Explore the vast range of titles available.

AbstractObjectivesTo estimate the burden of miscarriage in the Norwegian population and to evaluate the associations with maternal age and pregnancy history.DesignProspective register based study.SettingMedical Birth Register of Norway, the Norwegian Patient Register, and the induced abortion register.ParticipantsAll Norwegian women that were pregnant between 2009-13.Main outcome measureRisk of miscarriage according to the woman’s age and pregnancy history estimated by logistic regression.ResultsThere were 421 201 pregnancies during the study period. The risk of miscarriage was lowest in women aged 25-29 (10%), and rose rapidly after age 30, reaching 53% in women aged 45 and over. There was a strong recurrence risk of miscarriage, with age adjusted odds ratios of 1.54 (95% confidence interval 1.48 to 1.60) after one miscarriage, 2.21 (2.03 to 2.41) after two, and 3.97 (3.29 to 4.78) after three consecutive miscarriages. The risk of miscarriage was modestly increased if the previous birth ended in a preterm delivery (adjusted odds ratio 1.22, 95% confidence interval 1.12 to 1.29), stillbirth (1.30, 1.11 to 1.53), caesarean section (1.16, 1.12 to 1.21), or if the woman had gestational diabetes in the previous pregnancy (1.19, 1.05 to 1.36). The risk of miscarriage was slightly higher in women who themselves had been small for gestational age (1.08, 1.04 to 1.13).ConclusionsThe risk of miscarriage varies greatly with maternal age, shows a strong pattern of recurrence, and is also increased after some adverse pregnancy outcomes. Miscarriage and other pregnancy complications might share underlying causes, which could be biological conditions or unmeasured common risk factors.

Influenza infection is associated with significant morbidity in pregnant women. In this retrospective report from Norway, the safety of the 2009 pandemic influenza A (H1N1) vaccine was assessed with respect to fetal deaths in 2009–2010. During the 2009 influenza A (H1N1) pandemic, pregnant women were particularly vulnerable to severe influenza illness, with a heightened risk of adverse pregnancy outcomes and maternal death. 1 – 4 The susceptibility of pregnant women to influenza has also been observed in the past. 5 – 12 The World Health Organization's recommendation for the administration of seasonal influenza vaccine, which included vaccination of pregnant women, did not change during the H1N1 pandemic. 13 In addition, it was recommended that pregnant women receive a pandemic vaccine. 14 Before 2009, pregnant women in Norway were not routinely advised to be vaccinated against seasonal influenza. During the pandemic, a . . .

Background: Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear. Objective: We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy. Methods: We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K). Results: We found differential DNA methylation at epigenome-wide statistical significance (p-value < 1.06 × 10-7) for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1, and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor signaling pathway, which mediates the detoxification of the components of tobacco smoke. GFI1 is involved in diverse developmental processes but has not previously been implicated in responses to tobacco smoke. Conclusions: We identified a set of genes with methylation changes present at birth in children whose mothers smoked during pregnancy. This is the first study of differential methylation across the genome in relation to maternal smoking during pregnancy using the 450K platform. Our findings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure.

In this case–control study performed with the use of registry data in Norway, there was no evidence of an increased risk of first-trimester pregnancy loss associated with Covid-19 vaccination during early pregnancy.

National health care registries in the Nordic countries share many attributes, but different legal and ethical frameworks represent a challenge to promoting effective joint research. Internationally, there is a lack of knowledge about how ethical matters are considered in Nordic registry-based research, and a lack of knowledge about how Nordic ethics committees operate and what is needed to obtain an approval. In this paper, we review ethical aspects of registry-based research, the legal framework, the role of ethics review boards in the Nordic countries, and the structure of the ethics application. We discuss the role of informed consent in registry-based research and how to safeguard the integrity of study participants, including vulnerable subjects and children. Our review also provides information on the different government agencies that contribute registry-based data, and a list of the major health registries in Denmark, Finland, Iceland, Norway, and Sweden. Both ethical values and conditions for registry-based research are similar in the Nordic countries. While Denmark, Finland, Iceland, Norway, and Sweden have chosen different legal frameworks, these differences can be resolved through mutual recognition of ethical applications and by harmonizing the different systems, likely leading to increased collaboration and enlarged studies.

Increased risk of miscarriage has been reported for women with specific chronic health conditions. A broader investigation of chronic diseases and miscarriage risk may uncover patterns across categories of illness. The objective of this study was to study the risk of miscarriage according to various preexisting chronic diseases. We conducted a registry-based study. Registered pregnancies (n = 593,009) in Norway between 2010 and 2016 were identified through 3 national health registries (birth register, general practitioner data, and patient registries). Six broad categories of illness were identified, comprising 25 chronic diseases defined by diagnostic codes used in general practitioner and patient registries. We required that the diseases were diagnosed before the pregnancy of interest. Miscarriage risk according to underlying chronic diseases was estimated as odds ratios (ORs) using generalized estimating equations adjusting for woman's age. The mean age of women at the start of pregnancy was 29.7 years (SD 5.6 years). We observed an increased risk of miscarriage among women with cardiometabolic diseases (OR 1.25, 95% CI 1.20 to 1.31; p-value <0.001). Within this category, risks were elevated for all conditions: atherosclerosis (2.22; 1.42 to 3.49; p-value <0.001), hypertensive disorders (1.19; 1.13 to 1.26; p-value <0.001), and type 2 diabetes (1.38; 1.26 to 1.51; p-value <0.001). Among other categories of disease, risks were elevated for hypoparathyroidism (2.58; 1.35 to 4.92; p-value 0.004), Cushing syndrome (1.97; 1.06 to 3.65; p-value 0.03), Crohn's disease (OR 1.31; 95% CI: 1.18 to 1.45; p-value 0.001), and endometriosis (1.22; 1.15 to 1.29; p-value <0.001). Findings were largely unchanged after mutual adjustment. Limitations of this study include our inability to adjust for measures of socioeconomic position or lifestyle characteristics, in addition to the rareness of some of the conditions providing limited power. In this registry study, we found that, although risk of miscarriage was largely unaffected by maternal chronic diseases, risk of miscarriage was associated with conditions related to cardiometabolic health. This finding is consistent with emerging evidence linking cardiovascular risk factors to pregnancy complications.

Maternal fever during pregnancy is associated with several adverse child outcomes. We investigated associations between maternal fever and ADHD among offspring, as well as the sub-dimensions of ADHD - inattention and hyperactivity/impulsivity. Data came from the Norwegian Mother and Child Cohort Study, including more than 114,000 children. Information about children’s ADHD diagnoses was obtained from the Norwegian Patient Register. Mothers reported on inattention and hyperactivity/impulsivity symptoms in questionnaires at 8 years. Logistic regression analysis showed that children exposed to maternal fever in the first trimester received an ADHD diagnosis more often than unexposed children (Odds Ratio (OR) = 1.31, 95% confidence interval (CI) = 1.06–1.61). For children exposed twice or more in the first trimester, the OR was 2.64 (CI = 1.36–5.14). Linear regression analysis showed elevated inattention symptoms among children exposed to fever in the first (Cohen’s d = 0.09, CI = 0.03–0.15) and second (Cohen’s d = 0.05, CI = 0.01–0.09) trimester. Results were similar whether the mother had taken acetaminophen for their fever or not. Hyperactivity/impulsivity symptoms were not related to maternal fever. The results indicate that maternal fever in early pregnancy may be a risk factor for ADHD, and particularly for inattention problems. This risk is neither mitigated nor inflated by use of acetaminophen.

Offspring of older mothers are at increased risk of adverse birth outcomes, childhood cancers, type 1 diabetes, and neurodevelopmental disorders. The underlying biologic mechanisms for most of these associations remain obscure. One possibility is that maternal aging may produce lasting changes in the epigenetic features of a child's DNA. To test this, we explored the association of mothers' age at pregnancy with methylation in her offspring, using blood samples from 890 Norwegian newborns and measuring DNA methylation at more than 450,000 CpG sites across the genome. We examined replication of a maternal-age finding in an independent group of 1062 Norwegian newborns, and then in 200 US middle-aged women. Older maternal age was significantly associated with reduced methylation at four adjacent CpGs near the 2nd exon of KLHL35 in newborns (p-values ranging from 3x10-6 to 8x10-7). These associations were replicated in the independent set of newborns, and replicated again in women 40 to 60 years after their birth. This study provides the first example of parental age permanently affecting the epigenetic profile of offspring. While the specific functions of the affected gene are unknown, this finding opens the possibility that a mother's age at pregnancy could affect her child's health through epigenetic mechanisms.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated to infections and it has been suggested that vaccination can trigger the disease. However, little is known about the specific association between clinically manifest influenza/influenza vaccine and CFS/ME. As part of a registry surveillance of adverse effects after mass vaccination in Norway during the 2009 influenza A (H1N1) pandemic, we had the opportunity to estimate and contrast the risk of CFS/ME after infection and vaccination. Using the unique personal identification number assigned to everybody who is registered as resident in Norway, we followed the complete Norwegian population as of October 1, 2009, through national registries of vaccination, communicable diseases, primary health, and specialist health care until December 31, 2012. Hazard ratios (HRs) of CFS/ME, as diagnosed in the specialist health care services (diagnostic code G93.3 in the International Classification of Diseases, Version 10), after influenza infection and/or vaccination were estimated using Cox proportional-hazards regression. The incidence rate of CFS/ME was 2.08 per 100,000 person-months at risk. The adjusted HR of CFS/ME after pandemic vaccination was 0.97 (95% confidence interval [CI]: 0.91–1.04), while it was 2.04 (95% CI: 1.78–2.33) after being diagnosed with influenza infection during the peak pandemic period. Pandemic influenza A (H1N1) infection was associated with a more than two-fold increased risk of CFS/ME. We found no indication of increased risk of CFS/ME after vaccination. Our findings are consistent with a model whereby symptomatic infection, rather than antigenic stimulation may trigger CFS/ME.

WHO recommends that women wait at least 2 years after a livebirth and at least 6 months after a miscarriage or induced abortion before conceiving again, to reduce the risk of adverse birth outcomes in the subsequent pregnancy. No recommendation exists for the optimal interval after a stillbirth. We investigated the association between interpregnancy interval after stillbirth and birth outcomes in the subsequent pregnancy. In this international cohort study, we used data from birth records from Finland (1987–2016), Norway (1980–2015), and Western Australia (1980–2015). Consecutive singleton pregnancies in women whose most recent pregnancy had ended in stillbirth of at least 22 weeks' gestation were included in the analysis. Interpregnancy interval was defined as the time between the end of pregnancy (delivery date) and the start of the next pregnancy (delivery date of next pregnancy minus gestational age at birth). We calculated odds ratios (ORs) for stillbirth, preterm birth, and small-for-gestational-age birth by interpregnancy interval by country, adjusted for maternal age, parity, decade of delivery, and gestational length of the previous pregnancy. A fixed-effects meta-analysis was used to estimate pooled ORs. We identified 14 452 births in women who had a stillbirth in the previous pregnancy; median interpregnancy interval after stillbirth was 9 months (IQR 4–19). 9109 (63%) women conceived within 12 months of the stillbirth. Of the 14 452 births, 228 (2%) were stillbirths, 2532 (18%) were preterm births, and 1284 (9%) were small-for-gestational-age births. Compared with an interpregnancy interval of 24–59 months, intervals shorter than 12 months were not associated with increased odds of subsequent stillbirth (pooled adjusted OR 1·09 [95% CI 0·63–1·91] for <6 months; 0·90 [0·47–1·71] for 6–11 months), preterm birth (0·91 [0·75–1·11] for <6 months; 0·91 [0·74–1·11] for 6–11 months), or small-for-gestational-age birth (0·66 [0·51–0·85] for <6 months; 0·64 [0·48–0·84] for 6–11 months). Further, we noted no difference in the association between interpregnancy interval and birth outcomes by gestational length of the previous stillbirth. Conception within 12 months of a stillbirth was common and was not associated with increased risk of adverse outcomes in the subsequent pregnancy. These findings could be used when counselling women who are planning future pregnancies after a stillbirth and for informing future recommendations for pregnancy spacing in a high-income setting. National Health and Medical Research Council (Australia), and Research Council of Norway.