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AIMS/HYPOTHESIS: Children and adults born preterm have an increased risk of type 1 diabetes. However, there is limited information on risk patterns across the full range of gestational ages, especially after extremely preterm birth (23-27 weeks of gestation). We investigated the risk of type 1 diabetes in childhood and young adulthood across the full range of length of gestation at birth. METHODS: Data were obtained from national registers in Finland, Norway and Sweden. In each country, information on study participants and gestational age was collected from the Medical Birth Registers, information on type 1 diabetes diagnoses was collected from the National Patient Registers, and information on education, emigration and death was collected from the respective national register sources. Individual-level data were linked using unique personal identity codes. The study population included all individuals born alive between 1987 and 2016 to mothers whose country of birth was the respective Nordic country. Individuals were followed until diagnosis of type 1 diabetes, death, emigration or end of follow-up (31 December 2016 in Finland, 31 December 2017 in Norway and Sweden). Gestational age was categorised as extremely preterm (23-27 completed weeks), very preterm (28-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), full term (39-41 weeks; reference) and post term (42-45 weeks). HRs and 95% CIs from country-specific covariate-adjusted Cox regression models were combined in a meta-analysis using a common-effect inverse-variance model. RESULTS: Among 5,501,276 individuals, 0.2% were born extremely preterm, 0.5% very preterm, 0.7% moderately preterm, 4.2% late preterm, 17.7% early term, 69.9% full term, and 6.7% post term. A type 1 diabetes diagnosis was recorded in 12,326 (0.8%), 6364 (0.5%) and 16,856 (0.7%) individuals at a median age of 8.2, 13.0 and 10.5 years in Finland, Norway and Sweden, respectively. Individuals born late preterm or early term had an increased risk of type 1 diabetes compared with their full-term-born peers (pooled, multiple confounder-adjusted HR 1.12, 95% CI 1.07, 1.18; and 1.15, 95% CI 1.11, 1.18, respectively). However, those born extremely preterm or very preterm had a decreased risk of type 1 diabetes (adjusted HR 0.63, 95% CI 0.45, 0.88; and 0.78, 95% CI 0.67, 0.92, respectively). These associations were similar across all three countries. CONCLUSIONS/INTERPRETATION: Individuals born late preterm and early term have an increased risk of type 1 diabetes while individuals born extremely preterm or very preterm have a decreased risk of type 1 diabetes compared with those born full term.
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Diabetes Mellitus Tipo 1 , Edad Gestacional , Sistema de Registros , Humanos , Diabetes Mellitus Tipo 1/epidemiología , Finlandia/epidemiología , Noruega/epidemiología , Suecia/epidemiología , Femenino , Masculino , Recién Nacido , Niño , Adolescente , Adulto Joven , Nacimiento Prematuro/epidemiología , Factores de Riesgo , Adulto , EmbarazoRESUMEN
Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case-control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18-44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33-4.72) and 2-fold (OR = 2.03, 95% CI 1.41-2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17-2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22-2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer.
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Autoanticuerpos , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Femenino , Embarazo , Finlandia/epidemiología , Adulto , Estudios de Casos y Controles , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/sangre , Cáncer Papilar Tiroideo/sangre , Cáncer Papilar Tiroideo/epidemiología , Adolescente , Adulto Joven , Incidencia , Autoanticuerpos/sangre , Autoinmunidad , Carcinoma Papilar/sangre , Carcinoma Papilar/epidemiología , Hormonas Tiroideas/sangre , Hormonas Esteroides Gonadales/sangre , Estudios de Cohortes , Tirotropina/sangre , Glándula Tiroides/inmunología , Yoduro Peroxidasa/inmunologíaRESUMEN
PURPOSE: Uterine sarcomas are a rare group of uterine malignancies. Due to the low incidence and changes in uterine sarcoma classification, risk factors are not well characterized. Our objective was to evaluate risk factors for uterine sarcoma and compare risk factors between uterine sarcoma, malignant mixed Mullerian tumors (MMMTs), and type I endometrial carcinomas. METHODS: This nested case-control study utilized linked data from population-based medical birth and cancer registries in Denmark, Finland, Norway, and Sweden. Up to 10 controls were matched on country and birth year for each uterine cancer case. Using multivariable adjusted multinomial logistic regression, estimates of the associations between pregnancy-related factors and risk of uterine sarcoma, MMMTs, and type I endometrial carcinomas were determined. RESULTS: Having a very-low-birth-weight infant (< 1500 vs. 2500-3999 g: OR [95% CI] 2.83 [1.61-4.96]) was associated with an increased risk of uterine sarcoma. Whereas, having a more recent pregnancy was associated with reduced risks of MMMT (< 10 vs. ≥ 30 years: 0.66 [0.20-2.23]) and type 1 endometrial carcinomas (0.35 [0.30-0.41]) but not uterine sarcomas (1.33 [0.90-1.98], p-heterogeneity < 0.01). CONCLUSION: Our study provides evidence that risk factors for uterine sarcoma and MMMT, previously grouped with uterine sarcomas, vary substantially. Additionally, MMMT and type I endometrial carcinomas are more similar than uterine sarcoma in that pregnancy complications like gestational hypertension and preeclampsia were associated with reduced risks of both but not uterine sarcoma, suggesting different etiologies.
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Sarcoma , Neoplasias Uterinas , Humanos , Femenino , Estudios de Casos y Controles , Embarazo , Neoplasias Uterinas/epidemiología , Factores de Riesgo , Adulto , Persona de Mediana Edad , Sarcoma/epidemiología , Sistema de Registros , Países Escandinavos y Nórdicos/epidemiología , Suecia/epidemiología , Anciano , Finlandia/epidemiología , Noruega/epidemiología , Dinamarca/epidemiologíaRESUMEN
OBJECTIVE: This study was undertaken to examine the comparative safety of antiseizure medication (ASM) monotherapy in pregnancy with respect to risk of major congenital malformations (MCMs), overall and by MCM subtype. METHODS: We conducted a population-based cohort study using national health register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2020). We compared pregnancies with first trimester exposure to lamotrigine monotherapy to ASM-unexposed, carbamazepine, valproate, oxcarbazepine, levetiracetam, and topiramate to lamotrigine monotherapy, and stratified monotherapy groups by dose. The outcome was nongenetic MCM and specific subtypes. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) with log-binomial regression and propensity score weights. RESULTS: There was a higher crude risk of any MCM in pregnancies exposed to lamotrigine monotherapy (n = 8,339) compared to ASM-unexposed pregnancies (n = 4,866,362), but not after confounder adjustment (aRR = 0.97, 95% CI = 0.87-1.08). Compared to lamotrigine, there was an increased risk of malformations associated with valproate (n = 2,031, aRR = 2.05, 95% CI = 1.70-2.46) and topiramate (n = 509, aRR = 1.81, 95% CI = 1.26-2.60), which increased in a dose-dependent manner. We found no differences in malformation risk for carbamazepine (n = 2,674, aRR = 0.91, 95% CI = 0.72-1.15), oxcarbazepine (n = 1,313, aRR = 1.09, 95% CI = 0.83-1.44), or levetiracetam (n = 1,040, aRR = 0.78, 95% CI = 0.53-1.13). Valproate was associated with several malformation subtypes, including nervous system, cardiac, oral clefts, clubfoot, and hypospadias, whereas lamotrigine and carbamazepine were not. INTERPRETATION: Topiramate is associated with an increased risk of MCM similar to that associated with valproate, but lower doses may mitigate the risks for both drugs. Conversely, we found no increased risks for lamotrigine, carbamazepine, oxcarbazepine, or levetiracetam, which is reassuring. ANN NEUROL 2023;93:551-562.
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Anomalías Inducidas por Medicamentos , Epilepsia , Embarazo , Masculino , Femenino , Humanos , Ácido Valproico/efectos adversos , Lamotrigina/uso terapéutico , Topiramato/uso terapéutico , Epilepsia/tratamiento farmacológico , Oxcarbazepina/uso terapéutico , Levetiracetam/uso terapéutico , Estudios de Cohortes , Anticonvulsivantes/uso terapéutico , Carbamazepina , Benzodiazepinas/uso terapéuticoRESUMEN
STUDY QUESTION: What is the prospective risk of Type 2 diabetes (T2D) in Nordic women with polycystic ovary syndrome (PCOS) compared to controls? SUMMARY ANSWER: A diagnosis of PCOS and BMI ≥30 kg/m2 is a high-risk phenotype for a prospective risk of T2D diagnosis across Nordic countries. WHAT IS KNOWN ALREADY: The risk of T2D in women with PCOS is increased. The risk of T2D is related to BMI and the magnitude of risk in normal weight women with PCOS has been discussed. However, prospective data regarding risk of T2D in population-based cohorts of women with PCOS are limited. STUDY DESIGN, SIZE, DURATION: This national register-based study included women with PCOS and age-matched controls. The main study outcome was T2D diagnosis occurring after PCOS diagnosis. T2D was defined according to ICD-10 diagnosis codes and/or filled medicine prescriptions of anti-diabetic medication excluding metformin. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study cohort included women originating from Denmark (PCOS Denmark, N = 27 016; controls, N = 133 994), Finland (PCOS Finland, N = 20 467; controls, N = 58 051), and Sweden (PCOS Sweden, N = 52 409; controls, N = 254 010). The median age at cohort entry was 28 years in PCOS Denmark, Finland, and Sweden with a median follow-up time (interquartile range) in women with PCOS of 8.5 (4.0-14.8), 9.8 (5.1-15.1), and 6.0 (2.0-10.0) years, respectively. Cox regression analyses were adjusted for BMI and length of education. MAIN RESULTS AND THE ROLE OF CHANCE: The crude hazard ratio (HR, 95% CI) for T2D diagnosis in women with PCOS was 4.28 (3.98-4.60) in Denmark, 3.40 (3.11-3.74) in Finland, and 5.68 (5.20-6.21) in Sweden. In adjusted regression analyses, BMI ≥30 vs <25 kg/m2 was associated with a 7.6- to 11.3-fold risk of T2D. In a combined meta-analysis (PCOS, N = 99 892; controls, N = 446 055), the crude HR for T2D in PCOS was 4.64 (3.40-5.87) and, after adjustment for BMI and education level, the HR was 2.92 (2.32-3.51). LIMITATIONS, REASONS FOR CAUTION: Inclusion of more severe cases of PCOS in the present study design could have lead to an overestimation of risk estimates in our exposed population. However, some women in the control group would have undiagnosed PCOS, which would lead to an underestimation of T2D risk in women with PCOS. BMI data were not available for all participants. The present study should be repeated in study cohorts with higher background risks of T2D, particularly in populations of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: The prospective risk for diagnosis of T2D is increased in women with PCOS, and the risk is aggravated in women with BMI ≥30 kg/m2. STUDY FUNDING/COMPETING INTEREST(S): Funding in Denmark was from the Region of Southern Denmark, Overlægerådet, Odense University Hospital. Funding in Finland was from Novo Nordisk Foundation, Finnish Research Council and Sigrid Juselius Foundation, the National Regional Fund, Sakari Alhopuro Foundation and Finnish Diabetes Research Foundation. E.E. has received a research grant from Ferring Pharmaceuticals (payment to institution) and serves as medical advisor for Tilly AB, not related to this manuscript. The remaining authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
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Índice de Masa Corporal , Diabetes Mellitus Tipo 2 , Síndrome del Ovario Poliquístico , Humanos , Síndrome del Ovario Poliquístico/epidemiología , Síndrome del Ovario Poliquístico/complicaciones , Femenino , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Adulto , Dinamarca/epidemiología , Suecia/epidemiología , Finlandia/epidemiología , Estudios Prospectivos , Factores de Riesgo , Estudios de Casos y Controles , Adulto Joven , Estudios de Cohortes , Sistema de Registros , Persona de Mediana EdadRESUMEN
BACKGROUND: Timely outpatient follow-up and readmission after discharge are common quality indicators in psychiatric care, but their association varies in previous research. We aimed to examine whether the impact of outpatient follow-up and other factors on readmission risk evolves over time in people with non-affective psychotic disorder (NAP). METHODS: The Finnish Quality of Care Register includes all people diagnosed with NAP since January 2010. Here, we followed patients with a hospital discharge between 2017 and 2021 until readmission, death, or up to 365 days. Time of the first outpatient follow-up appointment, length of stay (LOS), number of previous hospitalizations, psychosis diagnosis, substance use disorder (SUD), residential status, economic activity, gender, age, year, and region were included. Follow-up time was divided into five periods: week 1, weeks 2-4, weeks 5-13, weeks 14-25, and weeks 26-52, and each period was analyzed separately with Cox regression. RESULTS: Of the 29 858 discharged individuals, 54.1% had an outpatient follow-up within a week. A total of 10 623 (35.6%) individuals were readmitted. Short LOS increased the readmission risk in the first four weeks, whereas lack of outpatient follow-up raised the risk (adjusted HRs between 1.15 (95% CI 1.04-1.26) and 1.53 (1.37-1.71) in weeks 5-52. The number of previous hospitalizations remained a consistent risk factor throughout the follow-up, while SUD increased risk after 4 weeks and living without family after 13 weeks. CONCLUSIONS: Risk factors of readmission vary over time. These temporal patterns must be considered when developing outpatient treatment programs.
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OBJECTIVE: This study was undertaken to characterize the use of higher doses of folic acid (≥1 mg daily) in relation to pregnancy in Denmark, Norway, and Sweden in women with epilepsy treated with antiseizure medication (ASM). METHODS: In this observational study, we used data from national medical birth, patient, and prescription registers in Denmark, Norway, and Sweden to retrospectively identify pregnancies in women with epilepsy treated with ASM from 2006 to 2017. The proportion of higher dose folic acid supplementation in pregnancies among women receiving ASM for epilepsy was calculated according to country of origin, time period, and type of ASM. Logistic regression with restricted cubic splines was used to model country-specific time trends. RESULTS: Among a total of 2 748 882 pregnancies, we identified 8695 (.3%) pregnancies after restricting the population to women with ASM-treated epilepsy. A prescription for higher dose folic acid was filled in 4719 (54.3%) of these pregnancies. The proportion supplemented with higher dose folic acid was highest in Sweden (74.3%) and lower in Norway (41.4%) and Denmark (34.3%). Furthermore, we observed a decreasing trend of higher dose folic acid use in Denmark and Norway from year 2012 to 2017. Among those who used higher dose folic acid, 42% did not start preconception supplementation with higher dose folic acid. SIGNIFICANCE: Supplementation with higher dose folic acid occurred in approximately half of pregnancies in women with ASM-treated epilepsy, with many not starting supplementation until after becoming pregnant. Considerable variability was observed in the use of higher dose folic acid across the countries, despite similar population characteristics and health care systems. Future guidelines should be simplified with clear recommendations developed in a collaborative manner by relevant specialists including neurologists, obstetricians, pediatricians, and public health specialists to enhance real-world applicability.
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Anticonvulsivantes , Epilepsia , Ácido Fólico , Pautas de la Práctica en Medicina , Complicaciones del Embarazo , Humanos , Femenino , Ácido Fólico/administración & dosificación , Ácido Fólico/uso terapéutico , Epilepsia/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/administración & dosificación , Embarazo , Adulto , Noruega/epidemiología , Dinamarca/epidemiología , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pautas de la Práctica en Medicina/tendencias , Complicaciones del Embarazo/tratamiento farmacológico , Suecia/epidemiología , Estudios Retrospectivos , Adulto Joven , Suplementos DietéticosRESUMEN
OBJECTIVE: Research points to disparities in disease burden and access to medical care in epilepsy. We studied the association between socioeconomic status (SES) and antiseizure medication (ASM) use in pregnancies with maternal epilepsy. METHODS: We conducted a cross-sectional study consisting of 21 130 pregnancies with maternal epilepsy identified from Nordic registers during 2006-2017. SES indicators included cohabitation status, migrant background, educational attainment, and household income. Main outcomes were the proportion and patterns of ASM use from 90 days before pregnancy to birth. We applied multiple imputation to handle SES variables with 2%-4% missingness. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) using modified Poisson regression with the highest SES category as reference. RESULTS: Mothers with the highest education and the highest income quintile used ASMs least frequently (56% and 53%, respectively). We observed increased risks of ASM discontinuation prior to or during the first trimester for low SES. The risk estimates varied depending on the SES indicator from aRR = 1.27 for low income (95% CI: 1.03-1.57) to aRR = 1.66 for low education (95% CI: 1.30-2.13). Migrant background was associated with ASM initiation after the first trimester (aRR 2.17; 95% CI 1.88-2.52). Low education was associated with the use of valproate during pregnancy in monotherapy (aRR 1.70; 95% CI 1.29-2.24) and in polytherapy (aRR 2.65; 95% CI 1.66-4.21). Low education was also associated with a 37% to 39% increased risk of switching from one ASM to another depending on the ASM used. For the other SES indicators, aRRs of switching varied from 1.16 (foreign origin; 95% CI 1.08-1.26) to 1.26 (not married or cohabiting; 95% CI 1.17-1.36). SIGNIFICANCE: Low SES was associated with riskier patterns of ASM use: discontinuation, late initiation, and switching during pregnancy. These findings may reflect unplanned pregnancies, disparities in access to preconception counseling, and suboptimal care.
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Anticonvulsivantes , Epilepsia , Complicaciones del Embarazo , Humanos , Femenino , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Embarazo , Anticonvulsivantes/uso terapéutico , Adulto , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/epidemiología , Estudios Transversales , Factores Socioeconómicos , Países Escandinavos y Nórdicos/epidemiología , Adulto Joven , Clase Social , Sistema de RegistrosRESUMEN
BACKGROUND: Endometriosis diagnosed in adults is associated with increased risk of various psychiatric disorders. However, little is known concerning psychiatric comorbidity and mortality due to external causes associated with endometriosis diagnosed at a young age. OBJECTIVE: This longitudinal cohort study aimed to investigate the link between surgical diagnosis of endometriosis at a young age and subsequent psychiatric disorders and mortality due to external causes. In addition, we compared the occurrence of the most common psychiatric disorders between different sites of surgically confirmed endometriosis (ovarian vs other) because of possible differences in pain manifestations. STUDY DESIGN: We conducted a retrospective register-based cohort study. Altogether 4532 women with surgically confirmed diagnosis of endometriosis before the age of 25 years from 1987 to 2012 were identified from the Finnish Hospital Discharge Register. They were matched with women without surgically diagnosed endometriosis for age and municipality on the index day (n=9014). Women were followed up from the index day until the end of 2019 for the outcomes of interest, which included 9 groups of psychiatric disorders (inpatient episodes since 1987, outpatient episodes since 1998) and death due to external causes, including deaths due to accidents, suicides, and violence (Finnish Register of Causes of Death). Cox proportional hazard models were applied to assess the crude and parity-adjusted hazard ratios and 95% confidence intervals. RESULTS: The cohort's median age was 22.9 years (interquartile range, 21.3-24.1) at the beginning and 42.5 years (36.7-48.3) after a median follow-up time of 20.0 years (14.5-25.7). We observed a higher hazard of depressive, anxiety, and bipolar disorders in women with endometriosis compared with the reference cohort, with depressive and anxiety disorders being the two most common psychiatric disorders. These differences appeared early and remained the same during the entire follow-up, irrespective of whether assessed from the data on inpatient episodes only or the data on both in- and outpatient episodes. The corresponding adjusted hazard ratios were 2.57 (95% confidence interval, 2.11-3.14) and 1.87 (1.65-2.12) for depressive disorders, 2.40 (1.81-3.17) and 2.09 (1.84-2.37) for anxiety disorders, and 1.71 (1.30-2.26) and 1.66 (1.28-2.15) for bipolar disorders, respectively. A higher hazard was observed for nonorganic sleeping disorders for the first 10 years only (3.83; 2.01-7.30) when assessed using the data on both in- and outpatient episodes. When based on inpatient records, a higher hazard for alcohol/drug dependence after 15 years of follow-up (2.07; 1.21-3.54) was observed. The difference in hazard for personality disorders tended to increase during follow-up (<10 years, 2.12 [1.28-3.52]; ≥10 years, 3.08 [1.44-6.57]). Depressive and anxiety disorders occurred more frequently in women with types of endometriosis other than ovarian endometriosis. No difference in deaths due to external causes was observed between the endometriosis and reference cohorts. CONCLUSION: Surgical diagnosis of endometriosis at a young age was associated with increased incidence of several psychiatric disorders. Moreover, within the endometriosis population, psychiatric comorbidity was more common in women with types of endometriosis other than ovarian endometriosis. We speculate that chronic pain is essential in the development of these psychiatric disorders, and that early and effective pain management is important in reducing the risk of psychiatric morbidity in young women. More research concerning the associations and management of endometriosis and associated psychiatric disorders is warranted.
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Endometriosis , Trastornos Mentales , Sistema de Registros , Humanos , Femenino , Endometriosis/epidemiología , Endometriosis/complicaciones , Finlandia/epidemiología , Estudios Longitudinales , Adulto , Adulto Joven , Trastornos Mentales/epidemiología , Estudios Retrospectivos , Causas de Muerte , Modelos de Riesgos Proporcionales , Estudios de Cohortes , Suicidio/estadística & datos numéricos , Trastornos de Ansiedad/epidemiología , Violencia/estadística & datos numéricos , Accidentes , Adolescente , Trastorno Bipolar/epidemiología , Enfermedades del Ovario/epidemiología , Enfermedades del Ovario/mortalidad , Trastorno Depresivo/epidemiologíaRESUMEN
BACKGROUND AND PURPOSE: Intracerebral hemorrhage during pregnancy or puerperium (pICH) is one of the leading causes of maternal death worldwide. However, limited epidemiological data exist on the etiology and outcomes of pICH, which is required to guide prevention and treatment. METHODS: A retrospective nationwide cohort study and a nested case-control study was performed in Finland 1987-2016. We identified women with incident pICH by linking the Medical Birth Register (MBR) and the Hospital Discharge Register (HDR). The clinical details were collected from patient records. Three matched controls with a pregnancy without ICH were selected for each case from the MBR. RESULTS: In total, 49 pICH cases were identified. Half of these cases occurred during pregnancy, and the other half during peripartum and puerperium. Based on the SMASH-U (structural vascular lesion, medication, amyloid angiopathy, systemic disease, hypertension, undetermined) classification, 35.4% of the patients had a systemic disease, most commonly preeclampsia, eclampsia, or HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome; 31.3% had a structural vascular lesion; 31.3% had an undetermined etiology; and one patient (2.1%) had hypertension. The most important risk factor was hypertensive disorders of pregnancy (HDP; odds ratio = 3.83, 95% confidence interval = 1.60-9.15), occurring in 31% of the cases. Maternal mortality was 12.5%, and 20.9% of the surviving women had significant disability (modified Rankin Scale = 3-5) 3 months after the pICH. Women with systemic disease had the worst outcomes. CONCLUSIONS: Even in a country with a comprehensive pregnancy surveillance system, the maternal mortality rate for pICH is high, and the sequelae are severe. Early recognition and treatment of the key risk factor, HDP, is crucial to help prevent this serious pregnancy complication.
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Hipertensión , Preeclampsia , Embarazo , Humanos , Femenino , Estudios de Cohortes , Estudios Retrospectivos , Estudios de Casos y Controles , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/etiología , Hipertensión/complicaciones , Periodo PospartoRESUMEN
BACKGROUND: Studies indicate that individuals who deliver after assisted reproductive technologies (ART) may have an increased risk of cardiovascular disease (CVD). A recent large study from the U.S. showed a higher risk of stroke during the first year after delivery. OBJECTIVES: To compare the risk of stroke during the first year after delivery according to the use of ART in the Nordic countries. METHODS: Registry-based cohort study using nationwide data from Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015) and Sweden (1985-2015). Data on ART conception were available from ART quality registries and/or Medical Birth Registries (MBRs). National data on stroke were available from hospital and cause-of-death registries. The risk of stroke during the first year after delivery was estimated with Cox proportional hazard regression, adjusting for age, calendar year of delivery, multiple births, and country. RESULTS: A total of 2,659,272 primiparous individuals had a registered delivery in the MBRs during the study period, and 91,466 (4%) of these gave birth after ART. We observed no overall increased risk of stroke during the first year after delivery among individuals conceiving after ART (adjusted hazard ratio [HR] 1.10, 95% CI 0.77, 1.57). Similarly, there was no convincing evidence that the short-term risk of stroke was higher within 1, 2, 3, or 6 months after delivery, with adjusted HRs ranging between 1.23 and 1.33 and confidence intervals including the null value for all time periods. A secondary analysis also including multiparous individuals (n = 3,335,478) at the start of follow-up yielded similar findings. CONCLUSIONS: We found no evidence of an increased short-term risk of stroke among individuals who delivered after using ART.
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Técnicas Reproductivas Asistidas , Accidente Cerebrovascular , Femenino , Humanos , Estudios de Cohortes , Países Escandinavos y Nórdicos , Noruega , Accidente Cerebrovascular/etiología , Sistema de RegistrosRESUMEN
The total burden of infections after transplantation has not been compared in detail between recipients of simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). We compared infection-related hospitalizations and bacteremias after transplantation during 1- and 5-year follow-up among 162 patients undergoing SPK. The control group consisted of 153 type 1 diabetics undergoing KTA with the inclusion criteria of donor and recipient age < 60, and BMI < 30. During the first year, SPK patients had more infection-related hospitalizations (0.54 vs. 0.31 PPY, IRR 1.76, p = <0.001) and bacteremias (0.11 vs. 0.01 PPY, IRR 17.12, p = <0.001) compared to KTA patients. The first infection-related hospitalizations and bacteremias occurred later during follow-up in KTA patients. SPK was an independent risk factor for infection-related hospitalization and bacteremia during the first year after transplantation, but not during the 5-year follow-up. Patient survival did not differ between groups, however, KTA patients had inferior kidney graft survival. SPK patients are at greater risk for infection-related hospitalizations and bacteremias during the first year after transplantation compared to KTA patients, however, at the end of the follow-up the risk of infection was similar between groups.
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Bacteriemia , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Riñón , Hospitalización , PáncreasRESUMEN
PURPOSE: To present the main findings of a post-authorization safety study assessing pregnancy and infant outcomes after prenatal golimumab exposure in a real-world setting. METHODS: This observational population-based cohort study included data from pregnancies ending in 2006-2018 (Finland) or 2019 (Denmark, Sweden). Infants born to women with rheumatic diseases or ulcerative colitis diagnoses were identified. Based on prescription fills from 90 days prior to pregnancy until delivery, infants were assigned to one of the four drug-exposure cohorts: golimumab, other anti-TNF biologics, other biologics, and nonbiologic systemic therapy, and the general population. Prevalence of adverse pregnancy outcomes, mortality, diagnoses of major congenital anomalies (MCA), and inpatient infections in the infants' first year of life were assessed. Odds ratios and 95% CIs were calculated for MCA and infection. RESULTS: Among 134 infants in the golimumab cohort, none were stillborn or died in the first year of life. MCA were diagnosed in 4.5% of the infants in the golimumab cohort, versus 6.8%, 10.9%, 5.5%, and 4.6% in the other anti-TNF biologics, other biologics, nonbiologic systemic therapy and general population cohorts, respectively. Inpatient infections were diagnosed in 11% of golimumab-exposed infants, compared with 9%-11% of infants in the other cohorts. Unadjusted and selected adjusted comparisons showed no association between prenatal golimumab exposure and MCA or infection compared with the other exposure cohorts or general population. CONCLUSIONS: The number of infants with prenatal golimumab exposure was low, but results are reassuringly consistent with the evidence available for other anti-TNF biologics. Continued monitoring is needed.
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Anticuerpos Monoclonales , Resultado del Embarazo , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Embarazo , Suecia/epidemiología , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Recién Nacido , Resultado del Embarazo/epidemiología , Adulto , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Finlandia/epidemiología , Lactante , Estudios de Cohortes , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Dinamarca/epidemiología , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/epidemiología , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/epidemiología , Anomalías Inducidas por Medicamentos/epidemiología , Adulto JovenRESUMEN
INTRODUCTION: Brachial plexus birth injury is the most common birth injury causing permanent disability in Finland. This study aimed to assess risk factors of a permanent brachial plexus birth injury and calculate the incidence. MATERIAL AND METHODS: This is a retrospective population-based study including all deliveries between 2006 and 2022 in Southern Finland. The number of children born, obstetric data, and migrant status were gathered from the registries of the Finnish Institute for Health and Welfare, and Statistics Finland. Race of the mothers of children with a permanent brachial plexus birth injury was recorded. The severity of permanent brachial plexus birth injury was assessed using the 3-month Toronto test score. A lower score was indicative of a more severe injury (scored 0-10). RESULTS: One hundred of the 298 428 children born during the 17-year study period sustained a permanent brachial plexus birth injury (0.34 per 1000). Mothers of children with a permanent brachial plexus birth injury had a higher body mass index (29 vs. 24 kg/m2) and their pregnancies were more often complicated by diabetes (28% vs. 12%), shoulder dystocia (58% vs. 0.3%), and/or assisted deliveries (45% vs. 10%) compared with all other mothers (p < 0.001). Thirty two of the 52 725 children born to migrant mothers had a permanent brachial plexus birth injury (0.61 per 1000). The incidence of permanent brachial plexus birth injury was 5.7 times higher among children of Black migrants from Africa (18/11 738, 1.53 per 1000) compared with children of native mothers (0.27 per 1000). Black mothers had a higher body mass index at the start of pregnancy (29 vs. 26 kg/m2, p = 0.02) compared with Caucasians. Children of Black mothers had a more severe injury compared with all others (p = 0.007) with a mean 3-month Toronto test score of 4.2 (range 0.0-6.5, SD ±1.6) vs. 5.6 (range 0.0-9.3, SD ±2.2). CONCLUSIONS: Shoulder dystocia and assisted delivery are the most important risk factors for a permanent brachial plexus birth injury. Black race was associated with a higher rate and a more severe permanent brachial plexus birth injury.
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Traumatismos del Nacimiento , Humanos , Femenino , Estudios Retrospectivos , Factores de Riesgo , Embarazo , Finlandia/epidemiología , Adulto , Traumatismos del Nacimiento/epidemiología , Traumatismos del Nacimiento/etnología , Plexo Braquial/lesiones , Incidencia , Recién Nacido , MasculinoRESUMEN
INTRODUCTION: Shoulder dystocia is a severe obstetric emergency that can cause substantial neonatal and maternal complications. This study aims to assess the performed obstetric maneuvers and their frequency, success, and association with maternal and neonatal complication rates. MATERIAL AND METHODS: The study population was collected among all deliveries in the Hospital District of Helsinki and Uusimaa between 2006 and 2015 (n = 181 352) by searching for ICD-10 codes for shoulder dystocia, brachial plexus injury and clavicle fracture. Shoulder dystocia cases (n = 537) were identified by reviewing the medical records. Shoulder dystocia cases treated with one or two maneuvers were compared with those treated with at least three. Medical records of a matched control group constituting of 566 parturients without any of the forementioned ICD-10 codes were also scrutinized. RESULTS: Using the four most common obstetric maneuvers (McRoberts maneuver, suprapubic pressure, rotational maneuvers, the delivery of the posterior arm) significantly increased during the study period with individual success rates of 61.0%, 71.9%, 68.1% and 84.8%, respectively. Concurrently, the rate of brachial plexus injury and combined neonatal morbidity significantly declined from 50% to 24.2% (p = 0.02) and from 91.4% to 48.5% (p < 0.001). Approximately 75% of shoulder dystocia cases treated with maneuvers were resolved by the McRoberts maneuver and/or suprapubic pressure, but each of the four most performed maneuvers significantly increased the cumulative success rate individually and statistically (p < 0.001). The rates of brachial plexus injury and combined neonatal morbidity were at their highest (52.9% and 97.8%) when none of the maneuvers were performed and at their lowest when two maneuvers were performed (43.0% and 65.4%). The increasing number (≥3) of maneuvers did not affect the combined maternal or neonatal morbidity or brachial plexus injury but increased the risk for third- or fourth-degree lacerations (odds ratio 2.91, 95% confidence interval 1.17 to 7.24). CONCLUSIONS: The increased use of obstetric maneuvers during the study period was associated with decreasing rates of neonatal complications; conversely, the lack of obstetric maneuvers was associated with the highest rate of neonatal complications. These emphasize the importance of education, maneuver training and urgently performing shoulder dystocia maneuvers according to the international protocol guidelines.
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INTRODUCTION: Women undergoing an induced abortion are highly fertile and at risk of subsequent unplanned pregnancy. We recently completed a randomized clinical trial showing that routine provision of intrauterine device (IUD) at the time of abortion significantly reduced the risk of subsequent abortion during a 5-year follow up. As the use of highly effective contraception may affect all subsequent pregnancies, we analyzed the rate and distribution of all subsequent pregnancies (deliveries, miscarriages, and abortions), and the risk factors for these various pregnancy outcomes in the above-mentioned randomized clinical trial. MATERIAL AND METHODS: We enrolled adult women requesting first-trimester induced abortion and candidates for IUD for post-abortion contraception. Women (n = 751) were randomized to receive an IUD (either levonorgestrel-releasing IUD or copper IUD) by the clinic responsible for abortion care vs. routine care of IUD provision in primary health care with oral contraceptives for interval contraception. In the present secondary analysis, we identified all deliveries, miscarriages, and abortions in the intervention (n = 375) and control (n = 373) cohorts during the 5-year follow up using the Finnish national registries. The trial is registered at Clinical Trials (NTC01223521). RESULTS: The overall delivery, miscarriage, and abortion rates were 42.0, 12.0 and 32.1/1000 years of follow up (yFU). Any new pregnancy occurred in 98 women in the intervention and in 129 women in the control cohort (hazard ratio 0.73, 95% confidence interval 0.56-0.95, p = 0.023). The effect of routine IUD provision in reducing pregnancies was limited to the first 2 yFU. The number of subsequent induced abortions and of women undergoing it were significantly reduced, and time to abortion was prolonged by the intervention. However, the overall number, the number of women with subsequent delivery or miscarriage, and the times to these events were not significantly affected. History of previous pregnancy (delivery or abortion) and smoking were risk factors for subsequent induced abortion, but not for delivery or miscarriage. CONCLUSIONS: Routine provision of IUD as part of abortion care did not reduce the rates of delivery or miscarriage during the 5-year follow up. The rates of all pregnancies and the need of subsequent induced abortion were reduced by IUD provision during the first 2 yFU.
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Aborto Inducido , Aborto Espontáneo , Dispositivos Intrauterinos de Cobre , Dispositivos Intrauterinos , Embarazo , Adulto , Femenino , Humanos , Aborto Espontáneo/etiología , Resultado del Embarazo , Primer Trimestre del Embarazo , Estudios de SeguimientoRESUMEN
INTRODUCTION: Maternal smoking during pregnancy and gestational diabetes mellitus (GDM) have opposite effects on fetal growth during pregnancy. The aim of the study was to evaluate the interaction of smoking during pregnancy and gestational diabetes mellitus on head circumference and birthweight of newborns. MATERIAL AND METHODS: The study included all primiparous women with singleton pregnancies (n = 290 602) without previously diagnosed diabetes or hypertension in Finland between 2006 and 2018. The information on gestational diabetes mellitus, newborn birthweight and head circumference, and maternal smoking and backgrounds was derived from the Finnish Medical Birth Register. Linear regression models were used in the analyses. RESULTS: In total 8.0% of parturients quit smoking during the first trimester and 9.9% continued smoking thereafter. The prevalence of GDM was 8.9% (n = 25 948). Newborns of women who continued smoking had a smaller head circumference (b = -0.24, SE = 0.01, p < 0.0001) and birthweight (b = -0.28, SE = 0.01, p < 0.0001) compared to newborns of women who did not smoke. Head circumference and birthweight were greater in newborns of women with GDM (b = 0.09, SE = 0.01, p < 0.0001 and b = 0.16, SE = 0.01, p < 0.0001, respectively) compared to newborns of women without GDM. In the interaction analyses, head circumference (b = -0.13, SE = 0.01, p < 0.0001) was smaller and birthweight (b = -0.13, SE = 0.02, p < 0.0001) was lower in newborns of women with GDM who continued smoking compared to newborns of women without GDM who did not smoke. CONCLUSIONS: Although smoking and GDM have opposite effects on fetal growth, the negative effects of exposure to smoking are also seen in newborns of women with GDM. Compared to smoking after the first trimester of pregnancy, cessation of smoking during the first trimester was associated with greater head circumference and birthweight in newborns.
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Peso al Nacer , Diabetes Gestacional , Cabeza , Fumar , Humanos , Femenino , Embarazo , Diabetes Gestacional/epidemiología , Recién Nacido , Adulto , Finlandia/epidemiología , Cabeza/anatomía & histología , Fumar/efectos adversos , Cefalometría , Desarrollo FetalRESUMEN
INTRODUCTION: Fear of childbirth (FOC) is a common obstetrical challenge that complicates about every 10th pregnancy. Background factors of FOC are diverse. We evaluated the association of induced abortion (IA) and FOC in subsequent pregnancy. MATERIAL AND METHODS: Population-based register study based on three Finnish national registers: the Register of Induced Abortions, the Medical Birth Register and the Hospital Discharge Register. The study cases were primigravid women undergoing an IA in 2000-2015 and subsequent pregnancy ending in live singleton birth up to 2017. Each case had three controls, matched by age and residential area, whose first pregnancy ended in a live birth. The main outcome was the incidence of FOC in the subsequent pregnancy. In a secondary analysis, we assessed other risk factors for FOC. RESULTS: The study cohort consisted of 21 455 women and 63 425 controls. Altogether, 4.2% of women had a diagnosis of FOC. The incidence was higher in women with a history of IA than in controls (5.6% vs 3.7%, P < 0.001). A history of IA was associated with higher odds for FOC: adjusted odds ratio [aOR] 1.20 with 95% confidence interval (CI) 1.11-1.30. In addition, a history of psychiatric diagnosis (aOR 3.48, 95% CI 3.15-3.83), high maternal age, 30-39 years old (aOR 1.55, 95% CI 1.43-1.67; P < 0.001) and ≥40 years old (aOR 3.00, 95% CI 2.37-3.77; P < 0.001) and smoking (aOR 1.20, 95% CI 1.11-1.31; P < 0.001) were associated with increased odds for FOC. Women living in densely populated or rural areas and those with lower socioeconomic class had lower odds for FOC. CONCLUSIONS: A history of IA is associated with increased odds for FOC in subsequent pregnancy. However, the associations of FOC with a history of psychiatric diagnosis and elevated maternal age (especially ≥40 years old) are more pronounced.
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Aborto Inducido , Parto , Embarazo , Femenino , Humanos , Adulto , Parto/psicología , Parto Obstétrico/psicología , Finlandia/epidemiología , Miedo/psicologíaRESUMEN
INTRODUCTION: To investigate the occurrence of previous cancer diagnoses in women suffering from premature ovarian insufficiency (POI) and compare it with the general population, shedding light on the association between cancer, cancer treatments, and POI. MATERIAL AND METHODS: We conducted a nationwide case-control study based on registry data from various sources, including the Social Insurance Institution, Finnish Population Information System, and Finnish Cancer Registry spanning from 1953 to 2018. Our participants comprised all women in Finland who, between 1988 and 2017, received hormone replacement therapy reimbursement for ovarian insufficiency before the age of 40 years (n = 5221). Controls, matched in terms of age and municipality of residence, were selected from the Finnish Population Information System (n = 20 822). Our main exposure variable was a history of cancer diagnosis preceding the diagnosis of POI. We analyzed odds ratios (OR) to compare the prevalence of previous cancers in women with POI with that in controls, stratifying results based on cancer type, age at cancer diagnosis, and the time interval between cancer diagnosis and POI. We also assessed changes in OR for previous cancer diagnoses over the follow-up period. RESULTS: Out of the women diagnosed with POI, 21.9% had previously been diagnosed with cancer, resulting in an elevated OR of 36.5 (95% confidence interval [CI] 30.9 to 43.3) compared with 0.8% of the controls. The risk of developing POI was most pronounced during the first 2 years following a cancer diagnosis, with an OR of 103 (95% CI 74.1 to 144). Importantly, this risk remained elevated even when the time interval between cancer and POI exceeded 10 years, with an OR of 5.40 (95% CI 3.54 to 8.23). CONCLUSIONS: This study reveals that 21.9% of women with POI have a history of cancer, making the prevalence of cancer among these women 27.5 times higher than age-matched controls in the Finnish population. The risk of developing POI is most substantial in the first 2 years following a cancer diagnosis. These findings underscore the role of cancer treatments as an etiological factor for POI and emphasize the importance of recognizing the risk of POI in cancer survivors for early diagnosis and intervention.
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Menopausia Prematura , Neoplasias , Insuficiencia Ovárica Primaria , Humanos , Femenino , Adulto , Estudios de Casos y Controles , Insuficiencia Ovárica Primaria/epidemiología , Finlandia/epidemiologíaRESUMEN
INTRODUCTION: The Coronavirus 2019 Disease (COVID-19) pandemic reached the Nordic countries in March 2020. Public health interventions to limit viral transmission varied across different countries both in timing and in magnitude. Interventions indicated by an Oxford Stringency Index ≥50 were implemented early (March 13-17, 2020) in Denmark, Finland, Norway and Iceland, and on March 26, 2020 in Sweden. The aim of the current study was to assess the incidence of COVID-19-related admissions of pregnant women in the Nordic countries in relation to the different national public health strategies during the first year of the pandemic. MATERIAL AND METHODS: This is a meta-analysis of population-based cohort studies in the five Nordic countries with national or regional surveillance in the Nordic Obstetric Surveillance System (NOSS) collaboration: national data from Denmark, Finland, Iceland and Norway, and regional data covering 31% of births in Sweden. The source population consisted of women giving birth in the included areas March 1-December 31, 2020. Pregnant women with a positive SARS-CoV-2 PCR test ≤14 days before hospital admission were included, and admissions were stratified as either COVID-19-related or non-COVID (other obstetric healthcare). Information about public health policies was retrieved retrospectively. RESULTS: In total, 392 382 maternities were considered. Of these, 600 women were diagnosed with SARS-CoV-2 infection and 137 (22.8%) were admitted for COVID-19 symptoms. The pooled incidence of COVID-19 admissions per 1000 maternities was 0.5 (95% confidence interval [CI] 0.2 to 1.2, I2 = 77.6, tau2 = 0.68, P = 0.0), ranging from no admissions in Iceland to 1.9 admissions in the Swedish regions. Interventions to restrict viral transmission were less stringent in Sweden than in the other Nordic countries. CONCLUSIONS: There was a clear variation in pregnant women's risk of COVID-19 admission across countries with similar healthcare systems but different public health interventions to limit viral transmission. The meta-analysis indicates that early suppression policies protected pregnant women from severe COVID-19 disease prior to the availability of individual protection with vaccines.