Tobias Svensson

Drug use during pregnancy in Sweden - assessed by the Prescribed Drug Register and the Medical Birth Register.

Purpose: The purpose of this research is to study drug use during pregnancy in Sweden and agreement between use according to antenatal medical records and dispensed drugs from a pharmacy database. Patients and methods: From the Swedish Medical Birth Register (MBR), we established a population-based cohort of 102,995 women who gave birth in 2007. Using the unique personal registration number, information on dispensed drugs from the Prescribed Drug Register (PDR) was obtained prior to, during, and after the pregnancies and compared with MBR information on drug use from standardized antenatal medical records. Results: According to the PDR, 57.6% of the 102,995 women filled a prescription with at least one drug during pregnancy and 50.9% during the lactating period (until 3 months after delivery). The most dispensed drugs during pregnancy were B-lactam antibacterials and penicillins. Agreement between drugs recorded in antenatal medical records and dispensed drugs was highest for drugs used for chronic conditions. The agreement was particularly high for thyroid therapy (85.3%), anti-intestinal inflammatory drugs (80.3%), antiepileptics (69.2%), immunosuppressants (67.4%), and insulin (63.8%). Agreement for drugs used for occasional use was generally lower, ranging between 42.5% for antihistamines and 0.8% for gynecological anti-infectives. Conclusions: A large proportion of women filled a prescription during pregnancy or the lactating period. Agreement between drug use in medical antenatal records and register information from a national pharmacy database was high for drugs used for chronic conditions but low for occasional use. For occasionally used drugs, medical record and register-based data may provide incomplete exposure information because of nonreporting or noncompliance.

Diverticular disease and the risk of colon cancer – a population-based case–control study

Aliment Pharmacol Ther 2011; 34: 675–681

The genetic influence on diverticular disease – a twin study

The contribution of hereditary factors to the development of diverticular disease (DD) of the colon is unknown. Prevalence and location of diverticula differ in Western world compared to in Asia and several case reports describing families with DD have been published.

Incidence and time trends of brain metastases admissions among breast cancer patients in Sweden.

Background:While treatment for breast cancer has been refined and overall survival has improved, there is concern that the incidence of brain metastases has increased.Methods:We identified patients in Sweden with incident breast cancer 1998–2006 in the National Cancer Register, and matched these to the National Patient Register to obtain information on hospital admissions for distant metastases. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed with Cox regression as estimates of relative risk.Results:Among 50 528 breast cancer patients, 696 (1.4%) were admitted with brain metastases during median 3.5 years of follow-up. Admissions for other metastases were found in 3470 (6.9%) patients. Compared with the period 1998–2000, patients diagnosed with breast cancer 2004–2006 were at a 44% increased risk of being admitted with brain metastases (HR 1.44, 95% CI 1.13–1.85).Conclusion:The incidence of admissions with brain metastases in breast cancer patients was increasing in the mid-2000s in Sweden. These findings support a true increase in incidence of brain metastases among breast cancer patients.

Incidence and trends in femur shaft fractures in Swedish children between 1987 and 2005.

Background The surgical treatment of femur shaft fractures in children is changing, and the time spent in hospital is shorter than before. The purpose of this nationwide epidemiology study is to report incidence of pediatric femur shaft fractures in Sweden during 1987 to 2005 by age, sex, cause of injury, severity of injury, and seasonal variation, and to analyze the change in incidence, treatment modalities, and length of hospital stay over time. Methods Children (N=4984) with a diagnostic code for femur shaft fracture in Sweden 1987 to 2005 were selected from the Swedish National Hospital Discharge Registry. Results The overall annual incidence per 100,000 children was 22.9 in boys and 9.5 in girls. The incidence declined by 42%, on average 3% per year, from 19.4 to 11.8 between 1987 and 2005 (P<0.001). The most common cause of injury in children younger than 4 years of age was fall of <1 m; in children 4 to 12 years of age, sports accidents were the most frequent cause of injury; and in children 13 to 14 years of age, traffic accidents. The month of occurrence for femur shaft fractures had a bimodal seasonal variation with a peak in March and in August. Treatment modalities were changing during the study period from the use of traction to an increased use of external fixation and elastic intramedullary nailing. The length of hospital stay decreased by 81%, from 26 days in 1987 to 5 days in 2005 (P<0.001), but had no correlation to the introduction of new surgical treatment methods. Conclusions The present nationwide study of femur shaft fractures shows a decrease of fracture incidence, a shift in the treatment modalities, and shorter length of hospital stay. Level of Evidence Level III, retrospective comparative study.

Psychosocial Stress Related to the Loss of a Close Relative the Year Before or During Pregnancy and Risk of Preeclampsia

The role of stress in the pathogenesis of preeclampsia has only been investigated in a few studies, and the findings are not conclusive. We analyzed whether maternal bereavement shortly before or during pregnancy is associated with an increased risk of preeclampsia. We conducted a cohort study of singleton births in Denmark during 1978–2008 and in Sweden during 1973–2006 (n=4 122 490) by linking national population-based registers. Mothers were considered exposed to bereavement if they lost a parent, a sibling, a partner, or a child the year before or during pregnancy (n=124 553). The risk of preeclampsia was slightly increased for women who lost a close relative during the 6 months before conception (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.06–1.23) or during the first trimester of pregnancy (OR, 1.15; 95% CI, 1.03–1.29). Exposure during these periods tended to be more closely related to early preeclampsia (delivery before 34 weeks of gestation; OR, 1.37; 95% CI, 1.12–1.67) than to late preeclampsia (OR, 1.13; 95% CI, 1.06–1.20). The strongest association was observed between loss of a child and early preeclampsia when the exposure window was from 6 months before pregnancy until start of second trimester (OR, 4.03; 95% CI, 2.46–6.61). Our results related to timing of exposure suggest that severe stress may influence early placentation. However, the public health implications of our findings are limited in populations with a low prevalence of severe stress exposures.

Birth outcomes among women exposed to neuraminidase inhibitors during pregnancy

To compare birth outcomes between women exposed and unexposed to the antiviral medications oseltamivir or zanamivir during pregnancy.

Dihydropyridine Calcium Channel Antagonists Disrupt Migrating Myoelectric Complexes and Counteract Intestinal Disorders Associated with Morphine Withdrawal Diarrhea

The effects of two dihydropyridine (DHP) calcium channel antagonists, nifedipine and nimodipine, on migrating myoelectric complexes (MMCs) of the small intestine were studied in naive and morphine-dependent rats. In addition, the effects of two other calcium channel antagonists, verapamil and diltiazem, on the MMCs were investigated. Nifedipine (1.0-4.0 mg kg-1 intravenously) or nimodipine (1.0-4.0 mg kg-1 intravenously) had an inhibitory effect on the spontaneously occurring MMCs, whereas verapamil (2.5-5.0 mg kg-1 intravenously) or diltiazem (2.5-5.0 mg kg-1 intravenously) had no effect. Bay K 8644 (0.25 mg kg-1 intravenously), a DHP calcium channel agonist, instantly reversed the inhibition induced by nifedipine or nimodipine. When given alone, Bay K 8644 induced irregular spiking activity. In morphine-dependent rats with regular MMCs naloxone (1.0 mg kg-1 intravenously) induced intense spiking activity and profuse diarrhea. Nifedipine (2.0 and 4.0 mg kg-1 intravenously) and nimodipine (2.0 and 4.0 mg kg-1 intravenously) given before naloxone prevented the intense, abstinence-evoked spiking and associated diarrhea. In healthy volunteers nimodipine at an infusion rate of 2 mg h-1 for 4 h did not inhibit the fasting motility pattern. Our findings indicate that DHP-binding sites are involved in the regulation of MMC in the rat and that drugs acting as antagonists at these sites can be used to suppress morphine withdrawal diarrhea and, tentatively, other functional disorders of the intestine.

Maternal and pregnancy characteristics and risk of infantile hypertrophic pyloric stenosis

BACKGROUND/PURPOSE The incidence of infantile hypertrophic pyloric stenosis (IHPS) in Sweden decreased dramatically during the 1990s. The aim of the study was to examine IHPS risk factors and the possible change in them as the incidence declined. METHODS This is a case-control study including 3608 surgically treated IHPS cases and 17588 matched controls during 1973-2008. Cases were identified in the Swedish National Patient Register and data on possible risk factors were collected from the Swedish Medical Birth Register. The association between study variables and IHPS was analyzed using conditional logistic regression for the whole study period and separately for periods with high and low IHPS incidences. RESULTS Prematurity (OR, 2.54; 95% CI, 2.06-3.14), caesarean delivery (OR, 1.67; 95% CI, 1.51-1.86), maternal smoking (OR, 1.82; 95% CI, 1.53-2.16), and young maternal age (< 20yrs) (OR, 1.42; 95% CI, 1.17-1.73) were associated with an increased IHPS risk. Birth order 2 (OR, 0.78; 95% CI, 0.71-0.85) or more was associated with a lower IHPS risk. ORs for smoking increased at low incidence rate. CONCLUSION We report caesarean section, prematurity, primiparity, young maternal age, and smoking as significant IHPS risk factors. The impact of smoking was higher during periods with a low incidence.

Maternal smoking during pregnancy and risks of suicidal acts in young offspring.

Obstetric and neonatal complications have been associated with completed and attempted suicide (suicidal acts) in young offspring. Maternal smoking is one of the most important risk factors for obstetric complications, but the association between prenatal smoking exposure and offspring risk of suicidal acts is unknown. We performed a population-based study of 1,449,333 single births born in Sweden between 1983 and 1996, derived from linked registry data. Maternal smoking and risks of suicidal acts in offspring were estimated using hazard ratios, derived from proportional-hazard models, controlling for potential confounding of parental socio-demographic factors and psychiatric care in first degree relatives. To control for unmeasured familial confounding, a matched case–control analysis of suicidal acts was performed within sibling pairs discordant for prenatal smoking exposure. In the cohort analysis, the adjusted hazard ratio for completed suicide among offspring to women smoking 1–9 cigarettes and at least 10 cigarettes per day were 1.67, 95% confidence interval (CI), 1.29–2.16, and 1.54, 95% CI, 1.12–2.10. For suicidal acts, corresponding hazard ratios were 1.28, 95% CI 1.21–1.35 and 1.48, 95% CI 1.39–1.57, respectively. However, in sibling pairs discordant for suicidal acts and prenatal smoking exposure, we found no evidence that prenatal smoking exposure increased the risk of suicidal acts. We conclude that the association between prenatal smoking exposure and offspring risk of suicidal acts is probably confounded by unmeasured familial factors.