13 ].…”