Kuo-Liang Chiang

Background: While attention deficit/hyperactivity disorder (ADHD) is characterized by neurodevelopmental heterogeneity, the influence of familial structural factors—particularly parental age and skipped-generation caregiving—on comorbidity patterns remains insufficiently studied. This study examined the associations between parent–child age gaps, skipped-generation family structures, and psychiatric comorbidities in children with ADHD. Methods: Data came from Taiwan’s NHIRD (2009–2013), including 79,163 ADHD cases and 395,815 matched controls. Key variables included maternal and paternal age at childbirth and grandparent-paid insurance premiums as a proxy for skipped-generation caregiving. Conditional logistic regression was used to estimate odds ratios (ORs) for 20 psychiatric and developmental comorbidities. Results: Children with ADHD exhibited significantly higher odds of various comorbidities, including oppositional defiant disorder (OR = 147.05, 95% CI = 101.0–214.1), somatoform disorder (OR = 25.78, 95% CI = 7.96–83.46), anxiety disorder (OR = 24.49, 95% CI = 17.9–33.5), emotional disturbances during childhood and adolescence (OR = 13.99, 95% CI = 9.15–21.4), and autism spectrum disorder (OR = 8.07, 95% CI = 6.63–9.82). Advanced maternal age (>35 years) was associated with increased odds of autism spectrum disorder (OR = 1.47, 95% CI: 1.29–1.67) and speech/language delay (OR = 1.33, 95% CI: 1.17–1.52), whereas younger maternal age (≤25 years) was linked to higher odds of anxiety disorder (OR = 1.23, 95% CI: 1.13–1.33) and adjustment reaction (OR = 1.41, 95% CI: 0.95–2.11). Maternal age under 20 years showed the highest odds for bipolar disorder (OR = 2.01, 95% CI: 1.04–3.88). For paternal age, older age (>35 years) was associated with increased odds of autism (OR = 1.14, 95% CI: 1.04–1.26) and speech/language delay (OR = 1.15, 95% CI: 1.04–1.27), whereas paternal age ≤20 years was strongly linked to bipolar disorder (OR = 3.58, 95% CI: 1.54–8.32) and anxiety (OR = 1.39, 95% CI: 1.01–1.93). Children from skipped-generation families—defined as grandparent-paid insurance premiums without parental cohabitation—had significantly higher odds of bipolar disorder (OR = 2.88, 95% CI: 1.36–6.11), personality disorder (OR = 9.23, 95% CI: 2.23–38.20), adjustment reaction (OR = 2.23, 95% CI: 1.39–3.59), and emotional disturbances during childhood/adolescence (OR = 1.69, 95% CI: 1.13–2.54). Conclusions: Both extremes of parental age and skipped-generation caregiving are linked to specific associations with certain psychiatric comorbidity patterns in children with ADHD. These findings highlight the importance of integrating family structure into diagnostic assessments and treatment planning and support the development of targeted early interventions.

Background: This study evaluated early childhood comorbidities of cerebral palsy (CP) in low birth weight (LBW) children and assessed the impact of maternal bio-psychosocial factors on CP risk in preterm infants of varying birth weights (BWs). Methods: Data from 15,181 preterm infants (2009–2013) and 151,810 controls were analyzed using Taiwan’s National Health Insurance Research Database. CP prevalence and LBW-associated comorbidities were examined, and odds ratios (ORs) were calculated. Results: This study confirmed increasing prematurity and LBW rates in Taiwan, with LBW infants showing higher CP prevalence. Significant maternal risk factors included age extremes (40 years). LBW infants exhibited higher risks for respiratory, circulatory, nervous system, and psycho-developmental comorbidities compared with controls, with the lowest BW having even higher ORs. Maternal factors such as family income, the number of hospital admissions, and length of hospital stay were remarkably correlated with BW and subsequent complications. Each additional gestational week crucially reduced the risk of complications in premature infants. Conclusions: LBW infants are at a higher risk for CP and various comorbidities, with maternal bio-psychosocial factors playing a critical role. Addressing these factors in prenatal care and interventions is essential to improve outcomes for premature infants.

This study aimed to evaluate the early-childhood comorbidities of cerebral palsy (CP) in children with low birth weight (LBW) and assess the impact of maternal bio-psychosocial factors on the risk of CP in preterm infants across varying birth weights. Data for 15,181 prematurely born infants from 2009 to 2013 and 151,810 matched controls from Taiwan's National Health Insurance Research Database were analyzed. Period prevalence of CP, and comorbidities of LBW were verified, and odds ratios (ORs) were calculated. Results confirmed that increasing prematurity and low birth weight (LBW) rates in Taiwan. LBW was associated with higher CP prevalence. Maternal age extremes (40 years) were significant risk factors of CP in LBW infants. LBW infants showed higher risks of respiratory, circulatory, and nervous system and psycho-developmental comorbidities compared to controls. Infants with the lowest birth weights had even higher ORs for these comorbidities. However, gastrointestinal and nutritional comorbidities were less prevalent in premature infants. Maternal factors such as family income, number of hospital admissions, and length of hospital stay were significantly correlated with birth weight and subsequent complications. Each additional gestational week significantly reduced the risk of complications in premature infants. Additionally, maternal bio-psychosocial factors were associated with birth weight and related outcomes in premature infants, emphasizing the importance of addressing these factors in prenatal care and interventions.

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS’s underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies.

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS's underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies.

Comorbidities are common in children with epilepsy, with nearly half of the patients having at least one comorbidity. Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder characterized by hyperactivity and inattentiveness level disproportional to the child’s developmental stage. The burden of ADHD in children with epilepsy is high and can adversely affect the patients’ clinical outcomes, psychosocial aspects, and quality of life. Several hypotheses were proposed to explain the high burden of ADHD in childhood epilepsy; the well-established bidirectional connection and shared genetic/non-genetic factors between epilepsy and comorbid ADHD largely rule out the possibility of a chance in this association. Stimulants are effective in children with comorbid ADHD, and the current body of evidence supports their safety within the approved dose. Nonetheless, safety data should be further studied in randomized, double-blinded, placebo-controlled trials. Comorbid ADHD is still under-recognized in clinical practice. Early identification and management of comorbid ADHD are crucial to optimize the prognosis and reduce the risk of adverse long-term neurodevelopmental outcomes. The identification of the shared genetic background of epilepsy and ADHD can open the gate for tailoring treatment options for these patients through precision medicine.