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1.
  • Calvert, Clara, et al. (author)
  • Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries
  • 2023
  • In: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7:4, s. 529-544
  • Journal article (peer-reviewed)abstract
    • Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.
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2.
  • KC, Ashish, 1982-, et al. (author)
  • Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.
  • 2023
  • In: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 7:4, s. 529-544
  • Journal article (peer-reviewed)abstract
    • Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.
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3.
  • Frier, Emily M, et al. (author)
  • Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids.
  • 2023
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3
  • Journal article (peer-reviewed)abstract
    • Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure.The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records.The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.
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4.
  • Gorasso, Vanessa, et al. (author)
  • Burden of disease attributable to risk factors in European countries: a scoping literature review
  • 2023
  • In: Archives of Public Health. - 0778-7367 .- 2049-3258. ; 81:1
  • Research review (peer-reviewed)abstract
    • Objectives: Within the framework of the burden of disease (BoD) approach, disease and injury burden estimates attributable to risk factors are a useful guide for policy formulation and priority setting in disease prevention. Considering the important differences in methods, and their impact on burden estimates, we conducted a scoping literature review to: (1) map the BoD assessments including risk factors performed across Europe; and (2) identify the methodological choices in comparative risk assessment (CRA) and risk assessment methods. Methods: We searched multiple literature databases, including grey literature websites and targeted public health agencies websites. Results: A total of 113 studies were included in the synthesis and further divided into independent BoD assessments (54 studies) and studies linked to the Global Burden of Disease (59 papers). Our results showed that the methods used to perform CRA varied substantially across independent European BoD studies. While there were some methodological choices that were more common than others, we did not observe patterns in terms of country, year or risk factor. Each methodological choice can affect the comparability of estimates between and within countries and/or risk factors, since they might significantly influence the quantification of the attributable burden. From our analysis we observed that the use of CRA was less common for some types of risk factors and outcomes. These included environmental and occupational risk factors, which are more likely to use bottom-up approaches for health outcomes where disease envelopes may not be available. Conclusions: Our review also highlighted misreporting, the lack of uncertainty analysis and the under-investigation of causal relationships in BoD studies. Development and use of guidelines for performing and reporting BoD studies will help understand differences, avoid misinterpretations thus improving comparability among estimates.
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5.
  • Engjom, Hilde, et al. (author)
  • COVID-19 in pregnancy—characteristics and outcomes of pregnant women admitted to hospital because of SARS-CoV-2 infection in the Nordic countries
  • 2021
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 100:9, s. 1611-1619
  • Journal article (peer-reviewed)abstract
    • Introduction: Population-based studies about the consequences of SARS-CoV-2 infection (COVID-19) in pregnancy are few and have limited generalizability to the Nordic population and healthcare systems. Material and methods: This study examines pregnant women with COVID-19 in the five Nordic countries. Pregnant women were included if they were admitted to hospital between 1 March and 30 June 2020 and had a positive SARS-CoV-2 PCR test ≤14 days prior to admission. Cause of admission was classified as obstetric or COVID-19-related. Results: In the study areas, 214 pregnant women with a positive test were admitted to hospital, of which 56 women required hospital care due to COVID-19. The risk of admission due to COVID-19 was 0.4/1000 deliveries in Denmark, Finland and Norway, and 3.8/1000 deliveries in the Swedish regions. Women hospitalized because of COVID-19 were more frequently obese (p < 0.001) and had a migrant background (p < 0.001) compared with the total population of women who delivered in 2018. Twelve women (21.4%) needed intensive care. Among the 56 women admitted due to COVID-19, 48 women delivered 51 infants. Preterm delivery (n = 12, 25%, p < 0.001) and cesarean delivery (n = 21, 43.8%, p < 0.001) were more frequent in women with COVID-19 compared with women who delivered in 2018. No maternal deaths, stillbirths or neonatal deaths were reported. Conclusions: The risk of admission due to COVID-19 disease in pregnancy was low in the Nordic countries. A fifth of the women required intensive care and we observed higher rates of preterm and cesarean deliveries. National public health policies appear to have had an impact on the risk of admission due to severe COVID-19 disease in pregnancy. Nordic collaboration is important in collecting robust data and assessing rare outcomes.
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6.
  • Kitahara, Cari M., et al. (author)
  • Maternal health, in-utero, and perinatal exposures and risk of thyroid cancer in offspring : a Nordic population-based nested case-control study
  • 2021
  • In: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 9:2, s. 94-105
  • Journal article (peer-reviewed)abstract
    • Background Thyroid cancer tends to be diagnosed at a younger age (median age 51 years) compared with most other malignancies (such as breast cancer [62 years] or lung cancer [71 years]). The incidence of thyroid cancer is higher in women than men diagnosed from early adolescence. However, few in-utero and early life risk exposures associated with increased risk of thyroid cancer have been identified. Methods In this population-based nested case-control study we used registry data from four Nordic countries to assess thyroid cancer risk in offspring in relation to maternal medical history, pregnancy complications, and birth characteristics. Patient with thyroid cancer (cases) were individuals born and subsequently diagnosed with first primary thyroid cancer from 1973 to 2013 in Denmark, 1987 to 2014 in Finland, 1967 to 2015 in Norway, or 1973 to 2014 in Sweden. Each case was matched with up to ten individuals without thyroid cancer (controls) based on birth year, sex, country, and county of birth. Cases and matched controls with a previous diagnosis of any cancer, other than non-melanoma skin cancer, at the time of thyroid cancer diagnosis were excluded. Cases and matched controls had to reside in the country of birth at the time of thyroid cancer diagnosis. Conditional logistic regression models were used to calculate odds ratios (ORs) with 95% CIs. Findings Of the 2437 cases, 1967 (81.4%) had papillary carcinomas, 1880 (77.1%) were women, and 1384 (56.7%) were diagnosed before age 30 years (range 0-48). Higher birth weight (OR per kg 1.14 [95% CI 1.05-1.23]) and congenital hypothyroidism (4.55 [1.58-13.08]); maternal diabetes before pregnancy (OR 1.69 [0.98-2.93]) and postpartum haemorrhage (OR 1.28 [1.06-1.55]); and (from registry data in Denmark) maternal hypothyroidism (18.12 [10.52-31.20]), hyperthyroidism (11.91 [6.77-20.94]), goiter (67.36 [39.89-113.76]), and benign thyroid neoplasms (22.50 [6.93-73.06]) were each associated with an increased risk of thyroid cancer in offspring. Interpretation In-utero exposures, particularly those related to maternal thyroid disorders, might have a long-term influence on thyroid cancer risk in offspring. 
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7.
  • Kitahara, Cari M., et al. (author)
  • Maternal Health, Pregnancy and Offspring Factors, and Maternal Thyroid Cancer Risk : A Nordic Population-Based Registry Study
  • 2023
  • In: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 192:1, s. 70-83
  • Journal article (peer-reviewed)abstract
    • Thyroid cancer incidence is higher in women than men, especially during the reproductive years, for reasons that remain poorly understood. Using population-based registry data from 4 Nordic countries through 2015, we examined associations of perinatal characteristics with risk of maternal thyroid cancer. Cases were women diagnosed with thyroid cancer >= 2 years after last birth (n = 7,425, 83% papillary). Cases were matched to controls (n = 67,903) by mother's birth year, country, and county of residence. Odds ratios (ORs) were estimated using conditional logistic regression models adjusting for parity. Older age at first pregnancy, postpartum hemorrhage (OR = 1.18, 95% (confidence interval) CI: 1.08, 1.29), and benign thyroid conditions (ORs ranging from 1.64 for hypothyroidism to 10.35 for thyroid neoplasms) were associated with increased thyroid cancer risk, as were higher offspring birth weight (per 1-kg increase, OR = 1.17, 95% CI: 1.12, 1.22) and higher likelihood of offspring being large for gestational age (OR = 1.26, 95% CI: 1.11, 1.43). Unmarried/noncohabiting status (OR = 0.91, 95% CI: 0.84, 0.98), maternal smoking (OR = 0.75, 95% CI: 0.67, 0.84), and preterm birth (OR = 0.90, 95% CI: 0.83, 0.98) were associated with reduced risk. Several factors (e.g., older age at first pregnancy, maternal smoking, goiter, benign neoplasms, postpartum hemorrhage, hyperemesis gravidarum, and neonatal jaundice) were associated with advanced thyroid cancer. These findings suggest that some perinatal exposures may influence maternal thyroid cancer risk.
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8.
  • Varpula, Reetta, et al. (author)
  • Early suppression policies protected pregnant women from COVID-19 in 2020 : A population-based surveillance from the Nordic countries
  • 2024
  • In: Acta Obstetricia et Gynecologica Scandinavica. - 0001-6349. ; 103:6, s. 1063-1072
  • Journal article (peer-reviewed)abstract
    • 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.
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9.
  • Wedenoja, Satu, et al. (author)
  • Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia
  • 2020
  • In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 59
  • Journal article (peer-reviewed)abstract
    • Background: Fetal immune tolerance is crucial for pregnancy success. We studied the link between preeclampsia, a severe pregnancy disorder with uncertain pathogenesis, and fetal human leukocyte antigen G (HLA-G) and other genes regulating maternal immune responses.Methods: We assessed sex ratios and regulatory HLA-G haplotypes in population cohorts and series of preeclampsia and stillbirth. We studied placental mRNA expression of 136 genes by sequencing and HLA-G and interferon alpha (IFNα) protein expression by immunohistochemistry.Findings: We found underrepresentation of males in preeclamptic births, especially those delivered preterm or small for gestational age. Balancing selection at HLA-G associated with the sex ratio, stillbirth, and preeclampsia. We observed downregulation of HLA-G, its receptors, and many other tolerogenic genes, and marked upregulation of IFNA1 in preeclamptic placentas.Interpretation: These findings indicate that an evolutionary trade-off between immune tolerance and protection against infections at the maternal-fetal interface promotes genetic diversity in fetal HLA-G, thereby affecting survival, preeclampsia, and sex ratio. We highlight IFNA1 as a potential mediator of preeclampsia and a target for therapeutic trials. 
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