Helle Kieler

Karolinska Institutet, Solna, Stockholm, Sweden

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Publications (110)430.74 Total impact

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    ABSTRACT: Background Up to one-third of women receive prescriptions for systemic antibacterial medications during pregnancy. This paper looks at the association between maternal use of systemic antibacterial medications during pregnancy and childhood cancer risk in the offspring using the prospective data on medication.MethodsA population-based follow-up study was carried out using Danish and Swedish register data. Exposure was maternal redemption of a prescription for a systemic antibacterial in the 3 months prior to pregnancy and during pregnancy (exposure window) documented in the national prescription registers, and offspring were followed up from birth to a cancer diagnosis, death, emigration, day before 15th birthday or end of follow-up, whichever came first. Timing, dosage, specific medication types and types of childhood cancer were also considered.ResultsMothers of 35.1% (n = 506 194) of the children filled at least one prescription for systemic antibacterials during the exposure window. Exposed children had a hazard ratio of 1.08 (95% confidence interval: 0.97, 1.20) compared with unexposed children. Statistically significant results were found for some specific medications (for example, ‘other antibacterials’/Anatomical Therapeutic Chemical code J01X) and combinations of cancer types and specific medications (leukaemia and other antibacterials, and hepatic cancers and tetracyclines).Conclusions The results of this study indicate that most antibacterial drugs used during pregnancy were not related to childhood cancer risk in the offspring. However, some may be associated with the development of some specific types of childhood cancers. Our findings need to be replicated in an independent data source. Copyright © 2015 John Wiley & Sons, Ltd.
    Pharmacoepidemiology and Drug Safety 05/2015; DOI:10.1002/pds.3806 · 3.17 Impact Factor
  • Maturitas 05/2015; 81(1):137. DOI:10.1016/j.maturitas.2015.02.116 · 2.86 Impact Factor
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    ABSTRACT: This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
    BMJ (online) 04/2015; 350(apr17 3):h1798-h1798. DOI:10.1136/bmj.h1798 · 16.38 Impact Factor
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    ABSTRACT: Several studies have shown that the prevalence of the frequent chronic conditions of atopic dermatitis, asthma, and allergy has increased substantially for reasons not fully understood. Atopic diseases affect quality of life in both children and their family members. Using national registers, we sought to establish up-to-date incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in the Danish and Swedish child populations. Children born in Denmark from 1997 to 2011 or born in Sweden from 2006 to 2010 participated in this cross-national, population-based cohort study. Incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in the Danish and Swedish child cohorts were ascertained through disease-specific dispensed prescribed medication, specific hospital contacts, or both. In both countries the incidence rate of atopic dermatitis was stable during the study periods. The incidence rate of asthma increased until 2006 and stabilized for the rest of the study period in Denmark and increased in Sweden. The incidence rate of allergic rhinoconjunctivitis decreased in both countries. The study revealed similar trends, with stable incidence rates of atopic dermatitis in both Danish and Swedish children, an increase and then stabilization in asthma incidence rates in Denmark and an increase in Sweden, and a decrease in allergic rhinoconjunctivitis incidence rates. At age 5 years, one third of all children were affected with at least one of the conditions of atopic dermatitis, asthma, or allergic rhinoconjunctivitis. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    The Journal of allergy and clinical immunology 03/2015; DOI:10.1016/j.jaci.2015.02.003 · 11.25 Impact Factor
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    ABSTRACT: This Swedish nationwide cohort study aims to examine the role of maternal characteristics (maternal age, education, smoking, BMI, diabetes, and preeclampsia) and multiple intrauterine growth measures on the risk of childhood lymphomas. A total of 3 444 136 singleton live births registered in the Swedish Medical Birth Register were analyzed, among whom there were 515 incident non-Hodgkin lymphoma (NHL) cases and 169 Hodgkin lymphoma (HL) cases aged 0-14 years at diagnosis (1973-2007) identified through linkage with the Swedish Cancer Register. Proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) of NHL and HL. Male sex (HR=2.00, 95% CI: 1.66-2.41), older maternal age (HR=1.03, 95% CI: 1.00-1.06, per 1-year increase), and large for gestational age compared with appropriate for gestational age (AGA) birth weight (HR=1.83, 95% CI: 1.20-2.79) were correlated with the risk of NHL; of note, in subanalysis by sex, the latter association was confined to girls (HR=3.37, 95% CI: 1.90-5.97, Pinteraction by sex=0.008). The risk of childhood HL overall was more evident among boys (HR=2.03, 95% CI: 1.46-2.81), whereas indices of accelerated fetal growth were not convincingly associated with the risk of HL. Apart from the established association with sex, the findings point to accelerated intrauterine growth as a risk factor for childhood NHL that may differ by sex. Given the rarity of this condition at birth, however, further studies with more elaborate indices are needed to conclude on its association with rare diseases such as HL.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 01/2015; Publish Ahead of Print. DOI:10.1097/CEJ.0000000000000122 · 2.76 Impact Factor
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    ABSTRACT: Epidemiological research is facilitated in Sweden by a history of national health care registers, making large unselected national cohort studies possible. However, for complex clinical populations, such as children with congenital heart disease (CHD), register-based studies are challenged by registration limitations. For example, the diagnostic code system International Classification of Diseases, 10th version (ICD-10) does not indicate the clinical significance of abnormalities, therefore may be of limited use if used as the sole parameter in epidemiological research. Palivizumab is indicated as a prophylactic treatment against respiratory syncytial virus infections in children with hemodynamically significant CHD. The aim of the study reported here was to develop and validate an algorithm to identify children with hemodynamically significant CHD according to recommendations for palivizumab prophylaxis in register-based research. By using a strategy of combining criteria for age at diagnosis, diagnostic codes, surgical procedure codes, and dispensing records, we created an algorithm to define the specific cases with hemodynamically significant CHD in which palivizumab could be advocated according to recommendations. The algorithm identified 928 children with hemodynamically significant CHD in the Swedish birth cohort born July 1, 2005 to December 31, 2010. A sensitivity (95% confidence interval) of 80% (70-88) for the algorithm was found by analyzing 121 children identified through local hospital data who were treated with palivizumab within a defined region and study period. The positive predictive value was estimated by medical record review in a random sample of 34 cases identified by the algorithm. In 79% (62-91) of these cases, the children were regarded as having hemodynamically significant CHD according to the recommendations for treatment with palivizumab. It was possible to identify a subgroup of children with hemodynamically significant CHD using an epidemiological approach and an algorithm with high validity. Our results will enable well-powered national cohort studies of individuals with complex clinical conditions such as hemodynamically significant CHD.
    Clinical Epidemiology 01/2015; 7:119-27. DOI:10.2147/CLEP.S73358
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    ABSTRACT: Register studies are a valuable tool, when monitoring the safety of drugs. The Swedish Prescribed Drug Register (PDR) was established in 2005 and keeps records of all prescribed drugs dispensed in community pharmacies. Drugs prescribed in-hospital are not registered on an individual level, which may hamper the validity of register-based studies on drugs potentially administered in-hospital. The objective was to assess the ability of the PDR to identify children treated with the monoclonal antibody palivizumab, which is used for prophylaxis against respiratory syncytial virus (RSV) infection in children. Palivizumab exposure as filled prescriptions recorded in the PDR was assessed by indication of treatment (preterm-born children, bronchopulmonary dysplasia, or hemodynamically significant heart disease) and presented as numbers and proportions. For a random sample of children with an indication for treatment and without record of palivizumab exposure in the drug register, numbers and proportions by indication of treatment as noted in medical records were presented. The extent of underreporting in the drug register was estimated by indication for treatment. Through the national health registers, 2,317 children were identified as being at risk for severe infection with RSV infection and 75% had no records indicating palivizumab exposure in the PDR. In a random sample of 176 children at high risk for RSV infection and with no records of palivizumab prescription fills in the PDR, 47% had been treated with palivizumab according to medical records. The PDR underestimated palivizumab treatment with 49% in children born preterm, 42% in children with bronchopulmonary dysplasia, and 23% in those with a hemodynamically significant heart disease. Our findings underline the need of improving the information in the Swedish national registers concerning drugs administered in-hospital.
    Clinical Epidemiology 01/2015; 7:45-51. DOI:10.2147/CLEP.S73337
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    ABSTRACT: Family history of venous thromboembolism (VTE) has been suggested to be more useful in risk assessment than thrombophilia testing. We investigated established genetic susceptibility variants for association with VTE and evaluated a genetic risk score in isolation and combined with known trigger factors, including family history of VTE. A total of 18 single nucleotide polymorphisms (SNPs) selected from the literature were genotyped in 2835 women participating in a Swedish nationwide case-control study (the ThromboEmbolism Hormone Study (TEHS)). Association with VTE was assessed by odds ratios (ORs) with 95% confidence interval (CI) using logistic regression. Clinical and genetic predictors that contributed significantly to the fit of the logistic regression model were included in the prediction models. SNP-SNP interactions were investigated and incorporated into the models if found significant. Risk scores were evaluated by calculating the area under the receiver-operating characteristics curve (AUC). Seven SNPs (F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446) with 4 SNP-SNP interactions contributed to the genetic risk score for VTE with an AUC of 0.66 (95% CI: 0.64-0.68). After adding clinical risk factors, which included family history of VTE, the AUC attained 0.84 (95% CI: 0.82-0.85). The goodness of fit of the genetic and combined scores improved when significant SNP-SNP interaction terms were included. Prediction of VTE in high-risk individuals was more accurate when a combination of clinical and genetic predictors with SNP-SNP interactions was included in a risk score. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 12/2014; 13(2). DOI:10.1111/jth.12808 · 5.55 Impact Factor
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    ABSTRACT: Bronchopulmonary dysplasia (BPD) is a frequent chronic lung disease in preterm infants and we aimed to identify factors associated with this condition in infants with respiratory distress syndrome (RDS). This case-control study, using national Swedish data, included 2,255 preterm infants, born before 33 gestational weeks. The 667 BPD cases were oxygen dependent at 36 weeks' post-menstrual age and the 1,558 controls only had RDS. Comparisons included perinatal conditions and pharmacological treatments. Adjusted odds ratios with 95% confidence intervals were calculated in a conditional logistic regression model, with gestational age as the conditioning term. An increased risk of BPD was associated with pre-labour preterm rupture of membranes of more than one week (3.35, 2.16-5.19), small for gestational age (2.73, 2.11-3.55), low Apgar score (1.37, 1.05-1.81), patent ductus arteriosus (1.70, 1.33-2.18), persistent pulmonary hypertension (5.80, 3.21-10.50), pulmonary interstitial emphysema (2.78, 1.37-5.64), pneumothorax (2.95, 1.85-4.72), late onset infections (2.69, 1.82-3.98), intubation (1.56, 1.20-2.03), chest compressions (2.05, 1.15-3.66) and mechanical ventilation (2.16, 1.69-2.77), but not antenatal corticosteroids. Growth restriction and inflammation increased the risk of BPD in preterm infants and pre-labour preterm rupture of membranes, small for gestational age, low Apgar score or need for resuscitation should raise clinical suspicions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Acta paediatrica (Oslo, Norway: 1992). Supplement 12/2014; 104(3). DOI:10.1111/apa.12888
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    ABSTRACT: To investigate the association between exposure to antibiotics in fetal and early life and asthma in childhood, with adjustment for confounding factors. Nationwide prospective population based cohort study, including sibling control design. Swedish population identified from national demographic and health registers. 493 785 children born 2006-10; 180 894 of these were eligible for sibling analyses. Asthma defined as having both an asthma diagnosis and dispensed asthma drugs. The association between antibiotic exposure and asthma was investigated in the whole cohort with Cox proportional hazard regression. A stratified proportional hazards model conditional on sibling group was used to adjust for shared factors within families. Confounding by respiratory infections was assessed by investigating whether specific groups of antibiotics were associated with asthma. Antibiotic exposure in fetal life was associated with an increased risk of asthma in cohort analyses (hazard ratio 1.28, 95% confidence interval 1.25 to 1.32), but not in sibling analyses (0.99, 0.92 to 1.07). In cohort analyses, antibiotics used to treat respiratory infections in childhood were associated with a more pronounced increased risk of asthma (4.12, 3.78 to 4.50) than antibiotics used for urinary tract and skin infections (1.54, 1.24 to 1.92). In sibling analyses, the excess risks after exposure to antibiotics for respiratory infections decreased (2.36, 1.78 to 3.13) and disappeared for antibiotics for urinary tract and skin (0.85, 0.47 to 1.55). Previous positive associations between exposure to antibiotics in fetal and early life and subsequent childhood asthma could have been caused by confounding by shared familial factors, in addition to confounding by respiratory infections. © Örtqvist et al 2014.
    BMJ Clinical Research 11/2014; 349(4):g6979. DOI:10.1136/bmj.g6979 · 14.09 Impact Factor
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    ABSTRACT: Objective To assess whether the use of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, mirtazapine, venlafaxine or other antidepressants is associated with late elective termination of pregnancy.DesignCase–control study using data from national registers.SettingDenmark, Finland, and Norway during the period 1996–2007.PopulationA total of 14 902 women were included as cases and 148 929 women were included as controls.Methods Cases were women with elective termination of pregnancy at 12–23 weeks of gestation. Controls continued their pregnancy and were matched with cases on key factors.Main outcome measuresAssociation between antidepressant use during pregnancy and elective termination of pregnancy at 12–23 weeks of gestation for fetal anomalies, or for maternal ill health or socio-economic disadvantage.ResultsAt least one prescription of antidepressants was filled by 3.7% of the cases and 2.2% of the controls. Use of any type of antidepressant was associated with elective termination of pregnancy for maternal ill health or socio-economic disadvantage (odds ratio, OR 2.3; 95% confidence interval, 95% CI 2.0–2.5). Elective termination of pregnancy for fetal anomalies was associated with the use of mirtazapine (OR 2.2, 95% CI 1.1–4.5). There was no association between the use of any of the other antidepressants and elective termination of pregnancy for fetal anomalies.Conclusions The use of any type of antidepressants was associated with elective termination of pregnancy at 12–23 weeks for maternal ill health or socio-economic disadvantage, but not with terminations for fetal anomalies. Further studies need to confirm the findings concerning mirtazapine and termination of pregnancy for fetal anomalies.
    BJOG An International Journal of Obstetrics & Gynaecology 11/2014; DOI:10.1111/1471-0528.13164 · 3.86 Impact Factor
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    ABSTRACT: Objectives The aim of this study was to explore the impact of severe mental illness (SMI) on myocardial infarction survival, and determine the influence of risk factor burden, myocardial infarction severity and different treatments.Design, setting and participantsThis population-based cohort study, conducted in Sweden during the period 1997–2010, included all patients with a first diagnosis of myocardial infarction in the Swedish nationwide myocardial infarction register SWEDEHEART (n = 209 592). Exposure was defined as a diagnosis of SMI (i.e. bipolar disorder or schizophrenia) in the national patient register prior to infarction. Bias-minimized logistic regression models were identified using directed acyclic graphs and included as covariates age, gender, smoking, diabetes, previous cardiovascular disease, myocardial infarction characteristics and treatment.Main outcome measuresThe primary outcomes were 30-day and 1-year mortality, obtained through linkage with national population registers.ResultsPatients with bipolar disorder (n = 442) and schizophrenia (n = 541) were younger (mean age 68 and 63 years, respectively) than those without SMI (n = 208 609; mean age 71 years). The overall 30-day and 1-year mortality rates were 10% and 18%, respectively. Compared with patients without SMI, patients with SMI had higher 30-day [odds ratio (OR) 1.99, 95% confidence interval (CI) 1.55–2.56] and 1-year mortality (OR 2.11, 95% CI 1.74–2.56) in the fully adjusted model. The highest mortality was observed among patients with schizophrenia (30-day mortality: OR 2.58, 95% CI 1.88–3.54; 1-year mortality: OR 2.55, 95% CI 1.98–3.29).ConclusionSMI is associated with a marked higher mortality after myocardial infarction, even after accounting for contributing factors. It is imperative to identify the reasons for this higher mortality.This article is protected by copyright. All rights reserved.
    Journal of Internal Medicine 11/2014; 277(6). DOI:10.1111/joim.12329 · 5.79 Impact Factor
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    ABSTRACT: Objective: This work aims to study the effects of hormone therapy (HT) on the risk of cardiovascular outcomes and all-cause mortality in women treated with statins. Methods: We included women aged 40 to 74 years and living in Sweden who filled a first statin prescription between 2006 and 2007. Women were categorized as HT users or as nonusers. Information on dispensed drugs, comorbidity, cardiovascular outcomes, and all-cause mortality was obtained from national health registers. Results: A total of 40,958 statin users-2,862 (7%) HT users and 38,096 nonusers-were followed for a mean of 4.0 years. In total, 70% of the women used statins as primary prevention. Among HT users, there were five cardiovascular deaths per 10,000 person-years. The corresponding rate among nonusers was 18, which yielded a hazard ratio of 0.38 (95% CI, 0.12-1.19). The all-cause mortality rates were 33 and 87, respectively, and the hazard ratio was 0.53 (95% CI, 0.34-0.81). There were no associations with cardiovascular events. A similar pattern was found for both primary and secondary prevention. Conclusions: HT is associated with a reduced risk of all-cause mortality in women treated with statins. Although confounding factors, such as lifestyle and disease severity, might have influenced the results, HT does not seem to be detrimental to statin-treated women. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
    Menopause (New York, N.Y.) 10/2014; 22(4). DOI:10.1097/GME.0000000000000345 · 2.81 Impact Factor
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    ABSTRACT: Treatment guidelines state that all patients with bipolar disorder should use pharmacological prophylaxis; however the actual use of prophylactic drugs after bipolar disorder diagnosis is unknown. Our aim was to assess the use of, and predictors for, pharmacoprophylaxis in newly diagnosed bipolar disorder patients.Methods Data from three Swedish nationwide registers were obtained. We identified patients aged 18–75 with a first time diagnosis of bipolar disorder between 2006 and 2012 (n=31,770) and reviewed subsequent mood-stabilizer and antipsychotic prescription fills. In multivariable Cox regression models, we studied demographic and illness related factors as predictors of prescription fills after diagnosis.ResultsIn total, 72.2% (95% confidence interval [CI] 71.7–72.7%) of the patients filled a prescription of a prophylactic drug within 3 months after diagnosis. Pharmacological prophylaxis was mainly associated with a longer duration of hospitalization at bipolar disorder diagnosis (adjusted hazard ratio [AHR] 2.18; CI 2.02–2.35 for a hospitalization of ≥28 days compared to <7 days) and previous use of any mood-stabilizer or antipsychotic (inpatients: AHR 1.24; CI 1.17–1.31 and outpatients: AHR 1.78; CI 1.73–1.84).LimitationsWe had no information on drug prescriptions that were never filled.Conclusions The proportion of newly diagnosed bipolar disorder patients without pharmacological prophylaxis is substantial. Patients who are naïve to mood-stabilizers and antipsychotics and are hospitalized for a brief period at diagnosis are the ones least likely to initiate pharmacoprophylaxis, suggesting that this group deserves attention in order to improve the long term prognosis.
    Journal of Affective Disorders 10/2014; 172. DOI:10.1016/j.jad.2014.09.044 · 3.71 Impact Factor
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    ABSTRACT: OBJECTIVE: To investigate associations between combined hormonal contraception and progestogen-only contraception and risks of venous thromboembolism by progestogen and carriership of genetic hemostatic variations. METHODS: This was a case-control study in Sweden carried out between 2003 and 2009, which included 948 patients with venous thromboembolism and 902 individuals in a control group, all aged 18-54 years. Information was obtained by telephone interviews and DNA analyses of blood samples. Radiologic referrals were used for case ascertainment. For comparisons, odds ratios were estimated by unconditional logistic regression analysis adjusting for smoking, body mass index (BMI), and immobilization. RESULTS: The odds ratio (OR) for current use of combined hormonal contraception was 5.3 (95% confidence interval [CI] 4.0-7.0). Desogestrel combinations had the highest OR (11.4, 95% CI 6.0-22.0). The OR for injection of medroxyprogesterone acetate was 2.2 (95% CI 1.34.0). In users of combined hormonal contraception with the factor V Leiden mutation, the OR was 20.6 (95% CI 8.9-58). In women who used progestogen-only contraception and carried the factor V Leiden mutation, the OR was 5.4 (95% CI 2.5-13). CONCLUSION: Risks of venous thromboembolism in association with combined hormonal contraception vary by type of progestogen and independently of BMI and smoking. Thrombophilic genotypes such as factor V Leiden increase risks of venous thromboembolism in users of combined hormonal contraception. Except for injection of medroxyprogesterone acetate, progestinonly contraception seems to be the least thrombogenic hormonal contraception for women carrying genetic hemostatic variations.
    Obstetrics and Gynecology 09/2014; 124(3):600-609. DOI:10.1097/AOG.0000000000000411 · 4.37 Impact Factor
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    ABSTRACT: Introduction We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case–control study (n = 2753) from Sweden. Materials and Methods 39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression. Results Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n = 7181). Conclusions It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.
    Thrombosis Research 08/2014; 134(2). DOI:10.1016/j.thromres.2014.03.054 · 2.43 Impact Factor
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    ABSTRACT: Bronchopulmonary dysplasia (BPD) is a serious, chronic lung disease affecting preterm infants. To identify prenatal risk factors for BPD, focusing on inflammation. Observational cohort study including 106,339 preterm infants, live born before gestational week 37 + 0, from 1988 to 2009 in Sweden. A total of 2,115 infants were diagnosed with BPD, of which 1,393 were born extremely preterm, before gestational week 28 + 0. Information on risk factors was obtained from national health registers and included maternal chronic inflammatory diseases, pregnancy related diseases, and drugs related to treatment of inflammation or infection during pregnancy. Adjusted odds ratios (OR) were calculated in multivariable logistic regression models and are presented with 95% confidence intervals [95% CI]. Preeclampsia was the strongest risk factor for BPD [adjusted OR 2.04, 95% CI 1.83, 2.29]. For extremely preterm infants the adjusted OR was 1.33 [95% CI 1.08, 1.64]. Chorioamnionitis was associated with an increased risk of BPD, but only when including all infants in the analyses [OR 1.33, 95% CI 1.19, 1.48]. No apparent associations were found between maternal chronic inflammatory disease or use of anti-inflammatory drugs and the risk of BPD. Maternal diabetes mellitus, gestational diabetes and maternal use of antibiotics were associated with reduced risks of BPD. Preeclampsia related disorders increased the risk and maternal diabetes mellitus and gestational diabetes reduced the risk for BPD. As angiogenic factors play a role in preeclampsia and diabetes our findings suggest that an impaired angiogenesis may contribute to BPD development. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.
    Pediatric Pulmonology 07/2014; 49(7). DOI:10.1002/ppul.22881 · 2.30 Impact Factor
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    ABSTRACT: Background/Aim: High-dose oestrogen treatment has been used to reduce growth in tall adolescent girls. The long-term safety with regard to cancer has not been clarified. Our aim was to study if this growth reduction therapy affects cancer risk later in life. Methods: A cohort study of 369 (172 treated, 197 untreated) Swedish women who in 1973-1993 were assessed for tall adolescent stature was designed. Data were collected from university hospital records, patient questionnaires, and the Swedish Cancer Register. Results: Risks are presented as odds ratios (ORs) with 95% confidence intervals comparing treated to untreated subjects. In treated subjects, the overall OR for having a tumour (malignant or non-malignant) was 1.7 (0.8-3.8). The ORs were 2.3 (0.4-12.8) for breast tumours, 0.8 (0.2-2.6) for gynaecological tumours, and 6.1 (1.04-∞) for melanoma. When limiting to malignant tumours, the crude ORs were of similar magnitude. Conclusion: The OR for any melanoma was higher in treated than in untreated women, suggesting an increased risk of melanoma associated with high-dose oestrogen treatment during adolescence. Although the risk estimates were increased for overall tumours, breast tumours, malignant gynaecological tumours, and malignant melanoma, these associations were not statistically significant. Our results need to be verified in a larger cohort. © 2014 S. Karger AG, Basel.
    Hormone Research in Paediatrics 06/2014; 82(2). DOI:10.1159/000360137 · 1.71 Impact Factor
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    ABSTRACT: Background RA, AS, and PsA are approved indications for infliximab (IFX). In the US, IFX is a pregnancy Category B drug. For RA and some PsA patients, IFX is administered with MTX, an agent with teratogenic and abortifacient properties. Objectives To characterize pregnancy outcomes in rheumatology patients treated with IFX, data available to the manufacturer through spontaneous reporting and through a pregnancy registry are presented. Methods Data from the Company safety database on individual, spontaneously reported pregnancies worldwide through Feb 23, 2013 were analyzed. The analysis focused on prospectively reported (ie, pregnancy outcome not known when first reported) cases of maternal IFX use for RA, AS, or PsA during pregnancy or within 2 months prior to conception and a known pregnancy outcome. In addition, data through Dec 31, 2010 from a Company-sponsored pregnancy registry study, undertaken to address health authority post-marketing commitments for IFX-exposed pregnancies, were analyzed; data were obtained from national medical registries in Sweden, Denmark and Finland. Maternal characteristics and pregnancy outcomes (births beyond 22 weeks of gestation) were analyzed among RA, AS, and PsA patients exposed to IFX or non-biologic systemic therapy during pregnancy or within 3 months prior to conception. Results 56 prospective reports (37 RA; 12 AS; 6 PsA; 1 RA&AS) of IFX exposure during pregnancy were identified. Mean maternal age was 31 years. 76.8% resulted in a live birth. Birth defects were reported for 3 live births: intestinal malrotation (1), hypospadias (1), and cardiac/coronary artery perforation (1). Of the 56 reports, MTX use was reported in 10 (8 RA), including the hypospadias case; it is possible that additional RA patients may have been exposed to MTX during their pregnancy. 23.2% of the pregnancies resulted in an induced (7) or spontaneous abortion [SAB] (6); 4 of the latter had MTX exposure. In the registry study, 27 IFX-exposed pregnancies were identified (18 RA; 5 AS; 4 PsA). Mean maternal age was 31.2 years. Birth defect was reported in 1 of the 27 IFX-exposed infants (atrial septal defect/metatarsus varus) and in 133 of the 1,974 infants exposed to non-biologic systemic therapy. Conclusions Review of pregnancy outcomes after IFX exposure in utero showed that 76.8% of spontaneous, prospectively reported pregnancies with known outcomes resulted in live births. The most frequently identified congenital anomalies were cardiovascular defects, the most common birth defect in the general population. While there did not appear to be an increased rate of birth defects compared to the general population, the rates in both datasets were based on small study populations. Additionally, the use of MTX, an agent contraindicated in pregnant women, was reported in more than half of the SABs. Spontaneous reporting is limited by the lack of a direct comparison group, the variable amount of data provided, and a possible reporting bias towards more serious cases. The registry study was limited to the Nordic population and data only included births from 22 weeks of gestation onwards. Disclosure of Interest S. Kalari Employee of: Janssen Research & Development, LLC., F. Granath Grant/research support: Janssen, C.-Y. Guo Employee of: Janssen Research & Development, LLC., D. Harrison Employee of: Janssen Research & Development, LLC., G. Broms Grant/research support: Janssen, A. Geldhof Employee of: Janssen Biologics Europe, R. Nissinen Employee of: Janssen Biologics Europe, M. Sanders Employee of: Janssen Research & Development, LLC., M. Gissler Grant/research support: Janssen, L. Pedersen Grant/research support: Janssen, H. Sorensen Grant/research support: Janssen, H. Kieler Grant/research support: Janssen DOI 10.1136/annrheumdis-2014-eular.2038
    Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):482-483. DOI:10.1136/annrheumdis-2014-eular.2038 · 10.38 Impact Factor
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    ABSTRACT: Ulcerative colitis (UC) and Crohn's disease (CD) have been associated with increased risks of adverse birth outcomes. Disease activity and drug exposure may contribute to the association. A cohort from the Swedish health registers including 470,110 singleton births in Sweden from July 2006 to December 2010; 1833 to women with UC and 1220 to women with CD. Birth outcomes for women with UC and CD were compared with outcomes among those without disease. Diseased women were categorized by drug exposure, need of surgery, and hospital admissions as (1) no disease activity and (2) stable or (3) flaring disease. Logistic regression was used to calculate odds ratios with adjustments (aOR) for maternal age, parity, smoking status, body mass index, and comorbidity. There were increased risks of preterm birth for both UC (aOR, 1.78; 95% confidence interval [CI], 1.49-2.13) and CD (aOR, 1.65; 95% CI, 1.33-2.06). Risks were more pronounced in women with flaring disease during pregnancy. Risks of small for gestational age, low Apgar score, and hypoglycemia were also increased. The risk of stillbirth was elevated in women with CD, particularly among those with flaring disease (aOR, 4.48; 95% CI, 1.67-11.90). Thiopurine exposure increased risks for preterm birth, both in women with stable (aOR, 2.41; 95% CI, 1.05-5.51) and with flaring disease (aOR, 4.90; 95% CI, 2.76-8.69). Women with UC and CD are at increased risk of adverse birth outcomes, such as stillbirth, growth restriction, and preterm birth, particularly when they suffer from flares throughout pregnancy. Thiopurine exposure seems to further increase risks, independently of disease activity.
    Inflammatory Bowel Diseases 05/2014; 20(6). DOI:10.1097/MIB.0000000000000060 · 5.48 Impact Factor

Publication Stats

1k Citations
430.74 Total Impact Points

Institutions

  • 2002–2015
    • Karolinska Institutet
      • • Center for Pharmacoepidemiology - CPE
      • • Department of Medicine, Solna
      • • Clinical Epidemiology Unit
      • • Department of Medical Epidemiology and Biostatistics
      Solna, Stockholm, Sweden
  • 2014
    • Lund University
      Lund, Skåne, Sweden
  • 2010–2014
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 1993–2011
    • Uppsala University
      • Department of Women's and Children's Health
      Uppsala, Uppsala, Sweden
  • 2003–2005
    • Uppsala University Hospital
      Uppsala, Uppsala, Sweden