Analysis of maternal risk factors and potential biomarkers for attention deficit and hyperactivity disorder

Neurobehavioral disorders are characterized by abnormal brain development that affects cognitive, emotional and adaptive functions. Attention-deficit/hyperactivity disorder (ADHD) often begins in childhood but can persist into adulthood. Symptoms of ADHD include learning disabilities such as inattention, hyperactivity and communication impairment at various stages of development (1).

The prevalence of ADHD among children is estimated to range from 3% to 8%. This percentage may increase with age, particularly due to late diagnosis (2). ADHD diagnosis is based on persisting clinical symptoms of inattention and hyperactive-impulsive behavior. The consequences of ADHD in adulthood extend to occupation, marital and parental relationships. Adults diagnosed with ADHD are also at higher risk for other mental disorders such as anxiety, depression and addiction. The treatment of ADHD in children frequently includes the administration of psychostimulants like methylphenidate, while adults may benefit from lisdexamfetamine in combination with cognitive behavioral therapies (3).

Although the exact etiology remains not fully understood, genetic factors play a significant role in the development of ADHD. Specifically, decreased global DNA methylation in genes associated with neuronal migration, DNA damage, and oxidative stress seems to be directly implicated in the pathogenesis (4).

Environmental exposure and lifestyle significantly contribute to the development of mental disorders (Figure 1). Studies have demonstrated a clear correlation between ADHD and maternal health, including changes in maternal immune response, exposure to toxicants, and nutritional deficiencies (5). Additionally, the family history of psychiatric disorders and socioeconomic status has been linked to the onset and more severe symptoms of ADHD (6).

Figure 1 Non-genetic maternal risk factors for attention-deficit/hyperactivity disorder.

Nicotine, alcohol, and heavy metals are widely recognized as risk factors for ADHD (7). Recent findings show a connection between prenatal exposure to flame retardants and organophosphates with thyroid endocrine disruption, which has been observed in individuals with ADHD (8). Lead exposure has been identified as a significant risk factor for hyperactivity and impulsivity scores in individuals with ADHD. Additionally, higher levels of lead have been associated with a suggestive grade of evidence in ADHD (9). Perinatal exposure to acetaminophen has been shown to disrupt brain cortical neurons, potentially leading to toxicity and an increased risk for neurodevelopment in patients with ADHD (10).

The occurrence of ADHD symptoms is notably more common in offspring of individuals with polycystic ovary syndrome (PCOS) in a manner that is independent of androgen levels (11). This suggests that factors such as obesity or hyperinsulinemia associated with PCOS may impact fetal development. Additionally, research has shown a correlation between ADHD diagnosis and maternal anxiety, as demonstrated by increased levels of placental C-reactive protein of ADHD births (12).

The discovery of potential biomarkers is crucial for the prevention and early detection of ADHD. Despite a limited number of biomarkers, several candidates have shown positive correlations between changes in maternal blood levels of circulating micronutrients, metals and cytokines and the development of ADHD. Meta-analysis reports have indicated that exposure to toxic metals during pregnancy may increase the risk of ADHD. Arsenic, cadmium, and manganese have been found to have a positive association with ADHD, while copper, mercury, and zinc have shown negative associations (13).

Ferritin levels are decreased in children with ADHD. Moreover, this decrease is correlated with more severe symptoms and cognitive deficits (14). Supplementation with polyunsaturated fatty acids led to improvement in ADHD children’s behavior. Furthermore, breastfeeding showed a protective effect against vitamin D deficiency observed in children with ADHD (15,16).

ADHD prevention must consider both risk and protective factors associated with the disease. The interaction between genetic factors and environmental exposure plays an important role in the onset of ADHD. Primary care interventions are typically applied during early prenatal care to prevent hazardous exposure, identify the disorder in children at early stages and propose family-centered strategies to minimize progression and clinical complications of ADHD. Educational programs addressing smoking and alcohol abuse have been shown to effectively reduce modifiable risk factors associated with ADHD. It is essential for families’ mental health a comprehensive collaboration of healthcare services in order to address the diverse nature of ADHD and challenges related to treatment adherence. Inattention can lead to poor academic performance and socioeconomic struggles over time, highlighting the implications to public health system. The complexity of ADHD etiology is still a major challenge for healthcare and requires a multifaceted assistance approach. The early identification of maternal risk factor can significantly improve early diagnosis and long-term outcomes for children with ADHD. Furthermore, it is essential to take into account the influence of socioeconomic status on preventive care to support effective interventions.

Acknowledgments

Funding: None.

Footnote

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