Correction: Perinatal outcomes after induced termination of pregnancy by methods: A nationwide register-based study of first births in Finland 1996-2013.

[This corrects the article DOI: 10.1371/journal.pone.0184078.].

Perinatal outcomes after induced termination of pregnancy by methods: A nationwide register-based study of first births in Finland 1996-2013.

BACKGROUND: Women with previous terminations of pregnancy (TOPs) before their first birth have been associated with poorer perinatal outcomes. However, previous studies on the perinatal outcomes by the method in previous TOPs are inconsistent. OBJECTIVE: To examine the perinatal outcomes of the first-time mothers with singleton births, by the method of previous TOP (medical and surgical vs no TOP, and surgical vs medical). METHOD: This is a nationwide register-based study including 419,879 first-time Finnish mothers with singleton birth during the time period 1996-2013. Mothers having their first birth were identified from the Medical Birth Register and linked to the Abortion Register by their identification numbers. Multinomial logistic regression analysis was performed to examine the risk for preterm birth, low birth weight, small for gestational age and perinatal death by the method in previous TOPs. RESULTS: Among the first-time mothers, 87.0% had no history of TOPs, 3.2% had a history of medical TOP(s), 9.2% had a history of surgical TOP(s) and 0.6% had a history of both (medical and surgical) TOP(s). No significant differences in perinatal outcomes were found among the women with surgical TOPs, compared to the women with no TOPs. In unadjusted analysis, increased odds for preterm birth and low birth weight were found when comparing women having previous surgical TOPs with medical TOPs. Even after the adjustment of potential confounders, odds for preterm birth < 37 weeks (OR = 1.19, 95% CI = 1.04-1.36) and low birth weight < 2500 g (OR = 1.16, 95% CI = 1.00-1.35) remained significant. After restricting data to the single TOP, the results were similar; OR for both preterm birth and low birth weight was 1.18 (95% CIs = 1.02-1.36 and 1.01-1.38). CONCLUSION: Perinatal outcomes did not differ among the mothers with surgical TOPs compared to the mothers with no TOPs, while the outcomes were poorer after surgical TOP(s) than after medical TOP(s).

Antidepressant use and violent crimes among young people: a longitudinal examination of the Finnish 1987 birth cohort.

BACKGROUND: The use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), has been questioned due to poor efficacy and safety. We examined whether young violent offenders were more likely antidepressant users prior to their first violent offence than other young persons. METHODS: The study is a follow-up of children born in Finland in 1987 (n=59 120), linking national registers to each other using personal identity codes. Data on psychotropic drug use came from a register of reimbursed drugs and data on crimes from a register on court convictions (after the age of 14 years). Participants were followed until the age of 18 years, and for some analyses until the end of the follow-up (mean 21 years). To adjust for differences in background characteristics, regression analyses for antidepressant use were made, using the no-conviction group as the reference. RESULTS: Proportions of young people convicted by the age of 18 years were: 5% of boys (1.7% for violent crimes) and 1% (0.5%) of girls. Antidepressant use (both overall and for SSRIs) prior to violent crime was more common among those convicted than among those without convictions. Among boys with repeated violent crimes, it was also more common than among boys with non-violent crimes. Adjustment for differences in background characteristics decreased the associations between antidepressant use and violent crime, but did not eliminate them. CONCLUSIONS: The results add further evidence for caution in prescribing antidepressants among young persons. It also calls for a reanalysis of violence measures in the original trial data.

Causes of death among women aged 17-49 years between 2007 and 2010 in Maputo, Mozambique.

OBJECTIVES: To describe causes of death among young women and estimate the role of HIV/AIDS as a cause in Maputo City, based on the civil death register. METHODS: Death data of 17-49 year-old women were abstracted from January 2007-March 2010 from the civil death register in Maputo City, registering overall about 15 000 deaths per-year. Causes of death in the register were either based on physicians' diagnoses on death certificates or determined by asking questions to deceased relatives. Causes of death were written in Portuguese; we translated them into English and classified them into 106 codes using ICD-9; these codes were then categorized into 10 groups. Estimated populations from the 2007 census were used to calculate annual mortality rates. An earlier study was used to compare deaths in 2001. FINDINGS: A total of 9640 deaths (6510 for residents of Maputo City) were registered and 77% had a specified cause of death reported. HIV-deaths represented 36% of all deaths and 40% among 25-39 year-olds. The death rate did not increase linearly by age, as there was a peak among women aged 30-34 years. The overall annual death rate was 6.7 deaths per 1000 population, with a notable decline by year. Death rates for HIV slightly declined by year. HIV-deaths explained most of the peak in death rate among 30-34-year-olds. The share of HIV-deaths among all deaths increased from 18% in 2001 to 35% in 2007-2010. Sixty-eight percent of all and 92% of HIV-related deaths occurred in hospital, with no increase over time. CONCLUSIONS: Routine death register was useful to study death rates, distribution of deaths, and change over time in the urban setting of Maputo during late 2000s. Over time, the death rate among 17-49 years old women seemed to have declined, but the relative contribution of HIV increased.

Effect of characteristics of women on attendance in blind and non-blind randomised trials: analysis of recruitment data from the EPHT Trial.

OBJECTIVES: To analyse the effect of women's characteristics on their willingness to join a blind or a non-blind subtrial or to be excluded by physicians. DESIGN: Primary prevention trial of postmenopausal hormone therapy (HT). A 2×2, randomised design with a non-blind HT arm or control arm and a blind HT arm or placebo arm. SETTING: 3 clinical centres in Estonia. METHODS: Interest in joining the trial was asked in a questionnaire together with demographic and health status data. Interested and eligible women were invited to a health examination that also informed whether they belonged to a blind or to a non-blind subtrial; the arm was not revealed. Trial physicians made further exclusions when checking the women's eligibility. Thereafter, informed consent was asked as detailed in the flow chart. Comparisons were made between non-blind and blind subtrials. Analyses were carried out for each of the background variables. OUTCOME MEASURES: The proportion of willingness, eligibility and attendance. RESULTS: Women randomised to the non-blind subtrial were more willing to join (relative risk (RR) 1.17) and more likely to be found eligible by physicians (RR 1.10) than women in the blind subtrial, resulting in larger attendance (RR 1.29). Women with higher education were differentially more willing to join the non-blind trial (RR 1.29) than those with basic education (RR 1.08); the differential willingness of never-smokers (RR 1.20) was larger than that of current smokers (RR 1.07). The differential exclusion by physicians by education and smoking were small. Some subjective symptoms (eg, diarrhoea/constipation, stomach pain) had reverse differential effects on attendance in the non-blind subtrial in comparison to the blind subtrial. Menopausal symptoms did not affect the differential interest, eligibility or attendance. CONCLUSIONS: Blinding in RCT reduces attendance, due to decisions of the women and the trial physicians. Differential attendance by blinding may affect the generalisability of the results from trials. TRIAL REGISTRATION NUMBER: ISRCTN35338757.

At what age does the risk for adverse maternal and infant outcomes increase? Nationwide register-based study on first births in Finland in 2005-2014.

INTRODUCTION: It is poorly understood if there are specific ages at which adverse outcomes during pregnancy and childbirth start to increase (threshold-ages). The purpose of this study was to examine at which maternal ages the use of maternity care and the risks for adverse maternal and infant outcomes increase. MATERIAL AND METHODS: National data from the Finnish Medical Birth Register including all first-time mothers aged 20 years or over with singleton pregnancies in 2005-2014 were analyzed (n = 228 348). Odds ratios for each outcome at different ages were calculated by logistic regression, using women aged 20-24 (n = 56 282) as the reference and adjusting for socioeconomic position and urbanity of residence. The threshold-age was defined as the first significant adjusted odds ratio after which the risk remained significant. RESULTS: The threshold-ages for use of maternity care varied from 25 years for cesarean section (OR 1.08, 95% CI 1.03-1.14) to 38 years for having 16 or more antenatal visits (1.13, 1.04-1.21). Four threshold-ages were found for maternal health outcomes: 25 years for gestational diabetes (OR 1.15, 1.09-1.23), 27 years for placenta previa (OR 1.75, 1.11-2.75), 33 years for gestational hypertension (1.14, 1.03-1.27), and 38 years for preeclampsia (OR 1.48, 1.12-1.96). The threshold-ages for infant health outcomes varied from 28 years for preterm birth (37 weeks, OR 1.10, 1.02-1.19) to 36 years for perinatal mortality (OR 2.10, 1.44-3.07). CONCLUSIONS: Different threshold-ages were identified. Most adverse outcomes occurred earlier than the traditional cut-off ages for high risk pregnancy, which have been set at 35 or 40 years.

Changes in work behavior during pregnancy in rural Anhui, China from 2001-03 to 2009: a population based cross-sectional study.

BACKGROUND: In low- and middle-income countries, many women continue working later into pregnancy. In our recent study on some areas in rural China, most women stopped working already during the first trimester (≤3 months) of pregnancy. In this paper we aimed to explore whether stopping work during early pregnancy has changed over an 8 year period (between 2001-03 and 2009); we also studied whether the reasons for stopping work early were the same in the two time periods. METHODS: A population-based cross-sectional survey with a representative sample of new mothers was carried out in one rural county in Anhui Province in 2001-03 (N = 1479 respondents) and in two other rural counties in 2009 (N = 1574 respondents). Both surveys were used to evaluate prenatal care interventions not related to work behavior. The surveys targeted all women who had recently given birth. Multilevel logistic regression analysis was used to examine the determinants of work behavior in the two time periods. RESULTS: There was a big change in the working behavior between the two survey years: in the period 2001-03 6 % and in 2009, 53 % of pregnant women stopped working at ≤3 months (percentage change 839, 95 % CI -15.90 to 1694.49). In 2001-03, 30 % and in 2009, 23 % of pregnant women worked the same as before pregnancy (percentage change -22.30, 95 % CI -90.28 to 45.68). In both time periods women with two children were less likely to stop work at ≤3 months of pregnancy. Non-farmers were more likely in 2001-03 but less likely in 2009 to stop work at ≤3 months of pregnancy. Women with medium township-level income were more likely to maintain the same level of work as before pregnancy in 2001-03, while in 2009 women with high township-level income were less likely to work the same. CONCLUSION: Stopping work very early during pregnancy appeared to have become very common from 2001-3 to 2009 in rural Anhui, China and was not explained by women's background characteristics.

Is selective prenatal iron prophylaxis better than routine prophylaxis: final results of a trial (PROFEG) in Maputo, Mozambique.

OBJECTIVE: To compare routine versus selective (ie, screening and treatment for anaemia) prenatal iron prophylaxis in a malaria-endemic and HIV-prevalent setting, an extended analysis including previously missing data. DESIGN: A pragmatic randomised controlled clinical trial. SETTING: 2 health centres in Maputo, Mozambique. PARTICIPANTS: Pregnant women (≥18 years old; non-high-risk pregnancy) were randomly allocated to routine iron (n=2184) and selective iron (n=2142) groups. INTERVENTIONS: In the routine group, women received 60 mg ferrous sulfate plus 400 µg folic acid daily. In the selective group, women received 1 mg of folic acid daily and haemoglobin (Hb) screening at each visit; with low Hb (cut-off 9 g/dL) treatment (120 mg+800 µg of folic acid daily) for a month. PRIMARY OUTCOMES: preterm birth, low birth weight; secondary outcomes: self-reported malaria, labour complications, caesarean section, perinatal death, woman's death. Nurses collected pregnancy data. Birth data were abstracted from hospital records for 52% of women and traced using various methods and linked with probabilistic matching for 24%. Women's deaths were collected from death registers. RESULTS: Birth data were available for 3301 (76%) of the women. Outcomes were similar in the two groups: preterm births (27.1% in the selective vs 25.3% in the routine group), low birthweight infants (11.0% vs 11.7%), perinatal deaths (2.4% vs 2.4%) and caesarean sections (4.0% vs 4.5%). Women's deaths during pregnancy or <42 days postpartum were more common in the selective group (0.8% among the two best matched women) than in the routine group (0.4%). Extra deaths could not be explained by the cause of death, Hb level or HIV status at recruitment. CONCLUSIONS: Birth outcomes were similar in the two iron groups. There might have been more women's deaths in the selective iron group, but it is unclear whether this was due to the intervention, other factors or chance finding. TRIAL REGISTRATION NUMBER: NCT00488579.

Short-term effects of the "Together at School" intervention program on children's socio-emotional skills: a cluster randomized controlled trial.

BACKGROUND: Together at School is a universal intervention program designed to promote socio-emotional skills among primary-school children. It is based on a whole school approach, and implemented in school classes by teachers. The aim of the present study is to examine the short-term effects of the intervention program in improving socio-emotional skills and reducing psychological problems among boys and girls. We also examine whether these effects depend on grade level (Grades 1 to 3) and intervention dosage. METHODS: This cluster randomized controlled trial design included 79 Finnish primary schools (40 intervention and 39 control) with 3 704 children. The outcome measures were the Strengths and Difficulties Questionnaire (SDQ) and the Multisource Assessment of Social Competence Scale (MASCS) with teachers as raters. The intervention dosage was indicated by the frequencies six central tools were used by the teachers. The data was collected at baseline and 6 months later. Intervention effects were analyzed using multilevel modeling. RESULTS: When analyzed across all grades no intervention effect was observed in improving children's socio-emotional skills or in reducing their psychological problems at 6-month follow-up. Among third (compared to first) graders the intervention decreased psychological problems. Stratified analyses by gender showed that this effect was significant only among boys and that among them the intervention also improved third graders' cooperation skills. Among girls the intervention effects were not moderated by grade. Implementing the intervention with intended intensity (i.e. a high enough dosage) had a significant positive effect on cooperation skills. When analyzed separately among genders, this effect was significant only in girls. CONCLUSIONS: These first, short-term results of the Together at School intervention program did not show any main effects on children's socio-emotional skills or psychological problems. This lack of effects may be due to the relatively short follow-up period given the universal, whole school-based approach of the program. The results suggest that the grade level where the intervention is started might be a factor in the program's effectiveness. Moreover, the results also suggest that for this type of intervention program to be effective, it needs to be delivered with a high enough dosage. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02178332 ; Date of registration: 03-April-2014.

Research ethics committees in the regulation of clinical research: comparison of Finland to England, Canada, and the United States.

BACKGROUND: The aim of this paper is to compare common features and variation in the work of research ethics committees (RECs) in Finland to three other countries - England, Canada, the United States of America (USA) - in the late 2000s. METHODS: Several approaches and data sources were used, including semi- or unstructured interviews of experts, documents, previous reports, presentations in meetings and observations. A theoretical framework was created and data from various sources synthesized. RESULTS: In Finland, RECs were regulated by a medical research law, whereas in the other countries many related laws and rules guided RECs; drug trials had specific additional rules. In England and the USA, there was a REC control body. In all countries, members were voluntary and included lay-persons, and payment arrangements varied. Patient protection was the main ethics criteria, but other criteria (research advancement, availability of results, payments, detailed fulfilment of legislation) varied. In all countries, RECs had been given administrative duties. Variations by country included the mandate, practical arrangements, handling of multi-site research, explicitness of proportionate handlings, judging scientific quality, time-limits for decisions, following of projects, role in institute protection, handling conflicts of interests, handling of projects without informed consent, and quality assurance research. The division of work between REC members and secretariats varied in checking of formalities. In England, quality assurance of REC work was thorough, fairly thorough in the USA, and not performed in Finland. CONCLUSIONS: The work of RECs in the four countries varied notably. Various deficiencies in the system require action, for which international comparison can provide useful insights.

Aging fatherhood in Finland - first-time fathers in Finland from 1987 to 2009.

AIM: The increase in maternal age has been well documented in Western societies, but information on paternal age trends is scarce. The aim of this study was to investigate changes in age and other background characteristics of first-time fathers in Finland in the period 1987-2009. MATERIALS AND METHODS: A random 60% sample of first-time fathers in each year from 1987 to 2009 was obtained from Statistics Finland (n=344,529). Five-year intervals were used (three years in 1987-1989). Sociodemographic characteristics of older first-time fathers (⩾40 years) were compared over time using logistic regression. In the logistic regression, immigrants were excluded from the study population as they may have had children before migrating to Finland. RESULTS: The mean age of first-time fathers increased from 28.7 to 30.4 years in 1987-2009. The change was greatest in the Capital Region and smallest in Northern and Eastern Finland. Fatherhood at the age of ⩾40 years doubled from 3.1% to 6.8%. From 2005 to 2009, men who lived in rural areas and the Capital Region, had a long education, were divorced or widowed, had been born in a rural area and were native Finnish speakers, were more likely than other men to be old when they became fathers. CONCLUSIONS DURING THE STUDY PERIOD, THE AVERAGE AGE OF FIRST-TIME FATHERS INCREASED BY TWO YEARS FURTHER STUDIES ARE NEEDED TO EXAMINE WHETHER DELAYS IN FIRST-TIME FATHERHOOD AFFECT FERTILITY, CHILD HEALTH AND THE USE OF SOCIAL AND HEALTH SERVICES.

Supplemental iron intake and the risk of glucose intolerance in pregnancy: re-analysis of a randomised controlled trial in Finland.

Observational studies suggest that high iron intake during pregnancy is associated with the risk of gestational diabetes. As such studies are prone to bias, we re-analysed data from a randomised controlled trial of iron supplementation to see whether it supports the risk found in observational studies. The trial was conducted in primary health care setting in five municipalities in Finland in 1985-1986. The participants were 2944 women (95% of pregnant women in the area) who were randomly allocated either to (1) the selective iron group (elemental iron 50 mg twice a day only if diagnosed as anaemic, continuing until their haemoglobin increased to 110 g L(-1)) or (2) the routine iron group (elemental iron 100 mg day(-1) throughout the pregnancy regardless of haemoglobin level). The numbers of women in the analyses were 1358 and 1336, respectively. The main outcome measure was a composite variable including any glucose intolerance-related outcome (e.g. glucosuria, gestational diabetes, large-for-gestational-age child) in mothers' or children's patient records during pregnancy and post-partum. There were no statistically significant differences in the incidence of the primary outcome between the selective iron and the routine iron groups (13.0 vs. 11.0%, P = 0.12). The most common outcome was large-for-gestational-age calculated from children's hospital data (8.3 vs. 8.2%, P = 0.95). The results were mainly similar when stratified by the mothers' baseline haemoglobin level, body mass index or gestational weight gain. Routine iron supplementation throughout pregnancy did not increase the risk of glucose intolerance during pregnancy. The results need to be confirmed in future trials.

Caesarean section rates in Mozambique.

BACKGROUND: The Caesarean section (C-section) rate is used as an indicator for availability and utilization of life-saving obstetric services. The purpose of the present study was to explore changes in C-section rates between 1995 and 2011 by area, place of delivery and maternal socioeconomic factors in Mozambique. METHODS: Cross-sectional data from the Demographic and Health Surveys conducted in Mozambique in 1997, 2003 and 2011 were used, including women having a live birth within 3 years prior to the survey. Descriptive statistics and logistic regressions were used to identify factors associated with having a C-section. RESULTS: The C-section rate decreased slightly from 2.5% in 1995-1997 to 2.1% in 2001-2003 and then increased to 4.7% in 2009-2011. In 2009-2011, C-section rates ranged in urban areas from 4.6% in the northern region to 12.2% in the southern region and in rural areas from 1.6% in the northern region to 3.9% in the southern region. 12.3% of the richest women had had a C-section, compared to 1.7% of the poorest women. C-sections were the most common at public hospitals (12.6% in 2009-2011), but C-sections at health centers increased from the second to the third period. The likelihood of having a C-section was associated with living in urban areas and in the southern region, having a formal education and living in a rich household, even adjusting for age and parity (and study periods). The strongest relationship was for the richest household wealth quintile [OR (95% CI): 9.8 (6.3-15.3)]. The highest rate (20.6%) was found among the richest women giving birth at public hospitals in the southern region in 2009-2011. CONCLUSION: In Mozambique, underuse of C-section was likely among the poor and in rural areas, but overuse in the most advantaged groups seemed to be emerging.

Decisions by Finnish Medical Research Ethics Committees: A Nationwide Study of Process and Outcomes.

Review by research ethics committees (RECs) is the key in medical research regulation. Data from meeting notes and project summaries were abstracted from all projects submitted in 2002 (n = 1,004) and 2007 (n = 1,045) to the official medical RECs in Finland. Data from consecutive submissions were combined per project. When comparing RECs, logistic regression was used to adjust for application characteristics. The number of projects handled varied notably by REC. In the first handling, 85% of applications in 2002 and 77% in 2007 were approved, while 13% and 20% were tabled. For 61% of the projects, the review time was <30 days, 16% had >89 days, and 6% had 6 months or longer. The variation by REC in approval rates, number of handlings, or long review times was not explained by project characteristics. In the last handling, 94% of the projects in both years were approved or concluded not to need a statement from that REC. The most common reason for tabling or not approving an application was patient autonomy, usually centered on the patient leaflet. The next most common reasons were requests for further information and dissatisfaction with the scientific aspects of the project. The reasons classified as "ethics" in the narrow sense were rare. The REC focus was to assure that researchers follow the various rules on medical research and to improve the quality of research and project documents. REC considerations could be divided into decisions based on ethics and recommendations covering other aspects.

[External regulation of clinical research requires a change]. / Kliinisen tutkimuksen ulkoinen säätely tarvitsee muutosta.

Key findings and recommendations from a study comparing clinical research regulation in Finland with those in England, Canada (Ontario) and USA are presented. Data were collected with various methods, including interviewing key experts. While the norms and ethical codes were similar, the interpretation partly differed. In each country there were various actors in regulation and practical arrangements differed. Research ethics committees (REC) were crucial, as well as drug authorities in research with drugs. Recommendations include reforming the medical research law, widening the dimensions of ethics judgment, restricting the REC tasks, including a central committee, and introducing quality assurance and restricting the drug control authority tasks.

Actors involved in the regulation of clinical research: comparison of Finland to England, Canada, and the USA.

BACKGROUND: The relevance and quantity of clinical research has caused concern and regulation is claimed to hinder clinical research. This paper compares clinical research regulations in Finland to those of England, Canada, and the USA around 2010-2011. METHODS: Several approaches and data sources were used, including semi- or unstructured interviews of experts. For the analysis, a theoretical framework was made, data from various sources was synthesized, and features of the systems were simplified and classified. The various specific names and terms used in the data were changed into general ones. RESULTS: Common structures for the regulation existed in all four countries, but the details and scope varied. The research regulated within the main system was determined by research type (Finland), the financer of the health system (England), or research site (Canada, USA). Only Finland had specific legislation on medical research. The overriding impression of the regulatory systems was one of complexity. All countries had extra regulation for drug research. The types of drug research covered varied from trials with unlicensed (new) products or new indications (USA and Canada), to all types of interventional drug research (England), where 'interventional' was interpreted broadly (Finland). The complexity of regulations had led to the creation of various big and small businesses to help researchers and sponsors. There was notable variation in the role played by the public research funder. The role played by health care was difficult to study and seemed to involve varying interests as researchers were also health care employees. Research ethics committees were important and their tasks also included aspects other than ethics. CONCLUSIONS: This study revealed that a comparison between countries can provide useful insights into the distinctive aspects of each country's system, as well as identifying common features that require international action.

A pragmatic randomised controlled trial on routine iron prophylaxis during pregnancy in Maputo, Mozambique (PROFEG): rationale, design, and success.

The effects of prophylactic iron during pregnancy on maternal and child health in developing settings with endemic malaria and high prevalence of HIV remain unclear. This paper describes the rationale, implementation and success of a pragmatic randomised controlled trial comparing routine iron supplementation vs. screening and treatment for anaemia during pregnancy. The setting was two health centres in Maputo, Mozambique. Pregnant women (≥ 12-week gestation; ≥ 18 years old; and not with a high-risk pregnancy, n=4326) were recruited. The main outcomes are preterm delivery and low birthweight. The women were randomly assigned to one of two iron administration policies: a routine iron group (n=2184) received 60 mg of ferrous sulphate plus 400 µg of folic acid daily while a selective iron group (n=2142) had screening and treatment for anaemia and a daily intake of 1 mg of folic acid. The recruitment, follow-up, and collection of follow-up data were successful; both groups were similar to each other in all the trial stages. Collection of delivery data was challenging and data on about 40% of births is missing. These are currently being traced through different hospitals and health centres. The compliance of the study personnel and the women with regard to regular measurement of haemoglobin and intake of the iron and folic acid tablets was high and similar in both trial arms. Taking into account the various constraints encountered, the stages of the present trial prior to delivery were carried out well.