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.

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.

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.

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.

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.

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.

Diagnosis of hyperkinetic disorder among children in Norway. / Diagnostikk av hyperkinetisk forstyrrelse hos barn i Norge.

BACKGROUND: Hyperkinetic disorder is one of the most frequently used psychiatric diagnoses among children and adolescents in Norway. It has previously been shown that use of the diagnosis varies widely by county. MATERIAL AND METHOD: We estimated the proportion of children with hyperkinetic disorder using patient data from the Norwegian Patient Registry and population data from the Norwegian Population Registry. The estimations were made for both Norway as a whole and by county. Assessment and documentation of the diagnosis were surveyed by linking the Norwegian Patient Registry and the Norwegian Mother and Child Cohort Study. We reviewed medical records from specialist mental health services for children and adolescents and assessed whether the diagnoses met the research criteria for hyperkinetic disorder. RESULTS: At 12 years of age, 5.4 % of Norwegian boys and 2.1 % of Norwegian girls had been diagnosed with hyperkinetic disorder by specialist health services. The proportion of children varied between 1.4 % and 5.5 % among the counties. A review of medical records for 549 children showed that 49 % of the diagnoses were reliably documented in the records. The main reasons that the diagnosis was not documented were a discrepancy between the information in the medical record and diagnostic criteria (38 %) and inadequate differential diagnostic assessment (46 %). INTERPRETATION: There was considerable geographic variation in the proportions of children and adolescents with hyperkinetic disorder. A large percentage of the diagnoses were not reliably documented in medical records. The guideline for evaluation, diagnostics and medical recordkeeping should be reviewed.