Marianne Simonsen

Five-Fold Increase in National Prevalence Rates of Attention-Deficit/Hyperactivity Disorder Medications for Children and Adolescents with Autism Spectrum Disorder, Attention-Deficit/Hyperactivity Disorder, and other Psychiatric Disorders: A Danish Register-Based Study

OBJECTIVE The purpose of this study was to estimate the prevalence and time trends in prescriptions of methylphenidate, dexamphetamine, and atomoxetine in children and adolescents, within three diagnostic groups: 1) autism spectrum disorder (ASD), 2) attention-deficit/hyperactivity disorder (ADHD), and 3) other psychiatric disorders. METHODS Data from six different national registers were used and merged to identify a cohort of all children and adolescents born in Denmark between 1990 and 2001 (n=852,711). Sociodemographic covariates on cohort members and their parents and lifetime prescriptions of methylphenidate, dexamphetamine, and atomoxetine were extracted from the registers. Prescriptions were also stratified by duration (<6 months. vs.≥ 6 months). RESULTS Sixteen percent of 9698 children and adolescents with ASD (n=1577), 61% of 11,553 children and adolescents with ADHD (n=7021) and 3% of 48,468 children and adolescents with other psychiatric disorders (n=1537) were treated with one or more ADHD medications. There was a significant increase in prescription rates of these medications for all three groups. From 2003 to 2010, youth 6-13 years of age with ASD, ADHD, and other psychiatric disorders had 4.7-fold (4.4-4.9), 6.3-fold (6.0-6.4), and 5.5-fold (5.0-5.9) increases, respectively, in prescription rates of ADHD medications. CONCLUSION This is the largest study to date assessing stimulant treatment in children and adolescents with ASD, and is the first prospective study quantifying the change over time in the prevalence of treatment with ADHD medications in a population-based national cohort of children and adolescents with ASD. The prevalence of stimulant treatment in youth with ASD of 16% is consistent with earlier studies. The past decade has witnessed a clear and progressive increase in the prescription rates of medications typically used to treat ADHD in children and adolescents in Denmark. This increase is not limited to only those with ADHD, but includes others with neuropsychiatric disorders, including ASD. The risks and benefits of this practice await further study.

Effect of drugs on the risk of injuries in children with attention deficit hyperactivity disorder: a prospective cohort study

BACKGROUND Injuries represent the largest disease burden and most common cause of death in children. Attention deficit hyperactivity disorder (ADHD) is associated with increased mortality, with accidents being the most common cause of death in ADHD. However, it is not known whether pharmacological treatment has any modifying effect on the risk of injuries in children and adolescents with ADHD. METHODS Using Danish national registers, we followed a cohort of 710 120 individuals, including 4557 individuals diagnosed with ADHD before age 10 years. Using a quasi-experimental, difference-in-difference design, we estimated the odds ratios (ORs) for injuries and the mean change in prevalence rates of injuries and emergency ward visits before and after treatment, with matched untreated children with ADHD at the same age serving as controls. FINDINGS Children with ADHD were more likely to sustain injuries, compared with children without ADHD, at age 10 years (adjusted OR=1·29, 95% CI 1·22-1·37) and at age 12 years (adjusted OR=1·30, 1·23-1·37). From age 5 to 10 years, the prevalence of injuries in children with ADHD who were treated with ADHD drugs decreased from 19% to 14%, compared with a prevalence of about 17% in non-treated children with ADHD. This corresponded to an adjusted difference-in-difference reduction in prevalence of injuries at age 10 years of 31·5% (8·2-54·8) and 43·5% (18·1-69·0) at age 12 years due to treatment. Pharmacological treatment also reduced the prevalence of emergency ward visits at age 10 years (28·2%, 6·3-50·1) and age 12 years (45·7%, 25·8-65·7). INTERPRETATION Children with ADHD had an increased risk of injuries compared with other children. Treatment with ADHD drugs reduced the risk of injuries by up to 43% and emergency ward visits by up to 45% in children with ADHD. Taken together with previous findings of accidents being the most common cause of death in individuals with ADHD, these results are of major public health importance. FUNDING The Lundbeck Foundation, the Danish Council for Independent Research, Centre For Integrated Register-based Research at Aarhus University, the Region of Southern Denmark Research Foundation, and Wørzners Foundation.

Cardiovascular Safety of Stimulants in Children with Attention-Deficit/Hyperactivity Disorder: A Nationwide Prospective Cohort Study

OBJECTIVE The purpose of this study was to determine whether stimulant users are at higher risk of a later cardiovascular event than are non-users, examining this association in both a national cohort and a population-based sample of children and adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD). We also aim to examine a possible dose-response relationship in such an association. METHODS We conducted a longitudinal, prospective cohort study of all children born in Denmark between 1990 and 1999. Within this cohort, children with ADHD were identified. Data from national health registers on psychiatric and somatic diagnoses, stimulant prescriptions, cardiovascular risk factors, pre- and perinatal and sociodemographic covariates in all children and their parents were merged, using the unique personal identification number. Hazard ratios (HR) for cardiovascular events were estimated using Cox regression, adjusted for other known risk factors. RESULTS In the total population (n=714,258 contributing a total of 6,767,982 person-years) use of stimulants increased the risk of a cardiovascular event; adjusted HR=1.83 (1.10-3.04). In children with ADHD (n=8300) stimulant treatment also increased the risk of a cardiovascular event (adjusted HR=2.20 [2.15-2.24]), with a complex time-dependent dose-response relationship. CONCLUSIONS This is the first nationwide cohort study of the cardiovascular safety of stimulants in children and adolescents, and it represents, to our knowledge, the longest prospective follow-up study. Cardiovascular events were rare but twice as likely in stimulant users as in non-users, both in the total national population and in children with ADHD. We found a complex, time- and dose-dependent interrelationship between cardiovascular adverse events and stimulant treatment in children and adolescents. Our results suggest a safety signal with an increased risk of cardiovascular disease associated with stimulant treatment in children and adolescents, even after adjusting for a number of potential confounders.

Bullying in Elementary School

Bullying is a widespread social phenomenon that is thought to have detrimental effects on life outcomes. This paper investigates the link between bullying and later school performance. We rely on rich survey and register-based data for children born in a region of Denmark during 1990–92, which allows us to carefully consider possible confounders including psychological factors. We implement an IV strategy inspired by Carrell and Hoekstra (2010) where we instrument victim status with the proportion of peers from troubled homes in one’s classroom. We show that bullied children suffer in terms of GPA and effects tend to increase with severity.

Price of High-Quality Daycare and Female Employment

Using local variation between municipalities, I analyze the degree to which the price of high-quality publicly subsidized childcare affects female employment following maternity leave. Importantly, prices are income dependent and thus likely endogenous, yet by exploiting information on minimum income compensation during non-employment, I bypass this problem. The results show that the price negatively affects employment. A price increase of €1 per month decreases employment by 0.08%, which corresponds to a price elasticity of −0.17. These effects prevail during the first 12 months after childbirth. I also find that availability of childcare increases employment.

Consequences of ADHD Medication Use for Children's Outcomes

This paper estimates effects of early ADHD medication use on key human capital outcomes for children diagnosed with ADHD while using rarely available register based data on diagnoses and prescription drug purchases. Our main identification strategy exploits plausible exogenous assignment of children to hospitals with specialist physicians, while our analysis of health outcomes also allows for an individual level panel data strategy. We find that the behavior of specialist physicians varies considerably across hospitals and that the prescribing behavior does affect the probability that a given child is treated. Results show that children diagnosed with ADHD in pharmacological treatment have fewer hospital contacts if treated and that treatment to some extent protects against criminal behavior.

Common Danish standards in prescribing medication for children and adolescents with ADHD

Assessing whether symptoms of attention-deficit hyperactivity disorder (ADHD) in children are age-inappropriate is essential. Hence, comparing children within one school grade is problematic and the risk of applying relative standards is inherent. Being young-for-grade increases the likelihood of receiving medication in countries with high prevalence of ADHD medication. We test the same hypothesis in a cohort of 418,396 children and find no difference between children who are young-for-grade and old-for-grade. The Danish system, with its restrictive approach to medication and clear diagnostic guidelines seems to have avoided a systematic bias of ADHD medication in young children reported in other countries.

Gender and injuries predict stimulant medication use.

OBJECTIVE The purpose of this article was to examine whether injuries in early childhood and gender predict prescriptions of stimulant medication in three groups of children: With attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and other psychiatric disorders (OPD). METHODS This was a population-based study with prospective and complete follow-up of children with ADHD (n=11,553), ASD (n=9698), and OPD (n=48,468), of whom 61%, 16%, and 3%, respectively, were treated with stimulants. For all 69,719 individual children data on psychiatric diagnoses, injuries, and drug prescriptions were obtained from national registers and merged. RESULTS Having sustained an injury before 5 years of age increased the likelihood of later stimulant treatment, in children with ADHD (odds ratio [OR]=1.09; 95% confidence interval [CI]=1.01-1.21), ASD (OR=1.19; 95% CI=1.02-1.40), and OPD (OR=1.24; 95% CI=1.08-1.42), with each injury increasing the likelihood by 3%, 10%, and 7%, respectively. Head injury did not increase the likelihood of later stimulant treatment. Within each of the three groups, ADHD, ASD, and OPD boys were more likely than girls to receive stimulant medication, OR=1.17 (95% CI=1.07-1.28); OR=1.71 (95% CI=1.47-2.01), and OR=2.41 (95% CI=2.16-2.71), respectively. CONCLUSIONS To our knowledge, this is the first prospective study assessing early life predictors of later ADHD medication in children with a psychiatric disorder, taken from a national cohort with complete follow-up of all cases. We found that the number of injuries prior to diagnosis was associated with initiation of stimulant treatment in all three groups of patients. In addition, male gender predicted treatment with ADHD medications. Our results suggest that the number of injuries early in life prior to diagnosis is associated with stimulant treatment, and may serve as a proxy for the level of later severity of ADHD symptoms, as it is universally associated with pharmacological treatment for ADHD.

Availability and Price of High Quality Day Care and Female Employment

In this paper I analyse to what degree availability and price of high quality publicly subsidised child care affects female employment for women living in couples following maternity leave. The results show that unrestricted access to day care has a significantly positive effect on female employment. The price effect is significantly negative: An increase in the price of child care of C=1 will decrease the female employment with 0.08% corresponding to a price elasticity of -0.17. This effect prevails during the first 12 months after childbirth.

The toll of fertility on mothers’ wellbeing

Using multiple births as source of variation, we study the impact of fertility on the overall wellbeing of mothers. First, using US Census data for the year 1980, we study the impact of number of children on family arrangements, welfare participation and poverty status. Second, using the National Health Interview Survey (NHIS) for the period 1982-2003, we study the impact on a series of health risk factors. The findings reveal, first, that an increase in family size increases the likelihood of marital breakdown. Second, we find evidence that mothers facing an increase in family size are not only more likely to live with other family members such as grandparents, aunts and uncles, they are also more likely to receive help from welfare programs. Third, consistent with an increase in welfare participation, families (mothers) are more likely to fall below the poverty line, and they face a reduction in total family income. The results using NHIS confirm a negative impact of fertility on marriage stability and an increase in welfare participation measured by the likelihood of using Medicaid and for some samples a reduction in the take-up of private health insurance. Finally, we find evidence that a shock in fertility increases the likelihood of mothers suffering from high blood pressure and becoming obese.