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We investigated common genetic variation in the entire ESR1 and EGF genes in relation to endometrial cancer risk, myometrial invasion and endometrial cancer survival. We genotyped a dense set of single-nucleotide polymorphisms (SNPs) in both genes and selected haplotype tagging SNPs (tagSNPs). The tagSNPs were genotyped in 713 Swedish endometrial cancer cases and 1567 population controls and the results incorporated into logistic regression and Cox proportional hazards models. We found five adjacent tagSNPs covering a region of 15 kb at the 5' end of ESR1 that decreased the endometrial cancer risk. The ESR1 variants did not, however, seem to affect myometrial invasion or endometrial cancer survival. For the EGF gene, no association emerged between common genetic variants and endometrial cancer risk or myometrial invasion, but we found a five-tagSNP region that covered 51 kb at the 5' end of the gene where all five tagSNPs seemed to decrease the risk of dying from endometrial cancer. One of the five tagSNPs in this region was in strong linkage disequilibrium (LD) with the untranslated A61G (rs4444903) EGF variant, earlier shown to be associated with risk for other forms of cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Publicly insured women usually have a different demographic background to privately insured women, which is related to poor neonatal outcomes after birth. Given the difference in nature and risk of preterm versus term births, it would be important to compare adverse neonatal outcomes after preterm birth between these groups of women after eliminating the demographic differences between the groups. Methods The study population included 3085 publicly insured and 3380 privately insured, singleton, preterm deliveries (32–36 weeks gestation) from Western Australia during 1998–2008. From the study population, 1016 publicly insured women were matched with 1016 privately insured women according to the propensity score of maternal demographic characteristics and pre-existing medical conditions. Neonatal outcomes were compared in the propensity score matched cohorts using conditional log-binomial regression, adjusted for antenatal risk factors. Outcomes included Apgar scores less than 7 at five minutes after birth, time until establishment of unassisted breathing (>1 minute), neonatal resuscitation (endotracheal intubation or external cardiac massage) and admission to a neonatal special care unit. Results Compared with infants of privately insured women, infants of publicly insured women were more likely to receive a low Apgar score (ARR = 2.63, 95% CI = 1.06-6.52) and take longer to establish unassisted breathing (ARR = 1.61, 95% CI = 1.25-2.07), yet, they were less likely to be admitted to a special care unit (ARR = 0.84, 95% CI = 0.80-0.87). No significant differences were evident in neonatal resuscitation between the groups (ARR = 1.20, 95% CI = 0.54-2.67). Conclusions The underlying reasons for the lower rate of special care admissions in infants of publicly insured women compared with privately insured women despite the higher rate of low Apgar scores is yet to be determined. Future research is warranted in order to clarify the meaning of our findings for future obstetric care and whether more equitable use of paediatric services should be recommended.

Abstract Background Increasing incidence and lack of survival improvement in adolescents and young adults (AYAs) with cancer have led to increased awareness of the cancer burden in this population. The objective of this study was to describe overall and type-specific cancer incidence and mortality trends among AYAs in Western Australia from 1982–2007. Methods Age–adjusted incidence and mortality rates were calculated for all malignancies combined and for each of the most common diagnostic groups, using five-year age–specific rates. Joinpoint regression analysis was used to derive annual percentage changes (APC) for incidence and mortality rates. Results The annual incidence rate for all cancers combined increased in males from 1982 until 2000 (APC = 1.5%, 95%CI: 0.9%; 2.1%) and then plateaued, whilst rates for females remained stable across the study period (APC = −0.1%; 95%CI: −0.2%; 0.4%) across the study period. For males, significant incidence rate increases were observed for germ cell tumors, lymphoblastic leukemia and thyroid cancer. In females, the incidence of Hodgkin’s lymphoma, colorectal and breast cancers increased. Significant incidence rate reductions were noted for cervical, central nervous system and lung cancers. Mortality rates for all cancers combined decreased from 1982 to 2005 for both males (APC = −2.6%, 95%CI:−3.3%;−2.0%) and females (APC = −4.6%, 95%CI:−5.1%;−4.1%). With the exception of bone sarcoma and lung cancer in females, mortality rates for specific cancer types decreased significantly for both sexes during the study period. Conclusions Incidence of certain AYA cancers increased, whilst it decreased for others. Mortality rates decreased for most cancers, with the largest improvement observed for breast carcinomas. Further research is needed to identify the reasons for the increasing incidence of certain cancers.

Abstract Background Relatively few studies have examined survival by pharmacotherapy level and the effects of patient characteristics on mortality by pharmacotherapy level in older chronic respiratory disease (CRD) patients. This study aimed to investigate these issues in older (≥ 65) CRD patients in Western Australia. Methods We identified 108,312 patients ≥ 65 years with CRD during 1992-2006 using linked medical, pharmaceutical, hospital and mortality databases held by the Commonwealth and State governments. Pharmacotherapy classification levels were designed by a clinical consensus panel. Cox regression was used to investigate the study aim. Results Patients using only short acting bronchodilators experienced similar, but slightly worse survival than patients in the highest pharmacotherapy level group using high dose inhaled corticosteroids (ICS) ± long acting bronchodilators (LABs) ± oral steroids. Patients using low to medium dose ICS ± LABs experienced relatively better survival. Also, male gender was associated with all-cause mortality in all patients (HR = 1.72, 95% CI 1.65-1.80) and especially in those in the highest pharmacotherapy level group (HR = 1.97, 95%CI = 1.84-2.10). The P-value of interaction between gender and pharmacotherapy level for the effect on all-cause death was significant (0.0003). Conclusions Older patients with CRD not using ICS experienced the worst survival in this study and may benefit from an escalation in therapeutic regime. Males had a higher risk of death than females, which was more pronounced in the highest pharmacotherapy level group. Hence, primary health care should more actively direct disease management to mild-to-moderate disease patients.

Background: Given its complexity, childbirth can elicit both positive and negative psychological reactions and, in some cases, women may experience symptoms of childbirth-related post-traumatic stress disorder (CB-PTSD). Several risk factors for CB-PTSD have been identified previously, including history of mental health issues and childbirth related complications. The aim of our study was to explore the role of satisfaction with care in CB-PTSD symptoms., Methods: CB-PTSD was measured with the City Birth Trauma Scale (CityBiTS), a questionnaire with 29 items distributed according to DSM-5 diagnostic criteria. A CityBiTS score >28 points was defined as CB-PTSD symptoms. Birth satisfaction was measured with the Birth Satisfaction Scale-Revised (BSS-R), a self-report questionnaire. Logistic-regression was used to calculate odds ratios and 95 % confidence intervals for the association between birth satisfaction and CB-PTSD, adjusted for age, relationship status, education, income, parity, mode of birth, postpartum depression and maternal and infant health-related problems during pregnancy and birth., Results: Of 600 participants, 34 (5.7 %) indicated symptoms of CB-PTSD. When adjusted for socio-demographic and pregnancy and birth-related factors, birth satisfaction was independently associated with symptoms of CB-PTSD. For each additional point on the BSS-R, the odds of having CB-PTSD symptoms decreased by 16%. Support during labor and birth, effective communication and shared decision making were factors significantly associated with CB-PTSD symptoms., Discussion: Increased satisfaction with care was strongly associated with less symptoms of CB-PTSD. Emphasizing sense of control with support, effective communication and shared decision making may significantly improve the overall experience for women and possibly reduce CB-PTSD symptoms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate the association of potential risk factors for urinary tract infections (UTI) caused by E. coli producing ESBL vs. not producing ESBL in Iceland., Methods: Observational, case-control study including a cohort of 27,747 patients (22,800 females, 4,947 males; 1207 cases, 26,540 controls) of all ages with UTI caused by E. coli in 2012 to 2021 at the clinical microbiology laboratory covering about 2/3 of the Icelandic population. Clinical patient data was obtained from three national databases. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as a measure of association between ESBL and exposure variables., Results: The proportion of samples with ESBL-producing E. coli increased during the study period, from 2.6% in 2012 to 7.6% in 2021 (p < 0.001). ESBL-positive strains were detected in 1207 individuals (4.4%), 905 females (4.0%) and 302 males (6.1%). The following risk factors were identified: Male sex, higher age, institution type (hospital, nursing home), hospital-associated UTI, Charlson comorbidity index score ≥ 3, history of cystitis or hospitalization in the past year, and prescriptions for certain antibiotics or proton pump inhibitors (PPIs: OR 1.51) in the past half year. The antibiotic associated with the highest risk was ciprofloxacin (OR 2.45)., Conclusion: The prevalence of UTIs caused by ESBL-producing E. coli has been increasing in Iceland. The strongest risk factors for ESBL production were previous antibiotic use, especially ciprofloxacin, and previous PPI use, both considered to be overprescribed. It is important to promote the prudent use of these drugs., (© 2024. The Author(s).)

Internationally accepted diagnostic criteria recommendations for gestational diabetes (GDM) in 2010 resulted in a rise in global prevalence of GDM. Our aim was to describe the trends in GDM before and after Icelandic guideline changes in 2012 and the trends in pregestational diabetes (PGDM). The study included all singleton births (N = 101 093) in Iceland during 1997-2020. Modified Poisson regression models were used to estimate prevalence ratios (PRs) with 95% confidence intervals (CIs) for risk of GDM overall and by maternal age group, as well as overall risk of PGDM, according to time period of birth. The overall prevalence of GDM by time period of birth ranged from 0.6% (N = 101) in 1997-2000 to 16.2% (N = 2720) in 2017-2020, and the prevalence of PGDM ranged from 0.4% (N = 57) in 1997-2000 to 0.7% (N = 120) in 2017-2020. The overall relative GDM prevalence rate difference before and after 2012 was 380%, and the largest difference was found among women aged <25 years at 473%. Risk of GDM increased in 2017-2020 (PR 14.21, CI 11.45, 17.64) compared to 1997-2000 and was highest among women aged >34 years with PR 19.46 (CI 12.36, 30.63) in 2017-2020. Prevalence rates of GDM and PGDM increased during the study period. An accelerated rate of increase in GDM was found after 2012, overall, and among all maternal age groups. Women aged >34 years had the greatest risk of GDM throughout all time periods, while women aged <25 years appear to have a higher relative rate difference after 2012., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Objective: Twin pregnancies are associated with increased antepartum and intrapartum risks. Limited multiple embryo transfers are associated with decreased twin birth rates. We aimed to study the effect of 2009 Icelandic regulations on twin birth rates and examine obstetric intervention rates for twin births during the study period., Methods: The study included all births (N = 94 028) in Iceland during 1997-2018. Twin birth rates and obstetric intervention rates were compared over birth year periods using modified Poisson regression adjusted for confounders., Results: An observed decrease in the twin birth rate trend was most notable from 2006 until 2009. Twin birth decreased in 2009-2013 (prevalence ratio [PR] 0.74, 95% confidence interval [CI] 0.64-0.86) and in 2014-2018 (PR 0.74, 95% CI 0.64-0.86) compared with 1997-2002. This decrease was only evident for women aged 30+ years in stratified analysis. Induction of labor rates increased from 26% in 1997-2002 to 44% in 2014-2018 (adjusted rate ratio [ARR] 2.10, 95% CI 1.72-2.57) whereas elective cesarean section (ARR 0.80, 95% CI 0.59-1.07) and urgent cesarean section (ARR 0.79, 95% CI 0.63-1.00) rates appeared to decline., Conclusion: Twin births decreased during the study period. International guidelines published before the Icelandic regulations may have affected twin birth rates in Iceland. Induction of labor rates for twins increased while cesarean section rates decreased., (© 2023 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

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., (© 2023. The Author(s).)

Background: 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., Methods: 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., Results and Discussion: 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Frier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Following the 2008 financial crisis, the Icelandic Government reduced the maximum parental payment until 2016, when it was increased again. The aim of this study was to investigate the effect of the changes in the maximum parental leave payment in Iceland during 2009 and 2016 on total fertility rates and birth rates during 2002-2019., Methods: Publicly available aggregated data on yearly total fertility rates, birth rates, unemployment rates, gross domestic product (GDP) and maximum parental leave payments were obtained for 2002-2019. Segmented regression analyses were used to measure the impact of changes in parental leave payment on term births for the two periods in which changes were implemented (2008-2010 and 2016-2017)., Results: The decrease in maximum parental leave payment during 2008-2010 was associated with a 15% decrease in the estimated total fertility rate compared with the expected rate (-15.7%; 95% CI -22.7 to -8.7), whereas the increased payments during 2016-2017 indicated a possible 3% increase in the estimated total fertility rate (3.2%; 95% CI -29.1 to 35.5). Neither adjustment for the unemployment rate nor the GDP appeared to affect these results. The overall birth rate followed a similar trend and was most pronounced for women aged 25-34 years., Conclusions: These results suggest that total fertility rates in Iceland may have been affected by changes in the maximum parental leave payment that occurred in 2009 and 2016, although the effect of the 2008 financial crisis cannot be excluded despite adjustment for the unemployment rate and GDP.

Objective: Most research on safety of attention-deficit/hyperactivity disorder (ADHD) medications during pregnancy concerns central nervous system stimulants, while little is known about the safety of atomoxetine, a primary treatment alternative. We assessed the prevalence of major congenital malformations overall, and cardiac malformations and limb malformations specifically, after first-trimester exposure., Methods: In this cohort study, we included all approximately 2.4 million pregnancies ending in live births recorded in the population-based nationwide health registers of Denmark, Iceland, Norway, and Sweden (2003-2017) and approximately 1.8 million publicly insured pregnancies ending in live births recorded in the US Medicaid Analytic eXtract (MAX, 2001-2013) health care claims database. We compared the prevalence of major congenital malformations in the newborn among pregnancies exposed and unexposed to atomoxetine. For each country, we calculated prevalence ratios (PRs), crude and stratified by propensity scores (PSs). We pooled the country-specific PS strata to obtain a PR adjusted for potential confounding factors., Results: We identified 368 pregnancies exposed to atomoxetine during the first trimester in the 4 Nordic countries and 622 in the US. The pooled crude PR for any major congenital malformation was 1.18 (95% CI, 0.88-1.60), and the adjusted PR was 0.99 (95% CI, 0.74-1.34). For cardiac malformations, the adjusted PR was 1.34 (95% CI, 0.86-2.09). For limb malformations, the adjusted PR was 0.90 (95% CI, 0.38-2.16)., Conclusions: After atomoxetine exposure in early pregnancy, we observed no increase in major congenital malformations overall and, although with some uncertainty due to sample size, no statistically increased risk estimates for cardiac malformations and limb malformations., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Women who are obese before pregnancy have a higher risk of caesarean section than normal weight women. We investigated the combined effect of pre-pregnancy weight and gestational weight gain on pre-labour and intrapartum caesarean section risk. We collected data on 22,763 singleton, term, live deliveries in 2003-2014 from the Icelandic Maternal and Child Health Study (ICE-MCH), based on Icelandic registries. These were the Icelandic Medical Birth Registry and the Saga Maternal and Child Health Database. Pre-pregnancy body mass index was categorised into underweight, normal weight, overweight and obese. Gestational weight gain was classified according to the Institute of Medicine´s recommendation into below, within and above the recommended range. Logistic regression models, adjusted for maternal and gestational characteristics, were used to calculate adjusted odds ratios (AOR) and 95% confidence intervals (CI) for the risk of caesarean section. Obese women had a higher risk of pre-labour (AOR 1.56, 95% CI 1.34-1.81) and intrapartum caesarean section (AOR 1.92, 95% CI 1.70-2.17) than normal weight women in all categories of gestational weight gain. Gestational weight gain above the recommended range, compared to within the range, increased the risk of intrapartum caesarean section among normal weight (AOR 1.46, 95% CI 1.23-1.73) and overweight women (AOR 1.291, 95% CI 1.04-1.60). Gestational weight gain below the recommended range, compared to within the range, increased the risk of pre-labour caesarean section (AOR 1.64, 95% CI 1.20-2.25), but only among overweight women. Women who are obese before pregnancy have a high risk of caesarean section regardless of gestational weight gain. However, women who are normal weight or overweight before pregnancy and gain weight above the recommended range during pregnancy may also have an increased risk of caesarean section., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Geir Gunnlaugsson was the Chief Medical Officer for Iceland from 2010 to 2014. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Other authors declare no conflict of interest., (Copyright: © 2023 Eloranta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Immigration is rapidly increasing in Iceland with 13.6% of the population holding foreign citizenship in 2020. Earlier findings identified inequities in childbirth care for some women in Iceland. To gain insight into the quality of intrapartum midwifery care, migrant women's use of pain management methods during birth in Iceland was explored., Methods: A population-based cohort study including all women with a singleton birth in Iceland between 2007 and 2018, in total 48 173 births. Logistic regression analyses with odds ratios (ORs) and 95% confidence intervals (CIs) were used to investigate the relationship between migrant backgrounds defined as holding foreign citizenship and the use of pain management during birth. The main outcome measures were use of nonpharmacological and pharmacological pain management methods., Results: Data from 6097 migrant women were included. Migrant women had higher adjusted OR (aORs) for no use of pain management (aOR = 1.23 95% CI [1.12, 1.34]), when compared to Icelandic women. Migrant women also had lower aORs for the use of acupuncture (0.73 [0.64, 0.83]), transcutaneous electrical nerve stimulation (TENS) (0.92 [0.01, 0.67]), shower/bath (0.73 [0.66, 0.82]), aromatherapy (0.59 [0.44, 0.78]), and nitrous oxide inhalation (0.89 [0.83, 0.96]). Human Development Index (HDI) scores of countries of citizenship <0.900 were associated with lower aORs for the use of various pain management methods., Conclusions: Our results suggest that being a migrant in Iceland is an important factor that limits the use of nonpharmacological pain management, especially for migrant women with citizenship from countries with HDI score <0.900., (© 2022 The Authors. Birth published by Wiley Periodicals LLC.)

Background: More research is needed on the relative contributions of different indications for cesarean birth and how they vary with maternal age and across time. We aimed to assess how the relative contribution of various indications varied with age and by time period in a study of intrapartum and prelabor singleton, term cesarean births (CB) in Iceland., Methods: The study was restricted to all singleton, term cesarean births in Iceland between 1997 and 2015 identified from the Icelandic Medical Birth Registry (n = 10 856). The contribution of indications was calculated according to maternal age- and birth-year groups for primiparas and multiparas. Logistic regression was used to estimate odds ratios and 95% confidence intervals., Results: For intrapartum cesarean births, the relative contribution of fetal distress (AOR = 1.35 [95% CI = 1.12-1.63]) and failed induction (1.53 [1.15-2.00]) increased with increasing maternal age, whereas dystocia decreased (0.70 [0.58-0.83]). For prelabor cesarean births, the contribution of malpresentation (0.83 [0.76-0.91]) and maternal-fetal-obstetric indications (0.59 [0.47-0.74]) decreased with both birth year and maternal age, whereas the contribution of fear of childbirth (1.80 [1.27-2.54]) and adverse obstetric history (1.24 [1.12-1.37]) increased. Previous CB as an indication for cesarean increased until the 2007-2011 time period, after which it decreased., Conclusions: For intrapartum cesarean births, the relative contribution of fetal distress and failed induction increased with maternal age, whereas dystocia decreased. For prelabor cesarean births, the relative contribution of more objective indications decreased, whereas more subjective indications increased with time and with increasing maternal age., (© 2021 Wiley Periodicals LLC.)

Background: Antipsychotics are increasingly used among women of childbearing age and during pregnancy., Objective: To determine whether children exposed to antipsychotics in utero are at increased risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), accounting for maternal diagnoses of bipolar, psychotic and other psychiatric disorders. Design Population-based cohort study, including a sibling analysis. Setting Nationwide data on all pregnant women and their live-born singletons in Denmark (1997-2017), Finland (1996-2016), Iceland (2004-2017), Norway (2004-2017), and Sweden (2006-2016). Participants 4 324 086 children were eligible for inclusion to the study cohort. Intervention Antipsychotic exposure in utero , assessed by pregnancy trimester, type of antipsychotic, and varying patterns of use. Main outcome measures Non-mutually exclusive diagnoses of ADHD and ASD. We used Cox proportional hazard models to calculate hazard ratios (HRs) controlling for maternal psychiatric disorders and other potential confounding factors., Findings: Among 4 324 086 singleton births, 15 466 (0.4%) were exposed to antipsychotics in utero . During a median follow-up of 10 years, we identified 72 257 children with ADHD and 38 674 children with ASD. Unadjusted HRs were raised for both outcomes but shifted substantially towards the null after adjustment; 1.10 (95%CI 1.00 to 1.27) for ADHD and 1.12 (0.97 to 1.29) for ASD. Adjusted HRs remained consistent by trimester of exposure and type of antipsychotic. Comparing in utero exposure with pre-pregnancy use yielded HRs of 0.74 (0.62 to 0.87) for ADHD and 0.88 (0.70 to 1.10) for ASD. Sibling analyses yielded HRs of 1.14 (0.79 to 1.64) for ADHD and 1.34 (0.75 to 2.39) for ASD., Discussion: Our findings suggest little or no increased risk of child ADHD or ASD after in utero exposure to antipsychotics., Clinical Implications: Results regarding child neurodevelopment are reassuring for women who need antipsychotics during pregnancy., Competing Interests: Competing interests: CEC, HK, and JR are employees of the Centre for Pharmacopidemiology at Karolinska Institutet, which receives funding from pharmaceutical companies and regulatory authorities for drug safety/utilisation studies, unrelated to the submitted work. ØK, KF and JMC are employees of an institution, which received funding from pharmaceutical companies to conduct post-authorisation safety studies (PASS) of drugs unrelated to the submitted work (no personal fees). HZ is an employee of the Centre for Big Data Research in Health, UNSW Sydney which received funding from AbbVie Australia to conduct post-marketing drug utilisation research, unrelated to the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The rate of labor induction has risen steeply throughout the world. This project aimed to estimate changes in the rates of adverse maternal and neonatal outcomes in Iceland between 1997 and 2018, and to assess whether the changes can be explained by an increased rate of labor induction., Methods: Singleton live births, occurring between 1997 and 2018, that did not start by prelabor cesarean, were identified from the Icelandic Medical Birth Register (n = 85 971). Rates of intrapartum cesarean birth (CB), obstetric emergencies, and neonatal outcomes were calculated, and adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) were estimated with log-binomial regression (reference: 1997-2001). Adjustments were made for: (a) maternal characteristics, and (b) labor induction and gestational age., Results: The rate of labor induction increased from 13.6% in the period 1997-2001 to 28.1% in the period 2014-2018. The rate of intrapartum CB decreased between the periods of 1997-2001 and 2014-2018 for both primiparous (aRR 0.76, 95% CI: 0.69 to 0.84) and multiparous women (aRR 0.55, 95% CI: 0.49 to 0.63). The rate of obstetric emergencies and adverse neonatal outcomes also decreased between these time periods. Adjusting for labor induction did not attenuate these associations., Conclusions: The rates of adverse maternal outcomes and adverse neonatal outcomes decreased over the study period. However, there was no evidence that this decrease could be explained by the increased rate of labor induction., (© 2021 Wiley Periodicals LLC.)

Introduction: Previous evidence has been conflicting regarding the effect of coronavirus disease 2019 (COVID-19) pandemic lockdowns on obstetric intervention and preterm birth rates. The literature to date suggests potentially differential underlying mechanisms based on country economic setting. We aimed to study these outcomes in an Icelandic population where uniform lockdown measures were implemented across the country., Material and Methods: The study included all singleton births (n = 20 680) during 2016-2020 identified from the population-based Icelandic Medical Birth Register. We defined two lockdown periods during March-May and October-December in 2020 according to government implemented nationwide lockdown. We compared monthly rates of cesarean section, induction of labor and preterm birth during lockdown with the same time periods in the 4 previous years (2016-2019) using logit binomial regression adjusted for confounders., Results: Our results indicated a reduction in the overall cesarean section rate, which was mainly evident for elective cesarean section, both during the first (adjusted odd ratio [aOR] 0.71, 95% CI 0.51-0.99) and second (aOR 0.72, 95% CI 0.52-0.99) lockdown periods, and not for emergency cesarean section. No change during lockdown was observed in induction of labor. Our results also suggested a reduction in the overall preterm birth rate during the first lockdown (aOR 0.69, 95% CI 0.49-0.97) and in the months immediately following the lockdown (June-September) (aOR 0.67, 95% CI 0.49-0.89). The reduction during the first lockdown was mainly evident for medically indicated preterm birth (although not statistically significant) and the reduction during June-September was mainly evident for spontaneous preterm birth., Conclusions: This study suggested a reduction in elective cesarean section during COVID-19 lockdown, possibly reflecting changes in prioritization of non-urgent health care during lockdown. We also found a reduction in overall preterm birth during the first lockdown and spontaneous preterm birth following the first lockdown, but further research is needed to shed light on the underlying mechanisms for these findings., (© 2021 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: This study aims to explore maternal and perinatal outcomes of migrant women in Iceland., Material and Methods: This prospective population-based cohort study included women who gave birth to a singleton in Iceland between 1997 and 2018, comprising a total of 92 403 births. Migrant women were defined as women with citizenship other than Icelandic, including refugees and asylum seekers, and categorized into three groups, based on their country of citizenship Human Development Index score. The effect of country of citizenship was estimated. The main outcome measures were onset of labor, augmentation, epidural, perineum support, episiotomy, mode of birth, obstetric anal sphincter injury, postpartum hemorrhage, preterm birth, a 5-minute Apgar <7, neonatal intensive care unit admission and perinatal mortality. Odds ratios (ORs) and 95% confidence intervals (CIs) for maternal and perinatal outcomes were calculated using logistic regression models., Results: A total of 8158 migrant women gave birth during the study period: 4401 primiparous and 3757 multiparous. Overall, migrant women had higher adjusted ORs (aORs) for episiotomy (primiparas: aOR 1.43, 95% CI 1.26-1.61; multiparas: 1.39, 95% CI 1.21-1.60) and instrumental births (primiparas: 1.14, 95% CI 1.02-1.27, multiparas: 1.41, 95% CI 1.16-1.72) and lower aORs of induction of labor (primiparas: 0.88, 95% CI 0.79-0.98; multiparas: 0.74, 95% CI 0.66-0.83), compared with Icelandic women. Migrant women from countries with a high Human Development Index score (≥0.900) had similar or better outcomes compared with Icelandic women, whereas migrant women from countries with a lower Human Development Index score than that of Iceland (<0.900) had additionally increased odds of maternal and perinatal complications and interventions, such as emergency cesarean and postpartum hemorrhage., Conclusions: Women's citizenship and country of citizenship Human Development Index scores are significantly associated with a range of maternal and perinatal complications and interventions, such as episiotomy and instrumental birth. The results indicate the need for further exploration of whether Icelandic perinatal healthcare services meet the care needs of migrant women., (© 2021 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).)

Background: Cesarean birth (CB) rates have increased in high-resource countries during the past two decades, yet it is not known whether CB rates have changed according to maternal age and/or gestational age., Methods: All singleton live births in Iceland between 1997 and 2015 were identified from the Icelandic Medical Birth Registry (80 130). Rates of cesarean births (intrapartum and prelabor) were calculated overall and separately for maternal age groups and gestational age groups and by parity. Logit binomial regression was used to calculate odds ratios (ORs) and confidence intervals (CIs) for annual change in cesarean birth rates adjusted for maternal characteristics and clinical indication groups., Results: The overall CB rate was 15.7% in 1997 and 15.8% in 2015; the CB rate did not change significantly during the study period. The overall CB rate for early-term deliveries (37-38 weeks) decreased for multiparas (annual aOR = 0.99 [95% CI = 0.98-0.99]), and the preterm (<37 weeks) prelabor cesarean rate increased significantly (1.11 [1.09-1.14]) for both primiparas and multiparas. For multiparas only, the intrapartum CB rate decreased (0.97 [0.97-0.98]), whereas the prelabor CB rate increased, predominantly for women aged over 35 years (1.03 [1.02-1.04]). Adjustment for clinical indication groups did not change these results., Conclusions: Findings indicate a rise in prelabor cesarean for preterm births and women aged over 35 years (multiparas only). As adjustment for clinical indications did not affect these results, changes in obstetric practice are more likely to have affected these rate changes rather than changes in clinical indications., (© 2020 Wiley Periodicals LLC.)

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread "natural experiment" of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic., Competing Interests: Competing interests: Helga Zoega is an employee of the Centre for Big Data Research in Health, UNSW Sydney which has received funding from AbbVie Australia to conduct research unrelated to the submitted work. Andrew Morris reports grants from the Bill & Melinda Gates Foundation during the conduct of this work. Kristin Palmer reports grants from GlaxoSmithKline, grants from Cerebral Palsy Alliance, grants from Equity Trustees, outside the submitted work. Clare Whitehead reports research funding from Bill & Melinda Gates Foundation Ferring International, unrelated to the submitted work. Aziz Sheikh reports grants from Health Data Research UK. He is a member of the ICODA Executive Leadership Team and Director of the Health Data Research UK BREATHE Hub., (Copyright: © 2021 Stock SJ et al.)

Purpose: To describe recent international trends in antiepileptic drug (AED) use during pregnancy and individual patterns of use including discontinuation and switching., Methods: We studied pregnancies from 2006 to 2016 within linked population-based registers for births and dispensed prescription drugs from Denmark, Finland, Iceland, Norway, Sweden, and New South Wales, Australia and claims data for public and private insurance enrollees in the United States. We examined the prevalence of AED use: the proportion of pregnancies with ≥1 prescription filled from 3 months before pregnancy until birth, and individual patterns of use by trimester., Results: Prevalence of AED use in almost five million pregnancies was 15.3 per 1000 (n = 75 249) and varied from 6.4 in Sweden to 34.5 per 1000 in the publicly-insured US population. AED use increased in all countries in 2006-2012 ranging from an increase of 22% in Australia to 104% in Sweden, and continued to rise or stabilized in the countries in which more recent data were available. Lamotrigine, clonazepam, and valproate were the most commonly used AEDs in the Nordic countries, United States, and Australia, respectively. Among AED users, 31% only filled a prescription in the 3 months before pregnancy. Most filled a prescription in the first trimester (59%) but few filled prescriptions in every trimester (22%)., Conclusions: Use of AEDs in pregnancy rose from 2006 to 2016. Trends and patterns of use of valproate and lamotrigine reflected the safety data available during this period. Many women discontinued AEDs during pregnancy while some switched to another AED., (© 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: The world was hit hard by the 2008 recession which led to increased unemployment and financial strain. However, how the recession affected people with pre-existing mental health problems has been understudied. This study investigates the effect of the 2008 recession in Iceland on stress, well-being and employment status of people with regard to whether they are suffering from mental health problems., Methods: The study cohort included participants (18-69 years old) of the 'Health and Wellbeing of Icelanders', a 3-wave survey conducted before (in 2007) and after (in 2009 and 2012) the recession in 2008. Self-assessed well-being was measured with the Short Warwick-Edinburgh Mental Well-being Scale and the 4-item Perceived Stress Scale. Logistic regression was used to assess the effect of the 2008 recession on self-assessed well-being and employment status in 2009 and 2012, using 2007 as a reference year., Results: Participants with no pre-recession mental health problems were at increased risk of both poor well-being, (with adjusted odds ratio at 1.66, in 2009 and 1.64 in 2012) and higher perceived stress, (with adjusted odds ratio at 1.48 in 2009 and 1.53 in 2012), after the recession. Interestingly, no significant change in well-being and perceived stress was observed among participants suffering from pre-recession mental health problems. Both groups had increased risk of unemployment after the recession., Conclusion: Results indicate that after recessions, the risk of stress and poor well-being increases only among those who do not suffer from pre-recession mental health problems., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Aim: To compare the prevalence and trends of antipsychotic drug use during pregnancy between countries across four continents., Methods: Individually linked health data in Denmark (2000-2012), Finland (2005-2014), Iceland (2004-2017), Norway (2005-2015), Sweden (2006-2015), Germany (2006-2015), Australia (New South Wales, 2004-2012), Hong Kong (2001-2015), UK (2006-2016), and the US (Medicaid, 2000-2013, and IBM MarketScan, 2012-2015) were used. Using a uniformed approach, we estimated the prevalence of antipsychotic use as the proportion of pregnancies where a woman filled at least one antipsychotic prescription within three months before pregnancy until birth. For the Nordic countries, data were meta-analyzed to investigate maternal characteristics associated with the use of antipsychotics., Results: We included 8,394,343 pregnancies. Typical antipsychotic use was highest in the UK (4.4%) whereas atypical antipsychotic use was highest in the US Medicaid (1.5%). Atypical antipsychotic use increased over time in most populations, reaching 2% in Australia (2012) and US Medicaid (2013). In most countries, prochlorperazine was the most commonly used typical antipsychotic and quetiapine the most commonly used atypical antipsychotic. Use of antipsychotics decreased across the trimesters of pregnancy in all populations except Finland. Antipsychotic use was elevated among smokers and those with parity ≥4 in the Nordic countries., Conclusion: Antipsychotic use during pregnancy varied considerably between populations, partly explained by varying use of the typical antipsychotic prochlorperazine, which is often used for nausea and vomiting in early pregnancy. Increasing usage of atypical antipsychotics among pregnant women reflects the pattern that was previously reported for the general population., Competing Interests: Declaration of competing interest JR, CC, LP, and GB, are employees of the Centre for Pharmacopidemiology which receives funding from pharmaceutical companies and regulatory authorities for drug safety/utilization studies, unrelated to the submitted work. BTB has participated as an investigator on grants to the Brigham and Women's Hospital from Pfizer, GSK, Lilly, Baxalta, and Pacira, not related to the topic of the submitted work. SH-D has participated as investigator in projects funded by Pfizer, GSK, and Lilly; and consulted for Boehringer-Ingelheim, Roche and UCB as a methods advisor for pregnancy studies. KFH has participated as an investigator on grants to the Brigham and Women's Hospital from Boehringer Ingelheim, Pfizer, Lilly and GSK, not related to the topic of the submitted work. The other authors declare no personal conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The frequency of preterm births has been increasing globally, mainly due to a rise in iatrogenic late preterm births. The aim of this study was to assess the prevalence of preterm births in Iceland during 1997-2016 by type of preterm birth., Methods: This study included all live births in Iceland during 1997-2016 identified from the Icelandic Medical Birth Registry. Risk of preterm birth by time period was assessed with Poisson regression models adjusted for demographic variables and indications for iatrogenic births., Results: The study population included 87 076 infants, of which 4986 (5.7%) were preterm. The preterm birth rate increased from 5.3% to 6.1% (adjusted rate ratio [ARR] = 1.16, confidence interval [CI] = 1.07-1.26) between 1997-2001 and 2012-2016 overall. The increase was only evident in multiples (ARR 1.41, 95% CI 1.21-1.65), not singletons (1.07, 0.97-1.19). The rate of late preterm births (34-36 weeks) increased significantly (1.24, 1.14-1.40), and the rate of iatrogenic preterm births more than doubled during this period even after adjustment for identified medical indications (2.40, 2.00-2.88). The rate of spontaneous preterm births decreased during the study period (0.63, 0.55-0.73), and the rate of PPROM increased (1.31, 1.09-1.57). The most common contributing indications for iatrogenic births were fetal distress (26.2%), hypertensive disorders (18.2%), and severe preeclampsia (16.9%)., Conclusions: Preterm birth rates increased in multiples in Iceland between 1997 and 2016, and late and iatrogenic preterm births increased overall. The increase in iatrogenic preterm births remained significant after adjusting for medical indications, suggesting that other factors might be affecting the rise., (© 2019 Wiley Periodicals, Inc.)

Objective: Diabetes in pregnancy and consequently the need for treatment with antidiabetic medication (ADM) has become increasingly prevalent. The prevalence and patterns of use of ADM in pregnancy from 2006 onward in seven different countries was assessed., Research Design and Methods: Data sources included individually linked data from the nationwide health registers in Denmark (2006-2016), Finland (2006-2016), Iceland (2006-2012), Norway (2006-2015), Sweden (2006-2015), state-wide administrative and claims data for New South Wales, Australia (2006-2012) and two US insurance databases: Medicaid Analytic eXtract (MAX; 2006-2012, public) and IBM MarketScan (2012-2015, private). The prevalence of ADM use was calculated as the proportion of pregnancies with at least one filled prescription of an ADM in the 90 days before pregnancy or within the three trimesters of pregnancy., Results: Prevalence of any ADM use in 5 279 231 pregnancies was 3% (n=147 999) and varied from under 2% (Denmark, Norway, and Sweden) to above 5% (Australia and US). Insulin was the most used ADM, and metformin was the most used oral hypoglycemic agent with increasing use over time in all countries. In 11.4%-62.5% of pregnancies with prepregnancy use, ADM (primarily metformin) was discontinued. When ADM treatment was initiated in late pregnancy for treatment of gestational diabetes mellitus, insulin was most often dispensed, except in the US, where glibenclamide was most often used., Conclusions: Prevalence and patterns of use of ADM classes varied between countries and over time. While insulin remained the most common ADM used in pregnancy, metformin use increased significantly over the study period., Competing Interests: Competing interests: CEC, GB, HK, LP, and IO are employees at the Centre for Pharmacoepidemiology, which receives grants from several entities (pharmaceutical companies, regulatory authorities and contract research organizations) for the performance of drug safety and drug utilization studies, unrelated to this work. HLG reports fees and grants from pharmaceutical companies in her previous position at Oslo University Hospital, unrelated to this work. SH-D reports receiving research grants to her institution from Eli Lilly, GlaxoSmithKline, and the National Institutes of Health and consulting fees from Roche unrelated to this work and having served as an epidemiologist with the North America AED pregnancy registry, which is funded by multiple companies. KFH reports receiving research grants to her institution from Eli Lilly, Pfizer, GlaxoSmithKline, and Boehringer-Ingelheim, unrelated to this work. BTB reports receiving grants to his institution from Eli Lilly, GlaxoSmithKline, Pacira, Baxalta, Pfizer, and Aetion unrelated to this work and having served on an expert panel for a postpartum hemorrhage quality improvement project that was conducted by the Association of Women’s Health, Obstetric, and Neonatal Nurses and funded by a grant from Merck for Mothers. All other authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: As obesity and type 2 diabetes (T2D) have been increasing worldwide, we investigated their association with breast cancer incidence in the Reykjavik Study., Methods: During 1968-1996, approximately 10,000 women (mean age = 53 ± 9 years) completed questionnaires and donated blood samples. T2D status was classified according to self-report (n = 140) and glucose levels (n  = 154) at cohort entry. A linkage with the Icelandic Cancer Registry provided breast cancer incidence through 2015. Cox regression with age as time metric and adjusted for known confounders was applied to obtain hazard ratios (HR) and 95% confidence intervals (CI)., Results: Of 9,606 participants, 294 (3.1%) were classified as T2D cases at cohort entry while 728 (7.8%) women were diagnosed with breast cancer during 28.4 ± 11.6 years of follow-up. No significant association of T2D (HR 0.95; 95% CI 0.56-1.53) with breast cancer incidence was detected except among the small number of women with advanced breast cancer (HR 3.30; 95% CI 1.13-9.62). Breast cancer incidence was elevated among overweight/obese women without (HR 1.18; 95% CI 1.01-1.37) and with T2D (HR 1.35; 95% CI 0.79-2.31). Height also predicted higher breast cancer incidence (HR 1.03; 95% CI 1.02-1.05). All findings were confirmed in women of the AGES-Reykjavik sub-cohort (n  = 3,103) who returned for an exam during 2002-2006. With a 10% T2D prevalence and 93 incident breast cancer cases, the HR for T2D was 1.18 (95% CI 0.62-2.27)., Conclusions: These findings in a population with low T2D incidence suggest that the presence of T2D does not confer additional breast cancer risk and confirm the importance of height and excess body weight as breast cancer risk factors.

Background: Rising cesarean rates call for studies on which subgroups of women contribute to the rising rates, both in countries with high and low rates. This study investigated the cesarean rates and contributing groups in Iceland using the Robson 10-group classification system., Methods: This study included all births in Iceland from 1997 to 2015, identified from the Icelandic Medical Birth Registry (81 839). The Robson distribution, cesarean rate, and contribution of each Robson group were analyzed for each year, and the distribution of other outcomes was calculated for each Robson group., Results: The overall cesarean rate in the population was 16.4%. Robson groups 1 (28.7%) and 3 (38.0%) (spontaneous term births) were the largest groups, and groups 2b (0.4%) and 4b (0.7%) (prelabor cesareans) were small. The cesarean rate in group 5 (prior cesarean) was 55.5%. Group 5 was the largest contributing group to the overall cesarean rate (31.2%), followed by groups 1 (17.1%) and 2a (11.0%). The size of groups 2a (RR 1.04 [95% CI 1.01-1.08]) and 4a (RR 1.04 [95% CI 1.01-1.07]) (induced labors) increased over time, whereas their cesarean rates were stable (group 2a: P = 0.08) or decreased (group 4a: RR 0.95 [95% CI 0.91-0.98])., Conclusions: In comparison with countries with high cesarean rates, the prelabor cesarean groups (singleton term pregnancies) in Iceland were small, and in women with a previous cesarean, the cesarean rate was low. The size of the labor induction group increased, yet the cesarean rate in this group did not increase., (© 2019 Wiley Periodicals, Inc.)

Background: Population data on obstetric interventions is often limited to cesarean delivery. We aimed to provide a more comprehensive overview of trends in use of several common obstetric interventions over the past 2 decades., Methods: The study was based on nationwide data from the Icelandic Medical Birth Register. Incidence of labor induction, epidural analgesia, cesarean, and instrumental delivery was calculated for all births in 1995-2014. Change over time was expressed as relative risk (RR), using Poisson regression with 95% confidence intervals (CI) adjusted for several maternal and pregnancy-related characteristics. Analyses were stratified by women's parity and diagnosis of diabetes or hypertensive disorder., Results: During the study period, there were 81 389 intended vaginal births and 5544 elective cesarean deliveries. Among both primiparous and multiparous women, we observed a marked increase across time for labor induction (RR 1.78 [CI 1.67-1.91] and RR 1.83 [CI 1.73-1.93], respectively) and epidural analgesia (RR 1.40 [CI 1.36-1.45] and RR 1.74 [CI 1.66-1.83], respectively). A similar trend of smaller magnitude was observed among women with hypertensive disorders but no time trend was observed among women with diabetes. Incidence of cesarean and instrumental delivery remained stable across time., Discussion: The use of labor induction and epidural analgesia increased considerably over time, while the cesarean delivery rate remained low and stable. Increases in labor induction and epidural analgesia were most pronounced for women without a diagnosis of diabetes or hypertensive disorder and were not explained by maternal characteristics such as advanced age., (© 2018 Wiley Periodicals, Inc.)

Background: β-Blockers are a class of antihypertensive medications that are commonly used in pregnancy., Objective: To estimate the risks for major congenital malformations associated with first-trimester exposure to β-blockers., Design: Cohort study., Setting: Health registries in the 5 Nordic countries and the U.S. Medicaid database., Patients: Pregnant women with a diagnosis of hypertension and their offspring., Measurements: First-trimester exposure to β-blockers was assessed. Outcomes were any major congenital malformation, cardiac malformations, cleft lip or palate, and central nervous system (CNS) malformations. Propensity score stratification was used to control for potential confounders., Results: Of 3577 women with hypertensive pregnancies in the Nordic cohort and 14 900 in the U.S. cohort, 682 (19.1%) and 1668 (11.2%), respectively, were exposed to β-blockers in the first trimester. The pooled adjusted relative risk (RR) and risk difference per 1000 persons exposed (RD1000) associated with β-blockers were 1.07 (95% CI, 0.89 to 1.30) and 3.0 (CI, -6.6 to 12.6), respectively, for any major malformation; 1.12 (CI, 0.83 to 1.51) and 2.1 (CI, -4.3 to 8.4) for any cardiac malformation; and 1.97 (CI, 0.74 to 5.25) and 1.0 (CI, -0.9 to 3.0) for cleft lip or palate. For CNS malformations, the adjusted RR was 1.37 (CI, 0.58 to 3.25) and the RD1000 was 1.0 (CI, -2.0 to 4.0) (based on U.S. cohort data only)., Limitation: Analysis was restricted to live births, exposure was based on dispensed medication, and cleft lip or palate and CNS malformations had few outcomes., Conclusion: The results suggest that maternal use of β-blockers in the first trimester is not associated with a large increase in the risk for overall malformations or cardiac malformations, independent of measured confounders., Primary Funding Source: The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Söderström König Foundation.

Introduction: Obstetric interventions appear to increase with advancing maternal age, but limited supporting evidence exists, particularly for young women and specifically for prelabor and intrapartum cesarean birth. The aim of this study was to explore the association between obstetric interventions and maternal age in a low-risk population., Methods: The study was restricted to all low-risk, nulliparous women with singleton, vertex, term births who gave birth in Iceland from 1997 to 2015, identified in the Icelandic Medical Birth Registry. Logistic regression models were used to calculate adjusted odds ratios (aORs) and 95% CIs for the risks of labor induction, instrumental birth, and cesarean birth (prelabor and intrapartum), according to maternal age group. All models were adjusted for gestational age, year of birth, and demographic factors, and the models for intrapartum cesarean birth were also adjusted for dystocia and fetal distress., Results: For women aged more than 40 years, the aOR for induction of labor was 4.69 (95% CI, 3.2-6.8) compared with women aged between 25 and 29 years. In women aged more than 40 years, the increased risks for prelabor cesarean birth and intrapartum cesarean birth were 7.4 (95% CI, 3.0-18.0) and 3.6 (95% CI, 2.1-6.0), respectively. The risk of instrumental birth was slightly increased for women aged between 35 and 39 years (aOR, 1.6; 95% CI, 1.3-2.0), compared with women aged between 25 and 29 years, but not for women aged at least 40 years (aOR, 1.1; 95% CI, 0.7-1.9). For women aged less than 20 years, the risk of induction of labor (aOR, 0.8; 95% CI, 0.7-0.9) and instrumental births (aOR, 0.6; 95% CI, 0.5-0.7) was reduced compared with women aged between 25 and 29 years., Discussion: The risk of interventions generally increased with increasing maternal age, but the risk of instrumental births was not increased for women aged over 40 years. Also, young women were at a decreased risk of induction of labor and instrumental births., (© 2018 by the American College of Nurse-Midwives.)

Introduction: This study examined the impact of antismoking activities targeting the general population and an advertising campaign targeting smoking during pregnancy on the prevalence of smoking during pregnancy in New South Wales (NSW), Australia., Methods: Monthly prevalence of smoking during pregnancy was calculated using linked health records for all pregnancies resulting in a birth (800 619) in NSW from 2003 to 2011. Segmented regression of interrupted time series data assessed the effects of the extension of the ban on smoking in enclosed public places to include licensed premises (evaluated in combination with the mandating of graphic warnings on cigarette packs), television advertisements targeting smoking in the general population, print and online magazine advertisements targeting smoking during pregnancy and increased tobacco tax. Analyses were conducted for all pregnancies, and for the population stratified by maternal age, parity and socioeconomic status. Further analyses adjusted for the effect of the Baby Bonus maternity payment., Results: Prevalence of smoking during pregnancy decreased from 2003 to 2011 overall (0.39% per month), and for all strata examined. For pregnancies overall, none of the evaluated initiatives was associated with a change in the trend of smoking during pregnancy. Significant changes associated with increased tobacco tax and the extension of the smoking ban (in combination with graphic warnings) were found in some strata., Conclusions: The declining prevalence of smoking during pregnancy between 2003 and 2011, while encouraging, does not appear to be directly related to general population antismoking activities or a pregnancy-specific campaign undertaken in this period., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form and declare: all authors had financial support from the National Health and Medical Research Council for the submitted work; AH also received financial support from the National Heart Foundation; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The linkage of routine data collections are valuable for population-based evaluation of smoking cessation pharmacotherapy in pregnancy where little is known about the utilisation or safety of these pharmacotherapies antenatally. The use of routine data collections to study smoking cessation pharmacotherapy is limited by disparities among data sources. This study developed an algorithm to resolve disparity between the evidence of pharmacotherapy utilisation for smoking cessation and the recording of smoking in pregnancy, examined its face validity and assessed the implications on estimates of smoking cessation pharmacotherapy utilisation., Methods: Perinatal records (n = 1,098,203) of women who gave birth in the Australian States of Western Australia and New South Wales (2004-2012) were linked to hospital admissions and pharmaceutical dispensing data. An algorithm, based on dispensing information about the type of smoking therapy, timing and quantity of supply reclassified certain groups of women as smoking during pregnancy. Face validity of the algorithm was tested by examining the distribution of factors associated with inaccurate recording of smoking status among women that the algorithm classified as misreporting smoking in pregnancy. Rate of utilisation among smokers, according to original and reclassified smoking status, was measured, to demonstrate the utility of the algorithm., Results: Smoking cessation pharmacotherapy were dispensed to 2184 women during pregnancy, of those 1013 women were originally recorded as non-smoking as per perinatal and hospital data. Application of the algorithm reclassified 730 women as smoking during pregnancy. The algorithm satisfied the test of face validity-the expected demographic factors of marriage, private hospital delivery and higher socioeconomic status, were more common in women whom the algorithm identified as misreporting their smoking status. Application of the algorithm resulted in smoking cessation pharmacotherapy utilisation estimates ranging from 2.3-3.6% of all pregnancies., Conclusion: Researchers can use the algorithm presented herein to improve the identification of smoking among women who use cessation pharmacotherapies during pregnancy. Improved identification can improve the validity of safety analyses of smoking cessation pharmacotherapy-providing clinicians with valuable evidence to use when counselling women on the role of pharmacotherapy for smoking cessation during pregnancy., Competing Interests: The authors have declared that no competing interests exist.

Importance: Given the rapidly increasing use of stimulant medications during pregnancy and among women of reproductive age who may become pregnant inadvertently, there is a need to better understand their safety., Objective: To examine the risk of congenital malformations associated with intrauterine exposure to stimulants., Design, Setting, and Participants: Cohort study of the Medicaid-insured population in the United States nested in the 2000-2013 US Medicaid Analytic eXtract, with follow-up of safety signals detected in the Medicaid Analytic eXtract data using the Nordic Health registries (2003-2013) (Denmark, Finland, Iceland, Norway, and Sweden). A total of 1 813 894 publicly insured pregnancies in the United States and 2 560 069 singleton pregnancies in the 5 Nordic countries ending in live births were included. Relative risks were estimated accounting for underlying psychiatric disorders and other potential confounders. Relative risk estimates for the US and Nordic data were pooled using a fixed-effects meta-analytic approach. The study was conducted from July 1, 2015, to March 31, 2017., Exposures: Methylphenidate and amphetamines dispensed during the first trimester., Main Outcomes and Measures: Major congenital malformations and subgroup of cardiac malformations., Results: In the US data, of the 1 813 894 pregnancies evaluated, 35.0 per 1000 infants not exposed to stimulants were diagnosed as having congenital malformations, compared with 45.9 per 1000 infants for methylphenidate and 45.4 for amphetamines. For cardiac malformations, the risks were 12.7 (95% CI, 12.6-12.9), 18.8 (95% CI, 13.8-25.6), and 15.4 (95% CI, 12.5-19.0) per 1000 infants, respectively. The adjusted relative risks for methylphenidate were 1.11 (95% CI, 0.91-1.35) for any malformation and 1.28 (95% CI, 0.94-1.74) for cardiac malformations. No increased risks were observed for amphetamines: 1.05 (95% CI, 0.93-1.19) for any malformations and 0.96 (95% CI, 0.78-1.19) for cardiac malformations. Findings were confirmed in sensitivity analyses accounting for proxies of unmeasured confounders and increasing the specificity of the exposure and outcome definitions. Replication of the analyses for methylphenidate using the Nordic data including 2 560 069 pregnancies yielded a relative risk of 1.28 (95% CI, 0.83-1.97) for cardiac malformations, resulting in a pooled estimate of 1.28 (95% CI, 1.00-1.64)., Conclusions and Relevance: These findings suggest a small increase in the risk of cardiac malformations associated with intrauterine exposure to methylphenidate but not to amphetamines. This information is important when weighing the risks and benefits of alternative treatment strategies for attention-deficit/hyperactivity disorder in women of reproductive age and during early pregnancy.