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Prenatal antidepressant exposure has been reported to be associated with adverse neurodevelopmental outcomes, yet studies considering confounding factors in Asian populations are lacking. This study utilized a nationwide data base in Taiwan, enrolling all liveborn children registered in the National Health Insurance system between 2004 and 2016. Subjects were divided into two groups: antidepressant-exposed (n = 55,707)) and antidepressant-unexposed group (n = 2,245,689). The effect of antidepressant exposure during different trimesters on autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) was examined. Sibling controls and parallel comparisons by paternal exposure status were treated as negative controls. Additional sensitivity analyses were conducted to examine the effects of antidepressant exposure before and after pregnancy. Prenatal antidepressant exposure was associated with increased risks of ASD and ADHD in population-wide and adjusted analysis. However when comparing antidepressant-exposed children with their unexposed siblings, no differences were found for ASD (Hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.76-1.42 in first trimester; HR: 0.96, 95% CI 0.62-1.50 in second trimester; HR: 0.69, 95% CI 0.32-1.48 in third trimester) and ADHD (HR: 0.98, 95%CI 0.84-1.15 in first trimester; HR: 0.91, 95% CI 0.73-1.14 in second trimester; HR: 0.79, 95% CI 0.54-1.16 in third trimester). Increased risks for ASD and ADHD were also noted in paternal control, before and after pregnancy analyses. These results imply that the association between prenatal antidepressant exposure and ASD and ADHD is not contributed to by an intrauterine medication effect but more likely to be accounted for by maternal depression, genetic, and potential environmental factors., Competing Interests: Declarations. Conflict of interest: The authors have no competing interests or financial support to disclose. Ethical standards: This study was approved by the Research Ethics Committee of China Medical University and Hospital (approval number: CMUH108-REC1-142) and was executed as per the Declaration of Helsinki. The requirement for informed consent was waived., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Our previous studies have revealed a correlation between urinary phthalates (PAE) metabolites and parabens and PM 2.5 exposure and susceptibility to attention-deficit/hyperactivity disorder (ADHD) in school-age children. Our goal was to examine the relationships between urinary organophosphate flame retardants (OPFRs) and their metabolites and the susceptibility to ADHD in the same cohort of children. We recruited 186 school children, including 132 with ADHD and 54 normal controls, living in southern Taiwan to investigate five OPFRs (1,3-dichloro-2-propyl phosphate (TDCPP), tri-n-butyl phosphate (TnBP), tris (2-chloroethyl) phosphate (TCEP), tris(2-butoxyethyl) phosphate (TBEP), and triphenyl phosphate (TPHP)) and five OPFR metabolites (bis(1,3-dichloro-2-propyl) phosphate (BDCPP), di-n-butyl phosphate (DNBP), bis(2-chloroethyl) hydrogen phosphate (BCEP), di-(2-butoxyethyl) phosphate (DBEP), and diphenyl phosphate (DPHP)) in urine. ADHD patients' behavioral symptoms and neuropsychological function were assessed using the Swanson, Nolan, and Pelham Version IV Scale (SNAP-IV) and the Conners' Continuous Performance Test 3rd Edition (Conners CPT3), respectively. BCEP was predominant among urinary OPFRs and the metabolites in both the ADHD and control groups. ADHD children had significantly higher levels of urinary BDCPP, BCEP, DBEP, DPHP, TCEP, TBEP, TNBP, TPHP, and Σ 10 OPFR compared to the controls. After controlling for age, gender, body mass index, PM 2.5 exposure scenarios, and urinary phthalate metabolites, parabens, bisphenol-A and creatinine, levels of urinary BDCPP, TDCPP, and TBEP in ADHD children showed significant and dose-dependent effects on core behavioral symptoms of inattention. DNBP levels were positively correlated with neuropsychological deficits (CPT detectability, omission, and commission), while urinary DPHP in ADHD children were negatively related to CPT detectability and commission. Hyperactivity and impulsivity were not correlated with urinary OPFRs and their metabolites in ADHD children. In conclusion, the ADHD symptom of inattention and CPT performance may be closely associated with certain urinary OPFRs and their metabolites, independent of urinary PAE metabolites, parabens, and bisphenol-A in school-age-ADHD children., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: How-Ran Chao reports financial support was provided by National Science and Technology Council. How-Ran Chao reports a relationship with National Science and Technology Council that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Attention-deficit hyperactivity disorder (ADHD) is diagnosed in ~7% of school-aged children. The role of endocrine-disrupting chemicals (EDC) and oxidative stress in ADHD etiology are not clear., Objective: Assessment of the associations between simultaneous exposure to multiple compounds and ADHD in children., Methods: The case-control study included 76 clinically diagnosed ADHD cases and 98 controls, aged 4-15 years old. Concentrations quartiles of urinary metabolites of acrylamide, acrolein, nonylphenol, phthalates, and organophosphate pesticides and biomarkers of oxidative stress were used to fit logistic regressions for each compound and weighted quantiles sum (WQS) regression for the mixture., Results: Positive dose-response relationships with ADHD were observed for 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) (odds ratio(OR) Q4  = 3.73, 95%CI [1.32, 11.04], p trend  = 0.003), dimethyl phosphate (DMP) (OR Q4  = 4.04, 95%CI [1.34, 12.94], p trend  = 0.014) and diethyl phosphate (OR Q4  = 2.61, 95%CI = [0.93, 7.66], p trend  = 0.030), and for the mixture of compounds (OR WQS  = 3.82, 95%CI = [1.78, 8.19]) with the main contributions from HNE-MA (28.9%) and DMP (18.4%)., Conclusions: The dose-response relationship suggests enhanced susceptibility to EDC burden in children even at lower levels, whereas the main risk is likely from organophosphate pesticides. HNE-MA is recommended as a sensitive biomarker of lipid peroxidation in the further elucidation of the oxidative stress role in ADHD etiology., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Many but not all studies suggest that gestational exposure to antidepressant drugs is associated with an increased risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in offspring. All of these studies have been observational in design, and observational research may suggest but cannot establish cause-effect relationships. In this context, a recent, large, population-based, observational study found that exposure to maternal depression before, during, or after pregnancy was each associated with an increased risk of ASD as well as ADHD. Strikingly, the same finding was obtained for paternal depression, as well, with mostly similar values for risk. If paternal depression before, during, or after pregnancy can increase the risk of ASD and ADHD in the offspring, it suggests that genetic variables, or environmental adversities engendered by behaviors related to paternal depression, may drive the risk for the adverse neurodevelopmental outcomes; some data exist to support this view. An understanding of these possibilities allows greater room for flexibility when considering the prescription of antidepressant drugs to depressed pregnant women., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

Background: Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders in childhood globally. Between the two components of ADHD, hyperactivity disorder is more prevalent than inattention during early childhood. Although some investigations have implied a relationship between childhood ADHD and gestational exposure to air pollution, the evidence is limited. The aim of this study was to investigate the association between gestational exposure to air pollution exposure and hyperactivity disorder in childhood in a population-based birth cohort., Methods: The Taiwan Birth Cohort Study started from all deliveries of Taiwan in 2005 by the birth registry, and recruited representative 12% of all mother-infant pairs by two-stage stratified sampling. At age of 8 years in each child, their main caretaker was inquired whether the child had ever received a hyperactivity diagnosis from a physician or other specialist, like special needs educator. Exposure to air pollutants during gestation was estimated through ordinary kriging based on data from air monitoring stations of Environmental Protection Administration, Taiwan. Logistic regression was used to determine adjusted odds ratios (aORs) of hyperactivity disorder in relation to air pollutants., Results: A total of 16,376 mother-infant pairs were included in the final analysis; 374 (2.3%) of the children had received a diagnosis of hyperactivity before 8 years of age. The occurrence of hyperactivity was significantly related to prenatal nitrogen oxide (NO x ), but not to particulate matter 10 μm or less in diameter or sulfur dioxide. Further analysis to separate effects by nitrogen dioxide (NO 2 ) and/or nitric oxide (NO) showed that only NO was significantly related to hyperactivity [aOR per interquartile range (3.14 ppb): 1.26, 95% confidence interval: 1.09-1.46]., Conclusions: In conclusion, our study found childhood hyperactivity disorder to be positively associated with prenatal NO exposure. Further confirmation on potential hazardous effects of NO and investigation on potential mechanisms are warranted., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Studies have suggested that a significant association exists between prenatal exposure to acetaminophen and the offspring's attention-deficit/hyperactivity disorder (ADHD) risk. However, this association has largely been unexplored among the Asian population, generally, and the Taiwanese population, specifically., Methods: In our study, 950 study pairs (children with ADHD [ICD-9-CM code: 314] and their mothers) and 3,800 control pairs (children without ADHD and their mothers) matched by demographic characteristics were identified between 1998 and 2008 from the Taiwan Longitudinal Health Insurance Database. Maternal use of acetaminophen was assessed in the first trimester, second trimester, and third trimester of pregnancy and over the period from 3 months before pregnancy to the date of last menstrual cycle., Results: Logistic regression analysis with adjustments for demographic data, gestational infections, comorbid perinatal conditions, and maternal mental health disorders indicated that exposure to acetaminophen in the second trimester (odds ratio [OR] = 1.19; 95% CI, 1.00-1.40), both the first and second trimesters (OR = 1.28; 95% CI, 1.00-1.64), or in any trimester (OR = 1.20; 95% CI, 1.01-1.42) was associated with an increased risk of ADHD in offspring. Sensitivity analysis excluding gestational infections and maternal mental health disorders confirmed this association (OR = 1.33; 95% CI, 1.04-1.69)., Conclusion: Prenatal exposure to acetaminophen was associated with an increased risk of ADHD in offspring, regardless of gestational infections and maternal mental health disorders. Additional studies are necessary to clarify the underlying mechanisms by which prenatal exposure to acetaminophen leads to neurodevelopmental risks., (© Copyright 2019 Physicians Postgraduate Press, Inc.)

Objective: To study the association between general anesthesia exposure before age 3 years and having a later ADHD diagnosis., Method: In a birth cohort, data were collected from a nationwide population database for children born between 1997 and 1999 who were exposed to general anesthesia before their third birthday. Age- and gender-matched enrollees without general anesthesia exposure were taken as the comparison. Groups were compared to identify the incidence of ADHD after age 4 and anesthesia-related predictive factors., Results: Among the 1,146 exposed children, 74 ADHD cases were identified, and 158 ADHD cases were identified in 3,438 matched controls. After adjusting for comorbid conditions and possible confounding factors, if exposure on more than one occasion or ≥3 hr, an increased likelihood of having a later ADHD diagnosis was found (HR, 1.71 and 2.43, respectively)., Conclusion: Children with multiple or ≥3 hr general anesthesia exposures before age 3 years have an increased likelihood of a later ADHD diagnosis.

Background: Postnatal exposure to anesthetics can cause neural apoptosis and degeneration in animals, but results from studies conducted on humans were discordant. Previous studies contained no information on the relationship between neurobehavioural disorders and anesthesia exposure in Asian children. We conducted a retrospective matched-cohort study in Taiwan to investigate the association of early life anesthesia exposure with risk of attention deficit/hyperactivity disorder (ADHD)., Methods: Data were obtained from the National Health Insurance Research Database of Taiwan. Children born between January 1, 2001 and December 31, 2005 were included. Each child with anesthesia exposure before 3 years of age was matched to four unexposed children. Observation was concluded on December 31, 2010. Proportional hazards regression was used to assess the association of anesthesia exposure with ADHD. Analyses were also made based on exposure number and age at the time of first exposure., Results: This matched-cohort comprised of 16 465 children, among which 3293 were exposed to general anesthesia before age 3 years. The adjusted hazard ratio of developing ADHD was 1.06 (95% CI: 0.86,1.31) for general anesthesia exposure. The adjusted hazard ratio of developing ADHD for single and multiple exposures were 1.11 (95% CI: 0.88, 1.41) and 0.96 (95% CI: 0.71,1.31), respectively. No trend of increasing risk was noted based on age at the time of first exposure., Conclusions: Exposure to general anesthesia before 3 years of age was not associated with ADHD., (© 2014 John Wiley & Sons Ltd.)