Abstract
BackgroundBoth genetic and pre- and perinatal factors, including birth weight, have been implicated in the onset of attention deficit hyperactivity disorder (ADHD) traits among children. This study aimed to elucidate to what extent the genetic risk of ADHD moderates the association between birth weight and ADHD traits among Japanese children.MethodsWe conducted a longitudinal birth cohort study (Hamamatsu Birth Cohort for Mother and Children Study) to investigate the association of genetic risk for ADHD and low birth weight with ADHD traits among Japanese children. Out of 1258 children, we included 796 who completed follow-ups at 8 to 9 years of age. Birth weight was categorized as <2000 g, 2000–2499 g, and ≥2500 g. Polygenic risk score for ADHD was generated using the summary data of a large-scale genome-wide association study. The Rating Scale IV (ADHD-RS) assessed ADHD traits (inattention and hyperactivity/impulsivity) based on parental reports. Following previous studies, sex, birth order of the child, gestational age at birth, mother’s age at delivery, educational attainment, pre-pregnancy body mass index, pre-pregnancy or during pregnancy smoking status, alcohol consumption during pregnancy, father’s age, education, and annual family income were considered as covariates. Multivariable negative binomial regression was applied to evaluate the association between birth weight and ADHD traits, while adjusting for potential covariates. The interaction term between birth weight categories and binary polygenic risk was added to the model.ResultsBirth weight of 2000–2499 g was not associated with ADHD traits. Birth weight under 2000 g was significantly associated with both inattention and hyperactivity. When accounting for higher and lower genetic risk for ADHD, only those with higher genetic risk and birth weight < 2000 g were associated with inattention (rate ratio [RR] 1.56, 95% CI 1.07–2.27) and hyperactivity (RR 1.87, 95% CI 1.14–3.06).ConclusionsBirth weight under 2000 g, together with the genetic risk of ADHD, contributes to higher levels of ADHD traits among Japanese children aged 8 to 9 years. The suggested association between low birth weight and ADHD is confined to children with a genetic susceptibility to ADHD, indicating the relevance of genetic-environmental interactions in the etiology.
Highlights
Both genetic and pre- and perinatal factors, including birth weight, have been implicated in the onset of attention deficit hyperactivity disorder (ADHD) traits among children
The suggested association between low birth weight and ADHD is confined to children with a genetic susceptibility to ADHD, indicating the relevance of geneticenvironmental interactions in the etiology
Note: aValues present median; bvalues present interquartile range; ADHD Rating Scale IV (ADHD-RS), attention deficit/hyperactivity disorder rating scale; BMI, body mass index; IQR, interquartile range; polygenic risk scores (PRS), polygenic risk score; SD, standard deviation; JPY, Japanese yen Higher genetic risk of ADHD and birth weight < 2000 g were associated with higher severity of ADHD traits (RR 1.82, 95% Confidence interval (CI) 1.10–3.01) compared to those born with normal birth weight or had lower genetic risk (Table 3)
Summary
Both genetic and pre- and perinatal factors, including birth weight, have been implicated in the onset of attention deficit hyperactivity disorder (ADHD) traits among children. Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders [1, 2], accounting for 1.14 million disability-adjusted life years globally in 2017 [3]. ADHD can be classified as predominantly inattentive, predominantly hyperactive/impulsive, or a combination of both and usually appears during early childhood and continues to manifest throughout the life course [1, 4]. The etiology of ADHD is complex and multifactorial, both pre- and perinatal conditions and genetic risk factors have been implicated in the development of ADHD symptoms among children [9–11]. Low birth weight [12] is the most consistent environmental factor identified in the literature to affect neurodevelopment and the onset of ADHD in childhood [13]
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