Mika Gissler

Outcomes of Nordic mental health systems: life expectancy of patients with mental disorders

BACKGROUND People with mental disorders evince excess mortality due to natural and unnatural deaths. The relative life expectancy of people with mental disorders is a proxy measure of effectiveness of social policy and health service provision. AIMS To evaluate trends in health outcomes of people with serious mental disorders. METHOD We examined nationwide 5-year consecutive cohorts of people admitted to hospital for mental disorders in Denmark, Finland and Sweden in 1987-2006. In each country the risk population was identified from hospital discharge registers and mortality data were retrieved from cause-of-death registers. The main outcome measure was life expectancy at age 15 years. RESULTS People admitted to hospital for a mental disorder had a two- to threefold higher mortality than the general population in all three countries studied. This gap in life expectancy was more pronounced for men than for women. The gap decreased between 1987 and 2006 in these countries, especially for women. The notable exception was Swedish men with mental disorders. In spite of the positive general trend, men with mental disorders still live 20 years less, and women 15 years less, than the general population. CONCLUSIONS During the era of deinstitutionalisation the life expectancy gap for people with mental disorders has somewhat diminished in the three Nordic countries. Our results support further development of the Nordic welfare state model, i.e. tax-funded community-based public services and social protection. Health promotion actions, improved access to healthcare and prevention of suicides and violence are needed to further reduce the life expectancy gap.

Maternal Smoking in Pregnancy, Fetal Development, and Childhood Asthma

OBJECTIVES We examined the relationships among maternal smoking in pregnancy, fetal development, and the risk of asthma in childhood. METHODS We conducted a population-based cohort study, where all 58 841 singleton births were followed for 7 years using nationwide registries. RESULTS Maternal smoking increased the risk of asthma (adjusted odds ratio = 1.35; 95% confidence interval = 1.13, 1.62 for high exposure). Low birthweight and preterm delivery increased the risk of asthma at the age of 7, whereas being small for gestational age did not. CONCLUSIONS Maternal smoking in pregnancy increases the risk of asthma during the first 7 years of life, and only a small fraction of the effect seems to be mediated through fetal growth.

Excess mortality, causes of death and life expectancy in 270,770 patients with recent onset of mental disorders in Denmark, Finland and Sweden.

Background Excess mortality among patients with severe mental disorders has not previously been investigated in detail in large complete national populations. Objective To investigate the excess mortality in different diagnostic categories due to suicide and other external causes of death, and due to specific causes in connection with diseases and medical conditions. Methods In longitudinal national psychiatric case registers from Denmark, Finland, and Sweden, a cohort of 270,770 recent-onset patients, who at least once during the period 2000 to 2006 were admitted due to a psychiatric disorder, were followed until death or the end of 2006. They were followed for 912,279 person years, and 28,088 deaths were analyzed. Life expectancy and standardized cause-specific mortality rates were estimated in each diagnostic group in all three countries. Results The life expectancy was generally approximately 15 years shorter for women and 20 years shorter for men, compared to the general population. Mortality due to diseases and medical conditions was increased two- to three-fold, while excess mortality from external causes ranged from three- to 77-fold. Mortality due to diseases and medical conditions was generally lowest in patients with affective disorders and highest in patients with substance abuse and personality disorders, while mortality due to suicide was highest in patients with affective disorders and personality disorders, and mortality due to other external causes was highest in patients with substance abuse. Conclusions These alarming figures call for action in order to prevent the high mortality.

Assisted reproductive technology in Europe, 2009: results generated from European registers by ESHRE

STUDY QUESTION The 13th European in vitro fertilization (IVF)-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2009: are there any changes in the trends compared with previous years? SUMMARY ANSWER Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year and, while pregnancy rates in 2009 remained similar to those reported in 2008, the number of transfers with multiple embryos (3+) and the multiple delivery rates declined. WHAT IS KNOWN ALREADY Since 1997, ART data in Europe have been collected and reported in 12 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, DURATION Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE); cycles started between 1st January and 31st December are collected on a yearly basis; the data are collected by the National Registers, when existing, or on a voluntary basis. PARTICIPANTS/MATERIALS SETTING, METHODS From 34 countries (-2 compared with 2008), 1005 clinics reported 537 463 treatment cycles including: IVF (135 621), intracytoplasmic sperm injection (ICSI, 266 084), frozen embryo replacement (FER, 104 153), egg donation (ED, 21 604), in vitro maturation (IVM, 1334), preimplantation genetic diagnosis/screening (PGD/PGS, 4389) and frozen oocyte replacements (FOR, 4278). European data on intrauterine insemination using husband/partners semen (IUI-H) and donor (IUI-D) semen were reported from 21 and 18 countries, respectively. A total of 162 843 IUI-H (+12.7%) and 29 235 IUI-D (+17.3%) cycles were included. Data available from each country are presented in the tables; total values (as numbers and percentages) refer to those countries where all data have been reported. MAIN RESULTS AND THE ROLE OF CHANCE In 21 countries where all clinics reported to the ART register, a total of 399 020 ART cycles were performed in a population of 373.8 million, corresponding to 1067 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.9 and 32.9%, respectively and for ICSI, the corresponding rates were 28.7 and 32.0%. In FER cycles, the pregnancy rate per thawing was 20.9%; in ED cycles, the pregnancy rate per transfer was 42.3%. The delivery rate after IUI-H was 8.3 and 13.4% after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 24.2, 57.7, 16.9 and 1.2%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 79.8, 19.4 and 0.8%, respectively, resulting in a total multiple delivery rate of 20.2%, compared with 21.7% in 2008, 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.0% (12.7% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 10.4/0.7% and 10.3/0.5%, following treatment with husband and donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS The 13th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than half a million of cycles reported in 2009. The use of ICSI has reached a plateau. Pregnancy and delivery rates after IVF and ICSI remained relatively stable compared with 2008 and 2007. The number of multiple embryo transfers (3+ embryos) and the multiple delivery rate have shown a clear decline.

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.

Perinatal outcome of children born after frozen and fresh embryo transfer: the Finnish cohort study 1995–2006

BACKGROUND The number of children born after frozen embryo transfer (FET) is steadily rising. However, studies on obstetric and perinatal outcomes are limited. Our primary aim was to compare the perinatal health of children born after FET and fresh embryo transfer, and to use data from children born after spontaneous conception as a reference. METHODS In a register-based cohort study we evaluated the obstetric and perinatal outcomes of children born after FET (n = 2293), fresh embryo transfer (n = 4151) and those born after spontaneous pregnancy (reference group; n = 31 946). Data were collected from the registers of two infertility outpatient clinics, two university hospitals and the Finnish Medical Birth Register (1995-2006). RESULTS After adjusting for confounding factors the FET group showed decreased risks of preterm birth [adjusted odd ratio (AOR) 0.83, 95% confidence interval (CI) 0.71-0.97], low birthweight (AOR 0.74; 0.62-0.88) and being small for gestational age (AOR 0.63; 0.49-0.83) compared with the fresh embryo transfer group. Mean birthweight was 134 g higher in the FET singletons versus the fresh embryo transfer singletons (P< 0.0001). When FET singletons were compared with the reference group, increased risks of preterm birth (AOR 1.45; 1.25-1.68) and low birthweight (AOR 1.22; 1.03-1.45) and a decreased risk of being small for gestational age (AOR 0.71; 0.54-0.92) were found. No excess of perinatal and infant mortality occurred between the groups. CONCLUSIONS Embryo freezing does not adversely affect perinatal outcome in terms of prematurity, low birthweight and being small for gestational age versus the fresh embryo transfer and the outcome is similar or even better, particularly regarding fetal growth. Our study, which is one of the largest on FET pregnancies, provides further evidence on the safety of FET.

Selective Serotonin Reuptake Inhibitors and Risk for Major Congenital Anomalies

OBJECTIVE: To estimate the risk of major congenital anomalies after exposure to selective serotonin reuptake inhibitors during pregnancy. METHODS: A retrospective cohort study based on national population-based registers (years 1996–2006) of births, congenital anomalies, and terminations of pregnancy because of severe fetal anomalies (maintained by National Institute for Health and Welfare, source offspring population n=635,583) and drug reimbursements (Social Insurance Institution) linked by a personal identification number. Offspring exposed to selective serotonin reuptake inhibitors during the first trimester (n=6,976) were compared with unexposed referent offspring. RESULTS: Overall major congenital anomalies were not more common in selective serotonin reuptake inhibitor-exposed offspring compared with unexposed referent offspring (adjusted odds ratio [OR] 1.08, 95% confidence interval [CI] 0.96–1.22). Fluoxetine was associated with an increased risk of isolated ventricular septal defects (adjusted OR 2.03, 95% CI 1.28–3.21) and paroxetine was associated with an increased risk of right ventricular outflow tract defects (adjusted OR 4.68, 95% CI 1.48–14.74). Citalopram use was associated with neural tube defects (adjusted OR 2.46, 95% CI 1.20–5.07). Fetal alcohol spectrum disorders were 10-times more common in the selective serotonin reuptake inhibitor-exposed offspring than in unexposed referent offspring. CONCLUSION: Fluoxetine use is associated with an increased risk of isolated ventricular septal defects and paroxetine is associated with right ventricular outflow tract defects. The absolute risk for these specific cardiac anomalies is small but should guide clinicians not to consider fluoxetine or paroxetine the first option when prescribing selective serotonin reuptake inhibitors to women planning pregnancy. Special attention should be given to alcohol use in pregnant women using selective serotonin reuptake inhibitors. LEVEL OF EVIDENCE: II

Age, parity, history of abortion and contraceptive choices affect the risk of repeat abortion

BACKGROUND The rate of repeat induced abortion varies from 30% to 38% in northern Europe. Thus, repeat abortion is an important public health issue. However, risk factors as regards repeat abortion are poorly understood. We characterized risk factors related to sociodemographic characteristics, history of abortion and post-abortal contraception. STUDY DESIGN A prospective cohort study of 1269 women undergoing medical abortion between August 2000 and December 2002 was conducted. The subjects were followed via the Finnish Registry of Induced Abortions until December 2005, the follow-up time (mean+/-SD) being 49.2+/-8.0 months. RESULTS Altogether, 179 (14.1%) of the subjects requested repeat abortion within the follow-up time. In univariate analysis, a history of prior abortion, being parous, young age, smoking and failure to attend the follow-up visit were associated with repeat abortion. Immediate--in contrast to postponed--initiation of any contraceptive method was linked to a lower risk of repeat abortion. In comparison with combined oral contraceptives, use of intrauterine contraception was most efficacious in reducing the risk of another pregnancy termination. In multivariate analysis, the effects of young age, being parous, smoking, a history of prior abortion and type of contraception on the risk of another abortion persisted. CONCLUSIONS An increased focus on young women, parous women and those with a history of abortion may be efficacious in decreasing repeat abortion. Contraceptive choices made at the time of abortion have an important effect on the rate of repeat abortion. Use of intrauterine contraceptives for post-abortal contraception was associated with decreased risk of repeat abortion.

Underreporting of pregnancy-related mortality in the United States and Europe.

OBJECTIVE: Available maternal mortality statistics do not allow valid international comparisons. Our objective was to uniformly measure underreporting of mortality from pregnancy in official statistics from selected regions within the U.S. and Europe, and to provide comparable revised profiles of pregnancy-related mortality. METHODS: We developed a standardized enhanced method to uniformly identify and classify pregnancy-associated deaths from 2 U.S. states, Massachusetts and North Carolina, and 2 European countries, Finland and France, for the years 1999–2000. Identification method included the use of all data available from the death certificate as well as computerized linkage of births and deaths registers. All cases were reviewed and classified by an international panel of experts. RESULTS: Four-hundred-and-four pregnancy-associated deaths were identified and reviewed. Underestimation of mortality causally related to pregnancy based on International Classification of Diseases cause-of-death codes alone varied from 22% in France to 93% in Massachusetts. Underreporting was greater in the regions with lower initial maternal mortality ratios. The distribution of causes of pregnancy-related mortality was specific to each region. The leading causes of death were cardiovascular conditions in Massachusetts; hemorrhage, pregnancy-induced hypertension, and peripartum cardiomyopathy in North Carolina; noncardiovascular medical conditions in Finland; and hemorrhage in France. CONCLUSION: This study shows the limitations of maternal mortality statistics based on International Classification of Diseases cause-of-death codes alone. Linkage of births and deaths registers should routinely be used in the ascertainment of pregnancy-related deaths. In addition, extension of the definition of a maternal death should be considered. Beyond pregnancy-related mortality ratios, considering the specific distribution of causes-of-death is important to define prevention strategies. LEVEL OF EVIDENCE: II-2

Preterm delivery after surgical treatment for cervical intraepithelial neoplasia.

OBJECTIVE: To study whether a treatment of cervical intraepithelial neoplasia (CIN) is associated with an adverse outcome in the subsequent pregnancies. METHODS: This study is a register-based retrospective cohort study from Finland. National data of 25,827 women having a surgical treatment of the cervix for CIN in 1986–2003 and their 8,210 subsequent singleton births in 1987–2004 were studied. Main outcome measures were preterm birth rate, low birth weight rate, and perinatal mortality rate. RESULTS: The risk of any preterm delivery (less than 37 weeks of gestation), especially the risk of very preterm delivery (28–31 weeks of gestation), and extremely preterm delivery (less than 28 weeks of gestation) was increased after cervical conization (relative risk [RR] 1.99, 95% confidence interval [CI] 1.81–2.20; RR 2.86, 95% CI 2.22–3.70; and RR 2.10, 95% CI 1.47–2.99, respectively). After cervical ablation, the risk of preterm delivery was also increased. The risk of low birth weight and perinatal death was increased after conization (RR 2.06, 95% CI 1.83–2.31 and RR 1.74, 95% CI 1.30–2.32, respectively). Adjusting for maternal age, parity, and maternal smoking did not affect our results. CONCLUSION: Any treatment for CIN, including loop electrosurgical excision procedure, increases the risk of preterm delivery. It is important to emphasize this when treating young women with CIN. LEVEL OF EVIDENCE: II