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author:("gisslen, Mika")
1.  Birth weight, gestational age, fetal growth and childhood asthma hospitalization 
Background
Childhood asthma may have a fetal origin through fetal growth and development of the immunocompetence or respiratory organs.
Objective
We examined to which extent short gestational age, low birth weight and fetal growth restriction were associated with an increased risk of asthma hospitalization in childhood.
Methods
We undertook a cohort study based on several national registers in Denmark, Sweden and Finland. We included all live singleton born children in Denmark during 1979-2005 (N = 1,538,093), in Sweden during 1973-2004 (N = 3,067,670), and a 90% random sample of singleton children born in Finland during 1987-2004 (N = 1,050,744). The children were followed from three years of age to first hospitalization for asthma, emigration, death, their 18th birthday, or the end of study (the end of 2008 in Denmark, and the end of 2007 in Sweden or Finland), whichever came first. We computed the pseudo-values for each observation and used them in a generalized estimating equation to estimate relative risks (RR) for asthma hospitalization.
Results
A total of 131,783 children were hospitalized for asthma during follow-up. The risk for asthma hospitalization consistently increased with lower birth weight and shorter gestational age. A 1000-g decrease in birth weight corresponded to a RR of 1.17 (95% confidence interval (CI) 1.15-1.18). A one-week decrease in gestational age corresponded to a RR of 1.05 (95% CI 1.04-1.06). Small for gestational age was associated with an increased risk of asthma hospitalization in term but not in preterm born children.
Conclusions
Fetal growth and gestational age may play a direct or indirect causal role in the development of childhood asthma.
doi:10.1186/1710-1492-10-13
PMCID: PMC3973844  PMID: 24602245
Asthma; Birth weight; Gestational age; Hospitalization; Small for gestational age
2.  Stillbirth, Early Death and Neonatal Morbidity among Offspring of Female Cancer Survivors 
Acta oncologica (Stockholm, Sweden)  2013;52(6):10.3109/0284186X.2012.758870.
Background
Increased awareness of the adverse effects of cancer treatments has prompted the development of fertility preserving regimens for the growing population of cancer survivors who desire to have children of their own.
Materials and methods
We conducted a registry-based study to evaluate the risk of stillbirth, early death and neonatal morbidity among children of female cancer survivors (0–34 years at diagnosis) compared with children of female siblings. A total of 3,501 and 16,908 children of female cancer patients and siblings, respectively, were linked to the national medical birth and cause-of-death registers.
Results
The risk of stillbirth or early death was not significantly increased among offspring of cancer survivors as compared to offspring of siblings: the risk (Odds Ratio (OR) of early neonatal death, i.e. mortality within the first week was 1.35, with a 95% confidence interval (CI) of 0.58–3.18, within 28 days 1.40, 95% CI 0.46–4.24 and within the first year of life 1.11, 95% CI 0.64–1.93 after adjustment for the main explanatory variables. All these risk estimates were reduced towards one after further adjustment for duration of pregnancy. Measures of serious neonatal morbidity were not significantly increased among the children of survivors. However, there was a significant increase in the monitoring of children of cancer survivors for neonatal conditions (OR 1.56, 95% CI 1.35–1.80), which persisted even after correcting for duration of pregnancy, that might be related to parental cancer and its treatment or increased surveillance among the children.
Conclusion
Offspring of cancer survivors were more likely to require monitoring or care in a neonatal intensive care unit, but the risk of early death or stillbirth was not increased after adjustment for prematurity. Due to the rarity of the mortality outcomes studied, collaborative studies may be helpful in ruling out the possibility of an increased risk among offspring of cancer survivors.
doi:10.3109/0284186X.2012.758870
PMCID: PMC3865710  PMID: 23327340
Offspring; cancer survivor; stillbirth; neonatal deaths
3.  Smoking among older childbearing women - a marker of risky health behaviour a registry-based study in Finland 
BMC Public Health  2013;13:1179.
Background
Smoking during pregnancy is known to negatively affect pregnancy outcomes and it has been associated with numerous complications during pregnancy. Smoking is more common in younger pregnant women, but previous research has shown that adverse pregnancy outcomes related to older maternal age and smoking are even more harmful than with younger smokers. The aim of this study was to compare pregnancy outcomes among smoking and non-smoking pregnant women aged <35 years and ≥35 years.
Methods
In this registry-based study, the data were collected from three national Finnish health registries: Finnish Medical Birth Register, Finnish Hospital Discharge Register, and Register of Congenital Malformations between the years 1997 and 2008. The data included information on 80 260 women who were smoking during pregnancy, of which 11 277 (9%) were ≥35 years and 68 983 (13%) were <35 years old. In multivariate modelling, the main outcome measures were preterm delivery, low Apgar scores at 1 min., low birth weight, small for gestational age, fetal death and preeclampsia.
Results
Fewer older women smoked during pregnancy (9%) than younger women did (13%). Smoking increased the risk of adverse pregnancy outcomes, most in the older group. Multivariate logistic regression using non-smoking women aged <35 years as a reference group indicated that smoking women <35 years had higher rates of preterm delivery (OR 1.27 CI 1.20-1.35), SGA (OR 2.18 CI 2.10-2.26) and LBW (OR 1.73 CI 1.62-1.84).
Non-smoking women ≥35 had higher rates of preterm delivery (OR 1.15 CI 1.10-1.20), fetal death (OR 1.36 CI 1.12-1.64), preeclampsia (OR 1.14 CI 1.09-1.20) and LBW (OR 1.13 CI 1.07-1.19).
Smoking women ≥35 had higher rates of preterm delivery (OR 1.60 CI 1.40-1.82), SGA (OR 2.55 CI 2.34-2.79), fetal death (OR 2.70 CI 1.80-4.05) and LBW (OR 2.50 CI 2.20-2.80).
Conclusions
Smoking during pregnancy increased the risk of adverse pregnancy outcomes in all women, but the rates were the highest for women aged ≥35 years. Pregnant women aged ≥35 years smoking during pregnancy was a distinctly high risk group. Maternity care should identify these women and support them in cessation of smoking during the first trimester of pregnancy.
doi:10.1186/1471-2458-13-1179
PMCID: PMC3866612  PMID: 24330715
Smoking; Registry-based study; Pregnancy outcome; Older mothers
4.  Fear of childbirth predicts postpartum depression: a population-based analysis of 511 422 singleton births in Finland 
BMJ Open  2013;3(11):e004047.
Objectives
To study how reproductive risks and perinatal outcomes are associated with postpartum depression treated in specialised healthcare defined according to the International Classification of Diseases (ICD)-10 codes, separately among women with and without a history of depression.
Design
A retrospective population-based case–control study.
Setting
Data gathered from three national health registers for the years 2002−2010.
Participants
All singleton births (n=511 422) in Finland.
Primary outcome measures
Prevalence of postpartum depression and the risk factors associated with it.
Results
In total, 0.3% (1438 of 511 422) of women experienced postpartum depression, the prevalence being 0.1% (431 of 511 422) in women without and 5.3% (1007 of 18 888) in women with a history of depression. After adjustment for possible covariates, a history of depression was found to be the strongest risk factor for postpartum depression. Other strong predisposing factors for postpartum depression were fear of childbirth, caesarean birth, nulliparity and major congenital anomaly. Specifically, among the 30% of women with postpartum depression but without a history of depression, postpartum depression was shown to be associated with fear of childbirth (adjusted OR (aOR 2.71, 95% CI 1.98 to 3.71), caesarean birth (aOR 1.38, 95% CI 1.08 to 1.77), preterm birth (aOR 1.65, 95% CI 1.08 to 2.56) and major congenital anomaly (aOR 1.67, 95% CI 1.15 to 2.42), compared with women with no postpartum depression and no history of depression.
Conclusions
A history of depression was found to be the most important predisposing factor of postpartum depression. Women without previous episodes of depression were at an increased risk of postpartum depression if adverse events occurred during the course of pregnancy, especially if they showed physician-diagnosed fear of childbirth.
doi:10.1136/bmjopen-2013-004047
PMCID: PMC3845069  PMID: 24293208
EPIDEMIOLOGY; MENTAL HEALTH; STATISTICS & RESEARCH METHODS
5.  Risk of Autism Spectrum Disorders in Low Birth Weight and Small for Gestational Age Infants 
The Journal of pediatrics  2012;161(5):830-836.
Objective
To examine the relationship between birth weight, gestational age, small for gestational age (SGA), and three most common autism spectrum disorder (ASD) subtypes.
Study design
In this population-based case-control study conducted in Finland, 4713 cases born between 1987 and 2005 with ICD-diagnoses of childhood autism, Asperger syndrome or PDD, were ascertained from the Finnish Hospital Discharge Register. Four controls, individually matched on sex, date of birth, and place of birth, were selected from the Finnish Medical Birth Register for each case. Conditional logistic regression models were used to assess whether birth weight and gestational age information predicted ASD after controlling for maternal age, parity, smoking during pregnancy and psychiatric history, as well as for infant’s major congenital anomalies.
Results
Very low (<1500g) and moderately low (<2500g) birth weight, very low gestational age (less than 32 weeks), and SGA increased risk of childhood autism (adjusted OR 3.05, 95% CI 1.4–6.5; 1.57, 1.1–2.3; 2.51, 1.3–5.0 and 1.72, 1.1–2.6, respectively). Very low and moderately low birth weight, very low gestational age, and SGA were also associated with increase in PDD risk (OR 3.44, 95% CI 1.9–6.3; 1.81, 1.4–2.4; 2.46, 1.4–2.3 and 2.24, 1.7–3.0, respectively). No associations were found between the perinatal characteristics and Asperger syndrome. The increased risks persisted after controlling for selected potential confounders.
Conclusions
The finding that low birth weight, prematurity and SGA were related to childhood autism and PDD but not to Asperger syndrome suggests that prenatal factors related to these exposures may differ for these ASD subtypes, which may have preventive implications.
doi:10.1016/j.jpeds.2012.04.058
PMCID: PMC3449022  PMID: 22677565
Epidemiology; Risk Factors
6.  Psychological Stress and Hospitalization for Childhood Asthma-a Nationwide Cohort Study in Two Nordic Countries 
PLoS ONE  2013;8(10):e78816.
Objective
Exposures to psychological stress in early life may contribute to the development or exacerbation of asthma. We undertook a cohort study based on data from several population-based registers in Denmark and Sweden to examine whether bereavement in childhood led to increased asthma hospitalization.
Methods
All singleton children born in Denmark during 1977-2008 and in Sweden during 1973-2006 were included in the study (N=5,202,576). The children were followed from birth to the date of first asthma hospitalization, emigration, death, their 18th birthday, or the end of study (31 December 2007 in Sweden and 31 December 2008 in Denmark), whichever came first. All the children were assigned to the non-bereaved group until they lost a close relative (mother, father or a sibling), from when they were included in the bereaved group. We evaluated the hazard ratio (HR) of first hospitalization for asthma in bereaved children using Cox proportional hazards regression models, compared to those who were in the non-bereaved group. We also did a sub-analysis on the association between bereavement and first asthma medication.
Results
A total of 147,829 children were hospitalized for asthma. The overall adjusted HR of asthma hospitalization in bereaved children was 1.10 (95% confidence interval (CI): 1.04-1.16), compared to non-bereaved children. The risk of asthma hospitalization was increased in those who lost a close relative at age of 14-17 years (HR=1.54, 95% CI: 1.23-1.92), but not in younger age groups. The association between bereavement and asthma hospitalization did not change over time since bereavement. In the sub-analysis in singleton live births during 1996-2008 recorded in the DMBR, bereavement was associated with a lower use of asthma medication (HR=0.87, 95% CI: 0.80-0.95).
Conclusions
Our data suggests that psychological stress following bereavement in late adolescence is associated with an increased risk of asthma hospitalization or lowers the threshold for asthma hospitalization.
doi:10.1371/journal.pone.0078816
PMCID: PMC3808299  PMID: 24205324
7.  Patterns in mortality among people with severe mental disorders across birth cohorts: a register-based study of Denmark and Finland in 1982–2006 
BMC Public Health  2013;13:834.
Background
Mortality among patients with mental disorders is higher than in general population. By using national longitudinal registers, we studied mortality changes and excess mortality across birth cohorts among people with severe mental disorders in Denmark and Finland.
Methods
A cohort of all patients admitted with a psychiatric disorder in 1982–2006 was followed until death or 31 December 2006. Total mortality rates were calculated for five-year birth cohorts from 1918–1922 until 1983–1987 for people with mental disorder and compared to the mortality rates among the general population.
Results
Mortality among patients with severe mental disorders declined, but patients with mental disorders had a higher mortality than general population in all birth cohorts in both countries. We observed two exceptions to the declining mortality differences. First, the excess mortality stagnated among Finnish men born in 1963–1987, and remained five to six times higher than at ages 15–24 years in general. Second, the excess mortality stagnated for Danish and Finnish women born in 1933–1957, and remained six-fold in Denmark and Finland at ages 45–49 years and seven-fold in Denmark at ages 40–44 years compared to general population.
Conclusions
The mortality gap between people with severe mental disorders and the general population decreased, but there was no improvement for young Finnish men with mental disorders. The Finnish recession in the early 1990s may have adversely affected mortality of adolescent and young adult men with mental disorders. Among women born 1933–1957, the lack of improvement may reflect adverse effects of the era of extensive hospitalisation of people with mental disorders in both countries.
doi:10.1186/1471-2458-13-834
PMCID: PMC3850635  PMID: 24025120
Birth cohort; Mental disorder; Mortality; Psychiatric care; Register study
8.  The Burden of OASIS Increases along with Socioeconomic Position – Register-Based Analysis of 980,733 Births in Finland 
PLoS ONE  2013;8(8):e73515.
Background
Obstetric anal sphincter injury (OASIS) has been identified as a major preventable risk factor for anal incontinence.
Objective
Aim was to measure national variation in incidence of OASIS by socioeconomic status (SES).
Methods
A retrospective population based case-control study using the data derived from the Finnish Medical Birth Register for the years 1991–2010. A total population of singleton vaginal births was reviewed. We calculated unadjusted incidences of OASIS stratified by SES and vaginal parity, and adjusted risks for OASIS in each social class, after controlling for parity, birthweight, mode of delivery, maternal age and maternal smoking. SES was recorded into five categories based on mother’s occupation at time of birth; upper white-collar workers such as physicians, lower white-collar workers such as nurses, blue-collar workers such as cleaners, others such as students, and cases with missing information.
Results
Seven per thousand (6,404 of 980,733) singleton births were affected by OASIS. In nulliparae the incidence of OASIS was 18% higher (adjusted OR 1.18 95% CI 1.04−1.34) for upper white-collar workers and 12% higher (adjusted OR 1.12 95% CI 1.02−1.24) for lower white-collar workers compared with blue-collar workers. Among women in these higher SES groups, 40% of the excess OASIS risk was explained by age, non-smoking, birthweight and mode of delivery. Despite the large effect of SES on OASIS, inclusion of SES in multivariable models caused only small changes in estimated adjusted effects for other established risk factors.
Conclusions
OASIS at the first vaginal delivery demonstrates a strong positive social gradient. Higher SES is associated with a number of risk factors for OASIS, including higher birthweight and non-smoking, but only 40% of the excess incidence is explained by these known risk factors. Further research should address other underlying causes including differences in lifestyle or environmental factors, and inequalities in healthcare provision.
doi:10.1371/journal.pone.0073515
PMCID: PMC3754956  PMID: 24013645
9.  Web-Based Versus Traditional Paper Questionnaires: A Mixed-Mode Survey With a Nordic Perspective 
Background
Survey response rates have been declining over the past decade. The more widespread use of the Internet and Web-based technologies among potential health survey participants suggests that Web-based questionnaires may be an alternative to paper questionnaires in future epidemiological studies.
Objective
To compare response rates in a population of parents by using 4 different modes of data collection for a questionnaire survey of which 1 involved a nonmonetary incentive.
Methods
A random sample of 3148 parents of Danish children aged 2-17 years were invited to participate in the Danish part of the NordChild 2011 survey on their children’s health and welfare. NordChild was conducted in 1984 and 1996 in collaboration with Finland, Iceland, Norway, and Sweden using mailed paper questionnaires only. In 2011, all countries used conventional paper versions only except Denmark where the parents were randomized into 4 groups: (1) 789 received a paper questionnaire only (paper), (2) 786 received the paper questionnaire and a log-in code to the Web-based questionnaire (paper/Web), (3) 787 received a log-in code to the Web-based questionnaire (Web), and (4) 786 received log-in details to the Web-based questionnaire and were given an incentive consisting of a chance to win a tablet computer (Web/tablet). In connection with the first reminder, the nonresponders in the paper, paper/Web, and Web groups were also present with the opportunity to win a tablet computer as a means of motivation. Descriptive analysis was performed using chi-square tests. Odds ratios were used to estimate differences in response rates between the 4 modes.
Results
In 2011, 1704 of 3148 (54.13%) respondents answered the Danish questionnaire. The highest response rate was with the paper mode (n=443, 56.2%). The other groups had similar response rates: paper/Web (n=422, 53.7%), Web (n=420, 53.4%), and Web/tablet (n=419, 53.3%) modes. Compared to the paper mode, the odds for response rate in the paper/Web decreased by 9% (OR 0.91, 95% CI 0.74-1.10) and by 11% (OR 0.89, 95% CI 0.73-1.09) in the Web and Web/tablet modes. The total number of responders for NordChild declined from 10,291 of 15,339 (67.09%) in 1984 and 10,667 of 15,254 (69.93%) in 1996 to 7805 of 15,945 (48.95%) in 2011 with similar declines in all 5 Nordic countries.
Conclusions
Web-based questionnaires could replace traditional paper questionnaires with minor effects on response rates and lower costs. The increasing effect on the response rate on participants replying for a nonmonetary incentive could only be estimated within the 2 Web-based questionnaire modes before the first reminder. Alternative platforms to reach higher participation rates in population surveys should reflect the development of electronic devices and the ways in which the population primarily accesses the Internet.
doi:10.2196/jmir.2595
PMCID: PMC3757995  PMID: 23978658
mixed-mode survey; patient participation rate; Web-based; paper; questionnaires; nonmonetary incentive
10.  Is teenage pregnancy an obstetric risk in a welfare society? A population-based study in Finland, from 2006 to 2011 
BMJ Open  2013;3(8):e003225.
Objective
To assess obstetric outcomes in teenage pregnancies in a country with a low teenage delivery rate and comprehensive high-quality prenatal care.
Design
Retrospective population-based register study.
Setting
Finland.
Participants
All nulliparous teenagers (13–15 years (n=84), 16–17 years (n=1234), 18–19 years (n=5987)) and controls (25-year-old to 29-year-old women (n=51 142)) with singleton deliveries in 2006–2011.
Main outcome measures
Risk of adverse obstetric outcomes adjusted for demographic factors and clinically relevant pregnancy complications, with main focus on maternal pregnancy complications.
Results
Teenage mothers were more likely than controls to live in rural areas (16% (n=1168) vs 11.8% (n=6035)), smoke (36.4% (n=2661) vs 7% (n=3580)) and misuse alcohol or drugs (1.1% (n=82) vs 0.2% (n=96); p<0.001 for all). Teenagers made a good mean number of antenatal clinic visits (16.4 vs 16.5), but were more likely to have attended fewer than half of the recommended visits (3% (n=210) vs 1.4% (n=716)). Teenagers faced increased risks of several obstetric complications, for example, anaemia (adjusted OR 1.8, 95% CI 1.6 to 2.1), proteinuria (1.8, 1.2 to 2.6), urinary tract infection (UTI; 2.9, 1.8 to 4.8), pyelonephritis (6.3, 3.8 to 10.4) and eclampsia (3.2, 1.4 to 7.3), the risks increasing with descending age for most outcomes. Elevated risks of pre-eclampsia (3.7, 1.5 to 9.0) and preterm delivery (2.5, 1.2 to 5.3) were also found among 13-year-olds to 15-year-olds. However, teenage mothers were more likely to have vaginal delivery (1.9, 1.7 to 2.0) without complications. Inadequate prenatal care among teenagers was a risk factor of eclampsia (12.6, 2.6 to 62.6), UTI (5.8, 1.7 to 19.7) and adverse neonatal outcomes.
Conclusions
Pregnant teenagers tended to be socioeconomically disadvantaged versus controls and faced higher risks of various pregnancy complications. Special attention should be paid to enrolling teenagers into adequate prenatal care in early pregnancy.
doi:10.1136/bmjopen-2013-003225
PMCID: PMC3753503  PMID: 23959755
PERINATOLOGY; PUBLIC HEALTH; Adolescent
11.  Changing associations of episiotomy and anal sphincter injury across risk strata: results of a population-based register study in Finland 2004–2011 
BMJ Open  2013;3(8):e003216.
Objectives
To evaluate the changing association between lateral episiotomy and obstetric anal sphincter injury (OASIS) for women with low and high baseline risk of OASIS.
Design
A population-based register study.
Setting
Data gathered from the Finnish Medical Birth Register for the years 2004−2011.
Participants
All women with spontaneous vaginal or vacuum-assisted singleton births in Finland (n=384 638).
Main outcome measure
OASIS incidence.
Results
During the study period, the incidence of OASIS increased from 1.3% to 1.7% in women with first vaginal births, including women admitted for first vaginal birth after a prior caesarean section and from 0.1% to 0.3% in women with at least one prior birth, whereas episiotomy rates declined from 56.7% to 45.5% and 10.1– 5.3%, respectively. At the study onset, when episiotomy was used more widely, it was negatively associated with OASIS in women with first vaginal births, but as episiotomy use declined it became positively associated with OASIS. Women with episiotomy were complicated by OASIS with clearly higher risk scores than women without episiotomy suggesting that episiotomy was clearly protective against OASIS. OASIS occurred with lower mean risk scores among women with and without episiotomy over time. However, OASIS incidences increased only among women with episiotomy, whereas it decreased or remained among women without episiotomy.
Conclusions
The cross-over effect between episiotomy and OASIS could be explained by increasing disparity in baseline OASIS risk between treated and untreated women, since episiotomy use declined most in women at low OASIS risk. Episiotomy rate can be safely reduced in low-risk women but interestingly along with the policy change the practice to cut the episiotomy became less protective among high-risk women.
doi:10.1136/bmjopen-2013-003216
PMCID: PMC3752051  PMID: 23955189
EPIDEMIOLOGY; OBSTETRICS
12.  Life Expectancy and Death by Diseases of the Circulatory System in Patients with Bipolar Disorder or Schizophrenia in the Nordic Countries 
PLoS ONE  2013;8(6):e67133.
Objective
Excess mortality from diseases and medical conditions (natural death) in persons with psychiatric disorders has been extensively reported. Even in the Nordic countries with well-developed welfare systems, register based studies find evidence of an excess mortality. In recent years, cardiac mortality and death by diseases of the circulatory system has seen a decline in all the Nordic countries, but a recent paper indicates that women and men in Denmark, Finland, and Sweden, who had been hospitalised for a psychotic disorder, had a two to three-fold increased risk of dying from a cardiovascular disease. The aim of this study was to compare the mortality by diseases of the circulatory system among patients with bipolar disorder or schizophrenia in the three Nordic countries Denmark, Sweden, and Finland. Furthermore, the aim was to examine and compare life expectancy among these patients. Cause specific Standardized Mortality Rates (SMRs) were calculated for each specific subgroup of mortality. Life expectancy was calculated using Wiesler’s method.
Results
The SMR for bipolar disorder for diseases of the circulatory system was approximately 2 in all countries and both sexes. SMR was slightly higher for people with schizophrenia for both genders and in all countries, except for men in Denmark. Overall life expectancy was much lower among persons with bipolar disorder or schizophrenia, with life expectancy being from 11 to 20 years shorter.
Conclusion
Our data show that persons in the Nordic countries with schizophrenia or bipolar disorder have a substantially reduced life expectancy. An evaluation of the reasons for these increased mortality rates should be prioritized when planning healthcare in the coming years.
doi:10.1371/journal.pone.0067133
PMCID: PMC3691116  PMID: 23826212
13.  Public health indicators for the EU: the joint action for ECHIM (European Community Health Indicators & Monitoring) 
Archives of Public Health  2013;71(1):12.
Background
Public health policies aim to improve and maintain the health of citizens. Relevant data and indicators are needed for a health policy that is based on factual information. After 14 years of work (1998–2012), the multi-phase action on European Community Health Indicators (ECHI) has created a health monitoring and reporting system. It has generated EU added value by defining the ECHI shortlist with 88 common and comparable key health indicators for Europe.
Methods
In the 2009-2012 Joint Action for ECHIM project the ECHI shortlist was updated through consultation with Member State representatives. Guidelines for implementation of the ECHI Indicators at national level were developed and a pilot data collection was carried out.
Results
67 of the ECHI Indicators are already part of regular international data collections and thus available for a majority of Member States, 14 are close to ready and 13 still need development work. By mid-2012 half of the countries have incorporated ECHI indicators in their national health information systems and the process is ongoing in the majority of the countries. Twenty-five countries were able to provide data in a Pilot Data Collection for 20 ECHI Indicators that were not yet (fully) available in the international databases.
Conclusions
The EU needs a permanent health monitoring and reporting system. The Joint Action for ECHIM has set an example for the implementation of a system that can develop and maintain the ECHI indicators,, and promote and encourage the use of ECHI in health reporting and health policy making. The aim for sustainable public health monitoring is also supported by a Eurostat regulation on public health statistics requiring that health statistics shall be provided according to the ECHI methodology. Further efforts at DG SANCO and Eurostat are needed towards a permanent health monitoring system.
doi:10.1186/0778-7367-71-12
PMCID: PMC3682857  PMID: 23721296
Public health indicators; Public health monitoring; Public health reporting
14.  Early life bereavement and childhood cancer: a nationwide follow-up study in two countries 
BMJ Open  2013;3(5):e002864.
Objective
Childhood cancer is a leading cause of child deaths in affluent countries, but little is known about its aetiology. Psychological stress has been suggested to be associated with cancer in adults; whether this is also seen in childhood cancer is largely unknown. We investigated the association between bereavement as an indicator of severe childhood stress exposure and childhood cancer, using data from Danish and Swedish national registers.
Design
Population-based cohort study.
Setting
Denmark and Sweden.
Participants
All live-born children born in Denmark between 1968 and 2007 (n=2 729 308) and in Sweden between 1973 and 2006 (n=3 395 166) were included in this study. Exposure was bereavement by the death of a close relative before 15 years of age. Follow-up started from birth and ended at the first of the following: date of a cancer diagnosis, death, emigration, day before their 15th birthday or end of follow-up (2007 in Denmark, 2006 in Sweden).
Outcome measures
Rates and HRs for all childhood cancers and specific childhood cancers.
Results
A total of 1 505 938 (24.5%) children experienced bereavement at some point during their childhood and 9823 were diagnosed with cancer before the age of 15 years. The exposed children had a small (10%) increased risk of childhood cancer (HR 1.10; 95% CI 1.04 to 1.17). For specific cancers, a significant association was seen only for central nervous system tumours (HR 1.14; 95% CI 1.02 to 1.28).
Conclusions
Our data suggest that psychological stress in early life is associated with a small increased risk of childhood cancer.
doi:10.1136/bmjopen-2013-002864
PMCID: PMC3664350  PMID: 23793702
Childhood cancer; bereavement; psychological stress; risk factor; follow up
15.  Sex Differences in Age-Related Cardiovascular Mortality 
PLoS ONE  2013;8(5):e63347.
Introduction
Sex-related physiological differences result in different expressions of diseases for men and women. Data are contradicting regarding the increase in the female risk for cardiovascular disease (CVD) at mid-life. Thus, we studied possible sex differences in age-adjusted mortality for CVD and non-vascular diseases stratifying our findings by specific age groups.
Methods
Over one million deaths (1 080 910) reported to the Finnish nationwide Causes of Death Register in 1986–2009 were analyzed. A total of 247 942 male deaths and 278 752 female deaths were of CVD origin, the remaining deaths were non-vascular. The annual mortality rates were calculated per 100 000 mid-year population, separately for men and women in 5-year age categories.
Results
The age-standardized risk of death from CVD was 80% higher for men (442/100 000) than for women (246/100 000). After age 45–54 the male CVD mortality rate elevated parallel to the non-vascular mortality, whereas in women the CVD mortality elevated considerably more rapidly than the non-vascular mortality from age 60 years onwards.
Conclusions
Heart disease mortality in men accelerates at a relatively young age, but in women the risk shows a steep increase at approximately 60 years of age. These data emphasize the need to identify and prevent risk factors for CVD, especially in women in their mid-life years.
doi:10.1371/journal.pone.0063347
PMCID: PMC3658978  PMID: 23700418
16.  International Comparisons of Fetal and Neonatal Mortality Rates in High-Income Countries: Should Exclusion Thresholds Be Based on Birth Weight or Gestational Age? 
PLoS ONE  2013;8(5):e64869.
Background
Fetal and neonatal mortality rates are essential indicators of population health, but variations in recording of births and deaths at the limits of viability compromises international comparisons. The World Health Organization recommends comparing rates after exclusion of births with a birth weight less than 1000 grams, but many analyses of perinatal outcomes are based on gestational age. We compared the effects of using a 1000-gram birth weight or a 28-week gestational age threshold on reported rates of fetal and neonatal mortality in Europe.
Methods
Aggregated data from 2004 on births and deaths tabulated by birth weight and gestational age from 29 European countries/regions participating in the Euro-Peristat project were used to compute fetal and neonatal mortality rates using cut-offs of 1000-grams and 28-weeks (2.8 million total births). We measured differences in rates between and within countries using the Wilcoxon signed rank test and 95% confidence intervals, respectively.
Principal Findings
For fetal mortality, rates based on gestational age were significantly higher than those based on birth weight (p<0.001), although these differences varied between countries. The use of a 1000-gram threshold included 8823 fetal deaths compared with 9535 using a 28-week threshold (difference of 712). In contrast, the choice of a cut-off made little difference for comparisons of neonatal deaths (difference of 16). Neonatal mortality rates differed minimally, by under 0.1 per 1000 in most countries (p = 0.370). Country rankings were comparable with both thresholds.
Conclusions
Neonatal mortality rates were not affected by the choice of a threshold. However, the use of a 1000-gram threshold underestimated the health burden of fetal deaths. This may in part reflect the exclusion of growth restricted fetuses. In high-income countries with a good measure of gestational age, using a 28-week threshold may provide additional valuable information about fetal deaths occurring in the third trimester.
doi:10.1371/journal.pone.0064869
PMCID: PMC3658983  PMID: 23700489
17.  Contribution of socioeconomic status to the risk of small for gestational age infants – a population-based study of 1,390,165 singleton live births in Finland 
Background
Small for gestational age (SGA) infants are at increased risk of short- and long-term adverse outcomes.
Methods
Population-based case–control study using data derived from the Finnish Medical Birth Register for the years 1987–2010 (total population of singleton live births n = 1,390,165). The aim was to quantify the importance of risk factors for SGA and describe their contribution to socioeconomic status (SES) disparities in SGA by using logistic regression analysis.
Results
Of all the singleton live births (n = 1,390,165), 3.1% (n = 42,702) were classified as SGA (defined as below 2 standard deviations of the sex-specific population reference mean for gestational age). The risk of SGA was 11 − 24% higher in the lower SES groups compared to the highest SES group. Smoking alone made the largest contribution, explaining 41.7 − 50.9% of SES disparities in SGA. The risk of SGA was 2.3-fold and 7% higher among women who smoked or had quit smoking during the first trimester of pregnancy (adjusted odds ratio (aOR) 2.34, 95% CI 2.28-2.42 and aOR 1.07, 95% CI 1.00 − 1.15, respectively) compared with the non-smokers.
Conclusions
SGA is substantially affected by SES. Smoking explained up to 50% of the difference in risk of SGA between high and low SES groups. Quitting smoking during the first trimester of pregnancy resulted in a 7% higher incidence of SGA comparable to that of non-smoking women. Thus, interventional attempts to reduce smoking during pregnancy might help to decrease the socioeconomic gradient of SGA.
doi:10.1186/1475-9276-12-28
PMCID: PMC3651324  PMID: 23634813
18.  Contribution of Risk Factors to Extremely, Very and Moderately Preterm Births – Register-Based Analysis of 1,390,742 Singleton Births 
PLoS ONE  2013;8(4):e60660.
Background
Preterm birth, defined as birth occurring before 37 weeks gestation, is one of the most significant contributors to neonatal mortality and morbidity, with long-term adverse consequences for health, and cognitive outcome.
Objective
The aim of the present study was to identify risk factors of preterm birth (≤36+6 weeks gestation) among singleton births and to quantify the contribution of risk factors to socioeconomic disparities in preterm birth.
Methods
A retrospective population–based case-control study using data derived from the Finnish Medical Birth Register. A total population of singleton births in Finland from 1987−2010 (n = 1,390,742) was reviewed.
Results
Among all singleton births (n = 1,390,742), 4.6% (n = 63,340) were preterm (<37 weeks), of which 0.3% (n = 4,452) were classed as extremely preterm, 0.4% (n = 6,213) very preterm and 3.8% (n = 54,177) moderately preterm. Smoking alone explained up to 33% of the variation in extremely, very and moderately preterm birth incidence between high and the low socioeconomic status (SES) groups. Reproductive risk factors (placental abruption, placenta previa, major congenital anomaly, amniocentesis, chorionic villus biopsy, anemia, stillbirth, small for gestational age (SGA) and fetal sex) altogether explained 7.7−25.0% of the variation in preterm birth between SES groups.
Conclusions
Smoking explained about one third of the variation in preterm birth groups between SES groups whereas the contribution of reproductive risk factors including placental abruption, placenta previa, major congenital anomaly, amniocentesis, chorionic villus biopsy, anemia, stillbirth, SGA and fetal sex was up to one fourth.
doi:10.1371/journal.pone.0060660
PMCID: PMC3618176  PMID: 23577142
19.  Infertility Treatment and Umbilical Cord Length–Novel Markers of Childhood Epilepsy? 
PLoS ONE  2013;8(2):e55394.
Background
Epilepsy is one of the most common neurologic disorders of childhood, affecting about 0.4−0.8% of all children up to the age of 20.
Methodology
A population-based retrospective cohort study. Aim was to determine incidence and identify perinatal and reproductive risk factors of epilepsy in children born between 1989 and 2008 among women (n = 43,389) delivered in Kuopio University Hospital. Risk factors of childhood epilepsy were determined by using logistic regression analysis.
Principal Findings
The incidence of childhood epilepsy was 0.7% (n = 302 of 43,389). Maternal epilepsy, major congenital anomalies and use of assisted reproductive technology (ART) were associated with 4.25-, 3.61-, and 1.67- fold increased incidence of childhood epilepsy. A 10 cm increase in umbilical cord length was associated with a 15% decrease in the incidence of epilepsy (adjusted OR 0.85, 95% CI 0.78−0.94). However, the above reproductive factors accounted for less than 2% of total incidence, whereas maternal epilepsy proved to be the highest risk factor.
Conclusions
Perinatal and reproductive factors were shown to be minor risk factors of childhood epilepsy, implying that little can be done in obstetric care to prevent childhood epilepsy. Infertility treatment and umbilical cord length, independent of gestational age and congenital malformations, may be novel markers of childhood epilepsy.
doi:10.1371/journal.pone.0055394
PMCID: PMC3572083  PMID: 23418441
20.  Excess Mortality, Causes of Death and Life Expectancy in 270,770 Patients with Recent Onset of Mental Disorders in Denmark, Finland and Sweden 
PLoS ONE  2013;8(1):e55176.
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.
doi:10.1371/journal.pone.0055176
PMCID: PMC3555866  PMID: 23372832
21.  Infant and childhood neurodevelopmental outcomes following prenatal exposure to selective serotonin reuptake inhibitors: overview and design of a Finnish Register-Based Study (FinESSI) 
BMC Psychiatry  2012;12:217.
Background
Experimental animal studies and one population-based study have suggested an increased risk for adverse neurodevelopmental outcome after prenatal exposure to SSRIs. We describe the methods and design of a population-based study examining the association between prenatal SSRI exposure and neurodevelopment until age 14.
Methods and design
This is a cohort study of national registers in Finland: the Medical Birth Register, the Register of Congenital Malformations, the Hospital Discharge Register including inpatient and outpatient data, the Drug Reimbursement Register, and the Population Register. The total study population includes 845,345 women and their live-born, singleton offspring aged 14 or younger and born during Jan 1st 1996-Dec 31st 2010. We will compare the prevalence of psychiatric and neurodevelopmental outcomes in offspring exposed prenatally to SSRIs to offspring exposed to prenatal depression and unexposed to SSRIs. Associations between exposure and outcome are assessed by statistical methods including specific modeling to account for correlated outcomes within families and differences in duration of follow-up between the exposure groups. Descriptive results. Of all pregnant women with pregnancy ending in delivery (n = 859,359), 1.9% used SSRIs. The prevalence of diagnosed depression and depression-related psychiatric disorders within one year before or during pregnancy was 1.7%. The cumulative incidence of registered psychiatric or neurodevelopmental disorders was 6.9% in 2010 among all offspring born during the study period (age range 0–14 years).
Discussion
The study has the potential for significant public health importance in providing information on prenatal exposure to SSRIs and long-term neurodevelopment.
doi:10.1186/1471-244X-12-217
PMCID: PMC3564781  PMID: 23206294
SSRI; Pregnancy; Neurodevelopment
22.  The 5-minute Apgar score as a predictor of childhood cancer: a population-based cohort study in five million children 
BMJ Open  2012;2(4):e001095.
Objective
The aetiology of childhood cancer remains largely unknown but recent research indicates that uterine environment plays an important role. We aimed to examine the association between the Apgar score at 5 min after birth and the risk of childhood cancer.
Design
Nationwide population-based cohort study.
Setting
Nationwide register data in Denmark and Sweden.
Study population
All live-born singletons born in Denmark from 1978 to 2006 (N=1 771 615) and in Sweden from 1973 to 2006 (N=3 319 573). Children were followed up from birth to 14 years of age.
Main outcome measures
Rates and HRs for all childhood cancers and for specific childhood cancers.
Results
A total of 8087 children received a cancer diagnosis (1.6 per 1000). Compared to children with a 5-min Apgar score of 9–10, children with a score of 0–5 had a 46% higher risk of cancer (adjusted HR 1.46, 95% CI 1.15 to 1.89). The potential effect of low Apgar score on overall cancer risk was mostly confined to children diagnosed before 6 months of age. Children with an Apgar score of 0–5 had higher risks for several specific childhood cancers including Wilms’ tumour (HR 4.33, 95% CI 2.42 to 7.73).
Conclusions
A low 5 min Apgar score was associated with a higher risk of childhood cancers diagnosed shortly after birth. Our data suggest that environmental factors operating before or during delivery may play a role on the development of several specific childhood cancers.
doi:10.1136/bmjopen-2012-001095
PMCID: PMC3425910  PMID: 22874628
Oncology; Epidemiology; Paediatric oncology; Preventive Medicine
23.  Smoking during Pregnancy Is Associated with a Decreased Incidence of Obstetric Anal Sphincter Injuries in Nulliparous Women 
PLoS ONE  2012;7(7):e41014.
Background
Smoking is a modifiable lifestyle factor that has been shown to be associated with adverse perinatal outcomes and to have adverse health and dose-dependent connective tissue effects. The objective of this study was to examine whether smoking during pregnancy was associated with the incidence of obstetric anal sphincter injuries (OASIS) among six birthweight groups in singleton vaginal deliveries, considering nulliparous and multiparous women separately between 1997 and 2007 in Finland.
Methodology
A retrospective population-based register study. Populations included women with spontaneous singleton vaginal deliveries, consisting of all 213,059 nulliparous and all 288,391 multiparous women. Incidence of OASIS (n = 2,787) between smoking status groups was adjusted using logistic regression analyses.
Principal Findings
Of the nulliparous women, 13.1% were smokers, 3.6% had given up smoking during the first trimester of their pregnancy and 81.1% were non-smokers. Among these groups 0.7%, 0.9% and 1.1%, respectively suffered OASIS (p≤0.001). Nulliparous women who smoked had a 28% (95% CI 16–38%, p≤0.001) lower risk of OASIS compared to non-smokers, when adjusting for background variables. In multiparous women, the overall frequencies of OASIS were much lower (0.0–0.2%). A similar inverse relationship between OASIS rates and smoking was significant in pooled univariate analysis of multiparous women, but multivariate analysis revealed statistically insignificant results between non-smokers and smokers.
Conclusions
Nulliparous women who were smokers had a 28% lower incidence of OASIS. However, smoking during pregnancy cannot be recommended since it has shown to be associated with other adverse pregnancy outcomes and adverse health effects. The observed association warrants clinical repetition studies and, if confirmed, also in vitro studies focusing on connective tissue properties at a molecular and cellular level.
doi:10.1371/journal.pone.0041014
PMCID: PMC3397985  PMID: 22815899
24.  Preeclampsia complicated by advanced maternal age: a registry-based study on primiparous women in Finland 1997–2008 
Background
Preeclampsia is a frequent syndrome and its cause has been linked to multiple factors, making prevention of the syndrome a continuous challenge. One of the suggested risk factors for preeclampsia is advanced maternal age. In the Western countries, maternal age at first delivery has been steadily increasing, yet few studies have examined women of advanced maternal age with preeclampsia. The purpose of this registry-based study was to compare the obstetric outcomes in primiparous and preeclamptic women younger and older than 35 years.
Methods
The registry-based study used data from three Finnish health registries: Finnish Medical Birth Register, Finnish Hospital Discharge Register and Register of Congenital Malformations. The sample contained women under 35 years of age (N = 15,437) compared with those 35 and over (N = 2,387) who were diagnosed with preeclampsia and had their first singleton birth in Finland between 1997 and 2008. In multivariate modeling, the main outcome measures were Preterm delivery (before 34 and 37 weeks), low Apgar score (5 min.), small-for-gestational-age, fetal death, asphyxia, Cesarean delivery, induction, blood transfusion and admission to a Neonatal Intensive Care Unit.
Results
Women of advanced maternal age (AMA) exhibited more preeclampsia (9.4%) than younger women (6.4%). They had more prior terminations (<0.001), were more likely to have a body mass index (BMI) >25 (<0.001), had more in vitro fertilization (IVF) (<0.001) and other fertility treatments (<0.001) and a higher incidence of maternal diabetes (<0.001) and chronic hypertension (<0.001). Multivariate logistic regression indicated that women of AMA had higher rates of: preterm delivery before 37 weeks 19.2% (OR 1.39 CI 1.24 to 1.56) and before 34 weeks 8.7% (OR 1.68 CI 1.43 to 2.00) low Apgar scores at 5 min. 7.1% (OR 1.37 CI 1.00 to 1.88), Small-for-Gestational Age (SGA) 26.5% (OR 1.42 CI 1.28 to 1.57), Asphyxia 12.1% (OR 1.54 CI 1.34 to 1.77), Caesarean delivery 50% (OR 2.02 CI 1.84 to 2.20) and admission to a Neonatal Intensive Care Unit (NICU) 31.6% (OR 1.45 CI 1.32 to 1.60).
Conclusions
Preeclampsia is more common in women with advanced maternal age. Advanced maternal age is an independent risk factor for adverse outcomes in first-time mothers with preeclampsia.
doi:10.1186/1471-2393-12-47
PMCID: PMC3495042  PMID: 22687260
25.  Preterm Delivery Among Female Survivors of Childhood, Adolescent and Young Adulthood Cancer 
We studied the deliveries of female cancer survivors and female siblings in a population-based setting in Finland. Nationwide cancer and birth registries were merged to identify 1309 first post-diagnosis deliveries of early onset (diagnosed under age 35) female cancer patients and 5916 first deliveries of female siblings occurring in 1987–2006. Multiple logistic regression models were used to estimate risk of preterm (<37weeks), low birth weight (LBW) (<2500g), and small-for-gestational-age (SGA) deliveries.
The risk of preterm delivery among cancer survivors compared to siblings was overall elevated (Odds ratio (OR) 1.46, 95% confidence interval (CI) 1.14–1.85), the increase in risk being visible in all diagnostic age groups. Risk of LBW was also significantly increased (OR 1.68; 95% CI 1.29–2.18) but not after adjustment for duration of pregnancy (OR 1.11; 95% CI 0.76–1.64). Neither was the risk of SGA increased. The risk of preterm delivery was most pronounced in survivors delivering ten years or more after diagnosis. Site specific analyses indicated that survivors of germ cell tumors and central nervous system (CNS) tumors were at increased risk of preterm delivery, although numbers were small. In childhood survivors, kidney tumors formed the main cause of preterm delivery.
Pediatric, adolescent and young adult cancer survivors are at risk for preterm delivery. Heightened surveillance is recommended especially for Wilms’, germ cell and CNS tumor survivors. Such adverse pregnancy outcomes can occur a decade or more after cancer diagnosis indicating a continued need for obstetric awareness, surveillance and counseling in former cancer patients.
doi:10.1002/ijc.25157
PMCID: PMC2919618  PMID: 20054856
Preterm; Cancer survivors; Pregnancy; Late-effects

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