Efficacy and Safety of Polyunsaturated Fatty Acids Supplementation in the Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Children and Adolescents: A Systematic Review and Meta-Analysis of Clinical Trials.

Based on epidemiological and animal studies, the rationale for using polyunsaturated fatty acids (PUFAs) as a treatment for Attention Deficit Hyperactivity Disorder (ADHD) seems promising. Here, the objective was to systematically identify and critically assess the evidence from clinical trials. The primary outcome was ADHD core symptoms. The secondary outcomes were behavioral difficulties, quality of life, and side effects. We performed a systematic search in Medline, Embase, Cinahl, PsycInfo, and the Cochrane Library up to June 2020. The overall certainty of evidence was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). We identified 31 relevant randomized controlled trials including 1755 patients. The results showed no effect on ADHD core symptoms rated by parents (k = 23; SMD: -0.17; 95% CI: -0.32, -0.02) or teachers (k = 10; SMD: -0.06; 95% CI: -0.31, 0.19). There was no effect on behavioral difficulties, rated by parents (k = 7; SMD: -0.02; 95% CI: -0.17, 0.14) or teachers (k = 5; SMD: -0.04; 95% CI: -0.35, 0.26). There was no effect on quality of life (SMD: 0.01; 95% CI: -0.29, 0.31). PUFA did not increase the occurrence of side effects. For now, there seems to be no benefit of PUFA in ADHD treatment; however, the certainty of evidence is questionable, and thus no conclusive guidance can be made. The protocol is registered in PROSPERO ID: CRD42020158453.

Non-pharmacological interventions for preventing weight gain in patients with first episode schizophrenia or bipolar disorder: A systematic review.

Weight gain is a side effect of antipsychotic medication and highly prevalent in people with schizophrenia or bipolar disorder, increasing their overall cardio-metabolic risk. We conducted a systematic review on non-pharmacological interventions for preventing/reducing weight gain or increase in waist-circumference in young, newly diagnosed patients with schizophrenia or bipolar disorder. We searched major electronic databases from inception to 04/2019 on RCTs, pre- and post-test studies, and non-randomized controlled clinical trials. From a potential of 2963 hits, eight studies met the inclusion criteria (n = 438, mean age of 18.8 (13-45) years). The interventions comprised supervised and individually adjusted aerobic exercise activities (5 studies), individual lifestyle counselling vs. control condition (2 RCTs), and dietetic counselling and practical training of cooking and shopping (1 study). Physical activity and practical dietetic interventions seem to be more efficient than lifestyle counselling. However, the results shall be taken with caution due to the non-randomized designs and other methodologically deficits in the majority of the included studies.

[Mindfulness as treatment for ADHD].

This review presents an overview of the present knowledge of the effectiveness of mindfulness interventions (MI) for patients with ADHD. A search was performed in four databases, and 15 papers were found. In adults, the effect of MI was significant on ADHD symptoms but unclear on other outcomes. For children and adolescents, results were uncertain but point toward improved planning, cognitive flexibility and better interactions in the families. No studies have compared the efficacy of MI to pharmacological treatment. Evidence in the field is still sparse due to small sample sizes and differences in study designs.

The early motor development in children diagnosed with ADHD: a systematic review.

Although there is limited knowledge about early signs of ADHD, deviations in motor development are suggested as a possible indicator of such early signs. The purpose of the present systematic review was to gather knowledge about motor development before three years of age in children later diagnosed with ADHD. A systematic search was completed in four research databases, and the quality of the identified studies was systematically assessed. Of 440 initial search results, only five studies met the inclusion criteria and were fully abstracted. Major methodological heterogeneity was found between the studies, and the results are pointing in various directions. One study found an association between delay in gross motor development and ADHD, while another did not. However, associations between both good early motor development as well as delayed were also found in one study. A study of premature infants showed no association between early motor development and attention problems at school age, and a study of high-risk children from a neonatal care unit found no association between abnormal general movements and later ADHD without comorbidity. The results of the studies are pointing in various directions. No firm conclusion can be drawn on early motor development in children with ADHD due to the very different results of the studies and the methodological heterogeneity.

EARLY REGULATION IN CHILDREN WHO ARE LATER DIAGNOSED WITH AUTISM SPECTRUM DISORDER. A LONGITUDINAL STUDY WITHIN THE DANISH NATIONAL BIRTH COHORT.

Studies have shown that children later diagnosed with autism spectrum disorders (ASD) in their first years of life might show symptoms in main developmental areas and that these signs might be sensed by the parents. The present study investigated in a large birth cohort if children later diagnosed with ASD had deviations at 6 and 18 months in areas such as the ability to self-regulate emotions, feeding, and sleeping. The study was based on prospective information collected from 76,322 mothers who participated in the Danish National Birth Cohort. When the children reached an average age of 11 years, 973 children with ASD and a control group of 300 children with intellectual disability (IDnoASD) were identified via Danish health registries. Associations were found between short periods of breast-feeding and the children later diagnosed with ASD and IDnoASD as well as associations at 18 months to deviations in regulation of emotions and activity. The similarities in these associations emphasize how difficult it is to distinguish between diagnoses early in life.

Maternal body mass index before pregnancy as a risk factor for ADHD and autism in children.

The risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) may be influenced by environmental factors such as maternal obesity before pregnancy. Previous studies investigating those associations have found divergent results. We aim to investigate in a large birth cohort this association further in children with ADHD, ASD and comorbid ADHD and ASD. Our study population consisted of 81,892 mother-child pairs participating in the Danish National Birth Cohort (DNBC). Information about pre-pregnancy weight and height was collected in week 16 of pregnancy; the analysis was divided into groups based on BMI. Children with a clinical diagnosis of ADHD and/or ASD were identified in the Danish health registries at an average age of 13.3 years. Hazard ratios (HRs) were estimated using time-to-event analysis. Compared to normal weight mothers, the risk of having a child with ADHD was significantly increased if the mother was overweight (HR = 1.28 [95% CI 1.15;1.48]), obese (HR = 1.47 [95% CI 1.26;1.71]) or severely obese (HR = 1.95 [95% CI 1.58;2.40]). The same pattern was seen for the combined ADHD and ASD group. Regarding ASD, an increased risk was observed in underweight (HR = 1.30 [95% CI 1.01;1.69]) and obese (HR = 1.39 [95% CI 1.11;1.75]) mothers. Subgroup analysis revealed that the association in the ADHD group could mostly be attributable to the hyperactive group. Maternal obesity before pregnancy is a risk factor for ADHD in children. Maternal obesity as well as underweight may also be associated with an increased risk for ASD.

Early development in Rett syndrome - the benefits and difficulties of a birth cohort approach.

PURPOSES: Typically, early (pre-diagnostic) development in individuals later diagnosed with Rett syndrome (RTT) has been investigated retrospectively using parent reports, medical records and analysis of home videos. In recent years, prospective research designs have been increasingly applied to the investigation of early development in individuals with late phenotypical onset disorders, for example, autism spectrum disorder. METHODS: In this study, data collected by the Danish National Birth Cohort lent itself to prospective exploration of the early development of RTT, in particular early motor-, speech-language, and socio-communicative behaviors, mood, and sleep. RESULTS AND CONCLUSIONS: Despite limitations, this quasi prospective methodology proved promising. In order to add substantially to the body of knowledge, however, specific questions relating to peculiarites in early development could usefully be added to future cohort studies. As this involves considerable work, it may be more realistic to consider a set of indicators which point to a number of developmental disorders rather than to one.

European studies on prevalence and risk of autism spectrum disorders according to immigrant status-a review.

BACKGROUND: Autism spectrum disorders (ASDs), once considered to be rare, are now reaching prevalence estimates of 1% and higher. Studies conducted in North America indicate large racial/ethnic disparities in the diagnosis of ASDs. Others show, that immigrant children have similar prevalence rates of ASDs as native children, although they are diagnosed later compared with native children. In relation to a EU funded network action, Enhancing the Scientific Study of Early Autism, it was considered important to review the literature on this subject. METHOD: A comprehensive literature search was undertaken for original articles reporting on prevalence and risk for ASD in Europe among immigrants and ethnic minorities and data across studies were compared. RESULTS: Seventeen studies conducted in Europe concerning immigrants and ethnic minorities were found. Fifteen studies suggest a higher prevalence rate of ASDs among children of immigrants in comparison to native children (RR = 1.02-1.74; OR = 0.6-10.5). One study revealed higher prevalence of autism (OR = 2.2; 95% CI 1.6-3.1) and lower prevalence of Asperger syndrome in immigrants (OR = 0.6; 95% CI 0.3-0.97). One study showed a lower prevalence of Asperger syndrome in immigrants (aOR = 0.1, 95% CI 0.01-0.5). The majority of those analyses involved immigrants from outside Europe, e.g. from Africa and South America. CONCLUSION: After analysing the results of studies conducted in Europe, it is unclear if higher prevalence estimates of ASDs among immigrants in this region reflect true differences, especially considering many potential confounding factors, e.g. genetic, biological, environmental and cultural. Considering the number of people migrating within Europe there is a substantial need to study further the prevalence of ASDs in immigrant groups.

Syntax and Morphology in Danish-Speaking Children with Autism Spectrum Disorder.

The current study examined delays in syntax and morphology, and vocabulary, in autism spectrum disorder (ASD). Children ages 4-6 years with ASD (n = 21) and typical development (n = 21), matched on nonverbal mental age, completed five language tasks. The ASD group had significant delays in both syntax and morphology, and vocabulary measures, with significant within-group heterogeneity; furthermore, syntactic and morphological measures were impaired even for subgroups matched on vocabulary. Children in the ASD group without early language delay showed syntactic and morphological impairment, with intact performance on vocabulary and sentence repetition. Findings indicate that syntactic and morphological impairments are a significant concern for high-functioning children with ASD, and may be overlooked if language evaluation focuses exclusively on vocabulary.

Early development in children that are later diagnosed with disorders of attention and activity: a longitudinal study in the Danish National Birth Cohort.

Not much is known about the early development in children that are later diagnosed with disorders of attention and activity (ADHD). Using prospective information collected from mothers in the Danish National Birth Cohort (DNBC), we investigated if developmental deviations in the first years of life are associated with later ADHD. In the DNBC 76,286 mothers were interviewed about their child's development and behaviour at age 6 and 18 months. At the end of follow-up, when the children were 8-14 years of age, 2034 were registered in Danish health registers with a clinical diagnosis of ADHD. The Hazard Ratio of ADHD was estimated using Cox regression model. At 6 months of age deviations in development showed associations with the child later being diagnosed with ADHD such as duration of breastfeeding, motor functioning, and incessant crying. At 18 months, many observations clearly associated with ADHD as for example the child not being able to fetch things on request [HR 3.0 (95 % CI 2.4; 3.7)], or the child being significantly more active than average [HR 2.0 (95 % CI 1.8; 2.2)]. An association to ADHD was shown, especially at 18 months, if the mother found it difficult to handle the child [HR 2.9 (95 % CI 2.4-3.5)]. However, it goes for all observations that the positive predictive values were low. Many children with ADHD showed signs of developmental deviations during the first years of their life. In general, however, ADHD cannot be identified solely on basis of the questions in DNBC.

Use of early intervention for young children with autism spectrum disorder across Europe.

Little is known about use of early interventions for autism spectrum disorder in Europe. Parents of children with autism spectrum disorder aged 7 years or younger (N = 1680) were recruited through parent organisations in 18 European countries and completed an online survey about the interventions their child received. There was considerable variation in use of interventions, and in some countries more than 20% of children received no intervention at all. The most frequently reported interventions were speech and language therapy (64%) and behavioural, developmental and relationship-based interventions (55%). In some parts of Europe, use of behavioural, developmental and relationship-based interventions was associated with higher parental educational level and time passed since diagnosis, rather than with child characteristics. These findings highlight the need to monitor use of intervention for children with autism spectrum disorder in Europe in order to contrast inequalities.

Early signs of autism in toddlers: a follow-up study in the Danish National Birth Cohort.

To identify possible early signs of autism spectrum disorder (ASD) within the Danish National Birth Cohort, we studied prospectively collected interviews from 76,441 mothers about their children's development and behaviour at 6 and 18 months. In Danish national registries, 720 children with ASD and 231 children with intellectual disability (ID) were identified. At 6 months, associations between early signs and ASD or ID were found only in few areas. At 18 months social, language, and motor skills were delayed, and suspicion of vision and hearing problems were increased for both groups. Signs distinguishing ASD from ID were unclear, and the positive predictive values regarding ASD were below 10 % for individual predictors and aggregated risk scores.

Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders.

Exposure to prenatal infection has been suggested to cause deficiencies in fetal neurodevelopment. In this study we included all children born in Denmark from 1980, through 2005. Diagnoses of autism spectrum disorders (ASDs) and maternal infection were obtained through nationwide registers. Data was analyzed using Cox proportional hazards regression. No association was found between any maternal infection and diagnosis of ASDs in the child when looking at the total period of pregnancy: adjusted hazard ratio = 1.14 (CI: 0.96-1.34). However, admission to hospital due to maternal viral infection in the first trimester and maternal bacterial infection in the second trimester were found to be associated with diagnosis of ASDs in the offspring, adjusted hazard ratio = 2.98 (CI: 1.29-7.15) and adjusted hazard ratio = 1.42 (CI: 1.08-1.87), respectively. Our results support prior hypotheses concerning early prenatal viral infection increasing the risk of ASDs.

Validity of childhood autism in the Danish Psychiatric Central Register: findings from a cohort sample born 1990-1999.

The purpose of this study was to assess the validity of the diagnosis of childhood autism in the Danish Psychiatric Central Register (DPCR) by reviewing medical records from 499 of 504 total children with childhood autism born 1990-1999. Based on review of abstracted behaviors recorded in case records from child psychiatric hospitals, case status determination was performed using a standardized coding scheme. In 499 children diagnosed with childhood autism in the DPCR, the diagnosis could be confirmed in 469 children (94%). Of the 30 non-confirmed cases, five were classified by the reviewers as non-autistic cases and the remaining 25 cases were either classified with another ASD diagnosis or the specific diagnosis was not possible to determine.