An association between asthma and antibiotic usage has been demonstrated, and the issue of reverse causation and confounding by indication is much debated.
Our aim was to study the association between different classes of antibiotics and prescription of asthma medication in a register-based cohort of all Swedish children, born between July 2005 and June 2009, ever treated with antibiotics.
Data on dispensed prescriptions of antibiotics (ATC-codes J01) and asthma medication (ATC-codes R03A-D) were requested from the Prescribed Drug Register. The association between dispensed prescriptions of different classes of antibiotics and asthma medication was analysed with Cox regression and a descriptive sequence symmetry analysis.
In total, 211 192 children had received prescriptions of antibiotics. There was a strong association between prescription of antibiotics and prescription of asthma medication. The hazard ratios (HRs) for asthma medication associated with prescription of amoxicillin, penicillin, cephalosporin and macrolides (Gram-positive infections) were stronger than HRs associated with prescription of sulphonamides, trimethoprim and quinolones (urinary tract infections) and flucloxacillin (skin and soft tissue infections), e.g. first year HR = 2.27 (95% confidence intervals 2.17-2.37) as compared with HR = 1.04 (0.78-1.40). The HR associated with broad spectrum antibiotics was significantly higher than the narrow spectrum.
Our data suggest that the association between antibiotics and asthma is subject to either reverse causation or confounding by indication due to respiratory tract infections. This implies that careful consideration is required as to whether or not symptoms from the respiratory tract in early childhood should be treated with antibiotics or asthma medication.
Does the intergenerational influence on birthweight and birth length remain within female dizygotic and monozygotic twin pairs?
The intergenerational influence on birthweight and birth length remained within dizygotic but not within monozygotic twin pairs.
Low birthweight is associated with increased morbidity and mortality in both the short and long term; therefore it is important to understand determinants of fetal growth. There is a known intergenerational association between parents' and offspring's size at birth.
This is a register-based cohort study with a nested within-twin-pair comparison. The study is retrospective, but based on prospectively collected information. The study population included 8685 monozygotic and like-sexed dizygotic female twins born in Sweden from 1926 to 1985, who had given birth to their first infant between 1973 and 2009.
This study is set in Sweden and used data from the Swedish Twin Register and the Swedish Medical Birth Register. We used generalized estimating equations to obtain regression coefficients with 95% confidence intervals (CI) for the outcomes: offspring birthweight and birth length. To control for genetic and shared environmental factors, we performed within-twin-pair analyses in 1479 dizygotic and 1526 monozygotic twin pairs.
In the cohort of both dizygotic and monozygotic twins, there was an association between mother's and offspring's size at birth. Within-dizygotic twin pairs, a 500-g increase from the twin pair's mean birthweight was associated with increased offspring birthweight [70 g (95% CI: 35-106)] and birth length [0.22 cm (95% CI: 0.07-0.38)]. The corresponding increase in birth length of 1 cm was estimated to increase offspring's birthweight by 26 g (95% CI: 12-40) and birth length by 0.11 cm (95% CI: 0.04-0.17). Within-monozygotic twin pairs there were no such associations.
This study is limited to twins who themselves or whose co-twin voluntarily responded to questionnaires.
The intergenerational influence on size at birth is suggested to be due to direct or indirect genetic factors.
Asthma is common in both children and adults in the Western world, just like anxiety and depression. While some research has revealed that these diseases might share important environmental and pathophysiological aspects, the exact mechanisms still remain unclear.
To study the correlation firstly between depression or anxiety and asthma diagnosis in adult twins and secondly the association between parental depression or anxiety and offspring asthma in children of twins.
In total, 24 685 adult twins aged 20-47 years were interviewed or completed a Web-based questionnaire and their children were identified through the Multi-Generation Register. Asthma diagnosis was obtained from the Patient Register and the Prescribed Drug Register. Assessment of depression and anxiety was obtained from questionnaires using Center for Epidemiologic Studies Depression Scale (CES-D), major depression and generalized anxiety disorder (GAD) from DSM-IV. The association between depression or anxiety and asthma was analyzed with logistic regression adjusting for confounders in twins and offspring. To address genetic and familial environmental confounding, we performed a cotwin analysis using disease-discordant twin pairs.
We found an association between asthma and CES-D, major depression and GAD, for example adjusted OR for major depression and register-based asthma 1.56 (1.36-1.79). Most of the point estimates remained in the co-twin control analysis, indicating that the association was likely not due to genetic or familial environmental factors. There was no association between parental depression and/or anxiety and asthma diagnosis in the offspring which implies lack of genetic confounding.
We found an association between own asthma diagnosis and anxiety or depression, but not with offspring asthma. Our results indicate that the associations were not due to confounding from genes or environment shared by the twins.
Studies have shown an increased risk of malignancies in women with endometriosis. Little is known about the impact of endometriosis on cancer survival. We investigated whether the survival after a diagnosis of a malignancy differs in women with a previously diagnosed endometriosis compared to other women. Women with a first time diagnosis of a malignancy in 1969-2005, were identified using the National Swedish Cancer Register (NSCR). By use of the National Swedish Patient Register (NSPR) we identified all women with a diagnosis of endometriosis during the same period and linked these patients with the data from the NSCR. The cohort comprised 4,278 women with endometriosis and a malignancy, and 41,831 randomly selected matched women without endometriosis. Cox regression was used for all calculations to obtain crude and adjusted cause specific mortality rates, measured as hazard ratios (HR) with 95% confidence intervals (CI). A total of 46,109 women entered the study. There was a statistically significant better survival for women with endometriosis for all malignancies combined (HR=0.92) and for breast cancer (HR=0.86) and ovarian cancer (HR=0.81) specifically. For breast cancer the survival enhancing effect in women with endometriosis decreased with increasing parity. There was poorer survival in malignant melanoma for women with endometriosis (HR=1.52). The survival in a malignancy is better in women with a previously diagnosed endometriosis compared to women without endometriosis especially for breast and ovarian cancers. The prognosis of malignant melanoma is poorer in women with endometriosis.
To assess the role of genetic and environmental factors in female alcoholism using a large population-based twin sample, taking into account possible differences between early and late onset disease subtype.
Twins aged 20-47 years from the Swedish Twin Registry (n=24 119) answered questions to establish lifetime alcohol use disorders. Subjects with alcoholism were classified for subtype. Structural equation modeling was used to quantify the proportion of phenotypic variance due to genetic and environmental factors and test whether heritability in women differed from that in men. The association between childhood trauma and alcoholism was then examined in females, controlling for background familial factors.
Lifetime prevalence of alcohol dependence was 4.9% in women and 8.6% in men. Overall, heritability for alcohol dependence was 55%, and did not differ significantly between men and women, although women had a significantly greater heritability for late onset (type I). Childhood physical trauma and sexual abuse had a stronger association with early onset compared to late onset alcoholism [odds ratio (OR) 2.54, 95% confidence interval (CI) 1.53-3.88 and OR 2.29, 95% CI 1.38-3.79 respectively]. Co-twin analysis indicated that familial factors largely accounted for the influence of physical trauma whereas the association with childhood sexual abuse reflected both familial and specific effects.
Heritability of alcoholism in women is similar to that in men. Early onset alcoholism is strongly association with childhood trauma, which seems to be both a marker of familial background factors and a specific individual risk factor per se.
Although the genetics of asthma has been extensively studied using both quantitative and molecular genetic analysis methods, both approaches lack studies specific to the childhood phenotype and including other allergic diseases. This study aimed to give specific estimates for the heritability of childhood asthma and other allergic diseases, to attempt to replicate findings from genomewide association studies (GWAS) for childhood asthma and to test the same variants against other allergic diseases.
In a cohort of 25 306 Swedish twins aged 9 or 12 years, data on asthma were available from parental interviews and population-based registers. The interviews also inquired about wheeze, hay fever, eczema, and food allergy. Through structural equation modeling, the heritability of all phenotypes was calculated. A subset of 10 075 twins was genotyped for 16 single nucleotide polymorphisms (SNPs) selected from previous GWAS; these were first tested for association with asthma and significant findings also against the other allergic diseases.
The heritability of any childhood asthma was 0.82 (95% CI 0.79-0.85). For the other allergic diseases, the range was approximately 0.60-0.80. Associations for six SNPs with asthma were replicated, including rs2305480 in the GSDMB gene (OR 0.80, 95% CI 0.74-0.86, P = 1.5*10(-8) ; other significant associations all below P = 3.5*10(-4) ). Of these, only rs3771180 in IL1RL1 was associated with any other allergic disease (for hay fever, OR 0.64, 95% CI 0.53-0.77, P = 2.5*10(-6) ).
Asthma and allergic diseases of childhood are highly heritable, and these high-risk genetic variants associated specifically with childhood asthma, except for one SNP shared with hay fever.
Impact of asthma medication and familial factors on the association between childhood asthma and attention-deficit/hyperactivity disorder: a combined twin- and register-based study: Epidemiology of Allergic Disease.
Asthma and attention-deficit/hyperactivity disorder (ADHD) are prevalent in childhood and may cause functional impairment and stress in families. Previous research supports an association between asthma and ADHD in children, but several aspects of this relationship are unclear.
Our aim was to study whether the association between asthma and ADHD is restricted to either the inattentive or the hyperactive/impulsive symptoms of ADHD, to explore the impact of asthma severity and asthma medication and the contribution of shared genetic and environmental risk factors on the asthma-ADHD relationship.
Data on asthma, ADHD, zygosity and possible confounders were collected from parental questionnaires at 9 or 12 years on 20 072 twins through the Swedish Twin Register, linked to the Swedish Medical Birth Register, the National Patient Register and the Prescribed Drug Register. The association between asthma and ADHD, the impact of asthma severity and medication, was assessed by generalized estimating equations. Cross-twin-cross-trait correlations (CTCT) were estimated to explore the relative importance of genes and environment for the association.
Asthmatic children had a higher risk of also having ADHD [odds ratio (OR) 1.53, 95% confidence interval (CI): 1.16-2.02]. The association was not restricted to either of the two dimensions of ADHD. The magnitude of the association increased with asthma severity (OR 2.84, 95% CI: 1.86-4.35) for = 4 asthma attacks in the last 12 months and was not affected by asthma treatment. The CTCTs possibly indicate that the genetic component in overlap of the disorders is weak.
Childhood asthma, especially severe asthma, is associated with ADHD. Asthma medication seems not to increase the risk of ADHD. Clinicians should be aware of the potential of ADHD in asthma. Optimal asthma care needs to be integrated with effective evaluation and treatment of ADHD in children with co-existing disorders.
Studies have found associations between birth weight and risk of atopic eczema or allergic rhinitis (AR), although this could be due to confounding.
We sought to evaluate associations between fetal growth and the risk of atopic eczema or AR in childhood, controlling for gestational age (GA), shared (familial) environmental and genetic factors.
Data on atopic eczema, AR, birth characteristics and confounders were collected from registers and telephone interviews with the parents of 9- and 12-year-old twins. Firstly, cohort analyses on all twins (eczema n=10 132 and AR n=10 896) were performed. Secondly, to control for genetic and shared environment, co-twin-control analyses were performed in twin pairs discordant for atopic eczema (n=480) and AR (n=332).
The rate of atopic eczema increased with birth weight, from 12.6% in twin children or=3500 g. The rate of AR varied between 7.8% and 8.8%. In the cohort analyses, the odds ratio (OR) for atopic eczema was 1.62 (95% CI: 1.27-2.06) for 500 g increase in birth weight and 1.00 (95% CI: 0.75-1.33) for AR. In co-twin-control analyses on atopic eczema, OR was 3.93 (95% CI: 1.55-9.98) for 500 g increase in birth weight, with no significant difference between monozygotic and dizygotic twins (P=0.84).
We found a positive association between fetal growth and childhood atopic eczema, but not AR, independent of GA, shared environmental and genetic factors. This indicates fetal growth affects the immune system, and supports further studies on early mechanisms.
Exposure to antibiotics in early life may affect future health. Most antibiotics are prescribed in outpatient care, but inpatient exposure is also important. We estimated how specific diagnoses in hospitals corresponded to individual antibiotic exposure.
All pregnant women and children from birth to 5 years of age with infectious diseases and common inpatient diagnoses between July 2005 and November 2011 were identified from the Swedish National Patient Register. Random samples of individuals from predefined groups were drawn, and medical records received from the clinics were manually reviewed for antibiotics.
Medical records for 4319 hospital visits were requested and 3797 (88%) were received. A quarter (25%) of children diagnosed as premature had received antibiotics, and in children from one to 5 years of age, diagnoses associated with bacterial infections were more commonly treated with antibiotics (62.4-90.6%) than those associated with viruses (6.3-22.2%). Pregnant women who had undergone a Caesarean section were more likely to be treated with antibiotics than those who had had a vaginal delivery (40.1% versus 11.1%).
This study defines the proportion of new mothers and young children who received individual antibiotic treatment for specific inpatient diagnoses in Sweden and provides a useful basis for future studies focusing on antibiotic use.
: Diverticulitis is a risk factor for fistula formation but little is known about the influence of hysterectomy in this association. A population-based nationwide matched cohort study was performed to determine the risk of fistula formation in hysterectomized women with, and without, diverticulitis.
: Women who had a hysterectomy between 1973 and 2003, and a matched control cohort, were identified from the Swedish Inpatient Register. Incidence of diverticulitis and fistula surgery was determined by cross-linkage to the Register, and risk was estimated using a Cox regression model.
: In a cohort of 168 563 hysterectomized and 614 682 non-hysterectomized women (mean follow-up 11.0 and 11.5 years respectively), there were 14 051 cases of diverticulitis and 851 fistulas. Compared with women who had neither hysterectomy nor diverticulitis, the risk of fistula surgery increased fourfold in hysterectomized women without diverticulitis (hazard ratio (HR) 4.0 (95 per cent confidence interval (c.i.) 3.5 to 4.7)), sevenfold in non-hysterectomized women with diverticulitis (HR 7.6 (4.8 to 12.1)) and 25-fold in hysterectomized women with diverticulitis (HR 25.2 (15.5 to 41.2)).
: Diverticulitis, and to a lesser extent hysterectomy, is strongly associated with the risk of fistula formation. Hysterectomized women with diverticulitis have the highest risk of developing surgically managed fistula.