Population-adjusted numbers, demographics and mental health among children and adolescents referred to the Norwegian National Center for Gender Incongruence over two decades.

Over the last decade, there has been a sharp increase in young people seeking medical treatment for gender dysphoria/gender incongruence (GD/GI). The aims of this study were to calculate yearly population-adjusted numbers of children and adolescents referred to the Norwegian National Center for Gender Incongruence (NCGI) at Oslo University Hospital (OUS) from 2000 to 2022; to describe the demographic characteristics and prevalence of psychiatric diagnoses, self-harm and suicide attempts among the referred from 2000 to 2020; and to investigate time trends. The study used data from the Gender Incongruence Registry for Children and Adolescents (GIRCA) in Norway. All persons under 18 years (n = 1258) referred to the NCGI between 2000 and 2020 were included: 68.4% assigned female gender at birth (AFAB) and 31.6% assigned male gender at birth (AMAB). We found a sharp increase in referrals to the NCGI favouring AFAB over AMAB. Nearly two in three (64.5%) had one or more registered psychiatric diagnoses. Self-harm was registered among 35.5%, and 12.7% had attempted suicide. Registered psychiatric diagnoses were significantly (p ≤ 0.001) more prevalent among AFAB (67.8%) than AMAB (57.4%). The number of registered diagnoses per person decreased significantly over time, with an average reduction of 0.02 diagnoses per person per year. Although there was a downward time trend in registered diagnoses per person, the total mental health burden among children and adolescents with GI emphasizes the need for a holistic approach.

Do maternal anxiety and depressive symptoms predict anxiety in children with and without ADHD at 8 years?

Maternal anxiety and depression during pregnancy and early childhood have been associated with child anxiety and attention-deficit/hyperactivity disorder (ADHD). However, previous studies are limited by their short follow-up, few assessments of maternal symptoms, and by not including maternal and child ADHD. The present study aimed to fill these gaps by investigating whether maternal anxiety and depressive symptoms from pregnancy to child age 5 years increase the risk of child anxiety disorders at age 8 years. This study is part of the population-based Norwegian Mother, Father, and Child Cohort Study. Maternal anxiety and depressive symptoms were assessed by the Hopkins Symptom Checklist (SCL) six times from pregnancy through early childhood, and ADHD symptoms by the Adult Self-Report Scale (ASRS). At age 8 years (n = 781), symptoms of anxiety disorders and ADHD were assessed, and disorders classified by the Child Symptom Inventory-4. Logistic regression models estimated the risk of child anxiety depending on maternal symptoms. The mothers of children classified with an anxiety disorder (n = 91) scored significantly higher on the SCL (at all time points) and ASRS compared with the other mothers. In univariable analyses, maternal anxiety and/or depression and ADHD were associated with increased risk of child anxiety (odds ratios = 2.99 and 3.64, respectively), remaining significant in the multivariable analysis adjusted for covariates. Our findings link maternal anxiety, depression, and ADHD during pregnancy and early childhood to child anxiety at age 8 years.

Anxiety and depression from age 3 to 8 years in children with and without ADHD symptoms.

Childhood anxiety and depressive symptoms may be influenced by symptoms of attention deficit/hyperactivity disorder (ADHD). We investigated whether parent- and teacher-reported anxiety, depressive and ADHD symptoms at age 3 years predicted anxiety disorders and/or depression in children with and without ADHD at age 8 years. This study is part of the longitudinal, population-based Norwegian Mother, Father and Child Cohort Study. Parents of 3-year-olds were interviewed, and preschool teachers rated symptoms of anxiety disorders, depression and ADHD. At age 8 years (n = 783), Child Symptom Inventory-4 was used to identify children who fulfilled the diagnostic criteria for anxiety disorders and/or depression (hereinafter: Anx/Dep), and ADHD. Univariable and multivariable logistic regression analyses were used. In the univariable analyses, parent-reported anxiety, depressive and ADHD symptoms, and teacher-reported anxiety symptoms at age 3 years all significantly predicted subsequent Anx/Dep. In the multivariable analyses, including co-occurring symptoms at age 3 years and ADHD at 8 years, parent-reported anxiety and depressive symptoms remained significant predictors of subsequent Anx/Dep. At age 3 years, regardless of ADHD symptoms being present, asking parents about anxiety and depressive symptoms, and teachers about anxiety symptoms, may be important to identify children at risk for school-age anxiety disorders and/or depression.

Association between gestational levels of toxic metals and essential elements and cerebral palsy in children.

Introduction: Cerebral palsy (CP) is the most common motor disability in childhood, but its causes are only partly known. Early-life exposure to toxic metals and inadequate or excess amounts of essential elements can adversely affect brain and nervous system development. However, little is still known about these as perinatal risk factors for CP. This study aims to investigate the associations between second trimester maternal blood levels of toxic metals, essential elements, and mixtures thereof, with CP diagnoses in children. Methods: In a large, population-based prospective birth cohort (The Norwegian Mother, Father, and Child Cohort Study), children with CP diagnoses were identified through The Norwegian Patient Registry and Cerebral Palsy Registry of Norway. One hundred forty-four children with CP and 1,082 controls were included. The relationship between maternal blood concentrations of five toxic metals and six essential elements and CP diagnoses were investigated using mixture approaches: elastic net with stability selection to identify important metals/elements in the mixture in relation to CP; then logistic regressions of the selected metals/elements to estimate odds ratio (OR) of CP and two-way interactions among metals/elements and with child sex and maternal education. Finally, the joint effects of the mixtures on CP diagnoses were estimated using quantile-based g-computation analyses. Results: The essential elements manganese and copper, as well as the toxic metal Hg, were the most important in relation to CP. Elevated maternal levels of copper (OR = 1.40) and manganese (OR = 1.20) were associated with increased risk of CP, while Hg levels were, counterintuitively, inversely related to CP. Metal/element interactions that were associated with CP were observed, and that sex and maternal education influenced the relationships between metals/elements and CP. In the joint mixture approach no significant association between the mixture of metals/elements and CP (OR = 1.00, 95% CI = [0.67, 1.50]) was identified. Conclusion: Using mixture approaches, elevated levels of copper and manganese measured in maternal blood during the second trimester could be related to increased risk of CP in children. The inverse associations between maternal Hg and CP could reflect Hg as a marker of maternal fish intake and thus nutrients beneficial for foetal brain development.

Early and repeated screening detects children with persistent attention-deficit/hyperactivity disorder.

Preschool screening of attention-deficit/hyperactivity disorder (ADHD) has been found too inaccurate to be clinically useful. This may be due to the known instability of ADHD symptoms from preschool onwards, and the use of a single screening only. We hypothesized that by identifying a group of children with persistent ADHD from preschool to school age and repeating the screening, the clinical usefulness of screening would increase. This study is part of the prospective longitudinal, population-based Norwegian Mother, Father and Child Cohort Study, with a diagnostic parent interview at 3.5 years and follow-up with parent questionnaires at ages 5 and 8 years (n = 707). We identified a group classified with ADHD at all three time points (persistent ADHD). We then used the Child Behavior Checklist ADHD DSM-oriented scale at ages 3.5 and 5 years to investigate the accuracies of single- and two-stage screening at different thresholds to identify children with persistent ADHD. About 30% of the children were classified with ADHD at least once across time (at ages 3.5, 5, and/or 8 years), but only 4% (n = 30) had persistent ADHD. At all thresholds, the two-stage screening identified children with persistent ADHD more accurately than single screening, mainly due to a substantial reduction in false positives. Only a small group of children were classified with persistent ADHD from preschool to school age, underlining that future screening studies should distinguish this group from those with fluctuating symptoms when estimating screening accuracies. We recommend a two-stage screening process to reduce false positives.

Attention-deficit/hyperactivity disorder from preschool to school age: change and stability of parent and teacher reports.

Identifying attention-deficit/hyperactivity disorder (ADHD) in pre-schoolers may improve their development if treated, but it is unclear whether ADHD symptoms from this age are stable enough to merit treatment. We aimed to investigate the stability of parent- and teacher-reported ADHD symptoms and ADHD classified above the diagnostic symptom thresholds, including for hyperactivity-impulsivity (HI), inattention and combined presentations from age 3 to 8 years. This study is part of the longitudinal, population-based Norwegian Mother, Father and Child Cohort Study. At child age 3 years, parents were interviewed and teachers rated ADHD symptoms. At age 8 years, parents (n = 783) and teachers (n = 335) reported ADHD symptoms by the Child Symptom Inventory-4. We found a significant reduction in the mean number of parent-reported ADHD and HI symptoms from age 3 to 8 years, but otherwise similar mean numbers. Parent-reported ADHD symptoms were moderately correlated between ages, while correlations were low for teachers. A total of 77/108 (71%) of the children classified with parent-reported HI presentation at age 3 years were no longer classified within any ADHD presentation at age 8 years, the only clear trend across time for either informant. There was a low to moderate parent-teacher-agreement in the number of reported symptoms, and very low informant agreement for the classified ADHD presentations. Overall, clinicians should exercise caution in communicating concern about HI symptoms in preschool children. Age 3 years may be too early to apply the ADHD diagnostic symptom criteria, especially if parents and teachers are required to agree.

The effect of special educational assistance in early childhood education and care on psycho-social difficulties in elementary school children.

BACKGROUND: Three to seven percent of pre-schoolers have developmental problems or child psychiatric disorders. Randomized controlled trials (RCTs) indicate that interventions in early childhood education and care (ECEC) improve long-term outcomes of children from disadvantaged backgrounds. It is unknown if such effects generalize beyond the well-structured context of RCTs and to children who may not have a disadvantaged background but have developmental problems or psychiatric disorders. METHODS: We used data from the population-based Norwegian Mother, Father and Child Cohort Study, recruiting pregnant women from 1999 to 2009, with child follow-up from ages 6, 18, and 36 months to ages 5, 7, and 8 years. This sub-study included 2499 children with developmental problems or psychiatric disorders at age five. We investigated the effects of special educational assistance at age five on mother-reported internalizing, externalizing, and communication problems at age eight. We analysed bias due to treatment by indication with directed acyclic graphs, adjusted for treatment predictors to reduce bias, and estimated effects in different patient groups and outcome domains with a hierarchical Bayesian model. RESULTS: In the adjusted analysis, pre-schoolers who received special educational assistance had on average by 0.1 (0.04-0.16) standardised mean deviation fewer psycho-social difficulties in elementary school. CONCLUSION: In a sample of children from mostly higher socioeconomic backgrounds we estimate a positive effects of special educational assistance during the transition from preschool to the school years. It may therefore be considered as an intervention for pre-schoolers with developmental or behaviour problems. More research with improved measurements of treatment and outcomes is needed to solidify the findings and identify success factors for the implementation of special educational assistance in ECEC.

Cognitive, emotional, and social functioning of preschoolers with attention deficit hyperactivity problems.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is associated with deficits in different functional domains. It remains unclear if deficits in different domains are equally strong in early childhood, and which deficits are specific to ADHD. Here, we describe functional domains in preschoolers and assess deficits in children with ADHD problems, by comparing them to preschoolers with other mental health problems or who develop typically. METHODS: The ADHD Study assessed 1195 ca. 3.5 years old preschoolers through a semi-structured parent interview, parent questionnaires, and with neuropsychological tests. We determined functional domains by applying factor analytic methods to a broad set of questionnaire- and test-scales. Using resulting factor scores, we employed a Bayesian hierarchical regression to estimate functional deficits in children with ADHD. RESULTS: We found that preschoolers' functioning could be described along the seven relatively independent dimensions activity level and regulation, executive function, cognition, language, emotion regulation, introversion, and sociability. Compared to typically developing preschoolers, those with ADHD had deficits in all domains except introversion and sociability. Only deficits in activity level regulation and executive functions were larger than 0.5 standardised mean deviations and larger than deficits of children with other mental health problems. CONCLUSIONS: Preschoolers with ADHD have deficits in multiple functional domains, but only impairments in activity level and regulation and executive functions are specific for ADHD and large enough to be clinically significant. Research on functioning in these domains will be important for understanding the development of ADHD, and for improving treatment and prevention approaches.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with attention-deficit/hyperactivity disorder and autism spectrum disorder in children.

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may be a risk factor for neurodevelopmental deficits and disorders, but evidence is inconsistent. OBJECTIVES: We investigated whether prenatal exposure to PFAS were associated with childhood diagnosis of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). METHODS: This study was based on the Norwegian Mother, Father and Child Cohort Study and included n = 821 ADHD cases, n = 400 ASD cases and n = 980 controls. Diagnostic cases were identified by linkage with the Norwegian Patient Registry. In addition, we used data from the Medical Birth Registry of Norway. The study included the following PFAS measured in maternal plasma sampled mid-pregnancy: Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonate (PFHxS), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonate (PFOS). Relationships between individual PFAS and ADHD or ASD diagnoses were examined using multivariable adjusted logistic regression models. We also tested for possible non-linear exposure-outcome associations. Further, we investigated the PFAS mixture associations with ASD and ADHD diagnoses using a quantile-based g-computation approach. RESULTS: Odds of ASD was significantly elevated in PFOA quartile 2 [OR = 1.71 (95% CI: 1.20, 2.45)] compared to quartile 1, and PFOA appeared to have a non-linear, inverted U-shaped dose-response relationship with ASD. PFOA was also associated with increased odds of ADHD, mainly in quartile 2 [OR = 1.54 (95% CI: 1.16, 2.04)] compared to quartile 1, and displayed a non-linear relationship in the restricted cubic spline model. Several PFAS (PFUnDA, PFDA, and PFOS) were inversely associated with odds of ADHD and/or ASD. Some of the associations were modified by child sex and maternal education. The overall PFAS mixture was inversely associated with ASD [OR = 0.76 (95% CI: 0.64, 0.90)] as well as the carboxylate mixture [OR = 0.79 (95% CI: 0.68, 0.93)] and the sulfonate mixture [OR = 0.84 (95% CI: 0.73, 0.96)]. CONCLUSION: Prenatal exposure to PFOA was associated with increased risk of ASD and ADHD in children. For some PFAS, as well as their mixtures, there were inverse associations with ASD and/or ADHD. However, the inverse associations reported herein should not be interpreted as protective effects, but rather that there could be some unresolved confounding for these relationships. The epidemiologic literature linking PFAS exposures with neurodevelopmental outcomes is still inconclusive, suggesting the need for more research to elucidate the neurotoxicological potential of PFAS during early development.

Gestational blood levels of toxic metal and essential element mixtures and associations with global DNA methylation in pregnant women and their infants.

BACKGROUND: Pregnant women and their fetuses are exposed to multiple toxic metals that together with variations in essential element levels may alter epigenetic regulation, such as DNA methylation. OBJECTIVES: The aim of the study was to investigate the associations between gestational levels of toxic metals and essential elements and mixtures thereof, with global DNA methylation levels in pregnant women and their newborn children. METHODS: Using 631 mother-child pairs from a prospective birth cohort (The Norwegian Mother, Father and Child Cohort Study), we measured maternal blood concentration (gestation week ~18) of five toxic metals and seven essential elements. We investigated associations as individual exposures and two-way interactions, using elastic net regression, and total mixture, using quantile g-computation, with blood levels of 5-methylcytocine (5mC) and 5-hydroxymethylcytosine (5hmC) in mothers during pregnancy and their newborn children (cord blood). Multiple testing was adjusted for using the Benjamini and Hochberg false discovery rate (FDR) approach. RESULTS: The most sensitive marker of DNA methylation appeared to be 5mC levels. In pregnant mothers, elastic net regression indicated associations between 5mC and selenium and lead (non-linear), while in newborns results indicated relationships between maternal selenium, cobalt (non-linear) and mercury and 5mC, as well as copper (non-linear) and 5hmC levels. Several possible two-way interactions were identified (e.g. arsenic and mercury, and selenium and maternal smoking in newborns). None of these findings met the FDR threshold for multiple testing. No net effect was observed in the joint (mixture) exposure-approach using quantile g-computation. CONCLUSION: We identified few associations between gestational levels of several toxic metals and essential elements and global DNA methylation in pregnant mothers and their newborn children. As DNA methylation dysregulation might be a key mechanism in disease development and thus of high importance for public health, our results should be considered as important candidates to investigate in future studies.

Estimating infectiousness throughout SARS-CoV-2 infection course.

Two elementary parameters for quantifying viral infection and shedding are viral load and whether samples yield a replicating virus isolate in cell culture. We examined 25,381 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Germany, including 6110 from test centers attended by presymptomatic, asymptomatic, and mildly symptomatic (PAMS) subjects, 9519 who were hospitalized, and 1533 B.1.1.7 lineage infections. The viral load of the youngest subjects was lower than that of the older subjects by 0.5 (or fewer) log10 units, and they displayed an estimated ~78% of the peak cell culture replication probability; in part this was due to smaller swab sizes and unlikely to be clinically relevant. Viral loads above 109 copies per swab were found in 8% of subjects, one-third of whom were PAMS, with a mean age of 37.6 years. We estimate 4.3 days from onset of shedding to peak viral load (108.1 RNA copies per swab) and peak cell culture isolation probability (0.75). B.1.1.7 subjects had mean log10 viral load 1.05 higher than that of non-B.1.1.7 subjects, and the estimated cell culture replication probability of B.1.1.7 subjects was higher by a factor of 2.6.

Metal and essential element concentrations during pregnancy and associations with autism spectrum disorder and attention-deficit/hyperactivity disorder in children.

BACKGROUND: Prenatal exposure to toxic metals or variations in maternal levels of essential elements during pregnancy may be a risk factor for neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring. OBJECTIVES: We investigated whether maternal levels of toxic metals and essential elements measured in mid-pregnancy, individually and as mixtures, were associated with childhood diagnosis of ADHD or ASD. METHODS: This study is based on the Norwegian Mother, Father and Child Cohort Study and included 705 ADHD cases, 397 ASD cases and 1034 controls. Cases were identified through linkage with the Norwegian Patient Registry. Maternal concentrations of 11 metals/elements were measured in blood at week 17 of gestation; cadmium; cesium; cobalt; copper; lead; magnesium; manganese; selenium; zinc; total arsenic; and total mercury. Multivariable adjusted logistic regression models were used to examine associations between quartile levels of individual metals/elements and outcomes. We also investigated non-linear associations using restricted cubic spline models. The joint effects of the metal/element mixture on ASD and ADHD diagnoses were estimated using a quantile-based g-computation approach. RESULTS: For ASD, we identified positive associations (increased risks) in the second quartile of arsenic [OR = 1.77 (CI: 1.26, 2.49)] and the fourth quartiles of cadmium and manganese [OR = 1.57 (CI: 1.07 2.31); OR = 1.84 (CI: 1.30, 2.59)], respectively. In addition, there were negative associations between cesium, copper, mercury, and zinc and ASD. For ADHD, we found increased risk in the fourth quartiles of cadmium and magnesium [OR = 1.59 (CI: 1.15, 2.18); [OR = 1.42 (CI: 1.06, 1.91)]. There were also some negative associations, among others with mercury. In addition, we identified non-linear associations between ASD and arsenic, mercury, magnesium, and lead, and between ADHD and arsenic, copper, manganese, and mercury. There were no significant findings in the mixture approach analyses. CONCLUSION: Results from the present study show several associations between levels of metals and elements during gestation and ASD and ADHD in children. The most notable ones involved arsenic, cadmium, copper, mercury, manganese, magnesium, and lead. Our results suggest that even population levels of these compounds may have negative impacts on neurodevelopment. As we observed mainly similarities among the metals' and elements' impact on ASD and ADHD, it could be that the two disorders share some neurochemical and neurodevelopmental pathways. The results warrant further investigation and replication, as well as studies of combined effects of metals/elements and mechanistic underpinnings.

The associations between maternal and child diet quality and child ADHD - findings from a large Norwegian pregnancy cohort study.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder. Effective long-term treatment options are limited, which warrants increased focus on potential modifiable risk factors. The aim of this study was to investigate associations between maternal diet quality during pregnancy and child diet quality and child ADHD symptoms and ADHD diagnosis. METHODS: This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). We assessed maternal diet quality with the Prenatal Diet Quality Index (PDQI) and Ultra-Processed Food Index (UPFI) around mid-gestation, and child diet quality using the Diet Quality Index (CDQI) at 3 years. ADHD symptoms were assessed at child age 8 years using the Parent Rating Scale for Disruptive Behaviour Disorders. ADHD diagnoses were retrieved from the Norwegian Patient Registry. RESULTS: In total, 77,768 mother-child pairs were eligible for studying ADHD diagnoses and 37,787 for ADHD symptoms. Means (SD) for the PDQI, UPFI and CDQI were 83.1 (9.3), 31.8 (9.7) and 60.3 (10.6), respectively. Mean (SD) ADHD symptom score was 8.4 (7.1) and ADHD diagnosis prevalence was 2.9% (male to female ratio 2.6:1). For one SD increase in maternal diet index scores, we saw a change in mean (percent) ADHD symptom score of - 0.28 (- 3.3%) (CI: - 0.41, - 0.14 (- 4.8, - 1.6%)) for PDQI scores and 0.25 (+ 3.0%) (CI: 0.13, 0.38 (1.5, 4.5%)) for UPFI scores. A one SD increase in PDQI score was associated with a relative risk of ADHD diagnosis of 0.87 (CI: 0.79, 0.97). We found no reliable associations with either outcomes for the CDQI, and no reliable change in risk of ADHD diagnosis for the UPFI. CONCLUSIONS: We provide evidence that overall maternal diet quality during pregnancy is associated with a small decrease in ADHD symptom score at 8 years and lower risk for ADHD diagnosis, with more robust findings for the latter outcome. Consumption of ultra-processed foods was only associated with increased ADHD symptom score of similar magnitude as for overall maternal diet quality, and we found no associations between child diet quality and either outcome. No causal inferences should be made based on these results, due to potential unmeasured confounding.

Prenatal phthalate exposures and executive function in preschool children.

BACKGROUND: Prenatal phthalate exposure has been linked with altered neurodevelopment, including externalizing behaviors and attention-deficit hyperactivity disorder (ADHD). However, the implicated metabolite, neurobehavioral endpoint, and child sex have not always been consistent across studies, possibly due to heterogeneity in neurodevelopmental instruments. The complex set of findings may be synthesized using executive function (EF), a construct of complex cognitive processes that facilitate ongoing goal-directed behaviors. Impaired EF can be presented with various phenotypes of poor neurodevelopment, differently across structured conditions, home/community, or preschool/school. We evaluated the relationship between prenatal phthalate exposure and comprehensive assessment of preschool EF. METHODS: Our study comprised 262 children with clinically significant/subthreshold ADHD symptoms and 78 typically developing children who were born between 2003 and 2008 and participated in the Preschool ADHD Substudy, which is nested within a population-based prospective cohort study, the Norwegian Mother, Father, and Child Cohort (MoBa). Twelve phthalate metabolites were measured from urine samples that their mothers had provided during pregnancy, at 17 weeks' gestation. All children, at approximately 3.5-years, took part in a detailed clinical assessment that included parent-and teacher-rated inventories and administered tests. We used instruments that measured constructs related to EF, which include a parent-and teacher-reported Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) and three performance-based tests: A Developmental NEuroPSYchological Assessment (NEPSY), Stanford-Binet intelligence test V (SB5), and the cookie delay task (CDT). The standard deviation change in test score per interquartile range (IQR) increase in phthalate metabolite was estimated with multivariable linear regression. We applied weighting in all models to account for the oversampling of children with clinically significant or subthreshold symptoms of ADHD. Additionally, we assessed modification by child sex and potential co-pollutant confounding. RESULTS: Elevated exposure to mono-benzyl phthalate (MBzP) during pregnancy was associated with poorer EF, across all domains and instruments, in both sex. For example, an IQR increase in MBzP was associated with poorer working memory rated by parent (1.23 [95% CI: 0.20, 2.26]) and teacher (1.13 [0.14, 2.13]) using BRIEF-P, and administered tests such as SB5 (no-verbal: 0.19 [0.09, 0.28]; verbal: 0.13 [0.01, 0.25]). Adverse associations were also observed for mono-n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP), although results varied by instruments. EF domains reported by parents using BRIEF-P were most apparently implicated, with stronger associations among boys (e.g., MnBP and inhibition: 2.74 [1.77, 3.72]; MiBP and inhibition: 1.88 [0.84, 2.92]) than among girls (e.g., MnBP and inhibition: -0.63 [-2.08, 0.83], interaction p-value: 0.04; MiBP and inhibition: -0.15 [-1.04, 0.74], interaction p-value: 0.3). Differences by sex, however, were not found for the teacher-rated BRIEF-P or administered tests including NEPSY, SB5, and CDT. CONCLUSION AND RELEVANCE: Elevated mid-pregnancy MBzP, MiBP, and MnBP were associated with more adverse profiles of EF among preschool-aged children across a range of instruments and raters, with some associations found only among boys. Given our findings and accumulating evidence of the prenatal period as a critical window for phthalate exposure, there is a timely need to expand the current phthalate regulations focused on baby products to include pregnancy exposures.

Social anxiety among unaccompanied minor refugees in Norway.The association with pre-migration trauma and post-migration acculturation related factors.

OBJECTIVE: Unaccompanied refugee minors (URMs), are at high risk for mental health problems, yet there is a lack of knowledge about social anxiety among these youths. The aim of this study was to investigate symptoms of social anxiety among URMs resettled in Norway, and the combined effects of pre-migration traumatic events, post-migration acculturation related factors (perceived discrimination and culture competence in relation both to the heritage and majority cultures) and demographic background variables, over and above the effect of concurrent depressive symptoms. METHODS: Cross-sectional self-report questionnaire data were collected from 557 URMs from 31 different countries, mainly from Afghanistan (49,6%), Somalia (11,1%), and Iraq (7,0%). RESULTS: The findings from structural equation model (SEM) showed that the effect of pre-migration traumatic events on social anxiety was non-significant (ß = 0.001, p = .09), while perceived discrimination and majority culture competence had unique effects on social anxiety (ß = 0.39, p < .001 and ß = -0.12, p = .008, respectively) over and above depressive symptoms (ß = 0.30, p < .001). CONCLUSIONS: The findings show that factors of the current socio-cultural developmental context rather than pre-migration war-related traumatic events the youths experienced before migration accounts for variation in social anxiety. Potential practical implications of the findings for social workers, educational staff and clinicians are discussed.

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 [ß = -0.08 (CI: -0.12, -0.03)] and a positive association between PFAS component 2 and verbal working memory [ß = 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.

Bias from self selection and loss to follow-up in prospective cohort studies.

Self-selection into prospective cohort studies and loss to follow-up can cause biased exposure-outcome association estimates. Previous investigations illustrated that such biases can be small in large prospective cohort studies. The structural approach to selection bias shows that general statements about bias are not possible for studies that investigate multiple exposures and outcomes, and that inverse probability of participation weighting (IPPW) but not adjustment for participation predictors generally reduces bias from self-selection and loss to follow-up. We propose to substantiate assumptions in structural models of selection bias through calculation of genetic correlations coefficients between participation predictors, outcome, and exposure, and to estimate a lower bound for bias due to self-selection and loss to follow-up by comparing effect estimates from IPP weighted and unweighted analyses. This study used data from the Norwegian Mother and Child Cohort Study and the Medical Birth Registry of Norway. Using the example of risk factors for ADHD, we find that genetic correlations between participation predictors, exposures, and outcome suggest the presence of bias. The comparison of exposure-outcome associations from regressions with and without IPPW revealed meaningful deviations. Assessment of selection bias for entire multi-exposure multi-outcome cohort studies is not possible. Instead, it has to be assessed and controlled on a case-by-case basis.

Estimating the Strength of Associations Between Prenatal Diet Quality and Child Developmental Outcomes: Results From a Large Prospective Pregnancy Cohort Study.

Our aim in this study was to estimate the strength of associations between prenatal diet quality and child behavioral, language, and motor functions in the Norwegian Mother and Child Cohort Study (1999-2008). We created a prenatal diet quality index (PDQI) based on adherence to Norwegian dietary guidelines. Child outcomes were defined as sum scores on the Child Behavior Checklist, the Ages and Stages Questionnaire, and the Child Development Index at ages 18, 36, and 60 months. Using a longitudinal cohort study design and Bayesian hierarchical modeling, we estimated association strengths using inverse probability weighting to account for selection bias. In total, 27,529 mother-child pairs were eligible for inclusion. A 1-standard-deviation increase in PDQI score was associated with an absolute reduction in outcome sum scores of 0.02-0.21 and a 3%-7% relative decrease, with larger decreases seen for language and motor functions than for behavioral functions. PDQI scores were inversely associated with all child functions, but the estimated strength of each association was low. The results indicate that the observed variations in PDQI scores in an industrialized Western society may not profoundly influence the child functions studied.

Screening with an ADHD-specific rating scale in preschoolers: A cross-cultural comparison of the Early Childhood Inventory-4.

The Early Childhood Inventory-4 (ECI-4) Hyperactivity-Impulsivity (HI) and Inattention (IA) subscales are screeners for attention-deficit/hyperactivity disorder (ADHD). There have been few studies of the screening properties of these subscales, particularly outside the United States. We investigated the classification accuracy of the parent and teacher versions of the HI and IA subscales and the cross-cultural validity of the cutoff values based on norms from a United States sample. The present study was part of the Norwegian Mother and Child Cohort Study. Parents and teachers rated boys (n = 332) and girls (n = 319) with the ECI-4 (mean Age 3.5 years). Interviewers who were blind to the ratings used the Preschool Age Psychiatric Assessment Interview to assign ADHD diagnoses. The ECI-4 HI and IA subscales showed acceptable accuracy in identifying ADHD in boys and girls (areas under the curve ranged from .67 to .85). In a multivariate regression analysis, the parent and teacher HI subscale scores significantly contributed to ADHD identification, but not the IA subscale scores. To achieve the necessary sensitivity to detect children with ADHD, lower cutoff levels than those specified by the United States ECI-4 norms were needed. For screening purposes, the parent and teacher ECI-4 showed acceptable accuracy in identifying preschoolers at risk for ADHD, and it may be sufficient to use the HI subscale scores. The suggested cutoff values provided by the United States ECI-4 norms had limited cross-cultural validity. (PsycINFO Database Record (c) 2019 APA, all rights reserved).