Prenatal exposure to perfluoroalkyl substances and associations with symptoms of attention-deficit/hyperactivity disorder and cognitive functions in preschool children

BACKGROUND: Perfluoroalkyl substances (PFASs) are persistent organic pollutants that are suspected to be neurodevelopmental toxicants, but epidemiological evidence on neurodevelopmental effects of PFAS exposure is inconsistent. We investigated the associations between prenatal exposure to PFASs and symptoms of attention-deficit/hyperactivity disorder (ADHD) and cognitive functioning (language skills, estimated IQ and working memory) in preschool children, as well as effect modification by child sex. MATERIAL AND METHODS: This study included 944 mother-child pairs enrolled in a longitudinal prospective study of ADHD symptoms (the ADHD Study), with participants recruited from The Norwegian Mother, Father and Child Cohort Study (MoBa). Boys and girls aged three and a half years, participated in extensive clinical assessments using well-validated tools; The Preschool Age Psychiatric Assessment interview, Child Development Inventory and Stanford-Binet (5th revision). Prenatal levels of 19 PFASs were measured in maternal blood at week 17 of gestation. Multivariable adjusted regression models were used to examine exposure-outcome associations with two principal components extracted from the seven detected PFASs. Based on these results, we performed regression analyses of individual PFASs categorized into quintiles. RESULTS: PFAS component 1 was mainly explained by perfluoroheptane sulfonate (PFHpS), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS) and perfluorooctanoic acid (PFOA). PFAS component 2 was mainly explained by perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA) and perfluorononanoic acid (PFNA). Regression models showed a negative association between PFAS component 1 and nonverbal working memory [β = -0.08 (CI: -0.12, -0.03)] and a positive association between PFAS component 2 and verbal working memory [β = 0.07 (CI: 0.01, 0.12)]. There were no associations with ADHD symptoms, language skills or IQ. For verbal working memory and PFAS component 2, we found evidence for effect modification by child sex, with associations only for boys. The results of quintile models with individual PFASs, showed the same pattern for working memory as the results in the component regression analyses. There were negative associations between nonverbal working memory and quintiles of PFOA, PFNA, PFHxS, PFHpS and PFOS and positive associations between verbal working memory and quintiles of PFOA, PFNA, PFDA and PFUnDA, with significant relationships mainly in the highest concentration groups. CONCLUSIONS: Based on our results, we did not find consistent evidence to conclude that prenatal exposure to PFASs are associated with ADHD symptoms or cognitive dysfunctions in preschool children aged three and a half years, which is in line with the majority of studies in this area. Our results showed some associations between PFASs and working memory, particularly negative relationships with nonverbal working memory, but also positive relationships with verbal working memory. The relationships were weak, as well as both positive and negative, which suggest no clear association - and need for replication.This research was funded by the Research Council of Norway (MILJØFORSK, project no. 267984/E50 “NeuroTox”), National Institutes of Health (NIH) R01ES021777, and National Institute of Environmental Health Sciences (NIEHS) P30 ES010126. The ADHD Study, from which the present data were drawn, was supported by funds and grants from the Norwegian Ministry of Health, the Norwegian Health Directorate, the South-Eastern Health Region, G&PJ Sorensen Fund for Scientific Research, and from the Norwegian Resource Centre for ADHD, Tourette syndrome and Narcolepsy. The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH, and National Institute of Neurological Disorders and Stroke (NINDS) (grant no.1 UO1 NS 047537-01 and grant no.2 UO1 NS 047537-06A1). We are grateful to all the participating families in Norway who take part in this on-going cohort study, and to the staff of the ADHD Study.publishedVersio

Adult ADHD Symptoms and Satisfaction With Life: Does Age and Sex Matter?

Objective:To investigate adult ADHD symptoms and satisfaction with life, with a focus on age and sex differences. Method: This study is based on parents in the Norwegian Mother and Child Cohort Study (MoBa). The Adult Self- Report Scale (ASRS-6) and Satisfaction With Life Scale (SWLS) scores were analyzed from 33,210 men and 41,983 women from young to middle adulthood. Results: Mean ASRS total score was significantly higher in men, where 5.1% scored above cutoff, compared with 2.9% in women. Factor loadings supported the two ASRS subscales: Inattention (Inatt) and Hyperactivity-Impulsivity (HyImp) in both sexes. A significant decline with age was found on HyImp, whereas Inatt scores were reasonably stable in men and u-curved in women. High ASRS scores were associated with lower SWLS, but poor satisfaction with life was found only in high-scoring women. Conclusion: Our findings suggest caution to age and sex when using the ASRS-6

The Use of Antidepressants, Antipsychotics, and Stimulants in Youth Residential Care

Objectives: To assess the use of three commonly prescribed psychotropic medications in youth placed in residential care (RC). Methods: Participants were youth aged 0-20 years placed in RC institutions at least once during 2016. Data on filled prescriptions were taken from the Norwegian Prescription Database to compare the use of antidepressants, antipsychotics, and stimulants in RC with the age and gender adjusted general child population (GenPop) and how this co-varied with reasons for RC placement, age and gender. Results: 1856 children and adolescents were identified in RC, with mean age 14 (range 0-20 years), 46% girls, 81% ≥13 years. Among those, 423 or 23% used any of the three psychotropics, significantly more than the 3.7% in GenPop. The prevalence ratios RC/GenPop were 6.6 for antidepressants, 17.9 for antipsychotics, and 4.4 for stimulants. The median number of days per year for the dispensed defined daily doses varied from 8.3 to 244.0 for the different antipsychotics, indicating short time use for most. Polypharmacy was not frequent in RC, as only 26% used ≥ 2 classes of medication, but still significantly more frequent than the 10% in GenPop. Youth placed in RC for serious behavior problems had significantly higher use of stimulants than those with other placement reasons. Psychotropics were not used below age 6 years, and while the use of antidepressants and antipsychotics overall increased with age, stimulants were mostly used by 6 to16 year olds. The girl/boy ratio for any psychotropic medication use in RC was 1.4 (CI: 1.1-1.6), significantly higher than the corresponding ratio in GenPop: 1.0 (CI: 0.9-1.0). Conclusion: The present findings do not necessarily suggest an overtreatment with medication in RC. However, the frequent short-term use of antipsychotics, presumably for non-psychotic symptoms, is a concern, as it may reflect that the youth are not provided with the recommended first-line psychological treatments

The Use of Antidepressants, Antipsychotics, and Stimulants in Youth Residential Care

Objectives: To assess the use of three commonly prescribed psychotropic medications in youth placed in residential care (RC). Methods: Participants were youth aged 0-20 years placed in RC institutions at least once during 2016. Data on filled prescriptions were taken from the Norwegian Prescription Database to compare the use of antidepressants, antipsychotics, and stimulants in RC with the age and gender adjusted general child population (GenPop) and how this co-varied with reasons for RC placement, age and gender. Results: 1856 children and adolescents were identified in RC, with mean age 14 (range 0-20 years), 46% girls, 81% ≥13 years. Among those, 423 or 23% used any of the three psychotropics, significantly more than the 3.7% in GenPop. The prevalence ratios RC/GenPop were 6.6 for antidepressants, 17.9 for antipsychotics, and 4.4 for stimulants. The median number of days per year for the dispensed defined daily doses varied from 8.3 to 244.0 for the different antipsychotics, indicating short time use for most. Polypharmacy was not frequent in RC, as only 26% used ≥ 2 classes of medication, but still significantly more frequent than the 10% in GenPop. Youth placed in RC for serious behavior problems had significantly higher use of stimulants than those with other placement reasons. Psychotropics were not used below age 6 years, and while the use of antidepressants and antipsychotics overall increased with age, stimulants were mostly used by 6 to16 year olds. The girl/boy ratio for any psychotropic medication use in RC was 1.4 (CI: 1.1-1.6), significantly higher than the corresponding ratio in GenPop: 1.0 (CI: 0.9-1.0). Conclusion: The present findings do not necessarily suggest an overtreatment with medication in RC. However, the frequent short-term use of antipsychotics, presumably for non-psychotic symptoms, is a concern, as it may reflect that the youth are not provided with the recommended first-line psychological treatments

Factor structure of the Behavior Rating Inventory of Executive Functions (BRIEF-P) at age three years

The preschool period is an important developmental period for the emergence of cognitive self-regulatory skills or executive functions (EF). To date, evidence regarding the structure of EF in preschool children has supported both unitary and multicomponent models. The aim of the present study was to test the factor structure of early EF as measured by the Behavior Rating Inventory of Executive Function-Preschool version (BRIEF-P). BRIEF-P consists of five subscales and three broader indexes, hypothesized to tap into different subcomponents of EF. Parent ratings of EF from a nonreferred sample of children recruited from the Norwegian Mother and Child Cohort Study (N = 1134; age range 37–47 months) were subjected to confirmatory factor analyses (CFA). Three theoretically derived models were assessed; the second-order three-factor model originally proposed by the BRIEF-P authors, a “true” first-order one-factor model and a second-order one-factor model. CFA fit statistics supported the original three-factor solution. However, the difference in fit was marginal between this model and the second-order one-factor model. A follow-up exploratory factor analysis (EFA) supported the existence of several factors underlying EF in early preschool years, with a considerable overlap with the five BRIEF-P subscales. Our results suggest that some differentiation in EF has taken place at age 3 years, which is reflected in behavior ratings. The internal consistency of the BRIEF-P five clinical subscales is supported. Subscale interrelations may, however, differ at this age from those observed in the preschool group as a whole

Predictive validity of attention-deficit/hyperactivity disorder from ages 3 to 5 Years

We investigated to what extent parent-rated attention-deficit/hyperactivity disorder (ADHD) and impairment at age 3 years predicted elevated ADHD symptoms at age 5 years, and whether teacher-rated ADHD symptoms improved these predictions. This study is part of the longitudinal, population-based Norwegian Mother, Father and Child Cohort Study. Parents of 3-year-old children (n = 1195) were interviewed about ADHD and impairment, and teachers rated child ADHD symptoms by the Strengths and Difficulties Questionnaire or the Early Childhood Inventory-4. At 5 years of age, the children (n = 957) were classified as ADHD-positive or -negative using Conners’ Parent Rating Scale. Relying solely on parent-rated ADHD or impairment at age 3 years did moderately well in identifying children with persistent elevation of ADHD symptoms, but gave many false positives (positive predictive values (PPVs): .40–.57). A small group of children (n = 20, 13 boys) scored above cut-off on both parent-rated ADHD and impairment, and teacher-rated ADHD symptoms, although adding teacher-rated ADHD symptoms slightly weakened the predictive power for girls. For this small group, PPVs were .76 for boys and .64 for girls. Limiting follow-up to these few children will miss many children at risk for ADHD. Therefore, we recommend close monitoring also of children with parent-reported ADHD symptoms and/or impairment to avoid delay in providing interventions. Clinicians should also be aware that teachers may miss ADHD symptoms in preschool girls

What can a national patient registry tell us about psychiatric disorders and reasons for referral to outpatient services in youth with hearing loss?

Background: Studies of reasons for referral to the Child and Adolescent Mental Health Services (CAMHS) and subsequent psychiatric disorders are missing in youth with Hearing loss (HL). Aims: To examine the referral reasons to CAMHS and the clinically diagnosed psychiatric disorders in youth with HL among the nationally representative population. Methods: The study population was a youth with HL referred to CAMHS and registered in the national Norwegian Patient Registry (NPR) during the years 2011–2016. The results were also compared with some data published from CAMHS for the General Youth Population (GenPop). Results: Among youth with HL, 18.1% had also been referred to CAMHS compared to about 5% in GenPop, at mean age 9.1 years, >70% before age 13 years vs. 46% in the GenPop. Boys with HL comprised 57% and were referred about two years earlier than girls with HL. Compared to the GenPop, youth with HL were referred more frequently for suspected neurodevelopmental- and disruptive disorders, and less frequently for suspected emotional disorders. Girls with HL were referred for suspected Attention-Deficit/Hyperactivity Disorder (ADHD) at about the same rate as boys with HL in the 7–12 year age group. The most frequently registered psychiatric disorders were ADHD: 29.8%, anxiety disorders: 20.4%, and autism spectrum disorders: 11.0%, while disruptive disorders constituted about 5.0%. Conclusions: Youth with HL were referred to CAMHS more often, but earlier than the GenPop, mostly due to ADHD disorders. Although more rarely referred for suspected anxiety disorders, these were frequently diagnosed, suggesting that anxiety was not recognized at referral in youth with H

Predictive validity of attention-deficit/hyperactivity disorder from ages 3 to 5 Years

We investigated to what extent parent-rated attention-deficit/hyperactivity disorder (ADHD) and impairment at age 3 years predicted elevated ADHD symptoms at age 5 years, and whether teacher-rated ADHD symptoms improved these predictions. This study is part of the longitudinal, population-based Norwegian Mother, Father and Child Cohort Study. Parents of 3-year-old children (n = 1195) were interviewed about ADHD and impairment, and teachers rated child ADHD symptoms by the Strengths and Difficulties Questionnaire or the Early Childhood Inventory-4. At 5 years of age, the children (n = 957) were classified as ADHD-positive or -negative using Conners’ Parent Rating Scale. Relying solely on parent-rated ADHD or impairment at age 3 years did moderately well in identifying children with persistent elevation of ADHD symptoms, but gave many false positives (positive predictive values (PPVs): .40–.57). A small group of children (n = 20, 13 boys) scored above cut-off on both parent-rated ADHD and impairment, and teacher-rated ADHD symptoms, although adding teacher-rated ADHD symptoms slightly weakened the predictive power for girls. For this small group, PPVs were .76 for boys and .64 for girls. Limiting follow-up to these few children will miss many children at risk for ADHD. Therefore, we recommend close monitoring also of children with parent-reported ADHD symptoms and/or impairment to avoid delay in providing interventions. Clinicians should also be aware that teachers may miss ADHD symptoms in preschool girls

What can a national patient registry tell us about psychiatric disorders and reasons for referral to outpatient services in youth with hearing loss?

Background Studies of reasons for referral to the Child and Adolescent Mental Health Services (CAMHS) and subsequent psychiatric disorders are missing in youth with Hearing loss (HL). Aims To examine the referral reasons to CAMHS and the clinically diagnosed psychiatric disorders in youth with HL among the nationally representative population. Methods The study population was a youth with HL referred to CAMHS and registered in the national Norwegian Patient Registry (NPR) during the years 2011–2016. The results were also compared with some data published from CAMHS for the General Youth Population (GenPop). Results Among youth with HL, 18.1% had also been referred to CAMHS compared to about 5% in GenPop, at mean age 9.1 years, >70% before age 13 years vs. 46% in the GenPop. Boys with HL comprised 57% and were referred about two years earlier than girls with HL. Compared to the GenPop, youth with HL were referred more frequently for suspected neurodevelopmental- and disruptive disorders, and less frequently for suspected emotional disorders. Girls with HL were referred for suspected Attention-Deficit/Hyperactivity Disorder (ADHD) at about the same rate as boys with HL in the 7–12 year age group. The most frequently registered psychiatric disorders were ADHD: 29.8%, anxiety disorders: 20.4%, and autism spectrum disorders: 11.0%, while disruptive disorders constituted about 5.0%. Conclusions Youth with HL were referred to CAMHS more often, but earlier than the GenPop, mostly due to ADHD disorders. Although more rarely referred for suspected anxiety disorders, these were frequently diagnosed, suggesting that anxiety was not recognized at referral in youth with HL

The use of sleep medication in youth residential care

Objectives: To investigate the use of sleep medication and concomitant psychotropic medication in children and adolescents placed under residential care (RC). Methods: Participants were youth 0–20 years of age placed in RC institutions at least once during 2016. Data on filled prescriptions were taken from the Norwegian Prescription Database to compare the use of sleep medication in RC with the general child population (GenPop) and how it covaried with gender, age, reasons for RC placement, and concomitant use of other psychotropic medications (antidepressants, anxiolytics, antipsychotics, and psychostimulants). Results: A total of 2171 youths were identified in RC at mean age 14 years (82% ‡ 13 years). Seventeen percent (371/2171) used sleep medications (melatonin 11%, alimemazine 7%, and benzodiazepines/z-hypnotics 2%) significantly more than the 2.3% who used in GenPop. The girl/boy ratio for medication use in RC was 1.8 (95% confidence interval [CI] = 1.5–2.2), not significantly different from the corresponding ratio in GenPop (1.4; 95% CI = 1.3–1.5). The use of sleep medication increased with age. When comparing reasons for placement in RC, medication use was particularly low among unaccompanied minor asylumseekers (2%). About half of the youths used concomitant psychotropic medication, with clear gender differences; Girls used about twice as much antidepressants, anxiolytics, and antipsychotics, whereas boys used 1.3 times more psychostimulants. Conclusion: Youths in RC used more sleep medication and concomitant psychotropic medication than the GenPop, most likely reflecting the increased psychosocial strain and mental disorders reported in this population. Further studies of prevalence, assessment, and treatment of sleep problems in RC populations are warranted