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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Short and long-term effects of antenatal corticosteroids assessed in a cohort of 7,827 children born preterm.

OBJECTIVE: To study the benefits of antenatal corticosteroids (ACS) in clinical settings and to evaluate the occurrence of long-term neuro-sensory effects such as epilepsy and cerebral palsy (CP). DESIGN: Observational population-based study including all births between gestational weeks 24 and 34 during 1976-1997 in Sweden. Exposure to ACS was evaluated at hospital level. Children were followed up to their ninth birthday. SAMPLE AND METHODS: Seven thousand eight hundred twenty-seven infants of which 5,632 were exposed to ACS. Data on hospital ACS routines was based on questionnaires and interviews with physicians and pharmacy sales. Outcomes were obtained from the national health registers and assessed according to gender of the child. Logistic regression was used to assess associations. MAIN OUTCOME MEASURES: Neonatal death, low Apgar score, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), CP, and epilepsy. RESULTS: After adjustment, exposed infants had reduced risks of RDS (OR 0.80, 95% CI 0.70-0.92), late neonatal death (OR 0.86, 95% CI 0.57-1.29), BPD (OR 0.87, 95% CI 0.62-1.22), ROP (OR 0.80, 95% CI 0.48-1.32), IVH (OR 0.93, 95% CI 0.67-1.3), and CP (OR 0.82, 95% CI 0.58-1.15). Males had a higher risk of epilepsy (OR 1.74, 95% CI 0.85-3.55) than females (OR 0.50, 95% CI 0.25-1.03). CONCLUSION: The results confirm the beneficial effect of ACS regarding RDS in clinical settings. Except for a tendency to increased risk of epilepsy among male infants there were no increased risks of neuro-sensory outcomes.

The incidence of adverse events in Swedish hospitals: a retrospective medical record review study.

OBJECTIVES: To estimate the incidence, nature and consequences of adverse events and preventable adverse events in Swedish hospitals. DESIGN: A three-stage structured retrospective medical record review based on the use of 18 screening criteria. SETTING: Twenty-eight Swedish hospitals. Population A representative sample (n = 1967) of the 1.2 million Swedish hospital admissions between October 2003 and September 2004. MAIN OUTCOME MEASURES: Proportion of admissions with adverse events, the proportion of preventable adverse events and the types and consequences of adverse events. RESULTS: In total, 12.3% (n = 241) of the 1967 admissions had adverse events (95% CI, 10.8-13.7), of which 70% (n = 169) were preventable. Fifty-five percent of the preventable events led to impairment or disability, which was resolved during the admission or within 1 month from discharge, another 33% were resolved within 1 year, 9% of the preventable events led to permanent disability and 3% of the adverse events contributed to patient death. Preventable adverse events led to a mean increased length of stay of 6 days. Ten of the 18 screening criteria were sufficient to detect 90% of the preventable adverse events. When extrapolated to the 1.2 million annual admissions, the results correspond to 105,000 preventable adverse events (95% CI, 90,000-120,000) and 630,000 days of hospitalization (95% CI, 430,000-830,000). CONCLUSIONS: This study confirms that preventable adverse events were common, and that they caused extensive human suffering and consumed a significant amount of the available hospital resources.

Characteristics of women giving birth at home in Sweden: a national register study.

OBJECTIVE: The objective of the study was to estimate the proportion of planned home births in Sweden and to identify maternal characteristics of women giving birth at home. STUDY DESIGN: This case-control study included register data of births from 1992 to 2001 in 352 women giving birth at home and 1760 women giving birth in a hospital. RESULTS: Four hundred thirty-nine out-of-hospital births were found during the study period, and the proportion of planned home births was less than 0.5/1000. Women with home birth were more likely to have 4 children or more (odds ratio 3.7 [1.4 to 9.9]), be born in a European country outside Sweden (odds ratio 3.5 [1.8 to 6.8]), have a family income below the median (odds ratio 2.9 [2.0 to 4.1]), not work outside the home (odds ratio 2.4 [1.7 to 3.5]), have a high level of education (odds ratio 2.1 [1.5 to 3.0]), and be older than 35 years (odds ratio 1.7 [1.1 to 2.5]). CONCLUSION: Women with planned home births appear to be a group having a different lifestyle, compared with Swedish women in general.

Trends in alcohol-related mortality in Sweden 1969-2002: an age-period-cohort analysis.

AIM: To study the effects of age, period and cohorts on alcohol-related mortality trends in Sweden. DESIGN: The study comprises an age-period-cohort analysis. SETTING AND PARTICIPANTS: The analysis was based on all deaths in the Swedish population between 1969 and 2002. MEASUREMENTS: Data on alcohol-related deaths in Sweden from 1969 to 2002 excluding accidental injury and homicide were used. The analysis covered 43 021 deaths. FINDINGS: Time period and birth cohort both influenced alcohol-related mortality. Male cohorts born in the 1930-40s exhibited the highest alcohol-related mortality, while for females those born in the 1940-50s had the highest alcohol-related mortality. For both men and women, those born in the 1960-70s had the lowest age-adjusted alcohol-related mortality. High-risk cohorts were young or in early adulthood during the periods that alcohol became more available in Sweden. The low-risk cohorts of the 1960-70s were brought up during a period when society was concerned with increasing alcohol problems and more emphasis was placed on issuing alcohol awareness information in schools. CONCLUSIONS: Cohort effects were found suggesting that the link between alcohol consumption and non-accident alcohol-related mortality at the population level is dependent on other factors that may change over time. One such factor may be that restrictive alcohol policies have a greater effect on drinking in those who are younger at the time they are put into effect.

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.

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.

Mortality, severe morbidity and injury among long-term lone mothers in Sweden.

BACKGROUND: Being a lone mother often implies disadvantage in terms of both socioeconomic circumstances and health. Our aim was to examine differences in mortality, severe morbidity and injury between lone mothers and mothers living with partners, on the assumption that the disadvantaged socioeconomic circumstances contribute to poor health. METHODS: The odds for receipt of hospital care or death between 1991 and 1994 were estimated for 26 619 lone mothers and 379 855 partnered mothers from data collected for the Swedish Population and Housing Census of 1990. We computed odds ratios by means of logistic regression, adjusting for confounders, mediators, and factors with an indeterminate position in various models. To control for health-selection effects, we only considered initially healthy women, as measured by non-hospitalization 4 years prior to follow-up. To reduce the impact of distress following divorce on health, we only included mothers who had been either lone or partnered for a period of > or =5 years. RESULTS: Lone mothers showed increased risks of total mortality, lung cancer, suicide/ suicide attempt, inflicted violence, traffic injury and other accident, psychiatric disease, and addiction. The main explanation for increased risks seems for most outcomes to lie in deficient household resources, as indicated here by receipt of social-welfare benefit and housing situation. For all the initially elevated outcomes, except for total mortality, significant risk increases remained unaccounted for even in the full model. Relationships varied according to subgroup. Lone motherhood was not related to accident, suicide and addiction among medium- and high-grade non-manual workers. Although lone mothers in general showed no increased risk of ischaemic heart disease, those receiving social benefit were exposed to a significantly increased risk. CONCLUSIONS: Our findings suggest that lone motherhood entails health disadvantages. Lack of household resources seems to play a major role in accounting for increased risks, but the risks are partly independent of socioeconomic circumstances, selection factors, and distress following divorce.

Gestational diabetes and preeclampsia.

OBJECTIVE: To determine whether gestational diabetes mellitus (GDM) increases the risk for preeclampsia independent of other risk factors. STUDY DESIGN: The association between GDM and preeclampsia was analyzed in a population of women who had given birth to singletons registered in Swedish Medical Birth Register from 1992 through 1996 (n=430,852). RESULTS: GDM occurred in 0.8% and preeclampsia in 2.9% of all pregnancies. The rate of preeclampsia was higher in the GDM than in the non-GDM group (6.1% versus 2.8%). High age, nullipara, chronic hypertension, kidney disease, and high body mass index (BMI) were all independently associated with increased risk for preeclampsia. Smoking was associated with decreased risk. Adjusted odds ratio for GDM as a risk factor for preeclampsia was 1.61 (95% confidence interval (CI) 1.39-1.86) when prepregnancy BMI, which was a true confounder, was included in the last step of the multiple logistic regression analysis. CONCLUSIONS: There is an independent and significant association between GDM and preeclampsia. Obesity is a major confounding factor but could not explain the total excess risk.