Estimation of Attributable Risk and Direct Medical and Non-Medical Costs of Major Mental Disorders Associated With Air Pollution Exposures Among Children and Adolescents in the Republic of Korea, 2011-2019.

BACKGROUND: Recent studies have reported the burden of attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and depressive disorder. Also, there is mounting evidence on the effects of environmental factors, such as ambient air pollution, on these disorders among children and adolescents. However, few studies have evaluated the burden of mental disorders attributable to air pollution exposure in children and adolescents. METHODS: We estimated the risk ratios of major mental disorders (ADHD, ASD, and depressive disorder) associated with air pollutants among children and adolescents using time-series data (2011-2019) obtained from a nationwide air pollution monitoring network and healthcare utilization claims data in the Republic of Korea. Based on the estimated risk ratios, we determined the population attributable fraction (PAF) and calculated the medical costs of major mental disorders attributable to air pollution. RESULTS: A total of 33,598 patients were diagnosed with major mental disorders during 9 years. The PAFs for all the major mental disorders were estimated at 6.9% (particulate matter < 10 µm [PM10]), 3.7% (PM2.5), and 2.2% (sulfur dioxide [SO2]). The PAF of PM10 was highest for depressive disorder (9.2%), followed by ASD (8.4%) and ADHD (5.2%). The direct medical costs of all major mental disorders attributable to PM10 and SO2 decreased during the study period. CONCLUSION: This study assessed the burden of major mental disorders attributable to air pollution exposure in children and adolescents. We found that PM10, PM2.5, and SO2 attributed 7%, 4%, and 2% respectively, to the risk of major mental disorders among children and adolescents.

Elevated level of prenatal testosterone and vitamin D3 deficiency during pregnancy, in the presence of prenatal maternal stress, and their association with the development of attention deficit hyperactivity disorder (ADHD)-like symptoms in toddlers.

INTRODUCTION: To investigate the hypothesis that the presence of prenatal maternal stress, increased level of prenatal testosterone, and low level of vitamin D3 in pregnancy is associated with the development of ADHD-like symptoms in toddlers (< 2 years old). MATERIAL AND METHODS: The study group comprised 53 pregnant women and 53 infants of these pregnancies. The population cohort of 53 pregnant women were recruited at their 35th to 37th week of pregnancy and investigated prospectively. The participants were selected through targeted selection. Maternal experience of stressful life events was assessed by stress standardised questionnaires, prenatal testosterone was determined in the mothers' saliva by using the immune enzymatic (ELISA) method, and maternal plasma D vitamin was measured using the ECLIA method, during pregnancy. When the age of the offspring was 6 months and then less than 2 years, the mothers completed the child behaviour and temperament checklist. RESULTS: A small but statistically significant association was found between the common symptom complex of ADHD and the level of testosterone and vitamin D3, in the presence of prenatal maternal stress. Multiple regression analysis showed that maternal stressful events during pregnancy significantly predicted ADHD behaviours in offspring. CONCLUSIONS: The study supported the hypothesis that prenatal maternal stress, increased level of prenatal testosterone, and low level of vitamin D3 during pregnancy increases the risk of development of ADHD-like symptoms in toddlers (< 2 years old). Also, the obtained results support the hypothesis that the influence of prenatal factors causes ADHD-like symptoms in offspring through a programming effect.

Maternal smoking cessation in the first trimester still poses an increased risk of attention-deficit/hyperactivity disorder and learning disability in offspring.

Background: Studies have found maternal smoking during pregnancy was linked to attention-deficit/hyperactivity disorder (ADHD) risk. It is unclear if maternal smoking cessation during pregnancy lowers ADHD and learning disability (LD) risk in offspring. This study aimed to explore the associations between maternal smoking cessation during pregnancy and ADHD and LD risk in offspring. Methods: Data from the National Health and Nutrition Examination Survey 1999-2004 (8,068 participants) were used. Logistic regression was used to analyze the associations between maternal smoking and smoking cessation during pregnancy and ADHD and LD risk in offspring. Results: Compared to non-smokers' offspring, maternal smoking during pregnancy increased the risk of ADHD (odds ratios [OR] = 2.07, 95% confidence interval [CI]: 1.67-2.56) and LD (OR = 1.93, 95% CI: 1.61-2.31) in offspring, even if mothers quit smoking later (ORADHD = 1.91, 95%CIADHD: 1.38-2.65, ORLD = 1.65, 95%CILD: 1.24-2.19). Further analysis of the timing of initiation of smoking cessation during pregnancy revealed that, compared to non-smokers' offspring, maternal quitting smoking in the first trimester still posed an increased risk of ADHD (OR = 1.72, 95% CI: 1.41-2.61) and LD (OR = 1.52, 95% CI: 1.06-2.17) in offspring. Maternal quitting smoking in the second or third trimester also had a significantly increased risk of ADHD (OR = 2.13, 95% CI: 1.26-3.61) and LD (OR = 1.82, 95% CI: 1.16-2.87) in offspring. Furthermore, maternal smoking but never quitting during pregnancy had the highest risk of ADHD (OR = 2.17, 95% CI: 1.69-2.79) and LD (OR = 2.10, 95% CI: 1.70-2.58) in offspring. Interestingly, a trend toward a gradual increase in the risk-adjusted OR for ADHD and LD risk was observed among the three groups: maternal quitting smoking in the first trimester, maternal quitting smoking in the second or third trimester, and maternal smoking but never quitting. Conclusion: Maternal smoking cessation in the first trimester still poses an increased risk of ADHD and LD in offspring. Furthermore, it seems that the later the mothers quit smoking during pregnancy, the higher the risk of ADHD and LD in their offspring. Therefore, early intervention of maternal smoking in preconception and prenatal care is vital for offspring neurodevelopment.

Mental health in children conceived by Assisted Reproductive Technologies (ARTs): Insights from a longitudinal study of Australian children.

BACKGROUND: The mental health of children conceived using Assisted Reproductive Technologies (ARTs) such as In-Vitro-Fertilization (IVF) is a subject of significant controversy. Existing studies suggest children conceived through ART meet physical and cognitive developmental milestones at similar rates to their spontaneously conceived peers, however, a significant number of studies have connected ART conception with mental health conditions, particularly depression and attention-deficit hyperactivity disorder (ADHD) in adolescence. This study, therefore, aimed to determine whether maternal use of ARTs to achieve pregnancy is associated with an increased risk of mental disorders in these children, and whether these effects are sex-dependent or confounded by known covariates in the ART population. METHODS: Secondary data analysis was performed using Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC) data; a nationally representative population-based cross-sequential cohort study. Multivariate logistic regression models examined the impact of ART (including IVF and other fertility drugs, from LSAC wave-1 and wave-2 conducted in 2004 and 2006, respectively) on mental health outcomes (i.e., autism, ADHD, anxiety and/or depression, from LSAC waves 8 conducted in 2018) in Australian adolescents aged 18-19 years in 2018 (n = 1735). Known sociological and obstetric covariates including maternal age, birth weight, smoking and drinking alcohol during pregnancy, maternal gestational diabetes, postnatal depression, hypertension, and socioeconomic status were considered to generate an adjusted logistic model. Variables with a p-value of <0.05 in the regression models were considered statistically significant. RESULTS: Of the 1735 mother-child dyads analysed, the maternal mean age was 35.6 years (Standard deviation = ±4.75), approximately 5% of mothers (n = 89) used ART to become pregnant, and 22% of adolescents (n = 384) had a mental disorder. Longitudinal analysis revealed no relationship between ART and children developing a mental disorder in the LSAC population. CONCLUSION: These results should reassure parents considering ART that there is no increased risk of psychological or neurodevelopmental problems in their ART conceived offspring.

Association of prenatal and postnatal exposure to air pollution with clinically diagnosed attention deficit hyperactivity disorder: a systematic review.

Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder in children, originates from a multifaceted interplay of genetic, neurological, and environmental factors. Recent studies have increasingly concentrated on environmental determinants, notably air pollution, and their impact on the risk of developing ADHD. Additionally, previous research has often conflated clinically diagnosed ADHD cases with instances of mere ADHD-like symptoms, a methodology that can introduce bias and obscure the true relationship between environmental factors and ADHD. To address this oversight, our systematic review meticulously investigates the relationship between both prenatal and postnatal exposures to particular air pollutants and strictly clinically diagnosed ADHD. Our comprehensive review encompassed 801 studies from PubMed, Cochrane Library, Web of Science, and Embase databases, out of which eight met our rigorous inclusion criteria. The Newcastle-Ottawa Scale (NOS) was utilized to gauge quality and bias. Our review found substantiated the connection between prenatal exposure to PM2.5 and NOx and a heightened risk of ADHD, while exposure to PM10 during the prenatal stage was not associated with ADHD. These findings hint at varied health impacts from different particulate matters and the prospect of gender-specific susceptibilities to such exposures. We also identified an association between postnatal exposure to PM2.5, PM10, and NO2 and an increased ADHD risk, underlining the potential neurodevelopmental harms from early exposure to these pollutants. These relationships, seemingly intricate and potentially dose-dependent, underscore the need for more detailed scrutiny. The unique value of our review is in its detailed exploration of the association between specific air pollution exposures and clinically diagnosed ADHD. Our findings offer much-needed clarity in this complex domain and emphasize the importance of future research to standardize exposure and outcome metrics, probe potential mechanisms, and reduce bias and heterogeneity.

[Symptoms and Pathogenesis of ADHD].

Diagnosis of ADHD in adulthood is increasing rapidly in Japan. The ADHD symptoms occur on a continuum with those of normal development and are likely to fluctuate with the growth process and environment at the time of diagnosis. Especially in adult cases, comorbid psychiatric disorders tend to influence the characteristics of ADHD. ADHD has diverse clinical manifestations and a heterogeneous biological background. In addition to the RDoC approach to elucidate the pathogenesis and etiology of the disorder, we expect that attempts will be made to classify the disorder into relatively homogeneous biological subcategories.

Early environmental predictors for attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and their co-occurrence: The prospective ABIS-Study.

ADHD and ASD are highly heritable and show a high co-occurrence and persistence into adulthood. This study aimed to identify pre and perinatal risk factors, and early psychosocial exposures related to later diagnosis of ADHD, ASD, and their co-occurrence. 16,365 children born 1997-1999 and their families, involved in the prospective population-based ABIS study (All Babies in Southeast Sweden), were included in this sub-study. Pre and perinatal factors and early environmental psychosocial exposures were collected from parental-questionnaires at birth and 1-year follow-up. Diagnoses from birth up to 23 years of age were obtained from the Swedish National Diagnosis Register in 2020. The cumulative incidence of ADHD, ASD, and their co-occurrence in the ABIS-cohort Study were 4.6%, 1.7%, and 1.1%, respectively. Being male was associated with an increased risk for ADHD, ASD, and their co-occurrence (aOR 1.30, 1.56, and 1.91, respectively), while higher household income reduced it (aOR 0.82, 0.73, and 0.64). Serious life events during pregnancy (aOR 1.40) and maternal smoking (aOR 1.51) increased the risk of ADHD, while older maternal age (aOR 0.96), higher parental education (aOR 0.72 maternal and aOR 0.74 paternal) and longer exclusive breastfeeding (aOR 0.72) reduced it. Non-Swedish paternal nationality (aOR 0.40) and higher maternal education (aOR 0.74) were associated with a lower risk of ASD, while a family history of autoimmune diseases increased the risk of the co-occurrence of both disorders (aOR 1.62). Obtained results suggest that the etiology of ADHD, ASD, and their co-occurrence is independently associated with environmental psychosocial predictors. The co-occurrence seems to overlap the etiology of ADHD, in which psychosocial determinants have a larger role, however, it is also independently influenced by a family history of autoimmune diseases.

Distinct attentional and executive profiles in neurofibromatosis type 1: Is there difference with primary attention deficit-hyperactivity disorder?

PURPOSE: Attentional and executive dysfunctions are the most frequent cognitive disorders in neurofibromatosis type 1 (NF1), with a high prevalence of attention deficit-hyperactivity disorder (ADHD). We (i) compared attentional profiles between NF1 children with and without ADHD and children with primary ADHD criteria and (ii) investigated the possible relationship between attentional disorders and "unidentified bright objects" (UBOs) in NF1. METHODS: This retrospective study included 47 NF1 children, 25 with ADHD criteria (NF1+adhd group), matched for age, sex, and cognitive level with 47 children with primary ADHD (ADHD group). We collected computer task (sustained-attention, visuomotor-decision, inhibition, and cognitive-flexibility tasks) scores normalized for age and sex, and brain magnetic resonance imaging data. RESULTS: (i) Working memory was impaired in all groups. (ii) Omissions (p < 0.002) and response-time variability (p < 0.05) in sustained-attention and visuomotor-decision tasks and errors (p < 0.02) in the cognitive-flexibility task were lower for the NFI+adhd and ADHD groups than for the NF1-no-adhd group. (iii) The NF1+adhd group had slower response times (p ≤ 0.02) for inhibition and visuomotor-decision tasks than the other groups. (iv) We found no relevant association between cognitive performance and UBOs. CONCLUSIONS: NF1 children with ADHD have an attentional and executive functions deficit profile similar to that of children with primary ADHD, but with a slower response-time, increasing learning difficulties. The atypical connectivity of fronto-striatal pathways, poorer dopamine homeostasis, and increased GABA inhibition observed in NF1 renders vulnerable the development of the widely distributed neural networks that support attentional, working-memory, and executive functions.

Attention Deficit/Hyperactivity Disorder in Individuals with Non-Syndromic Craniosynostosis: A Systematic Review and Meta-Analysis.

It is not yet understood whether, and to what extent, craniosynostosis impacts the development of Attention Deficit/Hyperactivity Disorder (ADHD). This PRISMA compliant and PROSPERO pre-registered (ID: CRD42023458640) systematic review and meta-analysis examines the association of single-suture, non-syndromic craniosynostosis with ADHD and inattention/hyperactivity symptoms. Data from 17 independent studies (Nparticipants = 2,389; Mage = 7.3 years) were analyzed, taking into consideration suture location, surgical status, age, and measures administered, where feasible. Few differences were found between cases and controls, but some studies reported high symptom levels. Additional research is required utilizing larger sample sizes and more comprehensive assessment of ADHD.

Intrapartum exposure to synthetic oxytocin, maternal BMI, and neurodevelopmental outcomes in children within the ECHO consortium.

BACKGROUND: Synthetic oxytocin (sOT) is frequently administered during parturition. Studies have raised concerns that fetal exposure to sOT may be associated with altered brain development and risk of neurodevelopmental disorders. In a large and diverse sample of children with data about intrapartum sOT exposure and subsequent diagnoses of two prevalent neurodevelopmental disorders, i.e., attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), we tested the following hypotheses: (1) Intrapartum sOT exposure is associated with increased odds of child ADHD or ASD; (2) associations differ across sex; (3) associations between intrapartum sOT exposure and ADHD or ASD are accentuated in offspring of mothers with pre-pregnancy obesity. METHODS: The study sample comprised 12,503 participants from 44 cohort sites included in the Environmental Influences on Child Health Outcomes (ECHO) consortium. Mixed-effects logistic regression analyses were used to estimate the association between intrapartum sOT exposure and offspring ADHD or ASD (in separate models). Maternal obesity (pre-pregnancy BMI ≥ 30 kg/m2) and child sex were evaluated for effect modification. RESULTS: Intrapartum sOT exposure was present in 48% of participants. sOT exposure was not associated with increased odds of ASD (adjusted odds ratio [aOR] 0.86; 95% confidence interval [CI], 0.71-1.03) or ADHD (aOR 0.89; 95% CI, 0.76-1.04). Associations did not differ by child sex. Among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of offspring ADHD (aOR 0.72; 95% CI, 0.55-0.96). No association was found among mothers without obesity (aOR 0.97; 95% CI, 0.80-1.18). CONCLUSIONS: In a large, diverse sample, we found no evidence of an association between intrapartum exposure to sOT and odds of ADHD or ASD in either male or female offspring. Contrary to our hypothesis, among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of child ADHD diagnosis.

Atopic Dermatitis: Disease Background and Risk Factors.

Multiple risk factors have been associated with the development of atopic dermatitis (AD). Recent advances in understanding the role of genetics in this disease have been made, with discovery of the filaggrin (FLG) gene as the most notable so far. In addition to FLG gene mutations as a risk factor for AD, a positive family history of atopic or allergic disease in either parent has been shown to confer a greater risk of developing AD. Atopic dermatitis usually presents early in life and is thought to represent the initial step in the "atopic march," which is characterized by the development of other atopic diseases later in life such as asthma, allergic rhinitis, and/or rhinoconjunctivitis, food allergies, and hay fever. Other comorbid diseases that have been associated with AD include increase risk of viral and bacterial skin infections, neuropsychiatric diseases such as attention-deficit hyperactivity disorders (ADHD), and autistic spectrum disorder (ASD). Patients with AD have also been found to have worse sleep quality overall compared to patients without AD. In this chapter, we will discuss the risk factors associated with development of atopic dermatitis as well as the most commonly reported comorbidities in patients with this disease.

[Recent research on the role of oxidative stress in the pathogenesis of attention deficit hyperactivity disorder]. / æ°§åŒ–åº”æ¿€åœ¨æ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢å‘ç— æœºåˆ¶ä¸­çš„ç ”ç©¶è¿›å±•.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents, and its etiology and pathogenesis are still unclear. Brain is the organ with the largest oxygen consumption in human body and is easily affected by oxidative imbalance. Oxidative stress has become the key research direction for the pathogenesis of ADHD, but there is still a lack of relevant studies in China. Based on the latest research findings in China and overseas, this article reviews the clinical and experimental studies on oxidative stress in ADHD and explores the association of oxidative stress with neurotransmitter imbalance, neuroinflammation, and cell apoptosis in the pathogenesis of ADHD, so as to provide new research ideas for exploring the pathogenesis of ADHD.

Prenatal maternal PTSD as a risk factor for offspring ADHD: A register-based Swedish cohort study of 553 766 children and their mothers.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is highly heritable, though environmental factors also play a role. Prenatal maternal stress is suggested to be one such factor, including exposure to highly distressing events that could lead to post-traumatic stress disorder (PTSD). The aim of this study is to investigate whether prenatal maternal PTSD is associated with offspring ADHD. METHOD: A register-based retrospective cohort study linking 553 766 children born in Sweden during 2006-2010 with their biological parents. Exposure: Prenatal PTSD. Outcome: Offspring ADHD. Logistic regression determined odds ratios (ORs) with 95% confidence intervals (CIs) for ADHD in the offspring. Adjustments were made for potential covariates, including single parenthood and possible indicators of heredity measured as parental ADHD and maternal mental disorders other than PTSD. Subpopulations, excluding children with indicators of heredity, were investigated separately. RESULTS: In the crude results, including all children, prenatal PTSD was associated with offspring ADHD (OR: 1.79, 95% CI: 1.37-2.34). In children with indicators of heredity, the likelihood was partly explained by it. Among children without indicators of heredity, PTSD was associated with offspring ADHD (OR: 2.32, 95% CI: 1.30-4.14), adjusted for confounders. CONCLUSIONS: Prenatal maternal PTSD is associated with offspring ADHD regardless of indicators of heredity, such as parental ADHD or maternal mental disorder other than PTSD. The association is partly explained by heredity and socioeconomic factors. If replicated in other populations, preferably using a sibling design, maternal PTSD could be identified as a risk factor for ADHD.

Combined and sequential exposure to prenatal second hand smoke and postnatal maternal distress is associated with cingulo-opercular global efficiency and attention problems in school-age children.

BACKGROUND: Prenatal exposure to secondhand (environmental) tobacco smoke (SHS) is associated with adverse neurodevelopmental outcomes, including altered functional activation of cognitive control brain circuitry and increased attention problems in children. Exposure to SHS is more common among Black youth who are also disproportionately exposed to socioeconomic disadvantage and concomitant maternal distress. We examine the combined effects of exposure to prenatal SHS and postnatal maternal distress on the global efficiency (GE) of the brain's cingulo-opercular (CO) and fronto-parietal control (FP) networks in childhood, as well as associated attention problems. METHODS: Thirty-two children of non-smoking mothers followed in a prospective longitudinal birth cohort at the Columbia Center for Children's Environmental Health (CCCEH) completed magnetic resonance imaging (MRI) at ages 7-9 years old. GE scores were extracted from general connectivity data collected while children completed the Simon Spatial Incompatibility functional magnetic resonance imaging (fMRI) task. Prenatal SHS was measured using maternal urinary cotinine from the third trimester; postnatal maternal distress was assessed at child age 5 using the Psychiatric Epidemiology Research Interview (PERI-D). The Child Behavior Checklist (CBCL) measured Attention and Attention Deficit Hyperactivity Disorder (ADHD) problems at ages 7-9. Linear regressions examined the interaction between prenatal SHS and postnatal maternal distress on the GE of the CO or FP networks, as well as associations between exposure-related network alterations and attention problems. All models controlled for age, sex, maternal education at prenatal visit, race/ethnicity, global brain correlation, and mean head motion. RESULTS: The prenatal SHS by postnatal maternal distress interaction term associated with the GE of the CO network (ß = 0.673, Bu = 0.042, t(22) = 2.427, p = .024, D = 1.42, 95% CI [0.006, 0.079], but not the FP network (ß = 0.138, Bu = 0.006, t(22) = 0.434, p = .668, 95% CI [-0.022, 0.033]). Higher GE of the CO network was associated with more attention problems (ß = 0.472, Bu = 43.076, t(23) = 2.780, p = .011, D = 1.74, n = 31, 95% CI [11.024, 75.128], n = 31) and ADHD risk (ß = 0.436, Bu = 21.961, t(29) = 2.567, p = .018, D = 1.81, 95% CI [4.219, 39.703], n = 30). CONCLUSIONS: These preliminary findings suggest that sequential prenatal SHS exposure and postnatal maternal distress could alter the efficiency of the CO network and increase risk for downstream attention problems and ADHD. These findings are consistent with prior studies showing that prenatal SHS exposure is associated with altered function of brain regions that support cognitive control and with ADHD problems. Our model also identifies postnatal maternal distress as a significant moderator of this association. These data highlight the combined neurotoxic effects of exposure to prenatal SHS and postnatal maternal distress. Critically, such exposures are disproportionately distributed among youth from minoritized groups, pointing to potential pathways to known mental health disparities.

Maternal smoking during pregnancy and cortical structure in children with attention-deficit/hyperactivity disorder.

Maternal smoking during pregnancy (MSDP) is considered a risk factor for ADHD. While the mechanisms underlying this association are not well understood, MSDP may impact the developing brain in ways that lead to ADHD. Here, we investigated the effect of prenatal smoking exposure on cortical brain structures in children with ADHD using two methods of assessing prenatal exposure: maternal recall and epigenetic typing. Exposure groups were defined according to: (1) maternal recall (+MSDP: n = 24; -MSDP: n = 85) and (2) epigenetic markers (EM) (+EM: n = 14 -EM: n = 21). CIVET-1.1.12 and RMINC were used to acquire cortical brain measurements and perform statistical analyses, respectively. The vertex with highest significance was tested for association with Continuous Performance Test (CPT) dimensions. While no differences of brain structures were identified between +MSDP and -MSDP, +EM children (n = 10) had significantly smaller surface area in the right orbitofrontal cortex (ROFc), middle temporal cortex (RTc) and parahippocampal gyrus (RPHg) (15% FDR) compared to -EM children (n = 20). Cortical surface area in the RPHg significantly correlated with CPT commission errors T-scores. This study suggests that molecular markers may better define exposure to environmental risks, as compared to human recall.

Behavioural disorders after prenatal exposure to anaesthesia for maternal surgery.

BACKGROUND: The association between prenatal exposure to general anaesthesia for maternal surgery during pregnancy and subsequent risk of disruptive or internalising behavioural disorder diagnosis in the child has not been well-defined. METHODS: A nationwide sample of pregnant women linked to their liveborn infants was evaluated using the Medicaid Analytic eXtract (MAX, 1999-2013). Multivariate matching was used to match each child prenatally exposed to general anaesthesia owing to maternal appendectomy or cholecystectomy during pregnancy with five unexposed children. The primary outcome was diagnosis of a disruptive or internalising behavioural disorder in children. Secondary outcomes included diagnoses for a range of other neuropsychiatric disorders. RESULTS: We matched 34,271 prenatally exposed children with 171,355 unexposed children in the database. Prenatally exposed children were more likely than unexposed children to receive a diagnosis of a disruptive or internalising behavioural disorder (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.23-1.40). For secondary outcomes, increased hazards of disruptive (HR, 1.32; 95% CI, 1.24-1.41) and internalising (HR, 1.36; 95% CI, 1.20-1.53) behavioural disorders were identified, and also increased hazards of attention-deficit/hyperactivity disorder (HR, 1.32; 95% CI, 1.22-1.43), behavioural disorders (HR, 1.28; 95% CI, 1.14-1.42), developmental speech or language disorders (HR, 1.16; 95% CI, 1.05-1.28), and autism (HR, 1.31; 95% CI, 1.05-1.64). CONCLUSIONS: Prenatal exposure to general anaesthesia is associated with a 31% increased risk for a subsequent diagnosis of a disruptive or internalising behavioural disorder in children. Caution is advised when making any clinical decisions regarding care of pregnant women, as avoidance of necessary surgery during pregnancy can have detrimental effects on mothers and their children.

The causal impact of maternal smoking around birth on offspring ADHD: A two-sample Mendelian randomization study.

BACKGROUND: The previous literature highlights a relationship between maternal smoking around birth (MSAB) and offspring attention-deficit/hyperactivity disorder (ADHD). These studies have focused on the causal effects of MSAB on offspring ADHD. METHOD: A Mendelian randomization analysis was conducted using summary statistics. Data on MSAB were obtained from a recent study including 391,992 participants. ADHD data were obtained from six sources for 246,888 participants. The present study used five methods to examine the causal impact from outcomes on exposures. The inverse variance weighted (IVW) was the main method of analysis, while the other four methods were supplementary methods. RESULT: The IVW revealed that MSAB was a risk factor for offspring ADHD (OR: 2.54; 95 % confidence interval [CI]: 1.61-4.00, p = 6.04 × 10-5). Concerning ADHD in both sexes, MSAB was associated with females (OR = 3.96, 95 % CI: 1.99-7.90, p = 8.98 × 10-5) and males (OR = 3.74, 95 % CI: 1.74-5.72, p = 1.48 × 10-4). In different diagnosis periods for ADHD, MSAB increased the risk of childhood (OR = 3.63, 95 % CI: 2.25-5.87, p = 1.31 × 10-7), late-diagnosed (OR = 2.99, 95 % CI: 1.74-5.14, p = 7.33 × 10-5), and persistent (OR = 4.77, 95 % CI: 1.88-12.14, p = 1.03 × 10-3) ADHD. The final analysis did not reveal heterogeneity. CONCLUSIONS: A causal impact of MSAB on offspring ADHD was observed. These findings highlight the need for careful consideration of prenatal exposure (MSAB) during the assessment of offspring ADHD. Additionally, it can provide targeted guidance for prenatal interventions. Future studies should analyze the effects of different doses of maternal smoking on ADHD.

Prenatal cannabis use and the risk of attention deficit hyperactivity disorder and autism spectrum disorder in offspring: A systematic review and meta-analysis.

BACKGROUND: It is plausible that exposure to cannabis in-utero could be associated with an increased risk of neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD) symptoms and autism spectrum disorder (ASD) during childhood and adolescence; however, mixed results have been reported. This study investigated whether there is an association between prenatal cannabis use and ADHD symptoms and ASD in offspring using a systematic review and meta-analysis methodology. METHODS: A systematic literature search was conducted in PubMed/Medline, Scopus, EMBASE, Web of Science, Psych-Info, and Google Scholar to identify relevant studies. The study protocol has been preregistered in the Prospective Register of Systematic Reviews (PROSPERO) (CRD42022345001), and the Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the methodological quality of included studies. An inverse variance weighted random effect meta-analysis was conducted to pool the overall effect estimates from the included studies. RESULTS: Fourteen primary studies, consisting of ten on ADHD and four on ASD, with a total of 203,783 participants, were included in this study. Our meta-analysis underscores an increased risk of ADHD symptoms and/or disorder [ß = 0.39: 95 % CI (0.20-0.58), I2 = 66.85 %, P = 0.001)] and ASD [RR = 1.30: 95 % CI (1.03-1.64), I2 = 45.5 %, P = 0.14] associated with in-utero cannabis exposure in offspring compared to their non-exposed counterparts. Additionally, our stratified analysis highlighted an elevated risk of ADHD symptoms [ß = 0.54: 95 % CI (0.26-0.82)] and a marginally significant increase in the risk of diagnostic ADHD among exposed offspring compared to non-exposed counterparts [RR = 1.13, 95 % CI (1.01, 1.26)]. CONCLUSION: This study indicated that maternal prenatal cannabis exposure is associated with a higher risk of ADHD symptoms and ASD in offspring.