Publications by authors named "Mika Gissler"

653 Publications

Visual impairment due to age-related macular degeneration during 40 years in Finland and the impact of novel therapies.

Acta Ophthalmol 2022 Aug 1. Epub 2022 Aug 1.

SILK, Department of Ophthalmology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Purpose: To evaluate the changes in visual impairment (VI) due to age-related macular degeneration (AMD) during the past 40 years and the impact of novel therapies at population level.

Methods: In this nationwide register-based study, we assessed the incidence, prevalence, severity, and onset age of VI due to AMD based on the Finnish Register of Visual Impairment data from 1980 to 2019. Our data included 30 016 visually impaired persons with AMD as the main diagnosis for VI. The number of persons treated with intravitreal injections in Finland was obtained from hospital data kept by the Finnish Institute for Health and Welfare.

Results: Between the 1980s and the 2010s, the incidence of reported VI doubled; however, this increase has stagnated in the 2010s. Since 2012, the prevalence of reported VI has decreased. The number of patients treated with intravitreal injections showed a 40-fold increase during 2005-2019. The severity of reported VI has decreased whereas the mean age at the onset of reported VI has increased during the 40 years. The age-adjusted incidence and prevalence of reported VI were significantly higher in females in comparison to males in all decades.

Conclusion: Increase in the incidence and prevalence of VI due to AMD in the past decades has stagnated and shifted to older age in the 2010s when therapies for exudative class became commonly available. Furthermore, the prognosis of VI has improved during the past 40 years. These positive trends are likely contributable to improved diagnostic tools, earlier diagnoses, and new therapy options.
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http://dx.doi.org/10.1111/aos.15224DOI Listing
August 2022

Preconception Mental Health, Socioeconomic Status, and Pregnancy Outcomes in Primiparous Women.

Front Public Health 2022 13;10:880339. Epub 2022 Jul 13.

Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: One in four women of childbearing age has some degree of mental disorders and are, therefore, prone to both pregnancy complications and adverse health outcomes in their offspring. We aimed to evaluate the impact of preconception severe mental disorders on pregnancy outcomes in primiparous women.

Methods: The study cohort was composed of 6,189 Finnish primiparous women without previously diagnosed diabetes, who delivered between 2009 and 2015, living in the city of Vantaa, Finland. Women were classified to have a preconception severe mental disorder if they had one or more outpatient visits to a psychiatrist or hospitalization with a psychiatric diagnosis 1 year before conception. Data on pregnancies, diagnoses, and pregnancy outcomes were obtained from national registers at an individual level.

Results: Primiparous women with preconception severe psychiatric diagnosis were younger, more often living alone, smokers, and had lower educational attainment and lower taxable income than women without psychiatric diagnosis (for all < 0.001). Of all women, 3.4% had at least one psychiatric diagnosis. The most common psychiatric diagnoses were depression and anxiety disorders. The most common comorbidity was the combination of depression and anxiety disorders. There were no differences in the need for respiratory treatments, admissions to the neonatal intensive care unit, or antibiotic treatments between the offspring's groups.

Conclusion: Although primiparous women had severe mental disorders, the well-being of newborns was good. The most common severe mental health disorders were depression and anxiety disorders, and psychiatric comorbidity was common. Women with severe mental disorders more often belonged to lower socioeconomic groups.
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http://dx.doi.org/10.3389/fpubh.2022.880339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326245PMC
July 2022

School Performance and Later Diagnoses of Non-Affective Psychoses, Bipolar Disorder and Depression.

Acta Psychiatr Scand 2022 Jul 25. Epub 2022 Jul 25.

Finnish Institute of Health and Welfare, Helsinki, Finland.

Objective: It is unclear whether there are differences between specific school subject performance and later psychiatric disorders. We examined whether mean grade point average (MGPA) and specific school subjects associated with diagnoses of non-affective psychoses, bipolar disorder and depression.

Methods: In this register-based study, we studied the Finnish population born in 1987 who had available MGPA and compulsory specific school grades (age = 15.4-16.4 years; n = 50,508). Grades were analyzed with smoothing splines. Covariates included sex, urbanicity, parental education level and parental diagnosed psychiatric disorders. Outcomes were incident non-affective psychosis, bipolar disorder and depression diagnosed in specialised services until year 2015 (age = 28.0-28.9 years).

Results: During the follow-up, 727 individuals were diagnosed with non-affective psychoses, 489 with bipolar disorder and 3492 with depression. MGPA was inversely associated with all outcomes. In multivariate models including specific school subjects and covariates, the school subject with largest risk ratios (RR) was Physical Education (RR and Bonferroni-corrected confidence interval [CI] at -1.5 SD: non-affective psychoses 1.63, 1.36-1.95; bipolar disorder 1.64, 1.30-2.05; depression 1.72, 1.53-1.93). Higher grades in Art were associated with non-affective psychoses and depression (RR and Bonferroni-corrected CI at +1.5 SD: non-affective psychoses 1.48, 1.11-1.96; depression 1.22, 1.07-1.38).

Conclusion: There was a robust association between poorer scores on Physical Education and risk for psychosis, bipolar disorder and depression. Higher grades in Art were also associated with risk for later disorders. Subject specific school performance may be more informative about mental disorder risk than overall school performance.
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http://dx.doi.org/10.1111/acps.13481DOI Listing
July 2022

Use of benzodiazepine and related drugs in migrants and Finnish-born persons: a nationwide register-based study.

Scand J Public Health 2022 Jul 25:14034948221112470. Epub 2022 Jul 25.

Finnish Institute for Health and Welfare, Equality Unit, Finland.

Aims: Benzodiazepines and related drugs (BZDR) are often used longer than generally recommended. The aim is to study patterns of use among migrant and Finnish-born users of BZDR, and to identify factors that are associated with long-term use and BZDR polytherapy.

Methods: This register-based study includes a nationwide sample of migrants (=8729) and their Finnish-born controls (=11 388) who had purchased BZDR in 2011-2014, but not in 2009-2010. Information on drug purchases was obtained from the National Prescription Register and the duration of drug use was estimated using PRE2DUP method. The main outcomes were long-term use of BZDR, polytherapy and time until discontinuation of BZDR use. Sociodemographic variables and information on preceding psychiatric diagnoses were included as covariates. Logistic and Cox regression analyses were the statistical methods used.

Results: Only migrants from Sub-Saharan Africa were more likely to discontinue the medication once initiated than Finnish-born users. Migrants were significantly less likely to be long-term users (adjusted odds ratio 0.79, 95% CI 0.70-0.89) or polytherapy users (aOR 0.90, 95% CI 0.84-0.97) of BZDR compared with Finnish-born participants.

Conclusions: Migrants had less long-term and concomitant use of several BZDR than Finnish-born participants. The pattern of use is more optimal among migrants, but it may also reflect poorer access to mental health treatment.
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http://dx.doi.org/10.1177/14034948221112470DOI Listing
July 2022

Hospital length of stay among children with and without congenital anomalies across 11 European regions-A population-based data linkage study.

PLoS One 2022 22;17(7):e0269874. Epub 2022 Jul 22.

Department of Paediatrics and Adolescent Medicine, Lillebaelt Hospital, University Hospital of Southern Denmark, Kolding, Denmark.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0269874PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307180PMC
July 2022

Changes in Visual Impairment due to Diabetic Retinopathy During 1980-2019 Based on Nationwide Register Data.

Diabetes Care 2022 Jul 15. Epub 2022 Jul 15.

SILK, Department of Ophthalmology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Objective: To evaluate changes in the incidence, prevalence, severity, and onset age of visual impairment (VI) due to diabetic retinopathy (DR) and compare these trends in the screening and treatment of diabetes during 40 years based on Finnish national register data.

Research Design And Methods: We included people with VI with nonproliferative DR (NPDR; n = 2,490, 73% women) or proliferative DR (PDR; n = 2,026, 53% women) as the main diagnosis for VI during 1980-2019 in the Finnish Register of Visual Impairment. The number of treated patients with diabetes during 1986-2019 was obtained from the Social Insurance Institution of Finland registers based on reimbursed medication data.

Results: The annual incidence of reported VI due to DR has decreased since it peaked in the 1990s: regarding NPDR, it decreased from 102.3 to 5.5 per 100,000 treated patients with diabetes between the 1990s and 2010s; regarding PDR, the respective change was from 39.9 to 7.4. The incidence of patients with diabetes treated for DR increased during this period. Annual prevalence of reported VI and differences between sexes steadily decreased in the 2000s and 2010s. The severity of reported VI has decreased, and the age at the onset of reported VI increased during the 40 years.

Conclusions: Prevalence and incidence of VI due to DR have dramatically decreased and shifted to older age during the 40 years despite the increasing prevalence of diabetes. These positive trends highlight the successful development and effectiveness of screening and therapies for diabetes and DR.
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http://dx.doi.org/10.2337/dc21-2369DOI Listing
July 2022

The effect of birth order on length of hospitalization for pediatric traumatic brain injury: an analysis of the 1987 Finnish birth cohort.

Arch Public Health 2022 Jul 11;80(1):167. Epub 2022 Jul 11.

Heidelberg Institute of Global Health (HIGH), University of Heidelberg, Im Neuenheimer Feld 130/3, 69120, Heidelberg, Germany.

Purpose: This study examines the relationship between birth order and length of hospitalization due to pediatric traumatic brain injury (TBI).

Methods: We prospectively followed 59,469 Finnish newborns from 1987 until age 18 years. Data on first diagnosis of TBI was recorded within the 1987 Finnish Birth Cohort (FBC). Hospitalization period was divided into two categories: 2 days or less and more than 2 days. The latter was considered in this study as longer hospitalization.

Results: Compared with first born siblings, later born siblings had an increased risk of a longer hospitalization for TBI (12.7% of fourth or higher born birth children diagnosed with TBI were hospitalized for 2 or more days, 11.3% of first born, 10.4% of third born and 9.0% of second born). Fourth or higher born children were more likely to experience a repeat TBI; 13.4% of fourth or higher born children diagnosed with TBI had 2-3 TBIs during the study period compared to 9% of third born, 7.8% of second born and 8.8% of the first born. Injuries in the traffic environment and falls were the most common contributors to pediatric TBI and occurred most frequently in the fourth or higher birth category; 29.3% of TBIs among fourth or higher birth order were due to transport accidents and 21% were due to falls.

Conclusions: This study revealed a significant increase in risk for longer hospitalization due to TBI among later born children within the same sibling group. The study provides epidemiological evidence on birth order as it relates to TBI, and its potential to help to explain some of the statistical variability in pediatric TBI hospitalization over time in this population.
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http://dx.doi.org/10.1186/s13690-022-00919-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275049PMC
July 2022

Surgically confirmed endometriosis in adolescents in Finland-A register-based cross-sectional cohort study.

Acta Obstet Gynecol Scand 2022 Jul 12. Epub 2022 Jul 12.

Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Introduction: Increasing awareness of endometriosis in adolescents requires data on the nature of the disease and its management. Our objective was to investigate the subtypes of surgically confirmed endometriosis in adolescents (aged <20 years) and trends in the incidence rates and endometriosis-related procedures during the study period, 1987-2012.

Material And Methods: In this register-based cohort study, we identified 526 adolescents receiving their initial surgical diagnosis of endometriosis between 1987 and 2012 from the Finnish Hospital Discharge Register. The age-specific incidence rate of surgically confirmed endometriosis was calculated by dividing the number of adolescents during specific periods by person-years. We calculated the relative differences in incidence rates between the periods using crude incidence ratios.

Results: Adolescents were divided into three age groups, <17, 17-18, and 19 years, which comprised 8.2% (43/526), 39.7% (209/526), and 52.1% (274/526) of the study cohort, respectively. Peritoneal endometriosis and ovarian endometriosis were the most common types (379/526 [72%] and 119/526 [23%], respectively). The incidence rate of surgically confirmed endometriosis per 100 000 person-years varied from 5.63 (95% confidence interval [CI] 4.24-7.33) to 11.42 (95% CI 9.64-13.44). The incidence rate in 2001-2005 was significantly higher and was 1.6- to 2.0-fold that of the periods 1987-1990 and 2006-2012, respectively. Comparing the periods in which International Classification of Diseases, Ninth Revision (ICD-9; 1987-1995) and Tenth Revision (ICD-10; 1996-2012) codes were used, the use of laparoscopy (78.2% vs 88.9%), day surgery (10.3% vs 31.6%), and procedures for ovarian (18.8% vs 34.1%) and deep (0.6% vs 10.8%) endometriosis increased. The types of endometriosis and procedures did not differ between the age groups.

Conclusions: Peritoneal endometriosis was the most common type of endometriosis overall and by age group. During the 26-year period, the incidence rate of initial surgical diagnosis of endometriosis peaked in 2001-2005 and decreased thereafter. The proportion of procedures performed for ovarian and deep endometriosis increased, as did the use of laparoscopy and day surgery.
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http://dx.doi.org/10.1111/aogs.14419DOI Listing
July 2022

Breaking the myth: the association between the increasing incidence of labour induction and the rate of caesarean delivery in Finland - a nationwide Medical Birth Register study.

BMJ Open 2022 07 4;12(7):e060161. Epub 2022 Jul 4.

Obstetrics and Gynecology, Helsinki University hospital and University of Helsinki, Helsinki, Finland.

Objectives: To determine the association between the rate of labour induction and caesarean delivery.

Design: Medical Birth Register-based study. We used data from the nationwide Medical Birth Register collecting data on delivery outcomes on all births from 22+0 weeks and/or birth weight of at least 500 g.

Setting: Finland.

Participants: 663 024 live births in Finland from 2008 to 2019.

Main Outcome Measures: The rates of labour induction and caesarean delivery.

Results: The rate of labour induction increased from 17.8% to 30.3%; p<0.001, during the study. The total caesarean delivery rate was 16.5% (n=109 178). An increase of approximately 0.5% in the caesarean delivery rate occurred during the study period. The rate of caesarean delivery following labour induction slightly decreased (15.41% vs 15.35%; p<0.001). In multivariate logistic regression analysis, induction of labour was associated with a reduced risk for caesarean delivery (OR 0.72, 95% CI 0.71 to 0.74). The frequency of advanced maternal age (18.0% vs 23.5%; p<0.001), obesity (11.4% vs 15.1%; p<0.001) and gestational diabetes (9.8% vs 23.3%; p<0.001) increased during the study.

Conclusions: The 70% increase in the rate of labour induction in Finland has not led to a significant increase in the rate of caesarean delivery, which has remained one of the lowest in the world. Pregnant women in Finland are more frequently obese, older and diagnosed with gestational diabetes, which may partly explain the increase in the rate of labour induction.
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http://dx.doi.org/10.1136/bmjopen-2021-060161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255400PMC
July 2022

Indications for intensive care unit treatment among neonates born to mothers with thyroid disease: A population-based cohort study.

Acta Obstet Gynecol Scand 2022 Jul 1. Epub 2022 Jul 1.

Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu and University Hospital of Oulu, Oulu, Finland.

Introduction: Thyroid diseases in pregnancy are relatively common and are associated with adverse pregnancy and perinatal outcomes, increasing a neonate's risk of admission to the neonatal intensive care unit (NICU). The aim of this study was to evaluate the indications for increased risk of NICU admission among the neonates of hypothyroid and hyperthyroid mothers.

Material And Methods: The study data consisted of all singleton deliveries (n = 734 773) between 2004 and 2016 in Finland collected from the Finnish Medical Birth Register. The odds of NICU admission (with 95% confidence intervals) were compared between the neonates of hypothyroid or hyperthyroid mothers and of mothers without any thyroid diseases by specified neonatal characteristics and morbidities using logistic regression analysis. The studied neonatal characteristics were preterm birth (<37+0 gestational weeks), low birthweight (<2500 g), the rate of small- and large-for-gestational age infants, and eight disease-specific neonatal outcomes: asphyxia, respiratory distress syndrome, meconium aspiration syndrome, pneumothorax, cardiovascular problems, infections, jaundice and hypoglycemia.

Results: The most common indications for NICU care were principally the same in the neonates of the mothers with and without thyroid disease: respiratory distress syndrome, infections, preterm birth, low birthweight and neonatal hypoglycemia. The preterm neonates, neonates with low birthweight, and large-for-gestational-age infants had increased odds of NICU admission if their mother had hypothyroidism. Also neonates with cardiovascular problems, jaundice or hypoglycemia associated with maternal diabetes had increased odds of NICU admissions if their mother had hypothyroidism. Further, the preterm neonates, large-for-gestational-age infants, and term infants with jaundice had increased odds of NICU admission if their mother had hyperthyroidism.

Conclusions: The most common indications for NICU care were similar for the neonates of the mothers with and without thyroid disease. However, the neonates of the mothers with thyroid diseases were more likely to need NICU care. The neonates of the mothers with thyroid diseases had higher odds of NICU treatment in cases of preterm birth, large for gestational age, and hypoglycemia.
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http://dx.doi.org/10.1111/aogs.14413DOI Listing
July 2022

Autistic Adult Services Availability, Preferences, and User Experiences: Results From the Autism Spectrum Disorder in the European Union Survey.

Front Psychiatry 2022 10;13:919234. Epub 2022 Jun 10.

Departamento de Personalidad, Evaluación y Tratamiento Psicológicos Salamanca, Instituto Universitario de Integración en la Comunidad, University of Salamanca, Salamanca, Spain.

There is very little knowledge regarding autistic adult services, practices, and delivery. The study objective was to improve understanding of current services and practices for autistic adults and opportunities for improvement as part of the Autism Spectrum Disorder in the European Union (ASDEU) project. Separate survey versions were created for autistic adults, carers of autistic adults, and professionals in adult services. 2,009 persons responded to the survey and 1,085 (54%) of them completed at least one of the services sections: 469 autistic adults (65% female; 55% <35 years old), 441 carers of autistic adults (27% female; 6% <35 years old), 175 professionals in adult services (76% female; 67% in non-medical services). Top choices by autistic adults, carers or professionals for services best suiting their current needs were: residential services: "help in own home" (adults, carers of high independent adults, professionals), "fulltime residential facility" (carers of low independent adults); employment services: "job mentors" (adults, carers of high independent adults, professionals), "Sheltered employment" (carers of low independent adults); education services: "support in regular education setting" (all groups); financial services: financial support in lieu of employment ("Supplementary income for persons unable to have full employment" for adults, "full pension" for carers of low independent adults) or to supplement employment earnings for carers of high independent adults and professionals; social services: "behavior training" (adults) and "life skills training" (carers and professionals). Waiting times for specific services were generally < 1 month or 1-3 months, except for residential services which could be up to 6 months; most professionals were uninformed of waiting times (>50% responded "don't know"). Five of seven residential services features recommended for autistic adults were experienced by <50% of adults. The knowledge of good local services models that work well for autistic adults was generally low across all services areas. The variation in services experiences and perceptions reported by autistic adults, carers, or professionals underscore the need to query all groups for a complete picture of community services availability and needs. The results showed areas for potential improvement in autistic adult services delivery in the EU to achieve recommended standards.
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http://dx.doi.org/10.3389/fpsyt.2022.919234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226363PMC
June 2022

Maternal childbirth experience and induction of labour in each mode of delivery: a retrospective seven-year cohort study of 95,051 parturients in Finland.

BMC Pregnancy Childbirth 2022 Jun 23;22(1):508. Epub 2022 Jun 23.

University of Helsinki and Helsinki University Hospital, Obstetrics and Gynecology, Helsinki, Finland.

Background: Childbirth experience has been shown to depend on the mode of delivery. However, it is unclear how labour induction influences the childbirth experience in different modes of delivery. Thus, we assessed the childbirth experience among mothers with spontaneous and induced labours.

Design: A retrospective cohort study.

Setting: Childbirths in four delivery hospitals in Helsinki and Uusimaa District, Finland, in 2012-2018.

Sample: 95051 childbirths excluding elective caesarean sections.

Methods: Obstetric data combined to maternal childbirth experience measured by Visual Analogue Scale (VAS) was analysed with univariate linear modelling and group comparisons. The primiparas and multiparas were analysed separately throughout the study due to the different levels of VAS.

Main Outcome Measures: Maternal childbirth experience measured by VAS.

Results: The negative effect of labour induction on the childbirth experience was discovered in each mode of delivery. Operative deliveries were perceived more negatively when they were preceded by labour induction. The rate of poor childbirth experience (VAS≤5) was higher for mothers with labour induction (ORs varying from 1.43 to 1.77) except in emergency caesarean sections. The negative effect of labour induction was smaller than the effect of mode of delivery, while successful vaginal delivery with induction (mean=8.00 [95% CI 7.96-8.04], mean=8.50 [8.47-8.53]) was perceived more positive than operational deliveries with spontaneous labour (means≤7.66 [7.61-7.70], means≤7.96 [7.89-8.03]). However, labour induction more than doubled the risk of caesarean section for both primiparas and multiparas.

Conclusions: Labour induction generates more negative experiences for both primiparas and multiparas. The negative effect of labour induction is detected for all modes of delivery, being worst among labour induction resulting in operative delivery. The parturients facing cumulative obstetric interventions require special support and counselling during and after delivery.
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http://dx.doi.org/10.1186/s12884-022-04830-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229460PMC
June 2022

Mortality in adult children of parents with alcohol use disorder: a nationwide register study.

Eur J Epidemiol 2022 Jun 23. Epub 2022 Jun 23.

Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.

Research suggests that adult children of parents with harmful alcohol use are at increased risk for premature death. This national cohort study investigated mortality in adult children of parents with alcohol use disorder (AUD), adjusting for sociodemographic variables. The study used 1973 to 2018 data from Swedish national registers to compare mortality risk in children who had ≥ 1 parent with AUD (ICD-10 code F10 and its ICD-8 and ICD-9 equivalents) (n = 122,947) and those who did not (n = 2,298,532). A Cox regression model adjusted for year of birth, sex, parental education, and childhood loss of a parent was used. Before the age of 18 years, about 5% of children born in Sweden lived with ≥ 1 parent who had a clinical diagnosis of AUD. Overall mortality was higher in adult children of parents with AUD: hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.71-1.82. Mortality remained elevated after adjustments for sociodemographic factors (HR 1.45, 95% CI 1.40-1.50). Children of parents with AUD had increased mortality from all investigated causes. The highest excess risk was for death from drug-related causes (excluding accidental poisonings) (HR 3.08, 95% CI 2.74-3.46). For most causes, mortality was higher if the mother had AUD than if the father had AUD. Patterns of mortality were similar in both sexes. This study provides evidence that parental AUD raises the risk of offspring mortality from preventable causes such as drug use, suicide (HR 2.16, 95% CI 1.98-2.36), accident (HR 2.00, 95% CI 1.87-2.13), and assault (HR 1.76, 95% CI 1.38-2.24).
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http://dx.doi.org/10.1007/s10654-022-00883-4DOI Listing
June 2022

New theory about the pathophysiology of preeclampsia derived from the paradox of positive effects of maternal smoking.

J Hypertens 2022 Jun;40(6):1223-1230

Department of General Practice, Institute of Clinical Medicine, University of Turku and Turku University Hospital, Turku.

Objective: The aim of this study was to evaluate if maternal height affects the link between the inverse association on smoking during pregnancy and preeclampsia.

Study Design: The study population consisted of all women with singleton pregnancies (n = 803 698) in Finland during the years 2004-2018, excluding women with unknown smoking and diagnosis of prepregnancy chronic hypertension. Information on smoking and background factors were derived from the Finnish Medical Birth Register. Smoking was categorized in three classes: no, quitted in the first trimester and continued throughout the pregnancy. Information on preeclampsia was derived from the Finnish Hospital Discharge Register and the Finnish Medical Birth Register. Multiple logistic regression models were used to estimate first the association between smoking and preeclampsia, and finally whether maternal height modified the association.

Results: In the standard comparison, we found evidence of an association between preeclampsia and continued smoking [adjusted odds ratio = 0.74, 95% confidence interval (95% CI) = 0.67-0.81], but no association was found between quitted smoking and preeclampsia. Thus, the interaction of continued smoking and maternal height by z-scores was estimated. Among taller mothers, continued smoking was associated with a higher risk for preeclampsia than in smoking mothers with average height (β = 0.33, SE = 0.14, P  = 0.02).

Conclusion: Our results partly challenge the smoking-preeclampsia paradox: smoking seems not to protect tall mothers against preeclampsia. We speculate the findings through a new theory about the pathophysiology of preeclampsia. It seems that tall pregnant smokers must raise their blood pressure aggressively to ensure perfusion in the dysfunctional placenta.
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http://dx.doi.org/10.1097/HJH.0000000000003142DOI Listing
June 2022

Use of reproductive health services among women using long- or short-acting contraceptive methods - a register-based cohort study from Finland.

BMC Public Health 2022 06 14;22(1):1185. Epub 2022 Jun 14.

Department of General Practice and Primary Care, University of Helsinki, Tukholmankatu 8 B, 00029 HUS, Helsinki, Finland.

Background: Long-acting reversible contraceptives (LARCs) have superior contraceptive efficacy compared to short-acting reversible contraceptives (SARCs) and choosing LARCs over SARC methods reduces the need for abortion care. However, little is known how initiating these methods associates with the subsequent overall need of reproductive health services including family planning services, and visits for gynecological reasons in primary and specialized care.

Methods: We followed altogether 5839 non-sterilized women aged 15-44 years initiating free-of-charge LARC methods (n = 1689), initiating or switching SARC methods (n = 1524), or continuing with the same SARC method (n = 2626) at primary care family planning clinics in the City of Vantaa, Finland, 2013-2014 for 2 years using Finnish national health registers. We assessed the use of reproductive health services, namely attending public primary or specialized health care for gynecological reasons or attending the family planning clinics by applying unadjusted and adjusted negative binomial regression models on visit counts.

Results: A total of 11,290 visits accumulated during the two-year follow-up: 7260 (64.3%) at family planning clinics, 3385 (30.0%) for gynecological reasons in primary, and 645 (5.7%) in specialized health care. Altogether 3804 (52.4%) visits at the family planning clinics were for routine checkup, and 3456 (47.6%) for other reasons. Women initiating LARC methods used reproductive health services for reasons other than routine checkups similarly as women initiating or switching SARC methods (adjusted incidence rate ratio 0.93, 95% CI 0.82-1.05), while women continuing with SARC methods used the services less frequently (0.65, 0.59-0.72). Women initiating free-of-charge LARC and those continuing with the same SARC method used services less for abortion care than women initiating or switching SARC (adjusted incidence rate ratios 0.05, 95% CI 0.03-0.08 and 0.16, 95% CI 0.11-0.24, respectively).

Conclusions: While women initiating LARC methods have lower need for abortion care compared to women initiating SARC methods, women initiating both LARC and SARC methods have similar overall need for reproductive health services. In contrast, women continuing with their SARC method need reproductive health services less than women initiating LARC or a new SARC method. These service needs should be acknowledged when planning and organizing family planning services, and when promoting long-acting reversible contraception.
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http://dx.doi.org/10.1186/s12889-022-13581-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9199191PMC
June 2022

Busy day effect on the use of obstetrical interventions and epidural analgesia during labour: a cross-sectional register study of 601 247 deliveries.

BMC Pregnancy Childbirth 2022 Jun 13;22(1):481. Epub 2022 Jun 13.

Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Haartmaninkatu 2, 00290, Helsinki, Finland.

Background: Daily delivery volume might affect the quality of obstetric care. We explored the busy day effect on selected obstetrical interventions and epidural analgesia performed during labour in different sized delivery hospitals and on the Finnish obstetric ecosystem.

Methods: We conducted a cross-sectional study on Finnish Medical Birth Register data of singleton pregnancies (N = 601,247) from 26 delivery hospitals from 2006 to 2016. Delivery hospitals were stratified by annual delivery volume: C (category) 1: < 1000, C2: 1000-1999, C3: 2000-2999, C4: ≥3000, and C5: university hospitals. The exposure variables were defined as quiet, optimal, and busy days determined based on daily delivery volume distribution in each hospital category. Quiet and busy days included approximately 10% of the lowest and highest delivery volume days, while the rest were defined as optimal. Outcome measures were unplanned caesarean section (CS), instrumental delivery, induction of labour, and epidural analgesia. We compared the incidence of outcomes in quiet vs. optimal, busy vs. optimal, and busy vs. quiet days using logistic regression. The statistical significance level was set at 99% to reduce the likelihood of significant spurious findings.

Results: In the total population, the incidence of instrumental delivery was 8% (99% CI 2-15%) lower on quiet than on optimal days. In smaller hospitals (C1 and C2), unplanned caesarean sections were performed up to one-third less frequently on busy than optimal and quiet days. More (27%, 99% CI 12-44%) instrumental deliveries were performed in higher delivery volume hospitals (C4) on busy than quiet days. In C1-C3, deliveries were induced (12-35%) less often and in C5 (37%, 99% CI 28-45%) more often on busy than optimal delivery days. More (59-61%) epidural analgesia was performed on busy than optimal and quiet days in C4 and 8% less in C2 hospitals.

Conclusions: Pooled analysis showed that busyness had no effect on outcomes at the obstetric ecosystem level, but 10% fewer instrumental deliveries were performed in quiet than on busy days overall. Furthermore, dissecting the data shows that small hospitals perform less, and large non-tertiary hospitals perform more interventions during busy days.
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http://dx.doi.org/10.1186/s12884-022-04798-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190134PMC
June 2022

Prenatal care adequacy of migrants born in conflict-affected countries and country-born parturients in Finland.

J Migr Health 2022 31;6:100122. Epub 2022 May 31.

Department of Nursing Science, University of Eastern Finland, P.O. Box 1627, Kuopio 70211, Finland.

Background: The 2015 refugee crisis led into a forced migration of millions of people globally. As a consequence, many countries experienced a quick change in the proportion of conflict-area born migrants. This group being stated as an especially vulnerable group for suboptimal maternal health, a timely inspection of preventive maternity care was required. This study investigated prenatal care in terms of gestation trimester at the first prenatal visit, number of check-ups prior to birth, and prepartum hospitalization in conflict-country born migrants and Finnish parturients in Finland.

Material And Methods: Cross-sectional study included all pregnancies of migrants born in conflict-affected countries ( = 3 155) and country-born parturients ( = 93 600) in Finland in 2015-16. The data were obtained through Medical Birth Registry and Population Information System. Statistical analysis employed T-test, Chi-square test, and logistic regression analysis. Odds ratios with 95% Confidence Intervals (CI) were adjusted for sociodemographic and health-related background variables.

Results: Migrant parturients had a higher probability for delayed enter in prenatal care compared with Finnish-born parturients (adjusted odds ratio aOR = 3.46; 95% Confidence Interval CI 3.06, 3.91). Recommended minimum number of check-ups was participated by 95.3% of the migrant, and 96.4% of the Finnish-born group ( <0.000). Migrants' probability for more than ten visits prior to term birth was significantly lower (aOR = 0.58; 95% CI 0.51, 0.66). No significant differences in prepartum hospitalization yielded between the groups.

Conclusions: Migrant parturients had significantly smaller number of check-ups and later entry in care compared with the country-born parturients. These findings add to earlier reported challenges in the organizing of conflict-affected country born migrants' prenatal care in a high-income setting, in which the proportion of conflict-area born migrants has risen rapidly and unexpectedly.
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http://dx.doi.org/10.1016/j.jmh.2022.100122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168177PMC
May 2022

Temporal and geographical variations in survival of children born with congenital anomalies in Europe: A multi-registry cohort study.

Paediatr Perinat Epidemiol 2022 Jun 8. Epub 2022 Jun 8.

Malformation Monitoring Centre Saxony-Anhalt, Medical Faculty Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.

Background: Congenital anomalies are a major cause of perinatal, neonatal and infant mortality.

Objectives: The aim was to investigate temporal changes and geographical variation in survival of children with major congenital anomalies (CA) in different European areas.

Methods: In this population-based linkage cohort study, 17 CA registries members of EUROCAT, the European network for the surveillance of CAs, successfully linked data on 115,219 live births with CAs to mortality records. Registries estimated Kaplan-Meier survival at 28 days and 5 years of age and fitted Cox's proportional hazards models comparing mortality at 1 year and 1-9 years of age for children born during 2005-2014 with those born during 1995-2004. The hazard ratios (HR) from each registry were combined centrally using a random-effects model. The 5-year survival conditional on having survived to 28 days of age was calculated.

Results: The overall risk of death by 1 year of age for children born with any major CA in 2005-2014 decreased compared to 1995-2004 (HR 0.68, 95% confidence interval [CI] 0.53, 0.89). Survival at 5 years of age ranged between registries from 97.6% to 87.0%. The lowest survival was observed for the registry of OMNI-Net (Ukraine) (87.0%, 95% CI 86.1, 87.9).

Conclusions: Survival of children with CAs improved for births in 2005-2014 compared with 1995-2004. The use of CA registry data linked to mortality data enables investigation of survival of children with CAs. Factors such as defining major CAs, proportion of terminations of pregnancy for foetal anomaly, source of mortality data and linkage methods are important to consider in the design of future studies and in the interpretation of the results on survival of children with CAs.
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http://dx.doi.org/10.1111/ppe.12884DOI Listing
June 2022

Association of Prenatal Exposure to Antiseizure Medication With Risk of Autism and Intellectual Disability.

JAMA Neurol 2022 07;79(7):672-681

National Centre for Register-Based Research, Department of Economics and Business Economics, Aarhus School of Business and Social Services, Aarhus University, Aarhus, Denmark.

Importance: Women with epilepsy frequently need antiseizure medication (ASM) to prevent seizures in pregnancy. Risk of neurodevelopmental disorders after prenatal exposure to AMSs is uncertain.

Objective: To determine whether children exposed prenatally to ASMs in monotherapy and duotherapy have increased risk of neurodevelopmental disorders.

Design, Setting, And Participants: The Nordic register-based study of antiepileptic drugs in pregnancy (SCAN-AED) is a population-based cohort study using health register and social register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2017; analysis performed February 2022). From 4 702 774 alive-born children with available mother-child identities and maternal prescription data, this study included 4 494 926 participants. Children from a multiple pregnancy or with chromosomal disorders or uncertain pregnancy length were excluded (n = 207 848).

Exposures: Prenatal exposure to ASM determined from maternal prescription fills between last menstrual period and birth.

Main Outcomes And Measures: We estimated cumulative incidence at age 8 years in exposed and unexposed children. Cox regression adjusted for potential confounders yielded adjusted hazard ratios (aHRs) with 95% CIs for autism spectrum disorder (ASD), intellectual disability (ID), or any neurodevelopmental disorder (ASD and/or ID).

Results: A total of 4 494 926 children were included; 2 306 993 (51.3%) were male, and the median (IQR) age at end of follow-up was 8 (4.0-12.1) years. Among 21 634 unexposed children of mothers with epilepsy, 1.5% had a diagnosis of ASD and 0.8% (numerators were not available because of personal data regulations in Denmark) of ID by age 8 years. In same-aged children of mothers with epilepsy exposed to topiramate and valproate monotherapy, 4.3% and 2.7%, respectively, had ASD, and 3.1% and 2.4% had ID. The aHRs for ASD and ID after topiramate exposure were 2.8 (95% CI, 1.4-5.7) and 3.5 (95% CI, 1.4-8.6), respectively, and after valproate exposure were 2.4 (95% CI, 1.7-3.3) and 2.5 (95% CI, 1.7-3.7). The aHRs were elevated with higher ASM doses compared with children from the general population. The duotherapies levetiracetam with carbamazepine and lamotrigine with topiramate were associated with increased risks of neurodevelopmental disorders in children of women with epilepsy: levetiracetam with carbamazepine: 8-year cumulative incidence, 5.7%; aHR, 3.5; 95% CI, 1.5-8.2; lamotrigine with topiramate: 8-year cumulative incidence, 7.5%; aHR, 2.4; 95% CI, 1.1-4.9. No increased risk was associated with levetiracetam with lamotrigine (8-year cumulative incidence, 1.6%; aHR, 0.9; 95% CI, 0.3-2.5). No consistently increased risks were observed for neurodevelopmental disorders after prenatal exposure to monotherapy with lamotrigine, levetiracetam, carbamazepin, oxcarbazepine, gapapentin, pregabalin, clonazepam, or phenobarbital.

Conclusions And Relevance: In this cohort study, prenatal exposure to topiramate, valproate, and several duotherapies were associated with increased risks of neurodevelopmental disorders.
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http://dx.doi.org/10.1001/jamaneurol.2022.1269DOI Listing
July 2022

Socioeconomic differences in the association between maternal age and maternal obesity: a register-based study of 707,728 women in Finland.

Scand J Public Health 2022 May 20:14034948221088003. Epub 2022 May 20.

Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Aims: To examine the association between maternal age and maternal obesity across socioeconomic groups and to determine whether socioeconomic status modifies the association between maternal age and maternal obesity with a view to informing public health policies.

Methods: Data for this register-based study were sourced from the Finnish Medical Birth Register and Statistics Finland, using the information of 707,728 women who gave birth in Finland from 2004 to 2015. We used multivariable regression models to assess the association between maternal age and maternal obesity across socioeconomic groups. We further assessed interactions on both multiplicative and additive scales.

Results: Across all socioeconomic groups, the adjusted odds ratio for the association between maternal age and maternal obesity increased, peaking for women 35 years or older. Using women below 20 years of age in the category of upper-level employees as a single reference group, in the category of upper-level employees, the adjusted odds ratio and 95% confidence intervals among women 35 years or older was 1.92 (1.39-2.64) for maternal obesity. Equally, the adjusted odds ratio and 95% confidence intervals in the category of long-term unemployed was 4.35 (3.16-5.98). Synergistic interactions on both multiplicative and additive scales were found across age and socioeconomic groups.

Conclusions:
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http://dx.doi.org/10.1177/14034948221088003DOI Listing
May 2022

Folic Acid and Risk of Preterm Birth, Preeclampsia and Fetal Growth Restriction Among Women With Epilepsy: A Prospective Cohort Study.

Neurology 2022 May 16. Epub 2022 May 16.

Department of Clinical Medicine, University of Bergen, Norway.

Background And Objectives: Women with epilepsy treated with antiseizure medication (ASM) have increased risk of pregnancy complications including preterm birth, fetal growth restriction and preeclampsia. We aimed to investigate whether folic acid supplementation is associated with these pregnancy complications in women with epilepsy using ASM.

Methods: Singleton pregnancies in the prospective Norwegian Mother and Child Cohort Study (MoBa) (1999-2008) were included. Information on maternal epilepsy, ASM, folic acid supplementation, and pregnancy outcomes was obtained from MoBa questionnaires and the Norwegian Medical Birth Registry. The main exposure, periconceptional folic acid supplementation, was defined as intake between 4 weeks before pregnancy and 12 weeks into pregnancy, retrospectively collected by recall of the mothers in week 17-19. The primary outcomes were preterm birth (gestational age <37 weeks at birth), small for gestational age (SGA), and preeclampsia.

Results: The study included 100,105 pregnancies; 99,431 without maternal epilepsy, 316 with maternal epilepsy and ASM exposure in pregnancy, and 358 with untreated maternal epilepsy. Among ASM-treated women with epilepsy, the risk of preterm birth was higher in those who did use periconceptional folic acid (n=64) compared to those who (n=245, the reference) (adjusted odds ratio (aOR) 3.3, 95% confidence interval (CI) 1.2-9.2), while the risk of preterm birth among the reference was similar to the risk among women without epilepsy using folic acid periconceptionally (aOR 0.9, 95% CI 0.5-1.6). ASM-treated women with epilepsy starting folic acid after the first trimester had a higher risk compared to women without epilepsy with similar timing of folic acid (aOR 2.6, 95% CI 1.1-6.5), and even higher if not using folic acid (aOR 9.4, 95% CI 2.6-34.8). Folic acid was not associated with risk of preterm birth among women with epilepsy without ASM or among women without epilepsy. Folic acid was not associated with risk of preeclampsia or SGA among women with epilepsy.

Discussion: In women with epilepsy using ASM, periconceptional folic acid was associated with a lower risk of preterm birth. This finding supports the recommendation that ASM-treated women with epilepsy of childbearing potential should use folic acid supplementation on a regular basis.

Classification Of Evidence: This study provides Class III evidence that for women with epilepsy using ASM, periconceptional folic acid supplementation decreases the risk of preterm birth.
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http://dx.doi.org/10.1212/WNL.0000000000200669DOI Listing
May 2022

Maternal childbirth experience and pain relief methods: a retrospective 7-year cohort study of 85 488 parturients in Finland.

BMJ Open 2022 05 9;12(5):e061186. Epub 2022 May 9.

Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Uusimaa, Finland.

Objectives: The aim of this study was to analyse the relation between the used labour pain relief and childbirth experience measured by Visual Analogue Scale (VAS).

Design: A retrospective cohort study.

Setting: Childbirth in five Helsinki University Hospital delivery units from 2012 to 2018.

Primary Outcome Measure: Childbirth experience measured by VAS and classified in three groups (negative VAS=1-5, positive VAS=6-8 and highly positive=9-10).

Results: The use of epidural or non-epidural compared with non-medical pain relief methods decreased the likelihood to experience highly positive childbirth for primiparous (adjusted OR (aOR)=0.64, 95% CI 0.57 to 0.73; and aOR=0.76, 95% CI 0.66 to 0.87) and multiparous (aOR=0.90, 95% CI 0.84 to 0.97 and aOR=0.80, 95% CI 0.74 to 0.86) parturients. The effects of epidural differed between primiparas and multiparas. In multiparas epidural was associated with decreased odds for experiencing negative childbirth compared with the non-medical group (aOR=0.70, 95% CI 0.57 to 0.87), while the effect of epidural was considered insignificant in primiparas (aOR=1.28, 95% CI 0.93 to 1.77).

Conclusion: While the use of medical-epidural and non-epidural-pain relief methods were not associated with odds for experiencing negative childbirth in primiparas, using epidural helps to avoid negative experience in multiparas. However, the odds for experiencing highly positive childbirth were decreased if the parturients used any medical pain relief for both primiparas and multiparas. Consequently, the effect of pain relief on the childbirth experience is strongly confounded by indication. Thus, the use of pain relief per se plays a limited role in the complex formation of the overall childbirth experience.
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http://dx.doi.org/10.1136/bmjopen-2022-061186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086622PMC
May 2022

Prevalence and 11-Year Incidence of Cataract and Cataract Surgery and the Effects of Socio-Demographic and Lifestyle Factors.

Clin Ophthalmol 2022 20;16:1183-1195. Epub 2022 Apr 20.

Department of Ophthalmology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Purpose: To assess the impact of cataract in ageing population by evaluating the prevalence, incidence, and background factors of cataract and cataract surgery.

Patients And Methods: Two health examination surveys representing Finnish population in 2000 and 2011 included 7380 and 5930 participants aged 30 years or older with cataract status known. An 11-year follow-up included 4840 persons who participated in both the surveys. The data include information on physician-made diagnoses, socio-demographic factors, and lifestyle factors based on self-reported assessment. Cataract diagnoses and surgeries recorded in the Finnish Care Register for Health Care were linked to the survey data. Cataract patients were compared to those without cataract using logistic regression. Differences in cataract surgery age were evaluated using linear regression. Univariable and multivariable models were included.

Results: During 2000-2011, the prevalence of cataract increased from 8.8% to 13.6% and cataract surgery from 5.7% to 8.9% in a representative sample of the Finnish adult population. Cataract and cataract surgery were associated with age, smoking, and high alcohol consumption. Cataract was also associated with female gender and low income in 2000, but this association declined during the 11 years. Smoking and high alcohol consumption were associated with younger surgery age.

Conclusion: The prevalence of cataract and cataract surgery is increasing with the ageing of the population. The increase in cataract surgery is likely also reflecting the improvements in eye care. The possibility to equally use health-care services throughout a country can reduce the impact of socio-demographic status. Healthy lifestyle delays the development of cataract, whereas smoking and high alcohol consumption are associated with earlier cataract development. Therefore, the availability of cataract services and promotion of healthy lifestyle will be the key to prevent the detrimental effects of cataract on patients and the society in countries where the population is rapidly ageing.
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http://dx.doi.org/10.2147/OPTH.S355191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035455PMC
April 2022

Mood and neurotic disorders among youth with prenatal substance exposure: A longitudinal register-based cohort study.

J Affect Disord 2022 07 16;308:328-336. Epub 2022 Apr 16.

Folkhälsan Research Center, Helsinki, Finland; University of Helsinki, Department of Public Health, Helsinki, Finland.

Background: Prenatal substance exposure is associated with mood and neurotic disorders but this association is complex and understudied. This study investigated the recorded use of specialised healthcare services for mood and neurotic disorders among youth with prenatal substance exposure in comparison with an unexposed matched cohort. Furthermore, the influence of adverse maternal characteristics and out-of-home care (OHC) is investigated.

Methods: This longitudinal register-based matched cohort study included 594 exposed and 1735 unexposed youth. Cox proportional hazard regression models were applied to study the first episode of mood and neurotic disorders in specialised healthcare from 13 years of age, and the influence of adverse maternal characteristics and OHC. Mediation analysis was applied to study the mediating effect of OHC on the association between prenatal substance exposure and the disorders.

Results: The exposed cohort had a two-fold higher likelihood of being treated at specialised healthcare for mood and neurotic disorders compared with the unexposed cohort (HR 2.34, 95% CI 1.86-2.95), but this difference was attenuated to non-significant levels (AHR 1.29, 95% CI 0.92-1.81) following adjustments with adverse maternal characteristics and OHC. OHC mediated 61% (95% CI 0.41-0.94) of the association between prenatal substance exposure and youth's mood and neurotic disorders.

Limitations: Register data likely include more severe cases of disorders, and as an observational study, causality cannot be assessed.

Conclusion: Mood and neurotic disorders are more common following prenatal exposure to substances and interlinked with significant adversities in the postnatal caregiving environment and OHC.
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http://dx.doi.org/10.1016/j.jad.2022.04.039DOI Listing
July 2022

Association of Maternal Autoimmune Diseases With Risk of Mental Disorders in Offspring in Denmark.

JAMA Netw Open 2022 04 1;5(4):e227503. Epub 2022 Apr 1.

Department of Clinical Medicine, Department of Clinical Epidemiology, Aarhus University, Denmark.

Importance: Maternal immune activation during pregnancy is associated with increased risks of several mental disorders in offspring during childhood, but little is known about how maternal autoimmune diseases during pregnancy are associated with mental health in offspring during and after childhood.

Objective: To investigate the association between maternal autoimmune diseases before childbirth and risk of mental disorders among offspring up to early adulthood.

Design, Setting, And Participants: This population-based nationwide cohort study used data from Danish national registers on singletons born in Denmark from 1978 to 2015 with up to 38 years of follow-up. Data analyses were conducted from March 1, 2020, through September 30, 2021.

Exposures: Maternal autoimmune disease diagnosed before or during pregnancy according to the Danish National Patient Register.

Main Outcomes And Measures: The main outcome was mental disorders, defined by hospital diagnoses, in offspring. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for mental disorders.

Results: Of the 2 254 234 singleton infants included in the study (median age, 16.7 years [IQR, 10.5-21.7 years]; 51.28% male), 2.26% were born to mothers with autoimmune diseases before childbirth. Exposed participants had an increased risk of overall mental disorders compared with their unexposed counterparts (HR, 1.16; 95% CI, 1.13-1.19; incidence, 9.38 vs 7.91 per 1000 person-years). Increased risks of overall mental disorders in offspring were seen in different age groups for type 1 diabetes (1-5 years: HR, 1.35 [95% CI, 1.17-1.57]; 6-18 years: HR, 1.24 [95% CI, 1.15-1.33]; >18 years: HR, 1.19 [95% CI, 1.09-1.30]) and rheumatoid arthritis (1-5 years: HR, 1.42 [95% CI, 1.16-1.74]; 6-18 years: HR, 1.19 [95% CI, 1.05-1.36]; >18 years: HR, 1.28 [95% CI, 1.02-1.60]). Regarding specific mental disorders, increased risk after exposure to any maternal autoimmune disorder was observed for organic disorders (HR, 1.54; 95% CI, 1.21-1.94), schizophrenia (HR, 1.35; 95% CI, 1.21-1.51), obsessive-compulsive disorder (HR, 1.42; 95% CI, 1.24-1.63), mood disorders (HR, 1.12; 95% CI, 1.04-1.21), and a series of neurodevelopmental disorders (eg, childhood autism [HR, 1.21; 95% CI, 1.08-1.36] and attention-deficit/hyperactivity disorder [HR, 1.19; 95% CI, 1.12-1.26]).

Conclusions And Relevance: In this cohort study in Denmark, prenatal exposure to maternal autoimmune diseases was associated with increased risks of overall and type-specific mental disorders in offspring. Maternal type 1 diabetes and rheumatoid arthritis during pregnancy were associated with offspring's mental health up to early adulthood. Individuals prenatally exposed to autoimmune disease may benefit from long-term surveillance for mental disorders.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.7503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9012963PMC
April 2022

Survival of children with rare structural congenital anomalies: a multi-registry cohort study.

Orphanet J Rare Dis 2022 03 29;17(1):142. Epub 2022 Mar 29.

Population Health Research Institute, St George's University of London, London, UK.

Background: Congenital anomalies are the leading cause of perinatal, neonatal and infant mortality in developed countries. Large long-term follow-up studies investigating survival beyond the first year of life in children with rare congenital anomalies are costly and sufficiently large standardized cohorts are difficult to obtain due to the rarity of some anomalies. This study aimed to investigate the survival up to 10 years of age of children born with a rare structural congenital anomaly in the period 1995-2014 in Western Europe.

Methods: Live births from thirteen EUROCAT (European network for the epidemiological surveillance of congenital anomalies) population-based registries were linked to mortality records. Survival for 12,685 live births with one of the 31 investigated rare structural congenital anomalies (CAs) was estimated at 1 week, 4 weeks and 1, 5 and 10 years of age within each registry and combined across Europe using random effects meta-analyses. Differences between registries were evaluated for the eight rare CAs with at least 500 live births.

Results: Amongst the investigated CAs, arhinencephaly/holoprosencephaly had the lowest survival at all ages (58.1%, 95% Confidence Interval (CI): 44.3-76.2% at 1 week; 47.4%, CI: 36.4-61.6% at 1 year; 35.6%, CI: 22.2-56.9% at 10 years). Overall, children with rare CAs of the digestive system had the highest survival (> 95% at 1 week, > 84% at 10 years). Most deaths occurred within the first four weeks of life, resulting in a 10-year survival conditional on surviving 4 weeks of over 95% for 17 out of 31 rare CAs. A moderate variability in survival between participating registries was observed for the eight selected rare CAs.

Conclusions: Pooling standardised data across 13 European CA registries and the linkage to mortality data enabled reliable survival estimates to be obtained at five ages up to ten years. Such estimates are useful for clinical practice and parental counselling.
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http://dx.doi.org/10.1186/s13023-022-02292-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966236PMC
March 2022

Association of maternal polycystic ovary syndrome and diabetes with preterm birth and offspring birth size: a population-based cohort study.

Hum Reprod 2022 05;37(6):1311-1323

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Study Question: Is the presence of polycystic ovary syndrome (PCOS) associated with more adverse infant outcomes in mothers with different types of diabetes?

Summary Answer: The presence of PCOS implies higher risks of total (medically indicated and spontaneously combined) and spontaneous preterm birth in mothers with non-insulin-treated type 2 diabetes and gestational diabetes mellitus (GDM), and lower risk of offspring being large for gestational age (LGA) in mothers with insulin-treated diabetes.

What Is Known Already: PCOS is suggested to be an independent risk factor for adverse infant outcomes, and it is highly prevalent in mothers with diabetes. However, the impact of PCOS on the associations of different types of maternal diabetes with preterm birth and offspring birth sizes has not been reported.

Study Design, Size, Duration: This is a population-based cohort study including all live births between 1996 and 2014 in Finland. Children with concurrent maternal diagnoses that could cause signs and symptoms similar to PCOS were excluded. A total of 1 097 753 children were included.

Participants/materials, Setting, Methods: National registries were linked to identify births with maternal PCOS (n = 24 682), stratified by diabetes types. Logistic regression was used to examine the association of maternal PCOS and comorbid insulin-treated diabetes, non-insulin-treated type 2 diabetes or GDM with offspring LGA and small for gestational age (SGA). Generalized estimating equation was used to assess the risk of preterm birth in relation to maternal PCOS and diabetes. Potential interaction between PCOS and diabetes was evaluated on both additive and multiplicative scales.

Main Results And The Role Of Chance: Using mothers with no PCOS and no diabetes as the reference and adjusting for maternal and birth factors, there were higher risks of total (odds ratio (OR) 2.84, 95% CI 2.21 - 3.66 vs. OR 1.91, 95% CI 1.77 - 2.07, P = 0.01) and spontaneous (OR 4.02, 95% CI 2.94 - 5.50 vs. OR 2.35, 95% CI 2.13 - 2.59, P = 0.001) preterm birth for those with PCOS in mothers with non-insulin-treated type 2 diabetes and higher risks of total (OR 1.42, 95% CI 1.27-1.58 vs. OR 0.89, 95% CI 0.86-0.91, P = 0.0001) and spontaneous (OR 1.80, 95% CI 1.59-2.05 vs. OR 1.01, 95% CI 0.98-1.05, P = 0.0001) preterm birth for those with PCOS in mothers with GDM. Among mothers with type 2 diabetes, further adjusting for maternal BMI eliminated the difference in preterm birth risks between those with and those without PCOS, and adjustment for infertility treatment and pre-eclampsia also reduced the preterm risks associated with PCOS significantly. For mothers with GDM, however, the risks of total and spontaneous preterm birth remained higher for those with PCOS following these aforementioned adjustments or stratified analysis. The risk of offspring being LGA was lower for those with PCOS than those without PCOS among mothers with insulin-treated diabetes (OR 18.90, 95% CI 14.21-25.14 vs. OR 32.04, 95% CI 29.79-34.46, P = 0.0001), showing departure from additivity (relative excess risk due to interaction -11.74, 95% CI -16.17 to -7.31, P < 0.001) and multiplicativity (P < 0.001). PCOS did not alter the risk estimate of preterm birth in mothers with insulin-treated diabetes or offspring LGA and SGA in mothers with type 2 diabetes or GDM.

Limitations, Reasons For Caution: The register-based diagnoses used in this study captured only women with PCOS seeking medical care and having live births. Including female infertility associated with anovulation as PCOS exposure was a risk for misclassification. Sample sizes for pregestational diabetes were small. Insulin purchase during pregnancy in those without a diabetes diagnosis was not accounted for in the analysis. For patients treated with insulin or other medications, we were unable to assess how they complied with such prescriptions. Also, maternal BMI was recorded only once in early pregnancy, thus the potential influence of gestational weight gain on birth outcomes could not be examined. Data on the causes for preterm birth were not available from the registers.

Wider Implications Of The Findings: The presence of PCOS implied higher risks of total and spontaneous preterm birth in mothers with type 2 diabetes or GDM, and lower risk of offspring being LGA in mothers with insulin-treated diabetes. The higher risks of preterm birth added by PCOS could be explained by prepregnancy BMI or in part by infertility treatment and pre-eclampsia in maternal non-insulin-treated type 2 diabetes, but not in maternal GDM. The differential effects of PCOS on the associations of different types of maternal diabetes with infant outcomes have implications for preventative strategies and clinical counseling for affected pregnancies.

Study Funding/competing Interest(s): This study was supported by Shandong Provincial Natural Science Foundation, China (ZR2020MH064 to X.C.), Shandong Province Medical and Health Technology Development Plan (2018WS338 to X.C.), the joint research funding of Shandong University and Karolinska Institute (SDU-KI-2019-08 to X.C. and C.L.), the Finnish National Institute for Health and Welfare: Drug and pregnancy project (M.G.), the Swedish Research Council (2014-10171 to C.L.), the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council (SLL20170292 and SLL20190589 to C.L.), the Swedish Brain Foundation (FO2019-0201 and FO2020-0305 to C.L.). X.C. received grants from the China Scholarship Council at the beginning of the study. The authors have no competing interests to disclose.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deac050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156851PMC
May 2022

Increasing Prevalence and High Risk of Associated Anomalies in Congenital Vertebral Defects: A Population-based Study.

J Pediatr Orthop 2022 May-Jun 01;42(5):e538-e543

Departments of Paediatric Surgery and Orthopaedics.

Background: Congenital vertebral anomalies are a heterogeneous group of diagnoses, and studies on their epidemiology are sparse. Our aim was to investigate the national prevalence and mortality of these anomalies, and to identify associated anomalies.

Methods: We conducted a population-based nationwide register study and identified all cases with congenital vertebral anomalies in the Finnish Register of Congenital Malformations from 1997 to 2016 including live births, stillbirths, and elective terminations of pregnancy because of major fetal anomalies. Cases were categorized based on the recorded diagnoses, associated major anomalies were analyzed, and prevalence and infant mortality were calculated.

Results: We identified 255 cases of congenital vertebral anomalies. Of these, 92 (36%) were diagnosed with formation defects, 18 (7.1%) with segmentation defects, and 145 (57%) had mixed vertebral anomalies. Live birth prevalence was 1.89 per 10,000, and total prevalence was 2.20/10,000, with a significantly increasing trend over time (P<0.001). Overall infant mortality was 8.2% (18/219); 3.5% (3/86) in patients with formation defects, 5.6% (1/18) in segmentation defects, and 12.2% (14/115) in mixed vertebral anomalies (P=0.06). Co-occurring anomalies and syndromes were associated with increased mortality, P=0.006. Majority of the cases (82%) were associated with other major anomalies affecting most often the heart, limbs, and digestive system.

Conclusions: In conclusion, the prevalence of congenital vertebral anomalies is increasing significantly in Finnish registers. Detailed and systematic examination is warranted in this patient population to identify underlying comorbidities as the majority of cases are associated with congenital major anomalies.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1097/BPO.0000000000002124DOI Listing
April 2022

Neonatal outcome in vaginal breech labor at 32 + 0-36 + 0 weeks of gestation: a nationwide, population-based record linkage study.

BMC Pregnancy Childbirth 2022 Mar 16;22(1):211. Epub 2022 Mar 16.

Department of Obstetrics and Gynecology, University Hospital (HUS), University of Helsinki, Haartmaninkatu 2, 00290, Helsinki, Finland.

Background: In many countries, vaginal breech labor at term is an option in selected cases. However, the safety of vaginal breech labor in preterm is still unclear. Therefore our study aimed to evaluate the safety of vaginal breech labor in late preterm deliveries.

Design: A retrospective register-based study.

Setting: Maternity hospitals in Finland, 2004-2017.

Participants: The study population included 762 preterm breech deliveries at 32 + 0-36 + 6 gestational weeks according to the mode of delivery, 535 (70.2%) of them were born vaginally in breech presentation, and 227 (29.8%) were delivered by non-urgent cesarean section.

Methods: The study compared short-term neonatal adverse outcomes of singleton vaginal breech deliveries with non-urgent cesarean deliveries at 32 + 0 to 36 + 6 weeks of gestation. An odd ratio with 95% confidence intervals was calculated to estimate the relative risk of adverse outcomes.

Outcome Measures: Neonatal death, an arterial umbilical pH below seven, a five-minute Apgar score below four and seven, admission to neonatal intensive care unit, neonatal intubation, neonatal antibiotic therapy, neonatal birth trauma, respiratory distress syndrome, neonatal convulsions, cerebral ischemia, hypoxic-ischemic encephalopathy, congenital hypotonia, and a composite of severe adverse outcomes.

Results: A five-minute Apgar scores below seven were increased in vaginal breech labor at 32 + 0 to 36 + 6 weeks of gestation compared to non-urgent cesarean sections (aOR 2.48, 95% CI 1.08-5.59). Neonatal antibiotic therapy, the admission to neonatal intensive care unit, and neonatal respiratory distress syndrome were decreased after vaginal breech labor compared to the outcomes of non-urgent cesarean section (neonatal antibiotic therapy aOR 0.60, 95% CI 0.40-0.89; neonatal NICU admission aOR 0.47, 95% CI 0.33-0.68; respiratory distress syndrome aOR 0.30, 95% CI 0.19-0.48).

Conclusion: Vaginal breech labor at 32 + 0-36 + 6 gestational weeks does not increase severe neonatal short-term morbidity or mortality compared to cesarean section.
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http://dx.doi.org/10.1186/s12884-022-04547-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928595PMC
March 2022

Body mass index in the middle-aged offspring of parents with severe mental illness.

Psychol Med 2022 Mar 2:1-7. Epub 2022 Mar 2.

Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland.

Background: People with severe mental illness (SMI) have an elevated risk of obesity but the causes and mechanisms are unclear. We explored the familial association between parental SMI and body mass index (BMI) in middle-aged offspring. Our objective was to determine if the offspring of either parent with SMI have an increased risk for obesity.

Methods: The Northern Finland Birth Cohort 1966 is a cohort study of offspring with expected date of birth in 1966. The data include originally 12 068 mothers and 12 231 children from the provinces of Lapland and Oulu in Finland. The final study sample included 5050 middle-aged offspring. Parental SMI was used as exposure in the study. BMI measured at the age of 46 years was used as a primary outcome.

Results: Risk for obesity was elevated in the offspring of mothers with SMI [overweight: adjusted odds ratio (OR) 1.93 (1.29-2.90), obese class I: 1.97 (1.20-3.25), obese classes II-III: 2.98 (1.67-5.33)]. For the offspring of either parent with SMI, statistically significant results were found in obese class I and obese classes II-III [overweight: adjusted OR 1.21 (0.94-1.54), obese class I: 1.52 (1.03-1.08), obese classes II-III: 1.53 (1.01-2.32)].

Conclusions: We found an elevated risk of obesity in the middle-aged offspring of either parent with SMI, especially in the offspring of mothers with SMI. Thus, there might be a common familial pathway leading to the co-occurrence of obesity and SMI.
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March 2022
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