Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations.

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.

Prevalence and risk factors of extended-spectrum beta-lactamase producing E. coli causing urinary tract infections in Iceland during 2012-2021.

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.

Trends in gestational diabetes in Iceland before and after guideline changes in 2012: a nationwide study from 1997 to 2020.

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.

Changes in maximum parental leave payment in Iceland and total fertility rates.

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.

[Postpartum hemorrhage in singleton births in Iceland 2013 - 2018, incidence proportion and risk factors].

INTRODUCTION: Many countries have reported an increased incidence proportion of postpartum hemorrhage (PPH). The proportion might also have increased at the National University Hospital of Iceland, based on the registration of the ICD-10 code O72. This study aimed to assess the incidence proportion and risk factors for ≥1000 ml PPH in singleton births in Iceland 2013-2018. METHODS: This population-based cohort study included data from the Icelandic Birth register on 21.110 singleton births in 2013-2018. Incidence proportion of PPH was assessed based on three definitions: PPH >500 ml, PPH ≥1000 ml, and O72. Binomial regression was used to assess both the change in the proportion of ≥1000 ml PPH over time, stratified by maternal BMI, and risk factors for ≥1000 ml PPH. RESULTS: There was an inconsistency in the proportion of PPH when defined by blood loss >500 ml and O72. In obese women, PPH ≥1000 ml was more than twice as likely in those delivering in 2018 compared with 2013 (OR 2.23; CI 1.35-3.81). The strongest risk factors were emergency cesarean (OR 2.68; CI 2.22-3.22) and instrumental delivery (OR 2.18; CI 1.80-2.64), but macrosomia, primiparity and BMI ≥30 were also independent risk factors. CONCLUSION: The incidence proportion of ≥1000 ml PPH has increased among obese women. The detrimental health effects of obesity and the increased prevalence of interventions among these women could explain these results. It is necessary to use registered blood loss in milliliters in the Icelandic Birth Register because of the under-registration of the diagnostic code O72.

Dietary patterns in adolescence and risk of colorectal cancer: a population-based study.

PURPOSE: To study whether dietary patterns in adolescence are associated with risk of colorectal cancer (CRC). METHODS: Food frequency data were obtained from the AGES-Reykjavik study, conducted between 2002 and 2006, which included 5,078 (58% women) participants with mean age of 77 (± 5.8) years. Principal component analysis was used to identify dietary patterns. Participants were followed through linkage to the Icelandic Cancer Registry. Multivariable Cox models were used to calculate hazard ratios (HR) of CRC and 95% confidence interval (CI) by dietary patterns. RESULTS: During the follow-up period (mean 8.2 years), 136 participants (75 women and 61 men) were diagnosed with CRC. The main dietary pattern in adolescence was characterized by high intake of traditional food items consumed in the earlier half of the twentieth century, namely, salted or smoked meat and fish, milk, offal, rye bread, and oatmeal. Compared to the lowest tertile, the middle tertile of this pattern was associated with increased risk of CRC (HR 1.63, 95% CI 1.04-2.57), while the highest tertile was not statistically associated with CRC (HR 1.48, 95% CI 0.93-2.37), except among women (HR 2.06, 95% CI 1.11-3.84). CONCLUSION: These data suggest that strong adherence to a traditional Icelandic diet in adolescence might increase the risk of CRC, particularly among women. More research is need on the association between food items and dietary patterns of relevance to CRC at different points in the life cycle.

Trends in labor induction indications: A 20-year population-based study.

INTRODUCTION: Use of labor induction has increased rapidly in most middle- and high-income countries over the past decade. The reasons for the stark rise in labor induction are largely unknown. We aimed to assess the extent to which the rising rate of labor induction is explained by changes in rates of underlying indications over time. MATERIAL AND METHODS: The study was based on nationwide data from the Icelandic Medical Birth Register on 85 620 singleton births from 1997 to 2018. The rate of labor induction and indications for induction was calculated for all singleton births in 1997-2018. Change over time was expressed as relative risk (RR), using Poisson regression with 95% confidence intervals (CI) adjusted for maternal characteristics and indications for labor induction. RESULTS: The crude rate of labor induction rose from 12.5% in 1997-2001 to 23.9% in 2014-2018 (crude RR = 1.91, 95% CI 1.81-2.01). While adjusting for maternal characteristics had little impact, adjusting additionally for labor induction indications lowered the RR to 1.43 (95% CI 1.35-1.51). Induction was increasingly indicated from 1997-2001 to 2014-2018 by gestational diabetes (2.4%-16.5%), hypertensive disorders (7.0%-11.1%), prolonged pregnancy (16.2%-23.7%), concerns for maternal wellbeing (3.2%-6.9%) and maternal age (0.5%-1.2%). No indication was registered for 9.2% of inductions in 2014-2018 compared with 16.3% in 1997-2001. CONCLUSIONS: Our results show that the increase in labor induction over the study period is largely explained by an increase in various underlying conditions indicating labor induction. However, indications for 9.2% of labor inductions remain unexplained and warrant further investigation.

Contributing indications to intrapartum and prelabor cesarean births in Iceland 1997-2015.

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.

Use of pain management in childbirth among migrant women in Iceland: A population-based cohort study.

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.

[Reducing rate of macrosomia in Iceland in relation to changes in the labor induction rate].

AIM: Diabetes and prolonged pregnancy are risk factors of macrosomia. The aim was to explore the relationship between the increased rate of labor induction and macrosomia in Iceland. Changes in the incidence proportion of macrosomia was estimated by gestational age. Further, the association between labor induction and macrosomia was estimated in reference to expectant management. MATERIAL AND METHODS: Data from the Iceland birth registry on 92,424 singleton births from 1997 to 2018 was used in this cohort study. Macrosomia was defined as birth weight more than 4.5 kg. The incidence proportion during three periods, 1997-2004, 2005-2011, 2012-2018, was calculated and stratified by gestational age. The relative risk reduction of macrosomia over time was calculated with log-binomial regression, using the first period as reference. The risk and relative risk of macrosomia compared with expectant management was estimated and adjusted for diabetes. RESULTS: The total number of macrosomic infants was 5110 and of those only 313 had a mother with diabetes. The incidence proportion of macrosomia was 6.5% during the period 1997-2004, but 4.6% during 2012-2018. A relative risk reduction of macrosomia over time was seen for deliveries after estimated due date. Labor induction decreased the risk of macrosomia, but the association persisted after adjustment for diabetes. CONCLUSION: The rate of macrosomia decreased in Iceland during the last two decades, but only a small proportion of macrosomic infants had a mother with diabetes. Labor induction decreased the risk of macrosomia, an association which seemed independent of diabetes.

The Comparative Effectiveness of Varenicline and Nicotine Patches for Smoking Abstinence During Pregnancy: Evidence From a Population-based Cohort Study.

INTRODUCTION: In the general population, varenicline is consistently shown to be more efficacious for smoking cessation than nicotine replacement therapy (NRT). Current clinical guidelines for the management of smoking during pregnancy recommend against the use of varenicline, whilst supporting the use of NRT. However, little is known about the comparative effectiveness of these smoking cessation therapies among pregnant women. AIMS AND METHODS: Routinely-collected records of all births in two Australian States during 2011 and 2012 were used to create a population-based cohort of women who smoked during the first half of pregnancy. Pharmaceutical dispensing data were used to identify varenicline and nicotine patch dispensings in the first half of pregnancy. Propensity score matching was used to account for the potentially different distribution of confounding factors between the treatment groups. The outcome was defined as smoking abstinence during the second half of pregnancy. RESULTS: After propensity score-matching, our cohort comprised 60 women who used varenicline and 60 who used nicotine patches during the first half of pregnancy. More varenicline users (33.3%, 95% CI: 21.7%-46.7%) quit smoking than nicotine patch users (13.3%, 95% CI: 5.9%-24.6%). The adjusted rate difference was 24.2% (95% CI: 10.2%-38.2%) and the adjusted relative risk was 2.8 (95% CI: 1.4-5.7). CONCLUSIONS: Varenicline was almost three times more effective than nicotine patches in assisting pregnant women to quit smoking. Further studies are needed to corroborate our results. Together with data on the safety of varenicline during pregnancy, evidence regarding the relative benefit of varenicline and NRT during pregnancy important for informing clinical decisions for pregnant smokers. IMPLICATIONS: This study is the first to measure the comparative effectiveness of varenicline and nicotine patches during pregnancy - women using varenicline were almost three times as likely to quit smoking than those using nicotine patches. This study addressed a clinically important question using an observational study, noting that there is an absence of evidence from randomized controlled trials because of the ethical issues associated with including pregnant women in clinical trials of medicines of unknown safety.

Changes in obstetric interventions and preterm birth during COVID-19: A nationwide study from Iceland.

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.

Challenges in migrant women's maternity care in a high-income country: A population-based cohort study of maternal and perinatal outcomes.

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.

Trends in cesarean birth rates in Iceland over a 19-year period.

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.

Cesarean birth, obstetric emergencies, and adverse neonatal outcomes in Iceland during a period of increasing labor induction.

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.

Use of smoking cessation pharmacotherapies during pregnancy is not associated with increased risk of adverse pregnancy outcomes: a population-based cohort study.

BACKGROUND: Varenicline, bupropion and nicotine replacement therapy (NRT) are three effective pharmacotherapies for smoking cessation, but data about their safety in pregnancy are limited. We assessed the risk of adverse perinatal outcomes and major congenital anomalies associated with the use of these therapies in pregnancy in Australia. METHODS: Perinatal data for 1,017,731 deliveries (2004 to 2012) in New South Wales and Western Australia were linked to pharmaceutical dispensing, hospital admission and death records. We identified 97,875 women who smoked during pregnancy; of those, 233, 330 and 1057 were exposed to bupropion, NRT and varenicline in pregnancy, respectively. Propensity scores were used to match exposed women to those who were unexposed to any smoking therapy (1:10 ratio). Propensity scores and gestational age at exposure were used to match varenicline-exposed to NRT-exposed women (1:1 ratio). Time-dependent Cox proportional hazards models estimated hazard ratios (HR) with 95% confidence intervals (95% CI) for any adverse perinatal event (a composite of 10 unfavourable maternal and neonatal outcomes) and any major congenital anomaly. RESULTS: The risk of any adverse perinatal event was not significantly different between bupropion-exposed and unexposed women (39.2% versus 39.3%, HR 0.93, 95% CI 0.73-1.19) and between NRT-exposed and unexposed women (44.8% vs 46.3%, HR 1.02, 95% CI 0.84-1.23), but it was significantly lower in women exposed to varenicline (36.9% vs 40.1%, HR 0.86, 95% CI 0.77-0.97). Varenicline-exposed infants were less likely than unexposed infants to be born premature (6.5% vs 8.9%, HR 0.72, 95% CI 0.56-0.92), be small for gestational age (11.4% vs 15.4%, HR 0.68, 95% CI 0.56-0.83) and have severe neonatal complications (6.6% vs 8.2%, HR 0.74, 95% CI 0.57-0.96). Among infants exposed to varenicline in the first trimester, 2.9% had a major congenital anomaly (3.5% in unexposed infants, HR 0.91, 95% CI 0.72-1.15). Varenicline-exposed women were less likely than NRT-exposed women to have an adverse perinatal event (38.7% vs 51.4%, HR 0.58, 95% CI 0.33-1.05). CONCLUSIONS: Pregnancy exposure to smoking cessation pharmacotherapies does not appear to be associated with an increased risk of adverse birth outcomes. Lower risk of adverse birth outcomes in varenicline-exposed pregnancies is inconsistent with recommendations that NRT be used in preference to varenicline.

Prevalence trends and individual patterns of antiepileptic drug use in pregnancy 2006-2016: A study in the five Nordic countries, United States, and Australia.

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.

Preterm births in Iceland 1997-2016: Preterm birth rates by gestational age groups and type of preterm birth.

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.

The effect of the 2008 recession on well-being and employment status of people with and without mental health problems.

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.

Type 2 diabetes and obesity in midlife and breast cancer risk in the Reykjavik cohort.

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.