Follow-up of an age-period-cohort analysis on alcohol-related mortality trends in Sweden 1970-2015 with predictions to 2025.

BACKGROUND AND AIMS: Several studies have indicated that birth cohorts are important in explaining trends in alcohol-related mortality. An earlier study from Sweden with data up to 2002 showed that birth cohorts that grew up under periods of more liberal alcohol policies had higher alcohol-related mortality than those cohorts growing up under more restrictive time periods. In spite of increasing alcohol consumption, predictions in 2002 also indicated lower alcohol-related mortality in the future. The aim of this study is to follow-up whether the effects of birth cohorts and the predictions made for Sweden still holds using data up to 2015. METHOD: The study comprised an age-period-cohort analysis and predictions based on population predictions from Statistics Sweden. The analysis was based on all alcohol-related deaths in the Swedish population between 1969 and 2015 for the cohorts born in the decades 1920 through 1990. Data were restricted to people 15-84 years of age. In total, the analysis covered 68,341 deaths and more than 284 million person-years. RESULTS: Male and female cohorts born in the 1940s to 1950s exhibited the highest alcohol-related mortality, while those born in the 1970s continued to have the lowest alcohol-related mortality rates. The predicted mortality rates for males are still anticipated to decrease somewhat through 2025. CONCLUSIONS: The updated age-period-cohort analysis further supports the importance of focusing on restrictive alcohol policies targeting adolescents.

Effects of ultrasound pregnancy dating on neonatal morbidity in late preterm and early term male infants: a register-based cohort study.

BACKGROUND: Assessing gestational age by ultrasound can introduce a systematic bias due to sex differences in early growth. METHODS: This cohort study included data on 1,314,602 births recorded in the Swedish Medical Birth Register. We compared rates of prematurity-related adverse outcomes in male infants born early term (gestational week 37-38) or late preterm (gestational week 35-36), in relation to female infants, between a time period when pregnancy dating was based on the last menstrual period (1973-1978), and a time period when ultrasound was used for pregnancy dating (1995-2010), in order to assess the method's influence on outcome by fetal sex. RESULTS: As expected, adverse outcomes were lower in the later time period, but the reduction in prematurity-related morbidity was less marked for male than for female infants. After changing the pregnancy dating method, male infants born early term had, in relation to female infants, higher odds for pneumothorax (Cohort ratio [CR] 2.05; 95 % confidence interval [CI] 1.33-3.16), respiratory distress syndrome of the newborn (CR 1.99; 95 % CI 1.33-2.98), low Apgar score (CR 1.26; 5 % CI 1.08-1.47), and hyperbilirubinemia (CR 1.12; 95 % CI 1.06-1.19), when outcome was compared between the two time periods. A similar trend was seen for late preterm male infants. CONCLUSION: Misclassification of gestational age by ultrasound, due to size differences, can partially explain currently reported sex differences in early term and late preterm infants' adverse neonatal outcomes, and should be taken into account in clinical decisions and when interpreting study results related to fetal sex.

Individual-based versus aggregate meta-analysis in multi-database studies of pregnancy outcomes: the Nordic example of selective serotonin reuptake inhibitors and venlafaxine in pregnancy.

PURPOSE: Compare analyses of a pooled data set on the individual level with aggregate meta-analysis in a multi-database study. METHODS: We reanalysed data on 2.3 million births in a Nordic register based cohort study. We compared estimated odds ratios (OR) for the effect of selective serotonin reuptake inhibitors (SSRI) and venlafaxine use in pregnancy on any cardiovascular birth defect and the rare outcome right ventricular outflow tract obstructions (RVOTO). Common covariates included maternal age, calendar year, birth order, maternal diabetes, and co-medication. Additional covariates were added in analyses with country-optimized adjustment. RESULTS: Country adjusted OR (95%CI) for any cardiovascular birth defect in the individual-based pooled analysis was 1.27 (1.17-1.39), 1.17 (1.07-1.27) adjusted for common covariates and 1.15 (1.05-1.26) adjusted for all covariates. In fixed effects meta-analyses pooled OR was 1.29 (1.19-1.41) based on crude country specific ORs, 1.19 (1.09-1.29) adjusted for common covariates, and 1.16 (1.06-1.27) for country-optimized adjustment. In a random effects model the adjusted OR was 1.07 (0.87-1.32). For RVOTO, OR was 1.48 (1.15-1.89) adjusted for all covariates in the pooled data set, and 1.53 (1.19-1.96) after country-optimized adjustment. Country-specific adjusted analyses at the substance level were not possible for RVOTO. CONCLUSION: Results of fixed effects meta-analysis and individual-based analyses of a pooled dataset were similar in this study on the association of SSRI/venlafaxine and cardiovascular birth defects. Country-optimized adjustment attenuated the estimates more than adjustment for common covariates only. When data are sparse pooled data on the individual level are needed for adjusted analyses. Copyright © 2016 John Wiley & Sons, Ltd.

Use of SSRI and SNRI Antidepressants during Pregnancy: A Population-Based Study from Denmark, Iceland, Norway and Sweden.

BACKGROUND: The purpose was to describe utilization of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), including trends in prevalence, characteristics of users, drug switching and changes in prescribed doses in a large group of pregnant women across four Nordic countries. METHODS: A drug utilization study based on linked individual-level data from the nationwide prescription- and medical birth registers in Denmark, Iceland, Norway and Sweden. The study population comprised all pregnancies in these countries, resulting in a live birth or stillbirth after gestational week 22 from January 1st 2008 to December 31st 2012 (N = 1 162 470). In addition to the main study drugs SSRIs and SNRIs, we included (concurrent) use of other antidepressants, antipsychotics, anxiolytics and hypnotics. RESULTS: A total of 38 219 (3.3%) pregnancies were exposed to SSRIs and 5 634 (0.5%) to SNRIs. Prevalence of SSRI and SNRI use varied by country (1.8% in Norway to 7.0% in Iceland). Use and prescribed dosages decreased with each passing trimester of pregnancy; prevalence was 2.7% at conception, and 2.1%, 1.7% and 1.3% respectively in 1st, 2nd and 3rd trimester. In 0.6% of pregnancies women filled a prescription before pregnancy and in every trimester. In one third of exposed pregnancies, women were also dispensed anxiolytics, hypnotics or sedatives. CONCLUSION: Use of SSRI and SNRI use during pregnancy varied between the Nordic countries, but the overall prevalence remained low and relatively stable from 2008 to 2012. The low prevalence of use and high proportion of women who discontinue treatment in pregnancy raise questions about adequate treatment of depression in pregnant women.

Exposure to systemic antibacterial medications during pregnancy and risk of childhood cancer.

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. METHODS: A 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. RESULTS: Mothers 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.

Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design.

OBJECTIVE: To assess whether use of specific selective serotonin reuptake inhibitors (SSRIs) or venlafaxine in early pregnancy is associated with an increased risk of birth defects, with emphasis on cardiovascular birth defects even when accounting for lifestyle or other familial confounding. DESIGN: Multicountry population based cohort study, including sibling controlled design. SETTING: Nordic population (Denmark, Finland, Iceland, Norway, and Sweden) identified from nationwide health registers at different periods in 1996-2010. POPULATION: The full study cohort included women giving birth to 2.3 million live singletons. The sibling cohort included 2288 singleton live births. The sibling controlled analyses included sibling pairs who were discordant for exposure to SSRIs or venlafaxine and birth defects. MAIN OUTCOME MEASURE: Prevalence of birth defects, including subtypes of cardiac defects. Odds ratio of birth defects from logistic and conditional logistic regression. RESULTS: Among 36,772 infants exposed to any SSRI in early pregnancy, 3.7% (n=1357) had a birth defect compared with 3.1% of 2,266,875 unexposed infants, yielding a covariate adjusted odds ratio of 1.13 (95% confidence interval 1.06 to 1.20). In the sibling controlled analysis the adjusted odds ratio decreased to 1.06 (0.91 to 1.24). The odds ratios for any cardiac birth defect with use of any SSRI or venlafaxine were 1.15 (95% confidence interval 1.05 to 1.26) in the covariate adjusted analysis and 0.92 (0.72 to 1.17) in the sibling controlled analysis. For atrial and ventricular septal defects the covariate adjusted odds ratio was 1.17 (1.05 to 1.31). Exposure to any SSRI or venlafaxine increased the prevalence of right ventricular outflow tract obstruction defects, with a covariate adjusted odds ratio of 1.48 (1.15 to 1.89). In the sibling controlled analysis the adjusted odds ratio decreased to 0.56 (0.21 to 1.49) for any exposure to SSRIs or venlafaxine and right ventricular outflow tract obstruction defects. CONCLUSIONS: In this large Nordic study no substantial increase was found in prevalence of overall cardiac birth defects among infants exposed to SSRIs or venlafaxine in utero. Although the prevalence of septal defects and right ventricular outflow tract defects was higher in exposed infants, the lack of an association in the sibling controlled analyses points against a teratogenic effect of these drugs.

Perinatal conditions related to growth restriction and inflammation are associated with an increased risk of bronchopulmonary dysplasia.

AIM: 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). METHODS: This case-control study, using national Swedish data, included 2255 preterm infants, born before 33 gestational weeks. The 667 BPD cases were oxygen dependent at 36 weeks' postmenstrual age, and the 1558 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. RESULTS: An increased risk of BPD was associated with prelabour preterm rupture of membranes of more than 1 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. CONCLUSION: Growth restriction and inflammation increased the risk of BPD in preterm infants and prelabour preterm rupture of membranes, small for gestational age, low Apgar score or need for resuscitation should raise clinical suspicions.

Prenatal inflammatory risk factors for development of bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a serious, chronic lung disease affecting preterm infants. OBJECTIVE: To identify prenatal risk factors for BPD, focusing on inflammation. METHODS: 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]. RESULTS: 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. CONCLUSION: 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.

Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality.

IMPORTANCE: Maternal psychiatric disease is associated with adverse pregnancy outcomes. Use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy has been associated with congenital anomalies, neonatal withdrawal syndrome, and persistent pulmonary hypertension of the newborn. However, the risk of stillbirth and infant mortality when accounting for previous maternal psychiatric disease remains unknown. OBJECTIVE: To study risk of stillbirth and infant mortality associated with use of SSRIs during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study from all Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) at different periods from 1996 through 2007. The study included women with singleton births. We obtained information on maternal use of SSRIs from prescription registries. Maternal characteristics, pregnancy, and neonatal outcomes were obtained from patient and medical birth registries. MAIN OUTCOME MEASURES: We used logistic regression to estimate relative risks of stillbirth, neonatal death, and postneonatal death associated with SSRI use during pregnancy taking into account maternal characteristics and previous psychiatric hospitalization. RESULTS: Among 1,633,877 singleton births in the study, 6054 were stillbirths; 3609, neonatal deaths; and 1578, postneonatal deaths. A total of 29,228 (1.79%) of mothers had filled a prescription for an SSRI during pregnancy. Women exposed to an SSRI presented with higher rates of stillbirth (4.62 vs 3.69 per 1000, P = .01) and postneonatal death (1.38 vs 0.96 per 1000, P = .03) than those who did not. The rate of neonatal death was similar between groups (2.54 vs 2.21 per 1000, P = .24). Yet in multivariable models, SSRI use was not associated with stillbirth (adjusted odds ratio [OR], 1.17; 95% CI, 0.96-1.41; P = .12), neonatal death (adjusted OR, 1.23; 95% CI, 0.96-1.57; P = .11), or postneonatal death (adjusted OR, 1.34; 95% CI, 0.97-1.86; P = .08). Estimates were further attenuated when stratified by previous hospitalization for psychiatric disease. The adjusted OR for stillbirth in women with a previous hospitalization for psychiatric disease was 0.92 (95% CI, 0.66-1.28; P = .62) and was 1.07 (95% CI, 0.84-1.36; P = .59) for those who had not been previously hospitalized. The corresponding ORs for neonatal death were 0.89 (95% CI, 0.58-1.39; P = .62) for women who were hospitalized and 1.14 (95% CI, 0.84-1.56; P = .39) for women who were not. For postneonatal death, the ORs were 1.02 (95% CI, 0.61-1.69; P = .95) for women who were hospitalized and 1.10 (95% CI, 0.71-1.72; P = .66) for women who were not. CONCLUSIONS AND RELEVANCE: Among women with singleton births in Nordic countries, no significant association was found between use of SSRIs during pregnancy and risk of stillbirth, neonatal mortality, or postneonatal mortality. However, decisions about use of SSRIs during pregnancy must take into account other perinatal outcomes and the risks associated with maternal mental illness.

Excess mortality in women of reproductive age from low-income countries: a Swedish national register study.

BACKGROUND: Cause-of-death statistics is widely used to monitor the health of a population. African immigrants have, in several European studies, shown to be at an increased risk of maternal death, but few studies have investigated cause-specific mortality rates in female immigrants. METHODS: In this national study, based on the Swedish Cause of Death Register, we studied 27,957 women of reproductive age (aged 15-49 years) who died between 1988 and 2007. Age-standardized mortality rates per 100,000 person years and relative risks for death and underlying causes of death, grouped according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, were calculated and compared between women born in Sweden and in low-, middle- and high-income countries. RESULTS: The total age-standardized mortality rate per 100,000 person years was significantly higher for women born in low-income (84.4) and high-income countries (83.7), but lower for women born in middle-income countries (57.5), as compared with Swedish-born women (68.1). The relative risk of dying from infectious disease was 15.0 (95% confidence interval 10.8-20.7) and diseases related to pregnancy was 6.6 (95% confidence interval 2.6-16.5) for women born in low-income countries, as compared to Swedish-born women. CONCLUSIONS: Women born in low-income countries are at the highest risk of dying during reproductive age in Sweden, with the largest discrepancy in mortality rates seen for infectious diseases and diseases related to pregnancy, a cause of death pattern similar to the one in their countries of birth. The World Bank classification of economies may be a useful tool in migration research.

Maternal mortality in Sweden 1988-2007: more deaths than officially reported.

OBJECTIVE: To obtain more accurate calculations of maternal and pregnancy-related mortality ratios in Sweden from 1988 to 2007 by using information from national registers and death certificates. DESIGN: A national register-based study, supplemented by a review of death certificates. SETTING: Sweden, 1988-2007. POPULATION: The deaths of 27 957 women of reproductive age (15-49 years). METHODS: The Swedish Cause of Death Register, Medical Birth Register, and National Patient Register were linked. All women with a diagnosis related to pregnancy in at least one of these registers within 1 year prior to death were identified. Death certificates were reviewed to ascertain maternal deaths. Maternal mortality ratio (the number of maternal deaths/100 000 live births, excluding and including suicides), and pregnancy-related mortality ratio (number of deaths within 42 days after termination of pregnancy, irrespective of cause of death/100 000 live births) were calculated. MAIN OUTCOME MEASURES: Direct and indirect maternal deaths and pregnancy-related deaths. RESULTS: The maternal mortality ratio in Sweden, based on the current method of identifying maternal deaths, was 3.6. After linking registers and reviewing death certificates, we identified 64% more maternal deaths, resulting in a ratio of 6.0 (or 6.5 if suicides are included). The pregnancy-related mortality ratio was 7.3. A total of 478 women died within a year after being recorded with a diagnosis related to pregnancy. CONCLUSIONS: By including the 123 cases of maternal death identified in this study, the mean maternal mortality ratio from 1988 to 2007 was 64% higher than reported to the World Health Organization.

Health consequences of prophylactic exposure to antenatal corticosteroids among children born late preterm or term.

OBJECTIVE: To investigate the duration of effects and health consequences of earlier antenatal corticosteroid exposure in infants born late preterm or term. DESIGN: Observational cohort study. SETTING: Children born after gestational week 34 in Sweden, 1976-1997, whose mothers were hospitalized for imminent preterm delivery. The children were followed to their 11th birthday. SAMPLE: The cohort consisted of 11 873 infants, of whom 8620 were exposed. METHODS: Exposure was estimated at hospital level. Infants born at a hospital practicing antenatal corticosteroid administration were classified as exposed. Estimation of hospital routines was based on questionnaire data, telephone interviews with physicians and pharmacy sales, validated in a random sample of medical records. Logistic regression was used to assess associations with adjustments for pregnancy length, birth year and hospital level. MAIN OUTCOME MEASURES: Rates and odds ratios of mortality, respiratory distress syndrome, bronchopulmonary dysplasia, epilepsy, cerebral palsy, childhood diabetes, birthweight, length and head circumference for all infants, and for preterm and term infants, respectively. RESULTS: Exposed infants had reduced risks of respiratory distress syndrome (odds ratio 0.54, 95% confidence interval 0.35-0.83) and small head circumference (odds ratio 0.47, 95% confidence interval 0.36-0.61), and an increased risk of low Apgar scores (odds ratio 1.40, 95% confidence interval 1.01-1.94), most pronounced in infants born after gestational week 37. CONCLUSIONS: Infants born after gestational week 34 seem to benefit from earlier antenatal corticosteroid administration, with reduced risks of respiratory distress syndrome. However, the treatment was less beneficial for term infants, because they also had increased risk of low Apgar scores.

Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries.

OBJECTIVE: To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs. DESIGN: Population based cohort study using data from the national health registers. SETTING: Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007. PARTICIPANTS: More than 1.6 million infants born after gestational week 33. MAIN OUTCOME MEASURES: Risks of persistent pulmonary hypertension of the newborn associated with early and late exposure to SSRIs during pregnancy and adjusted for important maternal and pregnancy characteristics. Comparisons were made between infants exposed and not exposed to SSRIs. RESULTS: Around 30 000 women had used SSRIs during pregnancy and 11 014 had been dispensed an SSRI later than gestational week 20. Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn: 33 of 11 014 exposed infants (absolute risk 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000); adjusted odds ratio 2.1 (95% confidence interval 1.5 to 3.0). The increased risks of persistent pulmonary hypertension in the newborn for each of the specific SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were of similar magnitude. Filling a prescription with SSRIs before gestational week 8 yielded slightly increased risks: adjusted odds ratio 1.4 (95% confidence interval 1.0 to 2.0). CONCLUSIONS: The risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold. The increased risk seems to be a class effect.

Insulin glargine use and short-term incidence of malignancies - a three-year population-based observation.

AIMS/HYPOTHESIS: To further investigate the association of cancer occurrence with the use of insulin glargine. METHODS: We followed 114 838 individuals using insulin between 1 July and 31 December 2005. From 1 January 2006 to 31 December 2008, we noted the occurrence of malignancies (cohort I). Insulin users between 1 July and 31 December 2006 were followed for the occurrence of malignancies in 2007 and 2008 (cohort II). Users of insulin during three consecutive six-month periods from 1 July 2005 to 31 December 2006 were followed for the occurrence of malignancies in 2007 and 2008 (cohort III). The Prescribed Drug Register, the Cancer Register, and the Causes of Death Register were used to obtain information on targeted person-time and outcome. We retrieved variables reflecting potential confounding factors from the Swedish National Diabetes Register, the Prescribed Drug Register, the Patient Register, the Medical Birth Register and the National Education Register. With Poisson regression we evaluated the association between insulin use and malignancy outcome with adjustment for confounders. RESULTS: The adjusted incidence rate ratio (and 95% confidence interval) for women who used insulin glargine alone compared with those who used other types of insulin, was 1.60 (1.10-2.32) for breast cancer but included 1.0 for malignancy outcomes other than breast cancer for men and women when analyzing cohort I with follow-up in 2006-2008. For cohort II and III the corresponding incidence rate ratios were 1.38 (0.87-2.18), and 0.87 (0.41-1.85), respectively. CONCLUSION/INTERPRETATION: We do not see an increased risk during 2008 for breast cancer in the insulin glargine group. We need data for additional years before we can state with reasonable certainty that the increase in breast cancer incidence that we observed in Sweden in 2006 and 2007 was due to a random fluctuation or whether there is an association with the use of insulin glargine.

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.

Frequency of serious complications after surgery for snoring and sleep apnea.

CONCLUSION: No case of death related to surgery in the form of uvulopalatopharyngoplasty, uvulopalatoplasty or nasal surgery for snoring or sleep apnea has been recorded in Sweden among 4876 patients treated between 1997 and 2005. Severe complications of surgery in the peri- and postoperative period, especially in the form of bleedings and infections, were most common after uvulopalatopharyngoplasty, occurring in 3.7%. OBJECTIVE: To investigate the frequency of serious complications, including death, of surgery for treatment of snoring and sleep apnea. METHODS: All Swedish adults who were treated surgically because of snoring or sleep apnea from January 1997 to December 2005 were identified in the National Patient Register. Mortality and serious complications within 30 days from surgery were obtained from the National Cause of Death Register and the National Patient Register. RESULTS: A total of 4876 patients were treated surgically. Uvulopalatopharyngoplasty was performed in 3572 patients, uvulopalatoplasty in 929 patients, and nasal surgery in 375 patients. None of the surgically treated patients died in the peri- and postoperative period. Severe complications, mainly bleedings and infections, were recorded in 37.1 per 1000 patients treated with uvulopalatopharyngoplasty, in 5.6 per 1000 patients after uvulopalatoplasty, and in 8.8 per 1000 patients after nasal surgery.

Ultrasound pregnancy dating leads to biased perinatal morbidity and neonatal mortality among post-term-born girls.

BACKGROUND: Ultrasound assessment of gestational length is based on the assumption that fetuses of the same gestational age have equal size at the time of investigation. However, there are detectable sex differences in fetal size by the end of the first trimester. We examined whether ultrasound dating introduces sex differences in risks of adverse perinatal outcomes related to post-term birth. METHODS: We used the Swedish Medical Birth Register to compare male and female newborns during 1973-1978, when gestational age was based on the last menstrual period, and 1995-2007, when gestational age was based on ultrasound. We included singleton births from 39 to 43 gestational weeks. RESULTS: During the first time period, the newborn male-to-female ratio by gestational age at delivery was constant around 1.0, but in the later time period it consistently increased by gestational age, reaching 1.60 at 43 weeks. In the first time period, post-term females had reduced risk for adverse perinatal outcomes compared with post-term males. After the introduction of ultrasound, post-term females had higher risks of stillbirth (odds ratio = 1.60 [95% confidence interval = 1.11 to 2.30]) and meconium aspiration (1.39 [1.10 to 1.75]), compared with post-term males. One-third of stillbirths among post-term girls today might be due to incorrect calculation of gestational age. CONCLUSIONS: Introduction of ultrasound for the estimation of gestational age may be associated with increased risks of adverse perinatal outcomes among females classified as post-term compared with their male counterparts.

Prenatal exposure to medicines and the risk of childhood brain tumor.

BACKGROUND: Childhood brain tumors are associated with high mortality and morbidity but little is known about its causes. About half of women use medicines when pregnant and some of the medicines commonly used might be carcinogenic. OBJECTIVE: The aim with this population-based case-control study was to analyze associations between specific groups of medicines taken during pregnancy and the risk of brain tumor in the offspring. METHODS: All children, up to 15 years of age, born in Sweden between 1975 and 1984 were eligible for the study. Cases (N=512) were children diagnosed with brain tumor and controls (N=525) were randomly selected from the Medical Birth Register. Exposure data on medicines was extracted blindly from antenatal medical records and grouped according to Anatomical Therapeutic Chemical (ATC) code. Information on maternal reproductive history was received from the Medical Birth Register. We used logistic regression to estimate associations between fetal exposure to medicines and childhood brain tumor. RESULTS: No significant changes in risk were noted after exposure to iron supplementation, antiemetics, analgesics, antibiotics or any other main ATC group. A tendency of protective effect was seen for prenatal exposure to folic acid (adjusted OR 0.6, 95% CI 0.3-1.1). Ten children with a diagnosis of brain tumor had been exposed to beta-blocking agents in fetal life as compared to two children without brain tumor (adjusted OR 5.3, 95% CI 1.2-24.8). CONCLUSIONS: In this case-control study, an increased risk of brain tumor was seen in children exposed to beta-blocking agents during fetal life. However, due to the low number of exposed the interpretation of this finding should be made with caution.

Influence of environmental factors in higher risk of sudden infant death syndrome linked with parental mental illness.

CONTEXT: Since national risk reduction campaigns have been conducted, sudden infant death syndrome (SIDS) has become increasingly concentrated among disadvantaged families, including those affected by mental illness. However, causal mechanisms specific to this group are poorly understood. OBJECTIVES: To estimate relative risk and compare risk factor prevalence in infants with and without parental psychiatric inpatient history, and to explore effect modification after the 1992 Swedish risk reduction campaign. DESIGN: National birth cohort. Parental psychiatric admissions, maternal prenatal smoking, obstetric and social risk factors, and cause-specific infant death were ascertained via linkage between national registers. SETTING: The Swedish population, 1978 through 2004. PARTICIPANTS: All singleton live births (N = 2.5 million). MAIN OUTCOME MEASURE: Incidence of SIDS. RESULTS: Risk of SIDS was higher with a history of parental inpatient care, especially if both parents were admitted with any mental illness (odds ratio, 6.8; 95% confidence interval, 4.7-10.0), or if the mother (6.5; 4.9-8.7) or both parents (9.5; 5.5-16.4) had an alcohol/drug disorder. A 2-fold higher risk was also seen if the mother or father was admitted with any psychiatric illness other than alcohol or other drug disorders. Elevated risk persisted even if the last maternal inpatient episode had occurred 5 or more years before the infant's birth. After the national campaign, risk factor prevalence (especially maternal antenatal smoking) remained high in this population, and relative risks therefore increased. During 1992 through 2004, smoking and individual social adversity measures jointly accounted for approximately half the excess risk linked with maternal psychiatric inpatient history, whereas the confounding effects of obstetric factors were minimal. CONCLUSIONS: Tailored approaches are needed to ensure that standard safety advice is effectively communicated to these vulnerable families. In particular, mentally ill pregnant women should be encouraged and better supported to stop smoking. Families with 2 affected parents require particularly strong support. A clearer understanding is needed as to why high risk factor prevalence persists among these parents.