Birth weight as an independent predictor of ADHD symptoms : a within-twin pair analysis

BACKGROUND: Studies have found an association between low birth weight and ADHD, but the nature of this relation is unclear. First, it is uncertain whether birth weight is associated with both of the ADHD dimensions, inattentiveness and hyperactivity-impulsivity. Second, it remains uncertain whether the association between birth weight and ADHD symptom severity is confounded by familial factors. METHOD: Parents of all Swedish 9- and 12-year-old twins born between 1992 and 2000 were interviewed for DSM-IV inattentive and hyperactive-impulsive ADHD symptoms by the Autism - Tics, AD/HD and other Comorbidities (A-TAC) inventory (N= 21,775 twins). Birth weight was collected prospectively through the Medical Birth Registry. We used a within-twin pair design to control for genetic and shared environmental factors. RESULTS: Reduced birth weight was significantly associated with a mean increase in total ADHD (beta = -.42; 95% CI: -.53, -.30), inattentive (beta = -.26; 95% CI: -.33, -.19), and hyperactive-impulsive (beta = -.16; 95% CI: -.22, -.10) symptom severity. These results imply that a change of one kilogram of birth weight corresponded to parents rating their child nearly one unit higher (going from "no" to "yes, to some extent" on a given symptom) on the total ADHD scale. These associations remained within pairs of MZ and DZ twins, and were also present when restricting the analyses to full term births. CONCLUSIONS: There is an independent association between low birth weight and all forms of ADHD symptoms, even after controlling for all environmental and genetic confounds shared within twin pairs. These results indicate that fetal growth restriction (as reflected in birth weight differences within twin pairs) and/or the environmental factors which influence it is in the casual pathway leading to ADHD.The Swedish Council for Working Life and Social ResearchThe Swedish Research CouncilManuscrip

Association between medication use and performance on higher education entrance tests in individuals with Attention-Deficit/Hyperactivity Disorder

Importance: Individuals with attention-deficit/hyperactivity disorder (ADHD) are at greater risk for academic problems. Pharmacologic treatment is effective in reducing the core symptoms of ADHD, but it is unclear whether it helps to improve academic outcomes. Objective: To investigate the association between the use of ADHD medication and performance on higher education entrance tests in individuals with ADHD. Design, Setting, and Participants: This cohort study observed 61640 individuals with a diagnosis of ADHD from January 1, 2006, to December 31, 2013. Records of their pharmacologic treatment were extracted from Swedish national registers along with data from the Swedish Scholastic Aptitude Test. Using a within-patient design, test scores when patients were taking medication for ADHD were compared with scores when they were not taking such medication. Data analysis was performed from November 24, 2015, to November 4, 2016. Exposures: Periods with and without ADHD medication use. Main Outcomes and Measures: Scores from the higher education entrance examination (score range, 1-200 points). Results: Among 930 individuals (493 males and 437 females; mean [SD] age, 22.2 [3.2] years) who had taken multiple entrance tests (n = 2524) and used ADHD medications intermittently, the test scores were a mean of 4.80 points higher (95% CI, 2.26-7.34; P < .001) during periods they were taking medication vs nonmedicated periods, after adjusting for age and practice effects. Similar associations between ADHD medication use and test scores were detected in sensitivity analyses. Conclusions and Relevance: Individuals with ADHD had higher scores on the higher education entrance tests during periods they were taking ADHD medication vs nonmedicated periods. These findings suggest that ADHD medications may help ameliorate educationally relevant outcomes in individuals with ADHD.Swedish Research Council, 340-2013-5867 and 1R01MH102221Swedish Initiative for Research on Microdata in the Social and Medical Sciences, 2013-2280National Institute of Mental HealthAustralian National Health and Medical Research CouncilAccepte

Familial Liability for Eating Disorders and Suicide Attempts: Evidence From a Population Registry in Sweden

IMPORTANCE: Suicide attempts are common in individuals with eating disorders. More precise understanding of the mechanisms underlying their concomitant occurrence is needed. OBJECTIVE: To examine the association between eating disorders and suicide attempts and whether familial risk factors contribute to the association. DESIGN, SETTING, AND PARTICIPANTS: A Swedish birth cohort including individuals born in Sweden between January 1, 1979, and December 31, 2001, was followed up from age 6 years to December 31, 2009 (N = 2,268,786). Information was acquired from Swedish national registers. All individuals were linked to their biological full siblings, maternal half siblings, paternal half siblings, full cousins, and half cousins. Data analysis was conducted from October 5, 2014, to April 28, 2015. MAIN OUTCOMES AND MEASURES: Eating disorders were captured by 3 variables (any eating disorder, anorexia nervosa, and bulimia nervosa) identified by any lifetime diagnoses recorded in the registers. Suicide attempts were defined as any suicide attempts, including death by suicide, recorded in the registers. We examined the association between eating disorders and death by suicide separately, but the study was underpowered to explore familial liability for this association. RESULTS: Of 2,268,786 individuals, 15,457 females (1.40% of all females) and 991 males (0.09% of all males) had any eating disorder, 7680 females (0.70%) and 453 males (0.04%) had anorexia nervosa, and 3349 females (0.30%), and 61 males (0.01%) had bulimia nervosa. Individuals with any eating disorder had an increased risk (reported as odds ratio [95% CI]) of suicide attempts (5.28 [5.04-5.54]) and death by suicide (5.39 [4.00-7.25]). The risks were attenuated but remained significant after adjusting for comorbid major depressive disorder, anxiety disorder, and substance use disorder (suicide attempts: 1.82 [1.72-1.93]; death by suicide: 2.04 [1.49-2.80]). Similar results were found for anorexia nervosa (suicide attempts: crude, 4.42 [4.12-4.74] vs adjusted, 1.70 [1.56-1.85]; death by suicide: crude, 6.46 [4.38-9.54] vs adjusted, 2.67 [1.78-4.01]) and bulimia nervosa (suicide attempts: crude, 6.26 [5.73-6.85] vs adjusted, 1.88 [1.68-2.10]; death by suicide: crude, 4.45 [2.44-8.11] vs adjusted, 1.48 [0.81-2.72]). Individuals (index) who had a full sibling with any eating disorder had an increased risk of suicide attempts (1.41 [1.29-1.53]). The risk was attenuated for any eating disorder in more-distant relatives (maternal half siblings, 1.10 [0.90-1.34]; paternal half siblings, 1.21 [0.98-1.49]; full cousins, 1.11 [1.06-1.18]; half cousins, 0.90 [0.78-1.03]). This familial pattern remained stable after adjusting for the index individuals' eating disorders. Similar patterns were found for anorexia nervosa and bulimia nervosa. CONCLUSIONS AND RELEVANCE: These results suggest an increased risk of suicide attempts in individuals with lifetime eating disorders and their relatives. The pattern of familial coaggregation suggests familial liability for the association between eating disorders and suicide. Psychiatric comorbidities partially explain this association, suggesting particularly high-risk presentations

Shared familial risk factors between attention-deficit/hyperactivity disorder and overweight/obesity : a population based familial co-aggregation study in Sweden

BACKGROUND: Despite meta-analytic evidence for the association between attention-deficit/hyperactivity disorder (ADHD) and overweight/obesity, the mechanisms underlying the association are yet to be fully understood. METHODS: By linking multiple Swedish national and regional registers, we identified 472,735 index males born during 1973-1992, with information on body weight and height directly measured before they were conscripted for military service. We further identified 523,237 full siblings born during 1973-2002 for the index males. All individuals were followed up from their third birthday to December 31, 2009 for ADHD diagnosis. Logistic regression models were used to estimate the association between overweight/obesity in index males and ADHD in their full siblings. RESULTS: Siblings of index males with overweight/obesity had increased risk for ADHD (overweight: OR = 1.14, 95% CI = 1.05-1.24; obesity: OR = 1.42, 95% CI = 1.24-1.63), compared with siblings of index males with normal weight. The results were adjusted for birth year of the index male and sex of the sibling. After further adjustment for ADHD status of the index male, the familial coaggregation remained significant (overweight: OR = 1.13, 95% CI = 1.04-1.22; obesity: OR = 1.38, 95% CI = 1.21-1.57). The results were similar across sex of the siblings. CONCLUSIONS: Attention-deficit/hyperactivity disorder and overweight/obesity share familial risk factors, which are not limited to those causing overweight/obesity through the mediation of ADHD. Future research aiming at identifying family-wide environmental risk factors as well as common pleiotropic genetic variants contributing to both traits is warranted.The Swedish Research CouncilThe Swedish Initiative for research on Microdata in the Social and Medical Sciences (SIMSAM)Accepte

Childhood injury after a parental cancer diagnosis

A parental cancer diagnosis is psychologically straining for the whole family. We investigated whether a parental cancer diagnosis is associated with a higher-than-expected risk of injury among children by using a Swedish nationwide register-based cohort study. Compared to children without parental cancer, children with parental cancer had a higher rate of hospital contact for injury during the first year after parental cancer diagnosis (hazard ratio [HR] = 1.27, 95% confidence interval [CI] = 1.22-1.33), especially when the parent had a comorbid psychiatric disorder after cancer diagnosis (HR = 1.41, 95% CI = 1.08-1.85). The rate increment declined during the second and third year after parental cancer diagnosis (HR = 1.10, 95% CI = 1.07-1.14) and became null afterwards (HR = 1.01, 95% CI = 0.99-1.03). Children with parental cancer also had a higher rate of repeated injuries than the other children (HR = 1.13, 95% CI = 1.12-1.15). Given the high rate of injury among children in the general population, our findings may have important public health implications

A genetically informed study of the associations between maternal age at childbearing and adverse perinatal outcomes

We examined associations of maternal age at childbearing (MAC) with gestational age and fetal growth (i.e., birth weight adjusting for gestational age), using two genetically informed designs (cousin and sibling comparisons) and data from two cohorts, a population-based Swedish sample and a nationally representative United States sample. We also conducted sensitivity analyses to test limitations of the designs. The findings were consistent across samples and suggested that, associations observed in the population between younger MAC and shorter gestational age were confounded by shared familial factors; however, associations of advanced MAC with shorter gestational age remained robust after accounting for shared familial factors. In contrast to the gestational age findings, neither early nor advanced MAC was associated with lower fetal growth after accounting for shared familial factors. Given certain assumptions, these findings provide support for a causal association between advanced MAC and shorter gestational age. The results also suggest that there are not causal associations between early MAC and shorter gestational age, between early MAC and lower fetal growth, and between advanced MAC and lower fetal growth.NonePublishe

Consequences for family members of being informal caregivers to a person with advanced cancer

Aim: The overall aim is to generate knowledge about consequences of informal caregiving for the family members of patients diagnosed with advanced cancer, over a one-year period, including the family members’ health, health-related quality of life, health care utilization, and associated costs. Furthermore, the family members’ management of their stressful daily life and the meanings of social support networks in the early stage will be explored in order to get deeper understanding. Method: The thesis is based on two quantitative prospective studies (I–II) and two qualitative cross-sectional studies (III–IV). Studies I–II involved data from the same study group of 36 family members to relative with cancer. Use was made of questionnaires about sociodemographic characteristics, informal caregiving, leisure activities and absence from work (Study I), also of the Short Form 36 Health Survey (SF–36) and EuroQol (EQ–5D) (Study II), during a 1-year period starting 3 months after diagnosis. Study I also included a telephone interview and a review of medical records. Twenty family members were interviewed in Study III, 17 in Study IV; and the interviews were subjected to latent content analysis. Results: The findings indicate that family members’ informal caregiving influence the risk of morbidity with increased health care utilization and lower health-related quality of life the year following the diagnosis. The number of hours spent giving the patients was highest in respect of emotional support. If professional caregivers as home help care assistants had provided the support, it would be equivalent to a cost of 327,000 SEK per 15 months. The medical records indicated increased morbidity with increased health service use (physician consultations), more psychiatric disorders and more musculoskeletal diseases during the follow-up period (Study I). No statistically significant differences in health-related quality of life (HRQOL) were found within the study group over the 1-year follow-up in either physical or mental dimensions. However, the family members did have mental HRQOL scores significantly lower than the norm-based ones as measured throughout the year by SF–36. In addition, results showed that older age and being a partner had a negative influence on HRQOL (Study II). Management employed by family members during the early stage after patient diagnosis was expressed by the theme Striving to be prepared for the painful, based on emotion-focused strategies except the problem-focused strategy to ‘Making things easier in everyday life’ both for the sick person and for themselves (Study III). The meaning of the social support network was expressed by the theme Confirmation through togetherness, covering emotional and, to a lesser extent, instrumental support. Confirmation through togetherness derived principally from information, understanding, encouragement, involvement and spiritual community. Need of support, Desire for a deeper relationship with relatives and Network to turn to were identified as antecedents to social support. Social support involves reciprocal exchange of verbal and non-verbal information (Study IV).   Conclusions: The results of this thesis provide knowledge of family members’ risk of morbidity, which motivates developing guidelines for preventing both physical and mental morbidity. Developing valid measurement of the meaning of social support network for the individual patient could encourage nurses and other health-care professionals to focus on family members’ personal networks as a way to strengthen their mental health

Health-related quality of life in family members of patients with an advanced cancer diagnosis : A one-year prospective study

Background: Receiving a cancer diagnosis affects family members as well as the person diagnosed. Familymembers often provide support for the sick person in daily life out of duty and love, and may not always think of their own vulnerability to illness. To individualise support for them, family members who are most at risk for becoming ill must be identified. The aim of this study was to investigate health-related quality of life (HRQOL) in family members of patients with advanced lung or gastrointestinal cancer 3 to 15 months after diagnosis. Methods: Data on mental and physical dimensions of HRQOL were collected from family members of these patients in this prospective quantitative study. Five assessments using the Short Form 36 Health Survey (SF-36) and EuroQol (EQ-5D) were conducted during a 1-year period starting 3 months after diagnosis. Thirty-six family members completed the study, i.e. participated in all five data collections. Results: No statistically significant changes in physical or mental HRQOL within the study group appeared over the 1-year follow-up. Compared with norm-based scores, family members had significantly poorer mental HRQOL scores throughout the year as measured by the SF-36. Family members also scored statistically significantly worse on the EQ-5D VAS in all five assessments compared to the norm-based score. Findings showed that older family members and partners were at higher risk for decreased physical HRQOL throughout the 1-year period, and younger family members were at higher risk for poorer mental HRQOL. Conclusions: It is well known that ill health is associated with poor HRQOL. By identifying family members with poor HRQOL, those at risk of ill health can be identified and supported. Future large-scale research that verifies our findings is needed before making recommendations for individualised support and creating interventions best tailored to family members at risk for illness

Towards non-conventional methods of designing register-based epidemiological studies: An application to pediatric research

Aims: Various epidemiological designs have been applied to investigate the causes and consequences of fetal growth restriction in register-based observational studies. This review seeks to provide an overview of several conventional designs, including cohort, case-control and more recently applied non-conventional designs such as family-based designs. We also discuss some practical points regarding the application and interpretation of family-based designs. Methods: Definitions of each design, the study population, the exposure and the outcome measures are briefly summarised. Examples of study designs are taken from the field of low birth-weight research for illustrative purposes. Also examined are relative advantages and disadvantages of each design in terms of assumptions, potential selection and information bias, confounding and generalisability. Kinship data linkage, statistical models and result interpretation are discussed specific to family-based designs. Results: When all information is retrieved from registers, there is no evident preference of the case-control design over the cohort design to estimate odds ratios. All conventional designs included in the review are prone to bias, particularly due to residual confounding. Family-based designs are able to reduce such bias and strengthen causal inference. In the field of low birth-weight research, family-based designs have been able to confirm a negative association not confounded by genetic or shared environmental factors between low birth weight and the risk of asthma. Conclusions: We conclude that there is a broader need for family-based design in observational research as evidenced by the meaningful contributions to the understanding of the potential causal association between low birth weight and subsequent outcomes