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Objective: To examine the effect of maternal exposure to asthma medications on the risk of congenital anomalies.Design: Meta-analysis of aggregated data from three cohort studies.Setting: Linkage between healthcare databases and EUROCAT congenital anomaly registries.Population: 519 242 pregnancies in Norway (2004-2010), Wales (2000-2010) and Funen, Denmark (2000-2010).Methods: Exposure defined as having at least one prescription for asthma medications issued (Wales) or dispensed (Norway, Denmark) from 91 days before to 91 days after the pregnancy start date. Odds ratios (ORs) were estimated separately for each register and combined in meta-analyses.Main Outcome Measures: ORs for all congenital anomalies and specific congenital anomalies.Results: Overall exposure prevalence was 3.76%. For exposure to asthma medication in general, the adjusted OR (adjOR) for a major congenital anomaly was 1.21 (99% CI 1.09-1.34) after adjustment for maternal age and socioeconomic position. The OR of anal atresia was significantly increased in pregnancies exposed to inhaled corticosteroids (3.40; 99% CI 1.15-10.04). For severe congenital heart defects, an increased OR (1.97; 1.12-3.49) was associated with exposure to combination treatment with inhaled corticosteroids and long-acting beta-2-agonists. Associations with renal dysplasia were driven by exposure to short-acting beta-2-agonists (2.37; 1.20-4.67).Conclusion: The increased risk of congenital anomalies for women taking asthma medication is small with little confounding by maternal age or socioeconomic status. The study confirmed the association of inhaled corticosteroids with anal atresia found in earlier research and found potential new associations with combination treatment. The potential new associations should be interpreted with caution due to the large number of comparisons undertaken.Tweetable Abstract: This cohort study found a small increased risk of congenital anomalies for women taking asthma medication. [ABSTRACT FROM AUTHOR]

Objective: To study the association between maternal age and emergency operative delivery. The roles of in-labour indications, and birthweight ≥ 4000 g, gestational age ≥ 42 weeks, induction of labour, and epidural use, according to maternal age were explored.Design: Population-based study.Setting: Medical Birth Registry of Norway and Statistics Norway.Population: We studied 169 583 low-risk primiparous mothers with singleton, cephalic labours, at ≥37 weeks of gestation, from 1999 to 2009.Methods: The associations between maternal age and mode of delivery were analysed using multinomial regression analyses, adjusting for sociodemographic factors.Main Outcome Measures: Emergency caesarean section and operative vaginal delivery.Results: Of women aged ≥40 years, 22% had emergency caesarean sections and 24% had operative vaginal deliveries, giving adjusted relative risk ratios (RRRs) of 6.60 (95% confidence interval, 95% CI 5.53-7.87) and 3.30 (95% CI 2.79-3.90), respectively, when compared with women aged 20-24 years. Adjustments for sociodemographic factors only slightly changed the estimates. Dystocia was the main indication, followed by fetal distress. All of the listed factors increased the level of emergency operative deliveries, mainly because of an increase in dystocia. The increase in risk for emergency caesarean section by all factors, and for operative vaginal deliveries by epidural, were greater in older than in younger women, but were significant for epidural only.Conclusions: We found a close association between maternal age and emergency operative delivery in low-risk primiparas. Contributory factors increased the risk for both emergency operative delivery and epidural more in older than in younger women. [ABSTRACT FROM AUTHOR]

Objective To examine the risk of pre-eclampsia ( PE) in women conceiving after assisted reproductive technologies ( ART). Potential confounding from maternal age, long intervals between births, new partner and smoking were evaluated. Design and setting Population-based cohort study with data from the Medical Birth Registry of Norway. Population A total of 501 766 mothers with offspring from 1988 to 2009. Methods Births to the same mother were linked in sibship data files with information of ART. Main outcome measures Odds ratio ( OR) (95% confidence intervals) of PE in pregnancies conceived by ART compared with spontaneous conception, stratified by parity. Results The prevalence of PE was 5.1% in first, 2.2% in second and 2.1% in third pregnancies. Corresponding figures in ART pregnancies were 6.0%, 3.3% and 4.4%. Hence, the odds ratios of PE in ART pregnancies relative to spontaneous pregnancies increased from 1.2 (1.1-1.3) in first, 1.5 (1.3-1.8) in second to 2.1 (1.4-3.3) in third pregnancies. Adjusting by maternal age lowered the odds ratio to 1.3 (1.1-1.6) and 1.8 (1.2-2.8) in second and third pregnancies, respectively. Multi-adjusted, birth interval had more impact than change of partner. Smoking was associated with a strongly reduced PE risk (odds ratio 0.65; 0.62-0.69), but there was no confounding by smoking on the ART associated risk. Conclusions Assisted reproductive technologies increases the risk of PE, and the risk may increase by parity. The association between ART pregnancies and PE is to some extent explained by interbirth intervals and advanced maternal age, but not to change of partner or smoking. [ABSTRACT FROM AUTHOR]

Objective To assess the availability of obstetric institutions, the risk of unplanned delivery outside an institution and maternal morbidity in a national setting in which the number of institutions declined from 95 to 51 during 30 years. Design Retrospective population-based, three cohorts and two cross-sectional analyses. Setting Census data, Statistics Norway. The Medical Birth Registry of Norway from 1979 to 2009. Population Women (15-49 years), 2000 ( n = 1 050 269) and 2010 ( n = 1 127 665). Women who delivered during the period 1979-2009 ( n = 1 807 714). Methods Geographic Information Systems software for travel zone calculations. Cross-table and multiple logistic regression analysis of change over time and regional differences. World Health Organization Emergency Obstetric and Newborn Care (Em OC) indicators. Main outcome measures Proportion of women living outside the 1-hour travel zone to obstetric institutions. Risk of unplanned delivery outside obstetric institutions. Maternal morbidity. Results The proportion of women living outside the 1-hour zone for all obstetric institutions increased from 7.9% to 8.8% from 2000 to 2010 (relative risk, 1.1; 95% confidence interval, 1.11-1.12), and for emergency obstetric care from 11.0% to 12.1% (relative risk, 1.1; 95% confidence interval, 1.09-1.11). The risk of unplanned delivery outside institutions increased from 0.4% in 1979-83 to 0.7% in 2004-09 (adjusted odds ratio, 2.0; 95% confidence interval, 1.9-2.2). Maternal morbidity increased from 1.7% in 2000 to 2.2% in 2009 (adjusted odds ratio, 1.4; 95% confidence interval, 1.2-1.5) and the regional differences increased. Conclusions The availability of and access to obstetric institutions was reduced and we did not observe the expected decrease in maternal morbidity following the centralisation. [ABSTRACT FROM AUTHOR]

Introduction: Although perinatal death rates in the Nordic countries are among the lowest in the world, the risk of perinatal death is unevenly distributed across the Nordic countries, despite similarity in health care systems and pregnancy care. Birth registration practices across countries may explain some of the differences. We investigated differences in national registration of perinatal mortality within the Nordic countries and its impact on perinatal mortality according to gestational age., Material and Methods: Each country provided information by answering a questionnaire about registration of perinatal deaths. Furthermore, we collected aggregated count data based on Medical Birth Registries (MBR) from all Nordic countries in 2000 to 2021. Perinatal mortality was defined as stillbirth or neonatal death occurring within first 7 days of life. Data were grouped into six groups by gestational age (GA): extremely preterm (>28 + 0 weeks, subdivided into 22 + 0-23 + 6 and 24 + 0-27 + 6), very preterm (GA 28 + 0-31 + 6), moderate preterm (GA 32 + 0-33 + 6), late preterm (GA 34 + 0-36 + 6), term (GA 37 + 0-40 + 6) and late term or post-term birth (GA ≥ 41 + 0). Perinatal mortality rate and risk ratio with 95% confidence intervals were calculated per country for each gestational age group. For Denmark, separate analyses included and excluded induced abortions., Results: The study included 6 343 805 live births, 22 727 stillbirths and 8932 liveborn infants who died within the first week of life after GA 22 + 0. Further 25 057 births were included with GA < 22 + 0, unknown GA and as a result of induced abortion. Overall, perinatal mortality rates decreased during year 2000-2021 in all Nordic countries. After exclusion of induced abortions, the perinatal mortality rate was similar in the five Nordic countries. The perinatal mortality rate for extremely preterm born infants was highest in Denmark, whereas the highest rate among infants born late term/post-term was in Sweden., Conclusions: The perinatal mortality rate in the Nordic countries is still decreasing, especially in the group of extremely preterm born infants. This study supports the need for further standardization of birth registration practices to ensure the validity of international comparisons., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: The objective of this study is to assess associations between pregnancy complications and pregnancy-associated maternal mortality (PAM) within 1 year after childbirth., Design: Population-based cohort study., Setting: Norway, 1967-2020., Population: 1 237 254 mothers with one or more singleton pregnancies registered in the Medical Birth Registry, 1967-2019 and followed in the Cause of Death Registry to 2020., Methods: Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for maternal education, age, year of first childbirth and chronic medical conditions., Main Outcome Measures: PAM by lifetime history of pregnancy complications: placental abruption, preeclampsia, preterm birth, perinatal death, small for gestational age (< 2.5 percentile), gestational diabetes and gestational hypertension., Results: Crude OR for PAM was 4.24 (95% CI 3.53-5.10), if complications occurred in the last pregnancy, whereas 2.52 (2.08-3.06) if complications occurred in the first pregnancy, compared to mothers without complications in any pregnancy. Adjusted ORs for PAM when complications occurred in the last pregnancy were, for placental abruption 3.75 (1.20-11.72), preeclampsia: 4.42 (3.17-6.15), preterm birth: 4.32 (3.25-5.75), perinatal death: 24.18 (16.66-35.08), small for gestational age: 2.90 (1.85-4.54), gestational diabetes: 1.43 (0.63-3.25) and pregnancy hypertension: 2.05 (1.12-3.74) compared to mothers without complications. The OR for PAM increased slightly by increasing the number of complicated pregnancies but the trend was stronger for increasing number of complications in the last pregnancy (e.g., during 1999-2019: one complication; 4.14 [2.79-6.13], two complications; 11.50 [6.81-19.43])., Conclusion: Complications in the last pregnancy were more strongly associated with PAM than those in the first pregnancy., (© 2024 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Partially driven by public concerns about modern food production practices, organic food has gained popularity among consumers. However, the impact of organic food consumption during pregnancy on offspring health is scarcely studied. We aimed to investigate the association between maternal intake of organic food during pregnancy and symptoms of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring at 8 years of age., Methods: This study was based on the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN). The total study sample included 40,707 mother-child pairs (children born 2002-2009). Organic food consumption during pregnancy was assessed by six questions from a food frequency questionnaire in mid-pregnancy (sum score 0-18). Symptoms of ADHD and ASD in the offspring aged 8 years were measured by ADHD (0-54) and ASD (0-39) symptom scores based on the Parent/Teacher Rating Scale for Disruptive Behaviour disorders and the Social Communication Questionnaire. Associations between maternal intake of organic food during pregnancy and symptoms of ADHD and ASD in the offspring were analyzed using regression models with adjustment for covariates such as maternal anxiety and depression, including sibling analysis., Results: Mean ADHD and ASD symptom scores in the offspring differed only slightly by maternal intake of organic food. The covariate-adjusted unstandardized regression coefficient (adjusted(Adj)beta) with 95% confidence interval for the ADHD symptom score with one unit increase in organic food sum score was 0.03 (0.01, 0.05). Similarly, Adjbeta for autism symptom score was 0.07 (0.04, 0.10). For ADHD, the adjusted estimates weakened when adjusting for maternal symptoms of ADHD. The sibling analyses showed no significant results with Adjbeta - 0.07 (- 0.15, 0.01) and - 0.001 (- 0.12, 0.12) for ADHD and ASD outcomes, respectively., Conclusions: We observed weak positive associations between frequent maternal organic food consumption during pregnancy and offspring ADHD and ASD symptom levels at 8 years of age. This trend weakened or disappeared after adjusting for maternal symptoms of ADHD, and in sibling analyses, suggesting that the associations mainly reflect genetic confounding. Our study indicates that consumption of organic food during pregnancy should neither be considered a risk factor nor protective against symptoms of ADHD and ASD in offspring., (© 2024. The Author(s).)

Objective: To investigate the incidence of severe postpartum haemorrhage among nulliparous women with a spontaneous onset of labour at term from 2000 to 2020., Design: Population-based cohort study., Setting: National, using the Medical Birth Registry of Norway., Population: Women (n = 330 244) who gave birth to their first singleton child in a cephalic presentation after a spontaneous onset of labour at term., Methods: Cross-tabulations and regression analysis with generalised linear models were used to assess time trends and adjust for potential confounding factors. We also stratified the analyses by maternal age groups, obstetric interventions, mode of delivery and institution size. Time trends were analysed using periods of 5 or 6 years as a unit, and the period from 2000 to 2004 was used as the reference., Main Outcome Measures: Severe postpartum haemorrhage (PPH) was defined as blood loss of >1500 mL within 24 h and/or in combination with blood transfusion., Results: Severe PPH occurred in 7601/330 244 (2.30%) women. The incidence increased from 1.24% in 2000-2004 to 3.83% in 2015-2020 (adjusted relative risk, aRR 2.90; 95% CI 2.70-3.12). Changes in maternal characteristics or obstetric interventions did not explain the increase, and we found similar increases across institutions of all sizes., Conclusions: The incidence of severe PPH among nulliparous women increased almost threefold over 21 years. The current high incidence warrants urgent efforts to assess unknown risk factors, the health care provided and health system factors that may contribute to the increase, to inform improvements in care., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

We invited individuals aged above 16 years with a congenital transverse reduction deficiency at and above the wrist born in Norway between 1970 and 2006 to complete the short version of the Disabilities of the Arm, Shoulder and Hand Outcome Measure, the 5-Level EuroQoL-5-Dimension instrument, the RAND 36-Item Short Form Health Survey and a single-item questionnaire on arm function, appearance, pain and prosthesis wear. Of 154 eligible participants, 58 (38%) responded. Their scores were not different from the general population. All had been offered prostheses, and 56 (97%) had been fitted at a median age of 1 year (interquartile range 0-2.8). Of the participants, 37 (64%) were still prosthesis wearers, while 21 (36%) were non-wearers or using gripping devices only. Prosthesis wearers had higher levels of 'vitality' as assessed by the RAND-36 and rated their arm appearance higher, but there were no other score differences, indicating that prosthesis rejection is not associated with worse functional outcomes. Level of evidence: III., Competing Interests: Declaration of conflicting interestsThe authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Previous studies have found that women who undergo cesarean delivery have fewer pregnancies. Cesarean delivery is also more common among women with lower fecundability. The potential role of cesarean delivery in reduced fecundability is not known., Objective: This study aimed to assess the bidirectional relationship between cesarean delivery and fecundability., Study Design: This was a prospective cohort study based on data from the Norwegian Mother, Father, and Child Cohort study linked with the Medical Birth Registry of Norway. We estimated the fecundability ratio (per cycle probability of pregnancy) and relative risk of infertility (time to pregnancy ≥12 months) by mode of delivery in the previous delivery among 42,379 women. For the reverse association, we estimated the relative risk of having a cesarean delivery by fecundability (the number of cycles women needed to conceive) among 74,024 women., Results: The proportion of women with infertility was 7.3% (2707/37,226) among women with a previous vaginal delivery and 9.9% (508/5153) among women with a previous cesarean delivery, yielding an adjusted relative risk of 1.21 (95% confidence interval, 1.10-1.33). Women with a previous cesarean delivery also had a lower fecundability ratio (0.90; 95% confidence interval, 0.88-0.93) than women with a previous vaginal delivery. When assessing the reverse association between fecundability and cesarean delivery, we found that women who did not conceive within 12 or more cycles had a higher risk for cesarean delivery (adjusted relative risk, 1.57; 95% confidence interval, 1.48-1.66) than women who conceived within the first 2 cycles. The associations remained after controlling for sociodemographic and clinical risk factors and were observed across parity groups., Conclusion: Among women with more than 1 child, those who had a previous cesarean delivery subsequently had a lower fecundability ratio and an increased infertility risk than those who had a vaginal delivery. However, women who needed a longer time to conceive were also more prone to be delivered by cesarean delivery, indicating a bidirectional relationship between cesarean delivery and fecundability. This could suggest a common underlying explanatory mechanism and that the surgical procedure itself may not or only partly directly influence fecundability., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

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, I 2  = 77.6, tau 2  = 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., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

We identified individuals born in Norway between 1970 and 2019 with transverse reduction deficiency at or above the wrist (TRDAW) from the Medical Birth Registry of Norway and from the CULA (congenital upper limb anomaly) North Oslo Registry. Infant outcomes and parental factors were compared for 202 individuals with TRDAW to 2,741,013 living individuals without TRDAW born during the same period. We found an overall TRDAW prevalence of 0.74/10,000. Infants with TRDAW had a higher risk for being small for gestational age, an Apgar score <7 and transfer to neonatal intensive care units after delivery. Nine of the infants with TRDAW had associated anomalies, most commonly in the lower limb, and at a higher proportion than the reference population. Other than twin pregnancies, we are unable to identify with certainty any other risk factors for TRDAW. Level of evidence: I., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Epidemiological studies suggest that maternal diet quality during pregnancy may influence the risk of neurodevelopmental disorders in offspring. Here, we investigated associations between maternal intake of dietary fiber and attention-deficit/hyperactivity disorder (ADHD) symptoms in early childhood., Methods: We used longitudinal data of up to 21,852 mother-father-child trios (49.2% female offspring) from MoBa (the Norwegian Mother, Father, and Child Cohort Study). The relationships between maternal fiber intake during pregnancy and offspring ADHD symptoms at ages 3, 5, and 8 years were examined using 1) multivariate regression (overall levels of ADHD symptoms), 2) latent class analysis (subclasses of ADHD symptoms by sex at each age), and 3) latent growth curves (longitudinal change in offspring ADHD symptoms). Covariates were ADHD polygenic scores in child and parents, total energy intake and energy-adjusted sugar intake, parental ages at birth of the child, and sociodemographic factors., Results: Higher maternal prenatal fiber intake was associated with lower offspring ADHD symptom scores at all ages (B age3  = -0.14 [95% CI, -0.18 to -0.10]; B age5  = -0.14 [95% CI, -0.19 to -0.09]; B age8  = -0.14 [95% CI, -0.20 to -0.09]). Of the derived low/middle/high subclasses of ADHD symptoms, fiber was associated with lower risk of belonging to the middle subclass for boys and girls and to the high subclass for girls only (middle: odds ratio boys 0.91 [95% CI, 0.86 to 0.97]/odds ratio girls 0.86 [95% CI, 0.81 to 0.91]; high: odds ratio girls 0.82 [95% CI, 0.72 to 0.94]). Maternal fiber intake and rate of change in child ADHD symptoms across ages were not associated., Conclusions: Low prenatal maternal fiber intake may increase symptom levels of ADHD in offspring during childhood, independently of genetic predisposition to ADHD, unhealthy dietary exposures, and sociodemographic factors., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the risk of adverse pregnancy outcomes between twin-born and singleton-born women. We also evaluated whether in utero exposure to pre-eclampsia or preterm delivery affected adverse pregnancy outcomes in women's own pregnancies., Design: Population-based cohort study., Setting: Medical Birth Registry of Norway 1967-2020., Population: 9184 twin-born and 492 894 singleton-born women during 1967-2005, with their later pregnancies registered during 1981-2020., Methods: Data from an individual's birth were linked to their later pregnancies. We used generalised linear models with log link binomial distribution to obtain exponentiated regression coefficients that estimated relative risks (RRs) with 95% confidence intervals (CIs) for associations between twin- or singleton-born women and later adverse pregnancy outcomes., Main Outcome Measures: Pre-eclampsia, preterm delivery or perinatal loss in twin-born compared with singleton-born women., Results: There was no increased risk for adverse outcomes in twin-born compared with singleton-born women: adjusted RRs for pre-eclampsia were 1.00 (95% CI 0.93-1.09), for preterm delivery 0.96 (95% CI 0.90-1.02) and for perinatal loss 1.00 (95% CI 0.84-1.18). Compared with singleton-born women exposed to pre-eclampsia in utero, twin-born women exposed to pre-eclampsia had lower risk of adverse outcomes in their own pregnancies; the aRR for pre-eclampsia was 0.73 (95% CI 0.58-0.91) and for preterm delivery was 0.71 (95% CI 0.56-0.90). Compared with preterm singleton-born women, preterm twin-born women did not differ in terms of risk of pre-eclampsia (aRR 1.05, 95% CI 0.92-1.21) or perinatal loss (aRR 0.99, 95% CI 0.71-1.37) and had reduced risk of preterm delivery (RR 0.83, 95% CI 0.74-0.94)., Conclusions: Twin-born women did not differ from singleton-born women in terms of risk of adverse pregnancy outcomes. Twin-born women exposed to pre-eclampsia in utero, had a lower risk of pre-eclampsia and preterm delivery compared with singleton-born women exposed to pre-eclampsia., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Gliomas constitute 75 % of all malignant primary adult brain tumors. Being the most frequent histologic subtype, glioblastomas (GBMs) cause substantial morbidity and mortality worldwide and the Nordic countries have some of the highest incidence rates in the world. Therefore, we investigated the incidence of gliomas in Norway including time trends and associations with education and occupation., Methods: We retrieved individual-level data from databases at Statistics Norway containing information on education and occupation and linked them to data on adult glioma patients diagnosed during 2004-21 from the Cancer Registry of Norway. Age-standardized incidence rates (ASIRs) (World Standard Population) were calculated and analyzed with regards to sex and morphology. Poisson regression was used to test for time-trends, and to analyze the associations between education, occupation and glioma incidence, adjusted for age, sex, and calendar year. Estimates were reported as incidence rate ratios (IRRs) with 95 % confidence intervals (CIs)., Results: The overall ASIR of gliomas (per 100,000 person-years) was 7.1 (95 % CI 6.9-7.3), with no specific time trend during the study period. The incidence increased with age. Compared to the other subtypes, GBMs were diagnosed at older ages. The risks of developing glioma overall and GBM were associated with occupation but not with educational level. The relative risk of glioma and GBM were respectively 1.17 (95 % CI 1.05-1.31) and 1.17 (95 % CI 1.02-1.35) among high-skilled white-collar workers compared to blue-collar workers., Conclusions: The overall and sex-specific ASIRs of gliomas and GBMs did not show any noticeable time trends. The higher risk of developing glioma overall and GBM in high-skilled white-collar workers compared to blue-collar workers calls for further investigations., Competing Interests: Declaration of Competing Interest The authors declare no competing interests. The material is original research, has not been previously published, and has not been submitted for publication elsewhere while under consideration., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Many human teratogens are associated with a spectrum of congenital anomalies rather than a single defect, and therefore the identification of congenital anomalies occurring together more frequently than expected may improve the detection of teratogens. Thirty-two EUROCAT congenital anomaly registries covering 6,599,765 births provided 123,566 cases with one or more major congenital anomalies (excluding chromosomal and genetic syndromes) for the birth years 2008-2016. The EUROCAT multiple congenital anomaly algorithm identified 8804 cases with two or more major congenital anomalies in different organ systems, that were not recognized as part of a syndrome or sequence. For each pair of anomalies, the odds of a case having both anomalies relative to having only one anomaly was calculated and the p value was estimated using a two-sided Fisher's exact test. The Benjamini-Hochberg procedure adjusted p values to control the false discovery rate and pairs of anomalies with adjusted p values < 0.05 were identified. A total of 1386 combinations of two anomalies were analyzed. Out of the 31 statistically significant positive associations identified, 20 were found to be known associations or sequences already described in the literature and 11 were considered "potential new associations" by the EUROCAT Coding and Classification Committee. After a review of the literature and a detailed examination of the individual cases with the anomaly pairs, six pairs remained classified as new associations. In summary, systematically searching for congenital anomalies occurring together more frequently than expected using the EUROCAT database is worthwhile and has identified six new associations that merit further investigation., (© 2023. The Author(s).)

Background: Prior studies on maternal cardiovascular disease (CVD) mortality and hypertensive disorders of pregnancy (HDP) have focused only on a woman's first birth and have not accounted for successive affected pregnancies., Objectives: The objective of this study is to identify mothers' risk of CVD mortality considering lifetime reproductive history., Methods: We used data from the Medical Birth Registry of Norway, the Norwegian Cause of Death Registry, and the Norwegian National Population Register to identify all mothers who gave birth from 1967 to 2020. Our outcome was mothers' CVD death before age 70. The primary exposure was the lifetime history of HDP. The secondary exposure was the order of HDP and gestational age at delivery of pregnancies with HDP. We used Cox regression models to estimate hazard ratio (HR) and 95% confidence interval (CI), adjusting for education, mother's age, and year of last birth. These models were stratified by the lifetime number of births., Results: Among 987,378 mothers, 86,294 had HDP in at least one birth. The highest CVD mortality, relative to mothers without HDP, was among those with a pre-term HDP in their first two births, although this represented 1.0% of mothers with HDP (HR 5.12, 95% CI 2.66, 9.86). Multiparous mothers with term HDP in their first birth only had no increased risk of CVD relative to mothers without HDP (36.9% of all mothers with HDP; HR 1.12, 95% CI 0.95, 1.32). All other mothers with HDP had a 1.5- to 4-fold increased risk of CVD mortality., Conclusions: This study identified heterogeneity in the risk of CVD mortality among mothers with a history of HDP. A third of these mothers are not at higher risk compared to women without HDP, while some less common patterns of HDP history are associated with severe risk of CVD mortality., (© 2024 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Objective: Maternal smoking is associated with as much as a 50% reduced risk of preeclampsia, despite increasing risk of other poor pregnancy outcomes that often co-occur with preeclampsia, such as preterm birth and fetal growth restriction. Researchers have long sought to understand whether this perplexing association is biologically based, or a result of noncausal mechanisms. We examined whether smoking-response genes modify the smoking-preeclampsia association to investigate potential biological explanations., Study Design: We conducted a nested case-control study within the Norwegian Mother, Father and Child Birth Cohort (1999-2008) of 2,596 mother-child dyads. We used family-based log-linear Poisson regression to examine modification of the maternal smoking-preeclampsia relationship by maternal and fetal single nucleotide polymorphisms involved in cellular processes related to components of cigarette smoke ( n  = 1,915 with minor allele frequency ≥10%). We further investigated the influence of smoking cessation during pregnancy., Results: Three polymorphisms showed overall ( p  < 0.001) multiplicative interaction between smoking and maternal genotype. For rs3765692 ( TP73 ) and rs10770343 ( PIK3C2G ), protection associated with smoking was reduced with two maternal copies of the risk allele and was stronger in continuers than quitters (interaction p  = 0.02 for both loci, based on testing 3-level smoking by 3-level genotype). For rs2278361 ( APAF1 ) the inverse smoking-preeclampsia association was eliminated by the presence of a single risk allele, and again the trend was stronger in continuers than in quitters (interaction p  = 0.01)., Conclusion: Evidence for gene-smoking interaction was limited, but differences by smoking cessation warrant further investigation. We demonstrate the potential utility of expanded dyad methods and gene-environment interaction analyses for outcomes with complex relationships between maternal and fetal genotypes and exposures., Key Points: · Maternal and fetal genotype may differentially influence preeclampsia.. · Smoking-related genes did not strongly modify smoking-preeclampsia association.. · Smoking cessation reduced strength of gene by smoking interactions.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Although often intended for long-term treatment, discontinuation of medication for ADHD is common. However, cross-national estimates of discontinuation are missing due to the absence of standardised measures. The aim of this study was to determine the rate of ADHD treatment discontinuation across the lifespan and to describe similarities and differences across countries to guide clinical practice., Methods: We did a retrospective, observational study using population-based databases from eight countries and one Special Administrative Region (Australia, Denmark, Hong Kong, Iceland, the Netherlands, Norway, Sweden, the UK, and the USA). We used a common analytical protocol approach and extracted prescription data to identify new users of ADHD medication. Eligible individuals were aged 3 years or older who had initiated ADHD medication between 2010 and 2020. We estimated treatment discontinuation and persistence in the 5 years after treatment initiation, stratified by age at initiation (children [age 4-11 years], adolescents [age 12-17 years], young adults [age 18-24 years], and adults [age ≥25 years]) and sex. Ethnicity data were not available., Findings: 1 229 972 individuals (735 503 [60%] males, 494 469 females [40%]; median age 8-21 years) were included in the study. Across countries, treatment discontinuation 1-5 years after initiation was lowest in children, and highest in young adults and adolescents. Within 1 year of initiation, 65% (95% CI 60-70) of children, 47% (43-51) of adolescents, 39% (36-42) of young adults, and 48% (44-52) of adults remained on treatment. The proportion of patients discontinuing was highest between age 18 and 19 years. Treatment persistence for up to 5 years was higher across countries when accounting for reinitiation of medication; at 5 years of follow-up, 50-60% of children and 30-40% of adolescents and adults were covered by treatment in most countries. Patterns were similar across sex., Interpretation: Early medication discontinuation is prevalent in ADHD treatment, particularly among young adults. Although reinitiation of medication is common, treatment persistence in adolescents and young adults is lower than expected based on previous estimates of ADHD symptom persistence in these age groups. This study highlights the scope of medication treatment discontinuation and persistence in ADHD across the lifespan and provides new knowledge about long-term ADHD medication use., Funding: European Union Horizon 2020 Research and Innovation Programme., Competing Interests: Declaration of interests SF reports personal fees, travel expenses, and research grants from Johnson & Johnson, Aardvark, Aardwolf, Tris, Otsuka, Ironshore, KemPharm/Corium, Akili, Supernus, Atentiv, Noven, Sky Therapeutics, Axsome, and Genomind; has a US patent (via his institution) for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD (US20130217707 A1); receives royalties from books published by Guilford Press (Straight Talk about Your Child's Mental Health), Oxford University Press (Schizophrenia: The Facts), and Elsevier (ADHD: Non-Pharmacologic Interventions); and is program director of www.ADHDEvidence.org and www.ADHDinAdults.com. JH reports honoraria as part of continuing medical education programmes sponsored by Shire, Takeda, Medice and Biocodex, all outside the submitted work. HL reports grants from Shire Pharmaceuticals; personal fees and speaker fees from Medice, Shire/Takeda Pharmaceuticals, and Evolan Pharma AB; and sponsorship for a conference on ADHD from Shire/Takeda Pharmaceuticals and Evolan Pharma AB, all outside the submitted work; and is Editor-in-Chief of JCPP Advances. KKCM reports grants from the C W Maplethorpe Fellowship, the National Institute for Health and Care Research, Innovation and Technology Commission of the Hong Kong Special Administration Region Government, and Hong Kong Research Grant Council; and personal fees from IQVIA, all outside the submitted work. IW reports research grants outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, Glaxo Smith Kline, Novartis, Takeda, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund, UK National Institute for Health Research, European Commission, and Australian National Health and Medical Research Council; and is a non-executive director of Jacobson Medical in Hong Kong and a consultant to WHO. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Individuals with major birth defects are at increased risk of developing cancer, indicating a common aetiology. However, whether the siblings of individuals with birth defects are also at an increased risk of cancer is unclear., Methods: We used nationwide health registries in four Nordic countries and conducted a nested case-control study. We included 40 538 cancer cases (aged 0-46 years) and 481 945 population controls (matched by birth year and country), born between 1967 and 2014. The relative risk of cancer among individuals whose siblings had birth defects was computed with odds ratios (OR) and 95% confidence intervals (CIs), using logistic regression models., Results: In the total study population (aged 0-46 years), we observed no overall difference in cancer risk between individuals whose siblings had birth defects and those who had unaffected siblings (OR 1.02; 95% CI 0.97-1.08); however, the risk of lymphoid and haematopoietic malignancies was elevated (1.16; 1.05-1.28). The overall risk of childhood cancer (0-19 years) was increased for siblings of individuals who had birth defects (1.09; 1.00-1.19), which was mainly driven by lymphoma (1.35; 1.09-1.66), neuroblastoma (1.51; 1.11-2.05) and renal carcinoma (5.03; 1.73-14.6). The risk of cancer also increased with the number of siblings with birth defects (Ptrend = 0.008)., Conclusion: Overall risk of cancer among individuals (aged 0-46 years) whose siblings had birth defects was not elevated, but the risk of childhood cancer (ages 0-19 years) was increased. Our novel findings are consistent with the common aetiologies of birth defects and cancer, such as shared genetic predisposition and environmental factors., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Introduction: Birthweight is an important pregnancy indicator strongly associated with infant, child, and later adult life health. Previous studies have found that second-born babies are, on average, heavier than first-born babies, indicating an independent effect of parity on birthweight. Existing data are mostly based on singleton pregnancies and do not consider higher order pregnancies. We aimed to compare birthweight in singleton pregnancies following a first twin pregnancy relative to a first singleton pregnancy., Material and Methods: This was a prospective registry-based cohort study using maternally linked offspring with first and subsequent pregnancies registered in the Medical Birth Registry of Norway between 1967 and 2020. We studied offspring birthweights of 778 975 women, of which 4849 had twins and 774 126 had singletons in their first pregnancy. Associations between twin or singleton status of the first pregnancy and birthweight (grams) in subsequent singleton pregnancies were evaluated by linear regression adjusted for maternal age at first delivery, year of first pregnancy, maternal education, and country of birth. We used plots to visualize the distribution of birthweight in the first and subsequent pregnancies., Results: Mean combined birthweight of first-born twins was more than 1000 g larger than mean birthweight of first-born singletons. When comparing mean birthweight of a subsequent singleton baby following first-born twins with those following first-born singletons, the adjusted difference was just 21 g (95% confidence interval 5-37 g)., Conclusions: Birthweights of the subsequent singleton baby were similar for women with a first twin or a first singleton pregnancy. Although first twin pregnancies contribute a greater combined total offspring birthweight including more extensive uterine expansion, this does not explain the general parity effect seen in birthweight. The physiological reasons for increased birthweight with parity remain to be established., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)