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Background: During the 1970s the Nordic countries liberalized their abortion laws. Objective: We assessed epidemiological trends for induced abortion on all Nordic countries, considered legal similarities and diversities, effects of new medical innovations and changes in practical and legal provisions during the subsequent years. Methods: New legislation strengthened surveillance of induced abortion in all countries and mandated hospitals that performed abortions to report to national abortion registers. Published data from the Nordic abortion registers were considered and new comparative analyses done. The data cover complete national populations. Results and conclusions: After an increase in abortion rates during the first years following liberalization, the general abortion rates stabilized and even decreased in all Nordic countries, especially for women under 25 years. From the mid-1980s higher awareness about pregnancy termination led women to present at an earlier gestational age, which was accelerated by the introduction of medical abortion some years later. Most terminations (80–86%) are now done before the 9th gestational week in all countries, primarily by medical rather than surgical means. Introduction of routine ultrasound screening in pregnancy during the late 1980s, increased the number of 2nd trimester abortions on fetal anomaly indications without an overall increase in the proportion of 2nd relative to 1st trimester abortions. Further refinement of ultrasound screening and non-invasive prenatal diagnostic methods led to a slight increase in the proportion of early 2nd trimester abortions after the year 2000. Country-specific differences in abortion rates have remained stable over the 50 years of liberalized abortion laws. [ABSTRACT FROM AUTHOR]

Background The aim was to investigate whether children born after assisted reproduction technology (ART), particularly after frozen-thawed embryo transfer (FET), are at higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception. Methods and findings We performed a registry-based cohort study using data from the 4 Nordic countries: Denmark, Finland, Norway, and Sweden. The study included 7,944,248 children, out of whom 171,774 children were born after use of ART (2.2%) and 7,772,474 children were born after spontaneous conception, representing all children born between the years 1994 to 2014 in Denmark, 1990 to 2014 in Finland, 1984 to 2015 in Norway, and 1985 to 2015 in Sweden. Rates for any cancer and specific cancer groups in children born after each conception method were determined by cross-linking national ART registry data with national cancer and health data registries and population registries. We used Cox proportional hazards models to estimate the risk of any cancer, with age as the time scale. After a mean follow-up of 9.9 and 12.5 years, the incidence rate (IR) of cancer before age 18 years was 19.3/100,000 person-years for children born after ART (329 cases) and 16.7/100,000 person-years for children born after spontaneous conception (16,184 cases). Adjusted hazard ratio (aHR) was 1.08, 95% confidence interval (CI) 0.96 to 1.21, p = 0.18. Adjustment was performed for sex, plurality, year of birth, country of birth, maternal age at birth, and parity. Children born after FET had a higher risk of cancer (48 cases; IR 30.1/100,000 person-years) compared to both fresh embryo transfer (IR 18.8/100,000 person-years), aHR 1.59, 95% CI 1.15 to 2.20, p = 0.005, and spontaneous conception, aHR 1.65, 95% CI 1.24 to 2.19, p = 0.001. Adjustment either for macrosomia, birth weight, or major birth defects attenuated the association marginally. Higher risks of epithelial tumors and melanoma after any assisted reproductive method and of leukemia after FET were observed. The main limitation of this study is the small number of children with cancer in the FET group. Conclusions Children born after FET had a higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception. The results should be interpreted cautiously based on the small number of children with cancer, but the findings raise concerns considering the increasing use of FET, in particular freeze-all strategies without clear medical indications. Trial registration Trial registration number: ISRCTN 11780826., Author(s): Nona Sargisian 1, Birgitta Lannering 2, Max Petzold 3, Signe Opdahl 4, Mika Gissler 5,6, Anja Pinborg 7, Anna-Karina Aaris Henningsen 7, Aila Tiitinen 8, Liv Bente Romundstad 9,10, [...]

Background Some earlier studies have found indications of significant changes in cardiometabolic risk factors in children born after assisted reproductive technology (ART). Most of these studies are based on small cohorts with high risk of selection bias. In this study, we compared the risk of cardiovascular disease, obesity, and type 2 diabetes between singleton children born after ART and singleton children born after spontaneous conception (SC). Methods and findings This was a large population-based cohort study of individuals born in Norway, Sweden, Finland, and Denmark between 1984 and 2015. Data were obtained from national ART and medical birth registers and cross-linked with data from national patient registers and other population-based registers in the respective countries. In total, 122,429 children born after ART and 7,574,685 children born after SC were included. Mean (SD) maternal age was 33.9 (4.3) years for ART and 29.7 (5.2) for SC, 67.7% versus 41.8% were primiparous, and 45.2% versus 32.1% had more than 12 years of education. Preterm birth ( Conclusions In this study, we observed no difference in the risk of cardiovascular disease or type 2 diabetes between children born after ART and children born after SC. For obesity, there was a small but significant increased risk for children born after ART. Trial registration number ISRCTN11780826., Author(s): Emma Norrman 1,*, Max Petzold 2, Mika Gissler 3,4, Anne Lærke Spangmose 5, Signe Opdahl 6, Anna-Karina Henningsen 5, Anja Pinborg 5, Aila Tiitinen 7, Annika Rosengren 8, Liv [...]

Background Compared to naturally conceived children, adverse perinatal outcomes are more common among children born after assisted reproductive technology with fresh embryo transfer (fresh-ET) or frozen embryo transfer (frozen-ET). However, most previous studies could not adequately control for family confounding factors such as subfertility. We compared birth size and duration of pregnancy among infants born after fresh-ET or frozen-ET versus natural conception, using a within-sibship design to account for confounding by maternal factors. Methods and findings This registry-based cohort study with nationwide data from Denmark (1994-2014), Norway (1988-2015), and Sweden (1988-2015) consisted of 4,510,790 live-born singletons, 4,414,703 from natural conception, 78,095 from fresh-ET, and 17,990 from frozen-ET. We identified 33,056 offspring sibling groups with the same mother, conceived by at least 2 different conception methods. Outcomes were mean birthweight, small and large for gestational age, mean gestational age, preterm ( Conclusions We found that infants conceived by fresh-ET had lower birthweight and increased odds of small for gestational age, and those conceived by frozen-ET had higher birthweight and increased odds of large for gestational age. Conception by either fresh-ET or frozen-ET was associated with increased odds of preterm birth. That these findings were observed within siblings, as well as in conventional multivariable population analyses, reduces the likelihood that they are explained by confounding or selection bias. Trial registration ClinicalTrials.gov ISRCTN11780826., Author(s): Kjersti Westvik-Johari 1,2,*, Liv Bente Romundstad 3,4, Deborah A. Lawlor 5,6,7, Christina Bergh 8, Mika Gissler 9,10, Anna-Karina A. Henningsen 11, Siri E. Håberg 3, Ulla-Britt Wennerholm 8, Aila [...]

Linking routinely collected healthcare administrative data is a valuable method for conducting research on morbidity outcomes, but linkage quality and accuracy needs to be assessed for bias as the data were not collected for research. The aim of this study was to describe the rates of linking data on children with and without congenital anomalies to regional or national hospital discharge databases and to evaluate the quality of the matched data. Eleven population-based EUROCAT registries participated in a EUROlinkCAT study linking data on children with a congenital anomaly and children without congenital anomalies (reference children) born between 1995 and 2014 to administrative databases including hospital discharge records. Odds ratios (OR), adjusted by region, were estimated to assess the association of maternal and child characteristics on the likelihood of being matched. Data on 102,654 children with congenital anomalies were extracted from 11 EUROCAT registries and 2,199,379 reference children from birth registers in seven regions. Overall, 97% of children with congenital anomalies and 95% of reference children were successfully matched to administrative databases. Information on maternal age, multiple birth status, sex, gestational age and birthweight were >95% complete in the linked datasets for most regions. Compared with children born at term, those born at ≤27 weeks and 28–31 weeks were less likely to be matched (adjusted OR 0.23, 95% CI 0.21–0.25 and adjusted OR 0.75, 95% CI 0.70–0.81 respectively). For children born 32–36 weeks, those with congenital anomalies were less likely to be matched (adjusted OR 0.78, 95% CI 0.71–0.85) while reference children were more likely to be matched (adjusted OR 1.28, 95% CI 1.24–1.32). Children born to teenage mothers and mothers ≥35 years were less likely to be matched compared with mothers aged 20–34 years (adjusted ORs 0.92, 95% CI 0.88–0.96; and 0.87, 95% CI 0.86–0.89 respectively). The accuracy of linkage and the quality of the matched data suggest that these data are suitable for researching morbidity outcomes in most regions/countries. However, children born preterm and those born to mothers aged <20 and ≥35 years are less likely to be matched. While linkage to administrative databases enables identification of a reference group and long-term outcomes to be investigated, efforts are needed to improve linkages to population groups that are less likely to be linked. [ABSTRACT FROM AUTHOR]

Background Variations in intervention rates, without subsequent reductions in adverse outcomes, can indicate overuse. We studied variations in and associations between commonly used childbirth interventions and adverse outcomes, adjusted for population characteristics. Methods and findings In this multinational cross-sectional study, existing data on 4,729,307 singleton births at [greater than or equal to]37 weeks in 2013 from Finland, Sweden, Norway, Denmark, Iceland, Ireland, England, the Netherlands, Belgium, Germany (Hesse), Malta, the United States, and Chile were used to describe variations in childbirth interventions and outcomes. Numbers of births ranged from 3,987 for Iceland to 3,500,397 for the USA. Crude data were analysed in the Netherlands, or analysed data were shared with the principal investigator. Strict variable definitions were used and information on data quality was collected. Intervention rates were described for each country and stratified by parity. Uni- and multivariable analyses were performed, adjusted for population characteristics, and associations between rates of interventions, population characteristics, and outcomes were assessed using Spearman's rank correlation coefficients. Considerable intercountry variations were found for all interventions, despite adjustments for population characteristics. Adjustments for ethnicity and body mass index changed odds ratios for augmentation of labour and episiotomy. Largest variations were found for augmentation of labour, pain relief, episiotomy, instrumental birth, and cesarean section (CS). Percentages of births at [greater than or equal to]42 weeks varied from 0.1% to 6.7%. Rates among nulliparous versus multiparous women varied from 56% to 80% versus 51% to 82% for spontaneous onset of labour; 14% to 36% versus 8% to 28% for induction of labour; 3% to 13% versus 7% to 26% for prelabour CS; 16% to 48% versus 12% to 50% for overall CS; 22% to 71% versus 7% to 38% for augmentation of labour; 50% to 93% versus 25% to 86% for any intrapartum pain relief, 19% to 83% versus 10% to 64% for epidural anaesthesia; 6% to 68% versus 2% to 30% for episiotomy in vaginal births; 3% to 30% versus 1% to 7% for instrumental vaginal births; and 42% to 70% versus 50% to 84% for spontaneous vaginal births. Countries with higher rates of births at [greater than or equal to]42 weeks had higher rates of births with a spontaneous onset (rho = 0.82 for nulliparous/rho = 0.83 for multiparous women) and instrumental (rho = 0.67) and spontaneous (rho = 0.66) vaginal births among multiparous women and lower rates of induction of labour (rho = -0.71/-0.66), prelabour CS (rho = -0.61/-0.65), overall CS (rho = -0.61/-0.67), and episiotomy (multiparous: rho = -0.67). Variation in CS rates was mainly due to prelabour CS (rho = 0.96). Countries with higher rates of births with a spontaneous onset had lower rates of emergency CS (nulliparous: rho = -0.62) and higher rates of spontaneous vaginal births (multiparous: rho = 0.70). Prelabour and emergency CS were positively correlated (nulliparous: rho = 0.74). Higher rates of obstetric anal sphincter injury following vaginal birth were found in countries with higher rates of spontaneous birth (nulliparous: rho = 0.65). In countries with higher rates of epidural anaesthesia (nulliparous) and spontaneous births (multiparous), higher rates of Apgar score < 7 were found (rhos = 0.64). No statistically significant variation was found for perinatal mortality. Main limitations were varying quality of data and missing information. Conclusions Considerable intercountry variations were found for all interventions, even after adjusting for population characteristics, indicating overuse of interventions in some countries. Multivariable analyses are essential when comparing intercountry rates. Implementation of evidence-based guidelines is crucial in optimising intervention use and improving quality of maternity care worldwide., Author(s): Anna E. Seijmonsbergen-Schermers 1,*, Thomas van den Akker 2,3, Eva Rydahl 4, Katrien Beeckman 5, Annick Bogaerts 6,7, Lorena Binfa 8, Lucy Frith 9, Mechthild M. Gross 10, Björn [...]

Background Antenatal corticosteroid therapy (ACT) is used clinically to prepare the fetal lung for impending preterm birth, but animal and human studies link corticosteroids to smaller birth size. Whether ACT is associated with birth size is debated; therefore, we assessed differences in birth size in treated versus untreated pregnancies. Methods and findings This observational register-based study used data from the Finnish Medical Birth Register (FMBR) covering all births in Finland (January 1, 2006-December 31, 2010). We used unadjusted and adjusted regression analyses as well as propensity score matching (PSM) to analyze whether birth size differed by ACT exposure. PSM provides a stringent comparison, as subsamples were created matched on baseline and medical characteristics between treated and untreated women. All analyses were stratified by timing of birth. The primary study outcome was birth size: birth weight (BWT), birth length (BL), ponderal index (PI), and head circumference (HC) measured immediately after birth and recorded in the FMBR. Additional analyses explored indicators of neonatal health in relation to ACT exposure and birth size. A total of 278,508 live-born singleton births with [greater than or equal to]24 gestational completed weeks were registered in the FMBR during the 5-year study period. Over 4% of infants were born preterm, and 4,887 women were treated with ACT (1.75%). More than 44% of the exposed infants (n = 2,173) were born at term. First, results of unadjusted regression analyses using the entire sample showed the greatest reductions in BWT as compared to the other analytic methods: very preterm -61.26 g (±SE 24.12, P < 0.01), preterm -232.90 g (±SE 17.24, P < .001), near term -171.50 g (±SE 17.52, P < .001), and at term -101.95 g (±SE 10.89, P < .001). Second, using the entire sample, regression analyses adjusted for baseline and medical conditions showed significant differences in BWT between exposed and unexposed infants: very preterm -61.54 g (±SE 28.62, P < .03), preterm -222.78 g (±SE 19.64, P < .001), near term -159.25 g (±SE 19.14, P < .001), and at term -91.62 g (±SE 11.86, P < .03). Third, using the stringent PSM analyses based on matched subsamples, infants exposed to ACT weighed less at birth: -220.18 g (±SE 21.43, P < .001), -140.68 g (±SE 23.09, P < .001), and -89.38 g (±SE 14.16, P < .001), born preterm, near term, and at term, respectively. Similarly, significant reductions in BL and HC were also observed using the three analytic methods. There were no differences among postterm infants regardless of analytic method. Likewise, we observed no differences with respect to PI. Additional analyses showed that exposed and unexposed infants had generally similar Apgar scores at birth, yet the ACT-treated infants received greater medical care during the first 7 days of life and beyond. Our study is mainly limited by lack of data in FMBR specifying the interval between treatment and birth as well as other potential confounders that could not be tested. Conclusions In this study, ACT was consistently associated with reduction in birth size for infants born preterm, near term, or at term. Further investigation is warranted alongside reevaluation of guidelines. Efforts need to be made to correctly identify and target patients who will deliver preterm. Reduced growth should be considered when deliberating early care decisions., Author(s): Alina Rodriguez 1,2,*, Yingbo Wang 1, Anohki Ali Khan 1, Rufus Cartwright 1,3, Mika Gissler 4,5, Marjo-Riitta Järvelin 1,6,7,8,9 Introduction Complications arising from preterm birth are the primary cause [...]

Aims: In most population-based epidemiological follow-up studies the aim is not to intervene in the life of the participants. Although the idea is not to intervene, being a member of the longitudinal follow-up study and studies conducted during follow-up may affect the target population. A population-based study including mental health enquiries might reduce the unmet need for psychiatric treatment by motivating people to seek treatment for their psychiatric ill-health. We examined the use of psychiatric care services in the population born in the year 1966 in Northern Finland, of whom 96.3% are participants in the prospective Northern Finland Birth Cohort 1966 (NFBC1966). Methods: As a study cohort we used people born in 1966 in Northern Finland (n = 11 447). The comparison cohort included all the people born in the years 1965 and 1967 in the same geographical area (n = 23 339). The follow-up period was from age 10 to 50 years. The outcome measure was the use of psychiatric care services, which was analysed using Cox Proportional Hazard regression and Zero-Truncated Negative Binomial Regression. Results: People born in 1966 in Northern Finland did not differ from those born in 1965 and 1967 in terms of the outcome measure. Conclusions: We found no association between participation in an epidemiological follow-up study and the use of psychiatric care services. The NFBC1966 may be regarded as a representative at the population level in terms of psychiatric outcomes despite the personal follow-up of the birth cohort. The associations of participation in epidemiological follow-up studies have previously been under-examined, and the results need to be replicated. [ABSTRACT FROM AUTHOR]

Background: Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure. Methods: The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records. Results and discussion: The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS. [ABSTRACT FROM AUTHOR]

Objective: To explore risk profiles of the different types of postpartum hemorrhage (PPH >500ml or severe PPH >1500ml) and their recurrence risks in a subsequent delivery. Methods: With data from The Medical Birth Registry of Norway and Statistics Norway we performed a population-based cohort study including all singleton deliveries in Norway from 1967–2017. Multilevel logistic regression was used to calculate odds ratio (OR), with 95% confidence interval (CI), with different PPH types (PPH >500ml or PPH >1500ml (severe PPH) combined with retained placenta, uterine atony, obstetric trauma, dystocia, or undefined cause) as outcomes. Result: We identified 277 746 PPH cases of a total of 3 003 025 births (9.3%) from 1967 to 2017. Retained placenta (and/or membranes) was most often registered as severe PPH (29.3%). Maternal, fetal, and obstetric characteristics showed different associations with the PPH types. Male sex of the neonate was associated with reduced risk of PPH. This effect was strongest on PPH due to retained placenta (adjusted OR, (aOR): 0.80, 95% CI 0.78–0.82), atony (aOR 0.92, 95% CI: 0.90–0.93) and PPH with undefined cause (aOR 0.96, 95% CI: 0.95–0.97). Previous cesarean section showed a strong association with PPH due to dystocia (aOR of 13.2, 95% CI: 12.5–13.9). Recurrence risks were highest for the same type: PPH associated with dystocia (aOR: 6.8, 95% CI: 6.3–7.4), retained placenta and/or membranes (aOR: 5.9, 95% CI: 5.5–6.4), atony (aOR: 4.0, 95% CI: 3.8–4.2), obstetric trauma (aOR: 3.9, 95% CI: 3.5–4.3) and PPH of undefined cause (aOR: 2.2, 95% CI: 2.1–2.3). Conclusion: Maternal, fetal and obstetric characteristics had differential effects on types of PPH. Recurrence differed considerably between PPH types. Retained placenta was most frequently registered with severe PPH, and showed strongest effect of sex; delivery of a boy was associated with lower risk of PPH. Previous cesarean increased the risk of PPH due to dystocia. [ABSTRACT FROM AUTHOR]

Background: Congenital anomalies are a leading cause of childhood morbidity, but little is known about the long-term outcomes. Objective: To quantify the burden of disease in childhood for children with congenital anomalies by assessing the risk of hospitalisation, the number of days spent in hospital and proportion of children with extended stays (≥10 days). Methods: European population-based record-linkage study in 11 regions in eight countries including children with congenital anomalies (EUROCAT children) and without congenital anomalies (reference children) living in the same regions. The children were born between 1995 and 2014 and were followed to their tenth birthday or 31/12/2015. European meta-analyses of the outcome measures were performed by two age groups, <1 year and 1–4 years. Results: 99,416 EUROCAT children and 2,021,772 reference children were linked to hospital databases. Among EUROCAT children, 85% (95%-CI: 79–90%) were hospitalised in the first year and 56% (95%-CI: 51–61%) at ages 1–4 years, compared to 31% (95%-CI: 26–37%) and 25% (95%-CI: 19–31%) of the reference children. Median length of stay was 2–3 times longer for EUROCAT children in both age groups. The percentages of children with extended stays (≥10 days) in the first year were 24% (95%-CI: 20–29%) for EUROCAT children and 1% (95%-CI: 1–2%) for reference children. The median length of stay varied greatly between congenital anomaly subgroups, with children with gastrointestinal anomalies and congenital heart defects having the longest stays. Conclusions: Children with congenital anomalies were more frequently hospitalised and median length of stay was longer. The outlook improves after the first year. Parents of children with congenital anomalies should be informed about the increased hospitalisations required for their child's care and the impact on family life and siblings, and they should be adequately supported. [ABSTRACT FROM AUTHOR]

Background: People who were born prematurely have high risks of many individual diseases and conditions in the early part of the life course. However, our knowledge of the burden of multiple diseases (multimorbidity) among prematurely born individuals is limited. We aimed to investigate the risk and patterns of chronic disease multimorbidity in adolescence and early adulthood among individuals born across the spectrum of gestational ages, comparing preterm and full-term born individuals. Methods and findings: We used individual-level data from linked nationwide registers to examine the associations of gestational age at birth with specialised healthcare records of ≥2 chronic diseases (multimorbidity) in adolescence (age 10–17 years) and early adulthood (age 18–30 years). Our study population comprised 951,116 individuals (50.2% females) born alive in Finland between 1st January 1987 and 31st December 2006, inclusive. All individuals were followed from age 10 years to the onset of multimorbidity, emigration, death, or 31 December 2016 (up to age 30 years). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for multimorbidity using flexible parametric survival models. During 6,417,903 person-years at risk (median follow-up: 7.9 years), 11,919 individuals (1.3%) had multimorbidity in adolescence (18.6 per 10,000 person-years). During 3,967,419 person-years at risk (median follow-up: 6.2 years), 15,664 individuals (1.7%) had multimorbidity in early adulthood (39.5 per 10,000 person-years). Adjusted HRs for adolescent multimorbidity, comparing preterm to full-term born individuals, were 1.29 (95% CI: 1.22 to 1.36) and 1.26 (95% CI: 1.18 to 1.35) in females and males, respectively. The associations of preterm birth with early adult multimorbidity were less marked, with the adjusted HRs indicating 1.18-fold risk in females (95% CI: 1.12 to 1.24) and 1.10-fold risk in males (95% CI: 1.04 to 1.17). We observed a consistent dose-response relationship between earlier gestational age at birth and increasing risks of both multimorbidity outcomes. Compared to full-term born males, those born at 37–38 weeks (early term) had a 1.06-fold risk of multimorbidity in adolescence (95% CI: 0.98 to 1.14) and this risk increased in a graded manner up to 6.85-fold (95% CI: 5.39 to 8.71) in those born at 23–27 weeks (extremely premature), independently of covariates. Among females, the same risks ranged from 1.16-fold (95% CI: 1.09 to 1.23) among those born at 37–38 weeks to 5.65-fold (95% CI: 4.45 to 7.18) among those born at 23–27 weeks. The corresponding risks of early adult multimorbidity were similar in direction but less marked in magnitude, with little difference in risks between males and females born at 36–37 weeks but up to 3-fold risks observed among those born at 23–27 weeks. Conclusions: Our findings indicate that an earlier gestational age at birth is associated with increased risks of chronic disease multimorbidity in the early part of the life course. There are currently no clinical guidelines for follow-up of prematurely born individuals beyond childhood, but these observations suggest that information on gestational age would be a useful characteristic to include in a medical history when assessing the risk of multiple chronic diseases in adolescent and young adult patients. [ABSTRACT FROM AUTHOR]

Background: Most evidence for interpregnancy interval (IPI) and adverse birth outcomes come from studies that are prone to incomplete control for confounders that vary between women. Comparing pregnancies to the same women can address this issue. Methods: We conducted an international longitudinal cohort study of 5,521,211 births to 3,849,193 women from Australia (1980–2016), Finland (1987–2017), Norway (1980–2016) and the United States (California) (1991–2012). IPI was calculated based on the time difference between two dates—the date of birth of the first pregnancy and the date of conception of the next (index) pregnancy. We estimated associations between IPI and preterm birth (PTB), spontaneous PTB, and small-for-gestational age births (SGA) using logistic regression (between-women analyses). We also used conditional logistic regression comparing IPIs and birth outcomes in the same women (within-women analyses). Random effects meta-analysis was used to calculate pooled adjusted odds ratios (aOR). Results: Compared to an IPI of 18–23 months, there was insufficient evidence for an association between IPI <6 months and overall PTB (aOR 1.08, 95% CI 0.99–1.18) and SGA (aOR 0.99, 95% CI 0.81–1.19), but increased odds of spontaneous PTB (aOR 1.38, 95% CI 1.21–1.57) in the within-women analysis. We observed elevated odds of all birth outcomes associated with IPI ≥60 months. In comparison, between-women analyses showed elevated odds of adverse birth outcomes for <12 month and >24 month IPIs. Conclusions: We found consistently elevated odds of adverse birth outcomes following long IPIs. IPI shorter than 6 months were associated with elevated risk of spontaneous PTB, but there was insufficient evidence for increased risk of other adverse birth outcomes. Current recommendations of waiting at least 24 months to conceive after a previous pregnancy, may be unnecessarily long in high-income countries. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is associated with increased risk of clear cell ovarian cancer and has even suggested being an etiological factor for this cancer. Association between endometriosis and extraovarian clear cell cancers is unclear. This study aimed to assess the association between surgically diagnosed endometriosis and risk of extraovarian clear cell cancers according to the type of endometriosis (i.e., ovarian, peritoneal, and other endometriosis) and the site of clear cell cancer. Methods: In this register-based historic cohort study we identified all women with surgically diagnosed endometriosis from the Finnish Hospital Discharge Registry 1987–2012. Data on extraovarian clear cell cancers of these women were obtained from the Finnish Cancer Registry. The follow-up started January 1st, 2007 or at endometriosis diagnosis (if later), and ended at emigration, death or on the December 31st, 2014. Standardized incidence ratios were calculated for each site of clear cell carcinoma (intestine, kidney, urinary tract, gynecological organs other than ovary), using the Finnish female population as reference. Results: The endometriosis cohort consisted of 48,996 women, including 22,745 women with ovarian and 19,809 women with peritoneal endometriosis. Altogether 23 extraovarian clear cell cancers were observed during 367,386 person-years of follow-up. The risk of extraovarian clear cell cancer was not increased among all women with surgically diagnosed endometriosis (standardized incidence ratio 0.89, 95% confidence interval 0.56–1.33) nor in different types of endometriosis. The incidence of clear cell cancer in any specific site was not increased either. Conclusions: The risk of extraovarian clear cell cancers in women with surgically diagnosed endometriosis is similar to that in the general population in Finland. [ABSTRACT FROM AUTHOR]

Background and aims: Compared to in-hospital births, the long-term outcome of children born out-of-hospital, planned or unplanned, is poorly studied. This study aimed to examine mortality and morbidity by seven years of age in children born out-of-hospital compared to those born in-hospital. Methods: This study was registered retrospectively and included 790 136 children born in Finland between 1996 and 2013. The study population was divided into three groups according to birth site: in-hospital (n = 788 622), planned out-of-hospital (n = 176), and unplanned out-of-hospital (n = 1338). Data regarding deaths, hospital visits, reimbursement of medical expenses, and disability allowances was collected up to seven years of age or by the year-end of 2018. The association between birth site and childhood morbidity was determined using multivariable-adjusted Cox hazard regression analysis. Results: No deaths were reported during the first seven years after birth in the children born out-of-hospital. The percentage of children with hospital visits due to infection by seven years of age was lower in those born planned out-of-hospital and in the combined planned out-of-hospital and unplanned out-of-hospital group compared to those born in-hospital. Furthermore, the percentage of children with hospital visits and who received disability allowances due to neurological or mental disorders was higher among those born unplanned out-of-hospital and out-of-hospital in total when compared to those born in-hospital. In the multivariable-adjusted Cox proportional hazard regression analysis, the hazard ratio for hospital visits due to asthma and/or allergic diseases (HR 0.84; 95% CI 0.72–0.98) was lower in children born out-of-hospital when compared to those born in-hospital. A similar decreased risk was found due to infections (HR 0.76; 95% CI 0.68–0.84). However, the risk for neurological or mental health disorders was similar between the children born in-hospital and out-of-hospital. Conclusions: Morbidity related to asthma or allergic diseases and infections by seven years of age appeared to be lower in children born out-of-hospital. Birth out-of-hospital seemed to not be associated with increased risk for neurological morbidity nor early childhood mortality. Our study groups were small and heterogeneous and because of this the results need to be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: Bereavement by spousal death and child death in adulthood has been shown to lead to an increased risk of mortality. Maternal death in infancy or parental death in early [...]

Background: To evaluate gestational age as a predictor of subsequent preterm birth. Materials and methods: This was a retrospective birth cohort study to evaluate gestational age as a predictor of subsequent preterm birth. Participants were mothers who gave birth to their first two children in Western Australia, 1980–2015 (N = 255,151 mothers). For each week of final gestational age of the first birth, we calculated relative risks (RR) and absolute risks (AR) of subsequent preterm birth defined as final gestational age before 28, 32, 34 and <37 weeks. Risks were unadjusted to preserve risk factor profiles at each week of gestation. Results: The relative risks of second birth before 28, 32, and 34 weeks' gestation were all approximately twenty times higher for mothers whose first birth had a gestational age of 22 to 30 weeks compared to those whose first birth was at 40 weeks' gestation. The absolute risks of second birth before 28, 32, and 34 weeks' gestation for these mothers had upper confidence limits that were all less than 16.74%. The absolute risk of second birth before 37 weeks was highest at 32.11% (95% CI: 30.27, 34.02) for mothers whose first birth was 22 to 30 weeks' gestation. For all gestational ages of the first child, the lowest quartile and median gestational age of the second birth were at least 36 weeks and at least 38 weeks, respectively. Sensitivity and positive predictive values were all below 35%. Conclusion: Relative risks of early subsequent birth increased markedly with decreasing gestational age of the first birth. However, absolute risks of clinically significant preterm birth (<28 weeks, <32 weeks, <34 weeks), sensitivity and positive predictive values remained low. Early gestational age is a strong risk factor but a poor predictor of subsequent preterm birth. [ABSTRACT FROM AUTHOR]

Introduction: The complex etiology of autism spectrum disorder (ASD) is still unresolved. Preterm birth (<37 weeks of gestation) and its complications are the leading cause of death of babies in the world, and those who survive often have long-term health problems. Length of gestation, including preterm birth, has been linked to ASD risk, but robust estimates for the whole range of gestational ages (GAs) are lacking. The primary objective of this study was to provide a detailed and robust description of ASD risk across the entire range of GAs while adjusting for sex and size for GA.Methods and Findings: Our study had a multinational cohort design, using population-based data from medical registries in three Nordic countries: Sweden, Finland, and Norway. GA was estimated in whole weeks based on ultrasound. Children were prospectively followed from birth for clinical diagnosis of ASD. Relative risk (RR) of ASD was estimated using log-binomial regression. Analyses were also stratified by sex and by size for GA. The study included 3,526,174 singletons born 1995 to 2015, including 50,816 (1.44%) individuals with ASD. In the whole cohort, 165,845 (4.7%) were born preterm. RR of ASD increased by GA, from 40 to 24 weeks and from 40 to 44 weeks of gestation. The RR of ASD in children born in weeks 22-31, 32-36, and 43-44 compared to weeks 37-42 were estimated at 2.31 (95% confidence interval [CI] 2.15-2.48; 1.67% vs 0.83%; p-value < 0.001), 1.35 (95% CI 1.30-1.40; 1.08% vs 0.83%; p-value < 0.001), and 1.37 (95% CI 1.21-1.54; 1.74% vs 0.83%; p-value < 0.001), respectively. The main limitation of this study is the lack of data on potential causes of pre- or postterm birth. Also, the possibility of residual confounding should be considered.Conclusion: In the current study, we observed that the RR of ASD increased weekly as the date of delivery diverged from 40 weeks, both pre- and postterm, independently of sex and size for GA. Given the unknown etiology of ASD and the lifelong consequences of the disorder, identifying groups of increased risk associated with a potentially modifiable risk factor is important.Author Summary: [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of changes in risk factors between the first two pregnancies on the occurrence of placental abruption (PA) in the same woman. Methods: Routinely collected obstetric data from Aberdeen Maternity and Neonatal Databank, the Maltese National Obstetric Information System and the Finnish Medical Birth Register were aggregated. Records of the first two singleton pregnancies from women who had PA in one pregnancy but not the other, were identified from this pooled dataset. A case-crossover study design was used; cases were pregnancies with abruption and matched controls were pregnancies without abruption in the same woman. Conditional logistic regression was used to investigate changes in risk factors for placental abruption in pregnancies with and without abruption. Results: A total of 2,991 women were included in the study. Of these 1,506 (50.4%) had PA in their first pregnancy and 1,485 (49.6%) in a second pregnancy. Pregnancies complicated by preeclampsia {194 (6.5%) versus 115 (3.8%) adj OR 1.69; (95% CI 1.23–2.33)}, antepartum haemorrhage of unknown origin {556 (18.6%) versus 69 (2.3%) adjOR 27.05; 95% CI 16.61–44.03)} and placenta praevia {80 (2.7%) versus 21 (0.7%) (adjOR 3.05; 95% CI 1.74–5.36)} were associated with PA. Compared to 20 to 25 years, maternal age of 35–39 years {365 (12.2) versus 323 (10.8) (adjOR 1.32; 95% CI 1.01–1.73) and single marital status (adjOR 1.36; 95% CI 1.04–1.76) were independently associated with PA. Maternal smoking, BMI and fetal gender were not associated with PA. Conclusion: Advanced maternal age, pregnancies complicated with unexplained bleeding in pregnancy, placenta praevia and preeclampsia were independently associated with a higher risk of placental abruption. [ABSTRACT FROM AUTHOR]

Objective: To assess the frequency and perinatal outcomes of gestational diabetes mellitus (GDM) defined by the criteria according to the International Association of Diabetes in Pregnancy Study Group (IADPSG) and the National Institute for Health and Care Excellence (NICE) diagnostic criteria for GDM. Design: A retrospective cohort study. Setting: Six secondary and tertiary delivery hospitals in Finland in 2009. Population: Pregnant women (N = 4,033) and their offspring. Methods: We used data on comprehensive screening of pregnant women with a 2-h 75-g oral glucose tolerance test (OGTT), performed between gestational weeks 24 and 40. OGTT glucose concentrations were used to identify women who fulfilled IADPSG and NICE criteria. While cut-offs according to Finnish national criteria partly overlapped with both criteria, a subgroup of IADPSG- or NICE-positive GDM women remained undiagnosed by Finnish criteria and hence non-treated. They were analysed as subgroups and compared to controls who were negative with all cut-offs. Main outcome measures: GDM prevalence, birth weight SD score (BWSDS), large for gestational age (LGA) and caesarean section (CS) rates. Results: Among the 4,033 women screened for GDM, 1,249 (31.0%) and 529 (13.1%) had GDM according to the IADPSG and NICE criteria, respectively. The LGA rate was similar in both groups. Regardless of the diagnostic criteria, women with GDM had a higher risk of induced delivery and CSs than controls. In IADPSG-positive non-treated women, offspring's BWSDS and CS rate were higher than in controls. Conclusions: GDM prevalence was 2.4-fold higher according to the IADPSG compared with the NICE criteria but the LGA rate did not differ. BWSDS and CS rate were increased already with mild untreated hyperglycaemia. [ABSTRACT FROM AUTHOR]

Objective: In this nationwide study we assessed the use and factors associated with future in vitro fertilization (IVF) treatment after induced abortion. Materials and methods: The study population was collected by means of record linkage between Finnish national registers. All women who underwent induced abortion between 2000 and 2009 in Finland were identified through the Register of Induced Abortions (n = 88 522). The study group consisted of women who underwent induced abortion and subsequently had an IVF treatment (n = 379); the comparison group were all women who had a spontaneous pregnancy and delivery 12–24 months after the index abortion (n = 7434). Demographic characteristics at the time of index abortion, and factors associated with the abortion (gestational age at abortion, indication and method of abortion, complications after abortion) were compared between the study groups. Logistic regression was used to assess whether some of the demographic characteristics or abortion associated factors increased the use of IVF treatment in the future. Results: The proportion of women with IVF treatment after induced abortion in the whole cohort was 0.4%. Women needing IVF treatment were older, of a higher socioeconomic status, and had fewer previous induced abortions and deliveries compared to women in the comparison group. No statistically significant differences were observed in the gestational age (≤ 12 weeks or >12 weeks of gestation) at abortion, method or complications of abortion. In multivariable analysis higher age increased, and history of previous deliveries or one or two abortions decreased the use of IVF. Conclusions: Infertility necessitating the use of IVF treatment after induced abortion is uncommon. The factors associated with use of IVF after abortion are those generally recognized as risk factors of infertility. Abortion-related outcomes are not associated with an increased need of future IVF-treatment. [ABSTRACT FROM AUTHOR]

Aims: Gestational diabetes (GDM) is often accompanied by maternal overweight. Our aim was to evaluate the separate and concomitant effects of GDM and maternal overweight/obesity on perinatal outcomes. Methods: We used the Finnish Medical Birth Register to identify all 24,577 women with a singleton pregnancy who delivered in 2009 in Finland and underwent an oral glucose tolerance test (OGTT). Women were divided into groups according to the result of OGTT (GDM/no GDM) and pre-pregnancy body mass index (BMI): normal weight (≤24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30.0 kg/m2). Primary outcomes included macrosomia, caesarean delivery, and treatment at neonatal ward. Normal weight women without GDM constituted the reference group. Results: Compared to reference group, overweight or obese women without GDM had an increased risk of macrosomia [odds ratio adjusted for age, parity, smoking and socio-economic status (aOR)1.18 (95% CI 1.09–1.28) and 1.50 (95% CI 1.19–1.88)], and caesarean delivery [aORs 1.17 (95% CI 1.07–1.28) and 1.52 (95% CI 1.37–1.69)], respectively. In normal weight GDM women the risk of macrosomia [aOR 1.17 (95% CI 0.85–1.62)] and caesarean delivery [aOR 1.10 (95% CI 0.96–1.27)] was not significantly increased as compared to normal weight women without GDM. GDM increased the risk of treatment at neonatal ward in all BMI categories and maternal obesity without GDM was also a risk factor for treatment at neonatal ward. Interaction p values between BMI and GDM on these outcomes were <0.001. Conclusions: Maternal overweight and obesity without GDM increased the risk of macrosomia and caesarean delivery when compared to the reference group. These risks were amplified when overweight/obesity was accompanied by GDM. Obesity without GDM was a risk factor for treatment at neonatal ward; GDM increased this risk in all BMI categories. Our results suggest that especially maternal obesity should be considered as a risk factor for adverse pregnancy outcomes and GDM further amplifies this risk. [ABSTRACT FROM AUTHOR]

Background: Asthma is the most common chronic disease during pregnancy and it may have influence on pregnancy outcome. Objectives: Our goal was to assess the association between maternal asthma and the perinatal risks as well as possible effects of asthma medication. Methods: The study was based on a nationwide Finnish register-based cohort between the years 1996 and 2012 in the Drug and Pregnancy Database. The register data comprised 962 405 singleton live and stillbirths, 898 333 (93.3%) pregnancies in mothers with neither confirmed asthma nor use of asthma medication (controls), and 26 674 (2.8%) pregnancies with confirmed maternal asthma. 71% of mothers with asthma used asthma medication. The diagnosis of asthma was based on the mothers’ right for subsidised medication which is carefully evaluated by strict criteria including pulmonary function testing. Odds ratio was used in comparison. Premature birth (PB), low birth weight, small for gestational age (SGA), neonatal death were the main outcome measures. Results: Maternal asthma was associated with adjusted odds ratios (aORs) for perinatal mortality 1.24 (95% CI 1.05 to 1.46), preterm birth 1.18 (1.11 to 1.25), low birth weight 1.29 (1.21 to 1.37), fetal growth restriction (SGA) 1.32, (1.24 to 1.40), and asphyxia 1.09 (1.02 to 1.17). Asthma treatment reduced the increased risk of preterm birth aOR 0.85 (95% CI 0.76 to 0.96) but mothers with treated asthma had higher risks of fetal growth restriction (SGA) aOR 1.26 (1.10 to 1.45), and asphyxia aOR 1.37 (1.17 to 1.61) than mothers with untreated asthma. Conclusion: Asthma is associated with increased risks of perinatal mortality, preterm birth, low birth weight, fetal growth restriction (SGA), and asphyxia. Asthma treatment reduces the risk of preterm delivery, but it does not seem to reduce other complications such as perinatal mortality. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Several studies on pregnancy-associated cancers have suggested an association with congenital anomalies in offspring. Previous studies have included maternal cancers diagnosed up to 2 years after pregnancy; however, long latency periods of some cancers mean that cancers diagnosed many years postpartum might have been present during pregnancy in a preclinical state. This paper considers the association between maternal cancers diagnosed from 2 years prior to pregnancy until the mother reaches 50 years of age, and congenital anomalies, as diagnosed at birth or within the first year of life. The current population-based study looks at associations of cancers in mothers with congenital anomalies in their children. Children were followed up from birth to diagnosis of a congenital anomaly, death, emigration or end of follow-up (whichever occurred first). A total of 56,016 children (2.6%) were considered exposed to a maternal cancer of any type; and they had a hazard ratio (HR) of 1.04 (95% confidence interval [CI]: 1.00, 1.09) compared with unexposed children. The greatest HR was seen among children whose mothers had been diagnosed with cancers before or during pregnancy (HR: 1.37, 95% CI: 1.07, 1.75). Similar results were seen when paternal cancers were used as a ‘negative control’. Statistically significant associations were seen for some specific congenital anomalies of organ systems (congenital anomalies of the musculoskeletal system [HR: 1.13, 95% CI: 1.02, 1.25]) and for some specific types of maternal cancer (leukaemia [HR: 1.31, 95% CI: 1.01, 1.61], The results of the main analyses suggest a small increase in risk of congenital anomalies in offspring of mothers diagnosed with cancer from 2 years before pregnancy, until the mother reaches 50 years of age; with the greatest increase seen for exposure in the pre-pregnancy and pregnancy period. These results may reflect shared causes for some cancers and some congenital anomalies. The similar results seen for paternal cancers indicate that the cause may be genetic or related to the families’ social and environmental conditions. [ABSTRACT FROM AUTHOR]

Background: In spite of the well-known harmful effects on the fetus, many women continue smoking during pregnancy. Smoking as an important source of toxic chemicals may contribute to the developmental origin of diseases. Objectives: The aim of this work was to pursue the possible association between maternal smoking and cancer in early life. Specifically, we wanted to identify the associated early life cancer types, and to quantify the associations. Methods: In a systematic literature search 825 articles were identified in PubMed and Web of Science, and 55 more through the reference lists. Of these 62 fulfilled the criteria for inclusion in meta-analyses. Using Mantel-Haenszel or DerSimonian and Laird method, depending on heterogeneity of the studies, pooled estimates and 95% confidence intervals for eight cancer types were calculated. Results: Smoking during pregnancy was associated with an increased risk for for brain and central nervous system tumors (OR = 1.09; 95% CI = 1.02–1.17). Although the risk for lymphoma was also associated (OR = 1.21; 95% CI = 1.05–1.34), it did not hold up in subgroup analyses. Leukemia was not found to be associated with maternal smoking. Five other cancer types (bone, soft tissue, renal, hepatic, and germ cell cancer) were also examined, but the number of studies was too limited to exclude the possibility of maternal smoking as a risk factor for cancer in offspring. Conclusions: According to our meta-analyses, maternal smoking is associated with nervous system cancers, but not with leukemia in early life. Confirming or rejecting associations of maternal smoking with lymphoma and the five other cancer types requires further studies. [ABSTRACT FROM AUTHOR]

Objective: Infants from multiple pregnancies have higher rates of preterm birth, stillbirth and neonatal death and differences in multiple birth rates (MBR) exist between countries. We aimed to describe differences in MBR in Europe and to investigate the impact of these differences on adverse perinatal outcomes at a population level. Methods: We used national aggregate birth data on multiple pregnancies, maternal age, gestational age (GA), stillbirth and neonatal death collected in the Euro-Peristat project (29 countries in 2010, N = 5 074 643 births). We also used European Society of Human Reproduction and Embryology (ESHRE) data on assisted conception and single embryo transfer (SET). The impact of MBR on outcomes was studied using meta-analysis techniques with random-effects models to derive pooled risk ratios (pRR) overall and for four groups of country defined by their MBR. We computed population attributable risks (PAR) for these groups. Results: In 2010, the average MBR was 16.8 per 1000 women giving birth, ranging from 9.1 (Romania) to 26.5 (Cyprus). Compared to singletons, multiples had a nine-fold increased risk (pRR 9.4, 95% Cl 9.1–9.8) of preterm birth (<37 weeks GA), an almost 12-fold increased risk (pRR 11.7, 95% CI 11.0–12.4) of very preterm birth (<32 weeks GA). Pooled RR were 2.4 (95% Cl 1.5–3.6) for fetal mortality at or after 28 weeks GA and 7.0 (95% Cl 6.1–8.0) for neonatal mortality. PAR of neonatal death and very preterm birth were higher in countries with high MBR compared to low MBR (17.1% (95% CI 13.8–20.2) versus 9.8% (95% Cl 9.6–11.0) for neonatal death and 29.6% (96% CI 28.5–30.6) versus 17.5% (95% CI 15.7–18.3) for very preterm births, respectively). Conclusions: Wide variations in MBR and their impact on population outcomes imply that efforts by countries to reduce MBR could improve perinatal outcomes, enabling better long-term child health. [ABSTRACT FROM AUTHOR]

Background: Mortality in children under five years has been widely studied, whereas mortality at 5–9 years has received little attention. Using unique data from national registers in three Nordic countries, we aimed to characterize mortality directionality in children aged 0 to 9 years. Methods and Findings: The cohort study included all children born in Denmark from 1973 to 2008 (n = 2,433,758), Sweden from 1973 to 2006 (n = 3,400,212), and a random sample of 89.3% of children born in Finland from 1987 to 2007 (n = 1,272,083). Children were followed from 0 to 9 years, and cumulative mortality and mortality rates were compared by age, gender, cause of death, and calendar periods. Among the 7,105,962 children, there were 48,299 deaths during study period. From 1981–1985 to 2001–2005, all-cause mortality rates were reduced by between 34% and 62% at different ages. Overall mortality rate ratio between boys and girls decreased from 1.25 to 1.21 with the most prominent reduction in children aged 5–9 years (from 1.59 to 1.19). Neoplasms, diseases of the nervous system and transport accidents were the most frequent cause of death after the first year of life. These three leading causes of death declined by 42% (from 6.2 to 3.6 per 100,000 person years), 43% (from 3.7 to 2.1) and 62% (from 3.9 to 1.5) in boys, and 25% (from 4.1 to 3.1 per 100000 person years), 42% (from 3.4 to 1.9) and 63% (from 3.0 to 1.1) in girls, respectively. Mortality from neoplasms was the highest in each age except infants when comparing cause-specific mortality, and half of deaths from diseases of the nervous system occurred in infancy. Mortality rate due to transport accidents increased with age and was highest in boys aged 5–9 years. Conclusions: Mortality rate in children aged 0–9 years has been decreasing with diminished difference between genders over the past decades. Our results suggest the importance of further research on mortality by causes of neoplasms, and causes of transport accidents—especially in children aged 5–9 years. [ABSTRACT FROM AUTHOR]

Background: Although rare, placental abruption is implicated in disproportionately high rates of perinatal morbidity and mortality. Understanding geographic and temporal variations may provide insights into possible amenable factors of abruption. We examined abruption frequencies by maternal age, delivery year, and maternal birth cohorts over three decades across seven countries. Methods: Women that delivered in the US (n = 863,879; 1979–10), Canada (4 provinces, n = 5,407,463; 1982–11), Sweden (n = 3,266,742; 1978–10), Denmark (n = 1,773,895; 1978–08), Norway (n = 1,780,271, 1978–09), Finland (n = 1,411,867; 1987–10), and Spain (n = 6,151,508; 1999–12) were analyzed. Abruption diagnosis was based on ICD coding. Rates were modeled using Poisson regression within the framework of an age-period-cohort analysis, and multi-level models to examine the contribution of smoking in four countries. Results: Abruption rates varied across the seven countries (3–10 per 1000), Maternal age showed a consistent J-shaped pattern with increased rates at the extremes of the age distribution. In comparison to births in 2000, births after 2000 in European countries had lower abruption rates; in the US there was an increase in rate up to 2000 and a plateau thereafter. No birth cohort effects were evident. Changes in smoking prevalence partially explained the period effect in the US (P = 0.01) and Sweden (P<0.01). Conclusions: There is a strong maternal age effect on abruption. While the abruption rate has plateaued since 2000 in the US, all other countries show declining rates. These findings suggest considerable variation in abruption frequencies across countries; differences in the distribution of risk factors, especially smoking, may help guide policy to reduce abruption rates. [ABSTRACT FROM AUTHOR]

A diet with restricted energy content reduces the occurrence of cancer in animal experiments. It is not known if the underlying mechanism also exists in human beings. To determine whether cancer incidence is reduced among patients with anorexia nervosa who tend to have a low intake of energy, we carried out a retrospective cohort study of 22 654 women and 1678 men diagnosed with anorexia nervosa at ages 10-50 years during 1968-2010 according to National Hospital Registers in Sweden, Denmark and Finland. The comparison group consisted of randomly selected persons from population registers who were similar to the anorexia nervosa patients in respect to sex, year of birth and place of residence. Patients and population comparisons were followed for cancer by linkage to Cancer Registries. Incidence rate ratios (IRR) were estimated using Poisson models. In total, 366 cases of cancer (excluding non-melanoma skin cancer) were seen among women with anorexia nervosa, and the IRR for all cancer sites was 0.97 (95% CI = 0.87-1.08) adjusted for age, parity and age at first child. There were 76 breast cancers corresponding to an adjusted IRR of 0.61 (95% CI = 0.49-0.77). Significantly increased IRRs were observed for esophageal, lung, and liver cancer. Among men with anorexia nervosa, there were 23 cases of cancer (age-adjusted IRR = 1.08; 95% CI = 0.71-1.66). There seems to be no general reduction in cancer occurrence among patients with anorexia nervosa, giving little support to the energy restriction hypothesis. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the independent association of episiotomy with obstetric anal sphincter injuries (OASIS) using first a cross-sectional and then a matched pair analysis. Design: A matched cohort. Setting: Data was gathered from the Finnish Medical Birth Register from 2004–2011. Population: All singleton vaginal births (n = 303,758). Methods: Women resulting matched pairs (n = 63,925) were matched based on baseline risk of OASIS defined based on parity (first or second/subsequent vaginal births), age, birth weight, mode of delivery, prior caesarean section, and length of active second stage of birth. Results: In cross-sectional analysis episiotomy was associated with a 12% lower incidence of OASIS (adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.80 to 0.98) in first vaginal births and with a 132% increased incidence of OASIS in second or subsequent vaginal births (aOR 2.32, 95% CI 1.77 to 3.03). In matched pair analysis episiotomy was associated with a 23% (aOR 0.77, 95% CI 0.69 to 0.86) lower incidence of OASIS in first vaginal births and a 61% (aOR 1.61, 95% CI 1.14 to 2.29) increased incidence of OASIS in second or subsequent vaginal births compared to women who gave birth without an episiotomy. The matched pair analysis showed a 12.5% and a 31.6% reduction in aORs of OASIS associated with episiotomy, respectively. Conclusions: A matched pair analysis showed a substantial reduction in the aORs of OASIS with episiotomy, due to confounding by indication. This indicates that results of observational studies evaluating an association between episiotomy and OASIS should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Objective: Research suggests autoimmune processes to be involved in psychiatric disorders. We aimed to address the prevalence and incidence of autoimmune diseases in a large Finnish patient cohort with anorexia nervosa, bulimia nervosa, and binge eating disorder. Methods: Patients (N = 2342) treated at the Eating Disorder Unit of Helsinki University Central Hospital between 1995 and 2010 were compared with general population controls (N = 9368) matched for age, sex, and place of residence. Data of 30 autoimmune diseases from the Hospital Discharge Register from 1969 to 2010 were analyzed using conditional and Poisson regression models. Results: Of patients, 8.9% vs. 5.4% of control individuals had been diagnosed with one or more autoimmune disease (OR 1.7, 95% CI 1.5–2.0, P<0.001). The increase in endocrinological diseases (OR 2.4, 95% CI 1.8–3.2, P<0.001) was explained by type 1 diabetes, whereas Crohn's disease contributed most to the risk of gastroenterological diseases (OR 1.8, 95% CI 1.4–2.5, P<0.001). Higher prevalence of autoimmune diseases among patients with eating disorders was not exclusively due to endocrinological and gastroenterological diseases; when the two categories were excluded, the increase in prevalence was seen in the patients both before the onset of the eating disorder treatment (OR 1.5, 95% CI 1.1–2.1, P = 0.02) and at the end of the follow-up (OR 1.4, 95% CI 1.1–1.8, P = 0.01). Conclusions: We observed an association between eating disorders and several autoimmune diseases with different genetic backgrounds. Our findings support the link between immune-mediated mechanisms and development of eating disorders. Future studies are needed to further explore the risk of autoimmune diseases and immunological mechanisms in individuals with eating disorders and their family members. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 nonsmokers, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]