Increased behavioural problems associated with corticosteroid use in children with nephrotic syndrome: a Southeast Asian perspective.

Introduction: The study was performed to determine the psychological problems in children with idiopathic nephrotic syndrome (INS) while they were on steroid therapy, as compared to healthy children. Methods: This prospective cohort study was conducted in a paediatric clinic of a tertiary hospital. Parents of the participants in the INS group and control group (comprising children without chronic illness) completed questionnaires using the Child Behavioural Checklist (CBCL). The CBCL measures a range of age-specific emotional and psychological problems, including internalising and externalising domains. Analyses of the CBCL scores between groups were done using Mann-Whitney U test. Results: A total of 140 children were recruited with an equal number in the INS and control groups. There was a significant difference in the mean total CBCL scores between the INS group and the control group, specifically in the withdrawal, somatic, anxious and aggressiveness subdomains. Similar findings were demonstrated in correlation between total psychological problems and corticosteroid dosage. In the INS group, steroid dose and cushingoid features were found to have a significant positive association with internalising psychological problems. Conclusion: Children with INS on corticosteroid treatment showed an increase in internalising and externalising scores, as compared to healthy children.

The effects of the exposure to neurotoxic elements on Italian schoolchildren behavior.

Neurodevelopmental disorders are constantly increasing on a global scale. Some elements like heavy metals are known to be neurotoxic. In this cross-sectional study we assessed the neurobehavioral effect of the exposure to trace elements including lead, mercury, cadmium, manganese, arsenic and selenium and their interactions among 299 schoolchildren residing in the heavily polluted Taranto area in Italy. Whole blood, urine and hair were collected for metal analyses, while the Child Behavior Checklist and the Social Responsiveness Scale, administered to the main teacher and the mothers were considered to identify behavioral problems in children. Blood lead mainly influenced social problems, aggressive behavior, externalizing and total problems. Urinary arsenic showed an impact on anxiety and depression, somatic problems, attention problems and rule breaking behavior. A significant interaction between lead and arsenic was observed, with a synergistic effect of the two metals increasing the risk of attention problems, aggressive behavior, externalizing problems and total problems. Overall, we were able to test that higher blood lead, urinary arsenic concentrations and their interaction increase the risk of neurobehavioral problems. This is in line with the U.S. Environmental Protection Agency's priority list of hazardous substances where arsenic and lead are ranked as first and second respectively.

Nutritional Intervention with Dried Bonito Broth for the Amelioration of Aggressive Behaviors in Children with Prenatal Exposure to Dioxins in Vietnam: A Pilot Study.

Dioxins have been suggested to induce inflammation in the intestine and brain and to induce neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), partly due to deficits in parvalbumin-positive neurons in the brain that are sensitive to inflammatory stress. Previously, we reported ADHD traits with increased aggressiveness in children with prenatal exposure to dioxins in Vietnam, whereas dried bonito broth (DBB) has been reported to suppress inflammation and inhibit aggressive behavior in animal and human studies. In the present study, we investigated the association between dioxin exposure and the prevalence of children with highly aggressive behaviors (Study 1), as well as the effects of DBB on the prevalence of children with highly aggressive behaviors (Study 2). METHODS: In Study 1, we investigated the effects of dioxin exposure on the prevalence of children with high aggression scores, which were assessed using the Children's Scale of Hostility and Aggression: Reactive/Proactive (C-SHARP) in dioxin-contaminated areas. The data were analyzed using a logistic regression model after adjusting for confounding factors. In Study 2, we performed nutritional intervention by administering DBB for 60 days to ameliorate the aggressiveness of children with high scores on the C-SHARP aggression scale. The effects of DBB were assessed by comparing the prevalence of children with high C-SHARP scores between the pre- and post-intervention examinations. RESULTS: In Study 1, only the prevalence of children with high covert aggression was significantly increased with an increase in dioxin exposure. In Study 2, in the full ingestion (>80% of goal ingestion volume) group, the prevalence of children with high covert aggression associated with dioxin exposure was significantly lower in the post-ingestion examination compared with in the pre-ingestion examination. However, in other ingestion (<20% and 20-79%) groups and a reference (no intervention) group, no difference in the prevalence of children with high covert aggression was found between the examinations before and after the same experimental period. CONCLUSIONS: The findings suggest that DBB ingestion may ameliorate children's aggressive behavior, which is associated with perinatal dioxin exposure.

Prenatal Exposure to General Anesthesia and Childhood Behavioral Deficit.

BACKGROUND: Exposure to surgery and anesthesia in early childhood has been found to be associated with an increased risk of behavioral deficits. While the US Food and Drug Administration (FDA) has warned against prenatal exposure to anesthetic drugs, little clinical evidence exists to support this recommendation. This study evaluates the association between prenatal exposure to general anesthesia due to maternal procedures during pregnancy and neuropsychological and behavioral outcome scores at age 10. METHODS: This is an observational cohort study of children born in Perth, Western Australia, with 2 generations of participants contributing data to the Raine Study. In the Raine Study, the first generation (Gen1) are mothers enrolled during pregnancy, and the second generation (Gen2) are the children born to these mothers from 1989 to 1992 with neuropsychological and behavioral tests at age 10 (n=2024). In the primary analysis, 6 neuropsychological and behavioral tests were evaluated at age 10: Raven's Colored Progressive Matrices (CPM), McCarron Assessment of Neuromuscular Development (MAND), Peabody Picture Vocabulary Test (PPVT), Symbol Digit Modality Test (SDMT) with written and oral scores, Clinical Evaluation of Language Fundamentals (CELF) with Expressive, Receptive, and Total language scores, and Child Behavior Checklist (CBCL) with Internalizing, Externalizing, and Total behavior scores. Outcome scores of children prenatally exposed to general anesthesia were compared to children without prenatal exposure using multivariable linear regression models adjusting for demographic and clinical covariates (sex, race, income, and maternal education, alcohol or tobacco use, and clinical diagnoses: diabetes, epilepsy, hypertension, psychiatric disorders, or thyroid dysfunction). Bonferroni adjustment was used for the 6 independent tests in the primary analysis, so a corrected P value <.0083 (P = .05 divided by 6 tests, or a 99.17% confidence interval [CI]) was required for statistical significance. RESULTS: Among 2024 children with available outcome scores, 22 (1.1%) were prenatally exposed to general anesthesia. Prenatally exposed children had higher CBCL Externalizing behavioral scores (score difference of 6.1 [99.17% CI, 0.2-12.0]; P = .006) than unexposed children. Of 6 tests including 11 scores and subscores, only CBCL Externalizing behavioral scores remained significant after multiple comparisons adjustment with no significant differences found in any other score. CONCLUSIONS: Prenatal exposure to general anesthetics is associated with increased externalizing behavioral problems in childhood. However, given the limitations of this study and that avoiding necessary surgery during pregnancy can have significant detrimental effects on the mother and the child, further studies are needed before changes to clinical practice are made.

Association Between Behavioral and Learning Outcomes and Single Exposures to Procedures Requiring General Anesthesia Before Age 3: Secondary Analysis of Data From Olmsted County, MN.

BACKGROUND: Two prior population-based (children born in Olmsted County, MN), retrospective cohort studies both found that multiple exposures to anesthesia before age 3 were associated with a significant increase in the frequency of attention-deficit hyperactivity disorder (ADHD) and learning disabilities (LD) later in life. The primary purpose of this secondary analysis of these data was to test the hypothesis that a single exposure to anesthesia before age 3 was associated with an increased risk of ADHD. We also examined the association of single exposures with LD and the need for individualized educational plans as secondary outcomes. METHODS: This analysis includes 5339 children who were unexposed to general anesthesia before age 3 (4876 born from 1976 to 1982 and 463 born from 1996 to 2000), and 1054 children who had a single exposure to anesthesia before age 3 (481 born from 1976 to 1982 and 573 born from 1996 to 2000). The primary outcome of interest was ADHD. Secondary outcomes included LD (reading, mathematics, and written language) and the need for individualized educational programs (speech/language and emotion/behavior). To compare the incidence of each outcome between those who were unexposed and singly exposed to anesthesia before the age of 3 years, an inverse probability of treatment weighted proportional hazards model was used. RESULTS: For children not exposed to anesthesia, the estimated cumulative frequency (95% confidence interval [CI]) of ADHD at age 18 was 7.3% (95% CI, 6.5-8.1) and 13.0% (95% CI, 10.1-16.8) for the 1976-1982 and 1996-2000 cohorts, respectively. For children exposed to a single anesthetic before age 3, the cumulative frequency of ADHD was 8.1% (95% CI, 5.3-12.4) and 17.6% (95% CI, 14.0-21.9) for the 1976-1982 and 1996-2000 cohorts, respectively. In weighted analyses, single exposures were not significantly associated with an increased frequency of ADHD (hazard ratio [HR], 1.21; 95% CI, 0.91-1.60; P = .184). Single exposures were also not associated with an increased frequency of any LD (HR, 0.98; 95% CI, 0.78-1.23), or the need for individualized education plans. CONCLUSIONS: This analysis did not find evidence that single exposures to procedures requiring general anesthesia, before age 3, are associated with an increased risk of developing ADHD, LD, or the need for individualized educational plans in later life.

Behavioral Problems at Age 11 Years After Prenatal and Postnatal Exposure to Acetaminophen: Parent-Reported and Self-Reported Outcomes.

Several studies have reported associations between prenatal acetaminophen exposure and behavioral outcomes in young children. We aimed to evaluate the associations of prenatal and postnatal exposures to acetaminophen with behavioral problems in children at age 11 years, using behavioral measures reported by parents and children. We studied 40,934 mother-child pairs from the Danish National Birth Cohort enrolled during 1996-2002. Parent-reported and child-reported Strengths and Difficulties Questionnaire (SDQ) responses were collected during the 11-year follow-up. We estimated risk ratios for behavioral problems including total difficulties as well as internalizing or externalizing behaviors following prenatal (during pregnancy) or postnatal (within the first 18 months after birth) acetaminophen exposure. Parent-reported and child-reported SDQ scores were moderately correlated; higher for externalizing (r = 0.59) than internalizing (r = 0.49) behaviors. Prenatal acetaminophen exposure was associated with 10%-40% higher risks for total difficulties and internalizing and externalizing problems based on parent- or child-reported SDQ, with the association being stronger for greater cumulative weeks of acetaminophen use. Postnatal exposure was associated with 16%-19% higher risks for parent-reported internalizing behaviors, but the associations were weak or null for child-reported scores except for prosocial behavior. Our study corroborates published associations between prenatal exposures to acetaminophen and behavioral problems and extends the literature to early adolescence.

Prospectively assessed neurodevelopmental outcomes in studies of anaesthetic neurotoxicity in children: a systematic review and meta-analysis.

BACKGROUND: Whether exposure to a single general anaesthetic (GA) in early childhood causes long-term neurodevelopmental problems remains unclear. METHODS: PubMed/MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane Library were searched from inception to October 2019. Studies evaluating neurodevelopmental outcomes and prospectively enrolling children exposed to a single GA procedure compared with unexposed children were identified. Outcomes common to at least three studies were evaluated using random-effects meta-analyses. RESULTS: Full-scale intelligence quotient (FSIQ); the parentally reported Child Behavior Checklist (CBCL) total, externalising, and internalising problems scores; and Behavior Rating Inventory of Executive Function (BRIEF) scores were assessed. Of 1644 children identified, 841 who had a single exposure to GA were evaluated. The CBCL problem scores were significantly higher (i.e. worse) in exposed children: mean score difference (CBCL total: 2.3 [95% confidence interval {CI}: 1.0-3.7], P=0.001; CBCL externalising: 1.9 [95% CI: 0.7-3.1], P=0.003; and CBCL internalising problems: 2.2 [95% CI: 0.9-3.5], P=0.001). Differences in BRIEF were not significant after multiple comparison adjustment. Full-scale intelligence quotient was not affected by GA exposure. Secondary analyses evaluating the risk of these scores exceeding predetermined clinical thresholds found that GA exposure was associated with increased risk of CBCL internalising behavioural deficit (risk ratio [RR]: 1.47; 95% CI: 1.08-2.02; P=0.016) and impaired BRIEF executive function (RR: 1.68; 95% CI: 1.23-2.30; P=0.001). CONCLUSIONS: Combining results of studies utilising prospectively collected outcomes showed that a single GA exposure was associated with statistically significant increases in parent reports of behavioural problems with no difference in general intelligence.

Autonomic functioning among cocaine-exposed kindergarten-aged children: Examination of child sex and caregiving environmental risk as potential moderators.

The purpose of this study was to examine the hypothesis that child sex moderates the association between prenatal cocaine exposure (PCE) and autonomic functioning as well as to examine the role that caregiving environmental risk played in sex differences in autonomic functioning among exposed children. Measures of the parasympathetic nervous system (indexed by respiratory sinus arrhythmia [RSA]) and the sympathetic nervous system (indexed by skin conductance level [SCL]) were obtained from 146 (75 cocaine-exposed, 38 male; and 71 nonexposed, 36 male) children during baseline and a task designed to elicit negative affect (NA). We also examined the role of caregiving environmental risk as a moderator of the association between PCE and autonomic functioning separately for boys and girls. PCE boys had a significantly higher baseline RSA and lower baseline SCL than PCE girls or nonexposed children. Environmental risk also moderated the association between PCE and baseline RSA for boys, but not girls, such that boys with PCE and high environmental risk had the highest baseline RSA. These findings indicate that exposed boys had significantly lower levels of sympathetic activation while at rest. However, for autonomic reactivity, the exposed girls had a larger change in both RSA and SCL relative to nonexposed girls while exposed boys had significantly smaller increases in SCL during environmental challenge. Finally, girls with both PCE and high environmental risk had the highest levels of parasympathetic reactivity during challenge. These results underscore the importance of examining sex differences and considering comorbid environmental risk factors when examining developmental outcomes in cocaine-exposed children and highlight the complexity involved with understanding individual differences in cocaine-exposed populations.

Associations between paracetamol (acetaminophen) intake between 18 and 32 weeks gestation and neurocognitive outcomes in the child: A longitudinal cohort study.

BACKGROUND: The majority of epidemiological studies concerning possible adverse effects of paracetamol (acetaminophen) in pregnancy have been focussed on childhood asthma. Initial results of a robust association have been confirmed in several studies. Recently, a few cohort studies have looked at particular neurocognitive outcomes, and several have implicated hyperactivity. OBJECTIVES: In order to confirm these findings, further information and results are required. Here, we assess whether paracetamol intake between 18 and 32 weeks gestation is associated with childhood behavioural and cognitive outcomes using a large population. METHODS: Data collected by the Avon Longitudinal Study of Parents and Children (ALSPAC) at 32 weeks gestation and referring to the period from 18 to 32 weeks, identified 43.9% of women having taken paracetamol. We used an exposome analysis first to determine the background factors associated with pregnant women taking the drug, and then allowed for those factors to assess associations with child outcomes (measured using regression analyses). RESULTS: We identified 15 variables independently associated with taking paracetamol in this time period, which were used as potential confounders. Of the 135 neurocognitive variables considered, adjusting for the likelihood of false discovery, we identified 56 outcomes for adjusted analyses. Adjustment identified 12 showing independent associations with paracetamol use at P < .05, four of which were at P < .0001 (all related to child behaviours reported by the mother at 42 and 47 months; eg conduct problems: adjusted mean score + 0.22 (95% confidence interval 0.10, 0.33)). There were few associations with behavioural or neurocognitive outcomes after age 7-8 years, whether reported by the mother or the teacher. CONCLUSIONS: If paracetamol use in mid-to-late pregnancy has an adverse effect on child neurocognitive outcome, it appears to mainly relate to the pre-school period. It is important that these results be tested using other datasets or methodologies before assuming that they are causal.

Associations of antenatal glucocorticoid exposure with mental health in children.

BACKGROUND: Synthetic glucocorticoids, to enhance fetal maturation, are a standard treatment when preterm birth before 34 gestational weeks is imminent. While morbidity- and mortality-related benefits may outweigh potential neurodevelopmental harms in children born preterm (<37 gestational weeks), this may not hold true when pregnancy continues to term (⩾37 gestational weeks). We studied the association of antenatal betamethasone exposure on child mental health in preterm and term children. METHODS: We included 4708 women and their children, born 2006-2010, from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction Study with information on both antenatal betamethasone treatment and child mental and behavioral disorders from the Finnish Hospital Discharge Register from the child's birth to 31 December 2016. Additional follow-up data on mother-reported psychiatric problems and developmental milestones were available for 2640 children at 3.5 (s.d. = 0.07) years-of-age. RESULTS: Of the children, 187 were born preterm (61 betamethasone-exposed) and 4521 at term (56 betamethasone-exposed). The prevalence of any mental and behavioral, psychological development, emotional and behavioral, and comorbid disorders was higher in the betamethasone-exposed, compared to non-exposed children [odds ratio 2.76 (95% confidence interval 1.76-4.32), 3.61 (2.19-5.95), 3.29 (1.86-5.82), and 6.04 (3.25-11.27), respectively]. Levels of psychiatric problems and prevalence of failure to meet the age-appropriate development in personal-social skills were also higher in mother-reports of betamethasone-exposed children. These associations did not vary significantly between preterm and term children. CONCLUSIONS: Antenatal betamethasone exposure may be associated with mental health problems in children born preterm and in those who end up being born at term.

Maternal acetaminophen use during pregnancy and childhood behavioural problems: Discrepancies between mother- and teacher-reported outcomes.

BACKGROUND: Maternal acetaminophen use during pregnancy is common and has been associated with childhood behavioural problems among offspring, specifically hyperactivity and conduct problems. OBJECTIVE: Assessments of child behaviour in many previous studies have relied on maternal or parent report. Acknowledging that results of behavioural assessments vary between informants, we examined the association between maternal acetaminophen use during pregnancy and behaviour problems in childhood based on mother- and teacher-report. METHODS: A longitudinal study of 560 mother-child pairs with data on illnesses and medication use during pregnancy and neurodevelopmental assessments during childhood was conducted. Acetaminophen use during pregnancy was captured using a standardised maternal interview, completed 1 year after delivery on average. Measures of childhood (6-12 years of age) behaviour were obtained via mother- and teacher-report, using the Child Behaviour Checklist and Teacher Report Form. Linear and log-binomial models were used to calculate adjusted mean differences (MD) and risk ratios (RR), respectively and 95% confidence intervals (CI) for internalising, externalising, and total behaviour problems comparing acetaminophen users to non-users. Stabilized inverse probability weights were used to account for loss to follow-up, and adjustments for indication were made. RESULTS: Approximately 60% (n = 354) of women reported use of acetaminophen during pregnancy. Acetaminophen use during pregnancy was associated with an increase in total behaviour problem score and risk of clinical behaviour problems according to mother report (MD 2.2, 95% CI 0.3, 4.1 and RR 1.93, 95% CI 0.99, 3.76) but not according to teacher report. Weighting to account for participation did not alter results, while adjustment for indications of acetaminophen use greatly attenuated the associations with mother-reported total behaviour problem score and risk of clinical behaviour problems (MD 0.1, 95% CI -2.1, 2.3 and RR 1.31, 95% CI 0.67, 2.58). CONCLUSIONS: Acetaminophen use during pregnancy was weakly associated with mother-reported behaviour problems and not associated with teacher-reported problems.

Associations of prenatal or infant exposure to acetaminophen or ibuprofen with mid-childhood executive function and behaviour.

BACKGROUND: Over-the-counter analgesics during pregnancy or infancy may be related to neurobehavioural problems in children, but little is known about effects of different analgesic types, dosage, and timing. OBJECTIVES: Examine associations of acetaminophen and ibuprofen use during pregnancy and infancy with executive function and behaviour problems in children. METHODS: We included 1225 mother-child pairs from Project Viva, a pre-birth cohort study. We assessed prenatal acetaminophen and ibuprofen use in early and mid-pregnancy and infant use in the first year of life using questionnaires. Parents and classroom teachers assessed child behaviours in mid-childhood (median 8 years), using the Behavior Rating Inventory of Executive Function (BRIEF) and the Strengths and Difficulties Questionnaire (SDQ), with higher scores indicating worse functioning for both. We examined associations of acetaminophen and ibuprofen use during pregnancy and infancy with mid-childhood neurobehavioural outcomes using linear regression models adjusted for potential confounders. RESULTS: During pregnancy, 46.1% of mothers used acetaminophen ≥10 times and 18.4% used any ibuprofen. In the first year, 65.3% and 39.6% of infants received acetaminophen and ibuprofen ≥6 times, respectively. Higher (≥10 vs <10 times) prenatal acetaminophen (ß 1.64 points; 95% confidence interval [CI] 0.59, 2.68) and any ibuprofen (ß 1.56, 95% CI 0.19, 2.92) were associated with higher parent-rated BRIEF global scores. Patterns of association were linear across categories and were similar for other parent- and teacher-rated outcomes. Infancy exposure (≥6 vs <6 times) to acetaminophen (ß 1.69, 95% CI 0.51, 2.87) and ibuprofen (ß 1.40, 95% CI 0.25, 2.55) were associated with higher parent-rated BRIEF GEC scores but associations with teacher-rated scores were weaker. CONCLUSIONS: Prenatal and early-life exposure to acetaminophen and ibuprofen were associated with poorer executive function and behaviour in childhood. These findings highlight the need for further research on the mechanisms through which analgesics may act on fetal and child brain development.

Maternal smoking during pregnancy and offspring utilisation of health care services: A population-based cohort study.

BACKGROUND: Maternal smoking during pregnancy (MSDP) has been associated with a wide range of adverse effects on offspring health, such as low birthweight, behavioural disorders, and asthma. The number of women that smoke during pregnancy in Denmark is still high, making it relevant to study the long-term health outcomes in offspring exposed to maternal smoking in utero. OBJECTIVE: We investigated whether exposure to MSDP is associated with more frequent use of health care services during the first 10 years of life. METHODS: This population-based cohort study included participants enrolled in the Danish National Birth Cohort between 1996 and 2003. Data on MSDP were obtained from two telephone interviews during pregnancy and one interview after pregnancy. The primary outcome was contacts to the health care system. From Danish national registries, we obtained information on number and type of contacts to the general practitioner (GP), and information on the specific types of services provided. Further, we obtained information on hospital admissions, and redemption of prescribed medicine. We fitted negative binomial regression models and Cox proportional hazards regression models to estimate associations. All analyses were adjusted for socio-economic status, birth year, and various maternal factors. RESULTS: We studied 83,905 liveborn singletons and found that offspring exposed to maternal smoking in utero had more contacts to the GP in the first 10 years of life with an incidence rate ratio of 1.05, 95% confidence interval [CI] 1.04, 1.06. A higher rate of admission to hospital in 9 out of 20 categories was found, as was a higher rate of being prescribed psychoanaleptics (hazard ratio [HR] 1.41, 95% CI 1.25, 1.60), drugs for obstructive pulmonary disease (HR 1.14, 95% CI 1.14, 1.20), and antibiotics (HR 1.03, 95% CI 1.01, 1.05). CONCLUSIONS: We found that offspring exposed to MSDP had a higher use of health care services than unexposed offspring.

The opioid epidemic, neonatal abstinence syndrome, and estimated costs for special education services.

Children whose mothers used or misused opioids during their pregnancies are at an increased risk of exhibiting cognitive or behavioral impairments in the future, which may result in identifiable disabilities that require special education services in school. The costs associated with these additional educational services, however, have remained unknown. Using data from available empirical work, we calculated a preliminary set of cost estimates of special education and related services for children diagnosed with neonatal abstinence syndrome (NAS). We estimated these costs for a single cohort of children from the Commonwealth of Pennsylvania with a diagnosis of NAS. The resulting cost estimates were $16,506,916 (2017 US$) in total educational services provisions, with $8,253,458 (2017 US$) of these costs attributable to the additional provision of special education services. This estimate includes both opioid use during pregnancy that was linked to NAS in general and NAS that resulted specifically from prescription opioid use. We estimate the total annual education costs for children born in Pennsylvania with NAS associated with maternal use of prescription opioids to be $1,012,506 (2017 US$). Of these costs, we estimate that $506,253 (2017 US$) are attributable to the additional provision of special education services. We detail the calculation of these cost estimates and provide an expanded set of estimates for additional years of special education services (3-year, 5-year, and 13-year, or the K-12 educational time frame). We conclude with a discussion of limitations and suggestions for future work.

Residential exposure to urban traffic is associated with the poorer neurobehavioral health of Ecuadorian schoolchildren.

PURPOSE: We investigated whether chronic traffic-generated air pollution containing fine and ultrafine particulate matter is associated with reduced neurobehavioral performance and behavioral dysfunction in urban Ecuadorian schoolchildren. Also, we examined the effect of child hemoglobin and sociodemographic risk factors on these neurocognitive outcomes. METHODS: A convenience sample of healthy children aged 8-14 years attending public schools were recruited in Quito, Ecuador. Child residential proximity to the nearest heavily trafficked road was used as a proxy for traffic-related pollutant exposure. These included high exposure (<100 m), medium exposure (100-199 m) and low exposure (≥ 200 m) from the nearest heavily trafficked road. The Behavioral Assessment and Research System (BARS), a computerized test battery assessing attention, memory, learning and motor function was used to evaluate child neurobehavioral performance. The Child Behavior Checklist (CBCL/6-18) was used to assess child behavioral dysfunction as reported by mothers. The data were analyzed using multiple linear regression. RESULTS: Children with the highest residential exposure to traffic pollutants (< 100 m) had significantly longer latencies as measured by match to sample (b = 410.27; p = 0.01) and continuous performance (b = 37.90; p = 0.02) compared to those living ≥ 200 m away. A similar but non-significant association was observed for reaction time latency. Children living within 100 m of heavy traffic also demonstrated higher scores across all CBCL subscales although only the relationship with thought problems (p = 0.05) was statistically significant in the adjusted model. CONCLUSION: The study findings suggest that children living within 100 m of heavy traffic appear to experience subtle neurobehavioral deficits that may result from fine and ultrafine particulate matter exposure.

Postmarketing experience with brivaracetam in the treatment of focal epilepsy in children and adolescents.

INTRODUCTION: This multicenter, retrospective study aimed to evaluate the efficiency, retention, safety, and tolerability of brivaracetam (BRV) in children and adolescents with focal epilepsy. METHODS: All patients aged ≤17 years with focal epilepsy who started BRV in 2016 and 2017 were analyzed. RESULTS: Thirty-four patients (mean age: 12.2 years, range: 3-17 years, 56% female) were treated with BRV for 25 days to 24 months, with a total exposure time of 19.7 years. Overnight switch from levetiracetam (LEV) to BRV was performed in 20 patients at a median ratio of 10:1. Retention rate was 97% at three months, with only one patient reporting a discontinuation of BRV treatment. Further dropouts were reported in one patient after seven months and in two patients after one year of treatment, respectively. The median length of exposure to BRV was 180 days. Efficacy at three months was 47% (50% responder rate), with 10 patients (29%) reporting seizure freedom. A long-term 50% responder rate was present in 12 patients [35%; four patients seizure-free (12%)] for more than six months and in seven patients (21%; no seizure-free patients) for more than 12 months. Treatment-emergent adverse events were observed in 12% of patients, with the most common being sedation, somnolence, loss or gain of appetite, and psychobehavioral adverse events. CONCLUSIONS: Use of BRV in children and adolescents seems to be safe and well-tolerated. The results with 50% responder rate of 47% are consistent with those from randomized controlled trials and postmarketing studies in adults. An immediate switch from LEV to BRV at a ratio of 10:1 is feasible. The occurrence of psychobehavioral adverse events seems less prominent than under LEV and a switch to BRV can be considered in patients with LEV-induced adverse events.

Major depressive disorder during pregnancy: Psychiatric medications have minimal effects on the fetus and infant yet development is compromised.

Psychotropic medication use and psychiatric symptoms during pregnancy each are associated with adverse neurodevelopmental outcomes in offspring. Commonly, studies considering medication effects do not adequately assess symptoms, nor evaluate children when the effects are believed to occur, the fetal period. This study examined maternal serotonin reuptake inhibitor and polypharmacy use in relation to serial assessments of five indices of fetal neurobehavior and Bayley Scales of Infant Development at 12 months in N = 161 socioeconomically advantaged, non-Hispanic White women with a shared risk phenotype, diagnosed major depressive disorder. On average fetuses showed the expected development over gestation. In contrast, infant average Bayley psychomotor and mental development scores were low (M = 84.10 and M = 89.92, range of normal limits 85-114) with rates of delay more than 2-3 times what would be expected based on this measure's normative data. Controlling for prenatal and postnatal depressive symptoms, prenatal medication effects on neurobehavioral development were largely undetected in the fetus and infant. Mental health care directed primarily at symptoms may not address the additional psychosocial needs of women parenting infants. Speculatively, prenatal serotonin reuptake inhibitor exposure may act as a plasticity rather than risk factor, potentially enhancing receptivity to a nonoptimal postnatal environment in some mother-infant dyads.

Co-use of tobacco and marijuana during pregnancy: Pathways to externalizing behavior problems in early childhood.

Use and co-use of tobacco and marijuana during pregnancy are associated with the development of social, cognitive, and behavioral problems for infants and children. However, less is known about the potential developmental impact of the use of tobacco and marijuana in tandem. The present study examined an etiological model for the development of externalizing behavior problems (EBP) in early childhood in a high risk sample (N = 247) of mother-infant dyads with prospective data from pregnancy to 36 months of child age. Co-use during pregnancy and continued maternal tobacco and marijuana use from infancy through early childhood were investigated. Although direct pathways from exposure during pregnancy to EBP were not significant, there was a significant indirect pathway from prenatal tobacco use to EBP via lower breastfeeding duration to lower maternal warmth/sensitivity to EBP, and a pathway from higher maternal affective dysregulation to higher EBP. These results highlight the importance of considering cascading effects of substance use during pregnancy on parental processes within the context of developmental risk and protection.

Does perinatal exposure to exogenous oxytocin influence child behavioural problems and autistic-like behaviours to 20 years of age?

BACKGROUND: The neuropeptide and hormone oxytocin is known to have a significant impact on social cognition and behaviour in humans. There is growing concern regarding the influence of exogenous oxytocin (OT) administration in early life on later social and emotional development, including autism spectrum disorder (ASD). No study has examined offspring development in relation to the dose of exogenous oxytocin administered during labour. METHODS: Between 1989 and 1992, 2,900 mothers were recruited prior to the 18th week of pregnancy, delivering 2,868 live offspring. The Child Behaviour Checklist was used to measure offspring behavioural difficulties at ages 5, 8, 10, 14 and 17 years. Autism spectrum disorder was formally diagnosed by consensus of a team of specialists. At 20 years, offspring completed a measure of autistic-like traits, the Autism Spectrum Quotient (AQ). Oxytocin exposure prior to birth was analysed using categorical and continuous approaches (maternal oxytocin dose) with univariate and multivariate statistical techniques. RESULTS: Categorical analyses of oxytocin exposure prior to birth demonstrated no group differences in any measures of child behaviour. A small in magnitude dose-response association was observed for clinically significant total behaviour symptoms (adjusted odds ratio 1.03; 95% CI: 1.01-1.06, p < .01). Exogenous oxytocin administration prior to birth was not associated with ASD (OR: 0.64; 95% CI: 0.15-2.12, p = .46) or high levels of autistic-like traits (p = .93), as assessed by the AQ. CONCLUSIONS: This study is the first to investigate longitudinal mental health outcomes associated with the use of oxytocin-based medications during labour. The results do not provide evidence to support the theory that exogenous OT has a clinically significant negative impact on the long-term mental health of children.

Prenatal triptan exposure and neurodevelopmental outcomes in 5-year-old children: Follow-up from the Norwegian Mother and Child Cohort Study.

BACKGROUND: Triptans are commonly used to treat migraine headaches, but data on the long-term safety of these medications during pregnancy are sparse. Triptans have a biologically plausible mechanism for effects on the fetal brain through binding to 5-HT1 -receptors, and previous studies show increased risks of externalising behaviour problems in toddlers exposed to triptans during pregnancy. METHODS: We included 3784 children in the Norwegian Mother and Child Cohort Study, whose mothers returned the 5-year-questionnaire and reported a history of migraine or triptan use; 353 (9.3%) mothers reported use of triptans during pregnancy, 1509 (39.9%) reported migraine during pregnancy but no triptan use, and 1922 (50.8%) had migraine prior to pregnancy only. We used linear and log-binomial models with inverse probability weights to examine the association between prenatal triptan exposure and internalising and externalising behaviour, communication, and temperament in 5-year-old children. RESULTS: Triptan-exposed children scored higher on the sociability trait than unexposed children of mothers with migraine (ß 1.66, 95% confidence interval [0.30, 3.02]). We found no other differences in temperament, or increased risk of behaviour or communication problems. CONCLUSIONS: Contrary to results from previous studies in younger children, we found no increased risk of externalising behaviour problems in 5-year-old children exposed to triptans in fetal life. Triptan-exposed children did have slightly more sociable temperaments, but the clinical meaning of this finding is uncertain.