The effect of maternal prenatal tobacco smoking on offspring academic achievement: A systematic review and meta-analysis.

BACKGROUND: Previous epidemiological studies examining the prospective association between maternal prenatal tobacco smoking and offspring academic achievement have reported conflicting results. Therefore, this systematic review and meta-analysis was conducted to examine the magnitude and consistency of association reported by those studies. METHODS: This systematic review and meta-analysis was guided by the PRISMA protocol. Relevant epidemiological studies on the topic were extracted from four main databases (PubMed/Medline, Embase, PsycINFO, and Scopus). The Newcastle-Ottawa Scale (NOS) was used to appraise the methodological quality of the included studies. We conducted a narrative assessment of the studies that did not report effect estimates. Inverse variance-weighted random effect meta-analysis was used to combine studies reporting effect sizes to estimate pooled adjusted odds ratio with 95% confidence intervals (95% CI). The review was prospectively registered in PROSPERO (CRD42022350901). RESULTS: Nineteen observational studies, published between 1973 and 2021 with a total of 1.25 million study participants were included in the final review. Of these, fifteen studies (79 %) reported reduced academic achievement in offspring exposed to maternal prenatal tobacco smoking. The eight primary studies (sample size = 723,877) included in the meta-analysis together suggested a 49 % higher risk of reduced academic achievement in offspring exposed to maternal prenatal tobacco smoking when compared to non-exposed offspring (Pooled odds ratio = 1.49, 95 % CI:1.17-1.91). CONCLUSION: Our review found a positive association between maternal prenatal tobacco smoking and offspring reduced academic achievement. However, variation in the adjustment of potential confounders and significant heterogeneity across included studies limited more conclusive inference. Mechanistic studies to identify causal pathways and specific academic impacts are needed to inform targeted developmental programs to assist child learning and academic performance.

[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.

Twin birth rates and obstetric interventions in Iceland: A nationwide study from 1997 to 2018.

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.

Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids.

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.

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

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.

Atomoxetine in Early Pregnancy and the Prevalence of Major Congenital Malformations: A Multinational Study.

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.

The combined effect of pre-pregnancy body mass index and gestational weight gain on the risk of pre-labour and intrapartum caesarean section-The ICE-MCH study.

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.

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.

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.

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.

[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.

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.

Antipsychotic use in pregnancy and risk of attention/deficit-hyperactivity disorder and autism spectrum disorder: a Nordic cohort study.

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.

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.

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.

The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol.

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.

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.

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.

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.