The association between psychostimulant use in pregnancy and adverse maternal and neonatal outcomes: results from a distributed analysis in two similar jurisdictions.

BACKGROUND: Conflicting evidence suggests a possible association between use of prescribed psychostimulants during pregnancy and adverse perinatal outcomes. METHODS: We conducted population-based cohort studies including pregnancies conceived between April 2002 and March 2017 (Ontario, Canada; N = 554 272) and January 2003 to April 2011 [New South Wales (NSW), Australia; N = 139 229]. We evaluated the association between exposure to prescription amphetamine, methylphenidate, dextroamphetamine or lisdexamfetamine during pregnancy and pre-eclampsia, placental abruption, preterm birth, low birthweight, small for gestational age and neonatal intensive care unit admission. We used inverse probability of treatment weighting based on propensity scores to balance measured confounders between exposed and unexposed pregnancies. Additionally, we restricted the Ontario cohort to social security beneficiaries where supplementary confounder information was available. RESULTS: In Ontario and NSW respectively, 1360 (0.25%) and 146 (0.10%) pregnancies were exposed to psychostimulants. Crude analyses indicated associations between exposure and nearly all outcomes [OR range 1.15-2.16 (Ontario); 0.97-2.20 (NSW)]. Nearly all associations were attenuated after weighting. Pre-eclampsia was the exception: odds remained elevated in the weighted analysis of the Ontario cohort (OR 2.02, 95% CI 1.42-2.88), although some attenuation occurred in NSW (weighted OR 1.50, 95% CI 0.77-2.94) and upon restriction to social security beneficiaries (weighted OR 1.24, 95% CI 0.64-2.40), and confidence intervals were wide. CONCLUSIONS: We observed higher rates of outcomes among exposed pregnancies, but the attenuation of associations after adjustment and likelihood of residual confounding suggests psychostimulant exposure is not a major causal factor for most measured outcomes. Our findings for pre-eclampsia were inconclusive; exposed pregnancies may benefit from closer monitoring.

ß-Blocker Use in Pregnancy and the Risk for Congenital Malformations: An International Cohort Study.

Background: ß-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 ß-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 ß-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 ß-blockers in the first trimester. The pooled adjusted relative risk (RR) and risk difference per 1000 persons exposed (RD1000) associated with ß-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 ß-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.

Utilization of Stimulants and Atomoxetine for Attention-Deficit/Hyperactivity Disorder among 5.4 Million Children Using Population-Based Longitudinal Data.

Use of stimulants to treat attention-deficit/hyperactivity disorder (ADHD) has increased over the past two decades and varies substantially between countries. The objective of this multinational population-based study was to examine utilization of ADHD drugs (stimulants and atomoxetine) including comedication with other psychotropic drugs in the entire child population in the five Nordic countries. We included longitudinal data on dispensed ADHD drugs from five Nordic prescription registers during 2008-2012, which in 2012 comprised 48,296 individuals among 5.42 million inhabitants aged 0-17 years. Prevalence of filling ≥1 prescriptions of ADHD drugs among children aged 6-17 years increased during 2008-2012 from 5.9 to 11.2 and 19.4 to 31.0 per 1000 girls and boys, respectively. Prevalence by country showed that Iceland, Finland and Sweden had a steady increase during the study period, while in Norway the prevalence was quite stable and in Denmark it levelled off from 2010. Use in preschoolers (aged 0-5 years) was rare. Iceland had much higher prevalence and incidence than the other Nordic countries. The incidence of ADHD drug use increased during the study period, from 4.0 to 4.9 and from 1.5 to 2.3 per 1000 boys and girls, respectively. The increasing number of new users levelled off somewhat after 2010. Comedication with other psychotropic drugs was more common among girls (33.9%) than boys (27.0%) and was mainly melatonin, followed by antidepressants and antipsychotics. Overall prevalence of ADHD drug use increased among Nordic girls and boys aged 6-17 years, whereas the incidence increased slightly during 2008-2010 but levelled off through 2012. The substantial differences in ADHD drug use across the Nordic countries and high degree of comedication with other psychotropic drugs underscore the importance of close monitoring of treatment for ADHD among children.

Pregnancy-Induced Hypertensive Disorders before and after a National Economic Collapse: A Population Based Cohort Study.

BACKGROUND: Data on the potential influence of macroeconomic recessions on maternal diseases during pregnancy are scarce. We aimed to assess potential change in prevalence of pregnancy-induced hypertensive disorders (preeclampsia and gestational hypertension) during the first years of the major national economic recession in Iceland, which started abruptly in October 2008. METHODS AND FINDINGS: Women whose pregnancies resulted in live singleton births in Iceland in 2005-2012 constituted the study population (N = 35,211). Data on pregnancy-induced hypertensive disorders were obtained from the Icelandic Medical Birth Register and use of antihypertensive drugs during pregnancy, including ß-blockers and calcium channel blockers, from the Icelandic Medicines Register. With the pre-collapse period as reference, we used logistic regression analysis to assess change in pregnancy-induced hypertensive disorders and use of antihypertensives during the first four years after the economic collapse, adjusting for demographic and pregnancy characteristics, taking aggregate economic indicators into account. Compared with the pre-collapse period, we observed an increased prevalence of gestational hypertension in the first year following the economic collapse (2.4% vs. 3.9%; adjusted odds ratio [aOR] 1.47; 95 percent confidence interval [95%CI] 1.13-1.91) but not in the subsequent years. The association disappeared completely when we adjusted for aggregate unemployment rate (aOR 1.04; 95% CI 0.74-1.47). Similarly, there was an increase in prescription fills of ß-blockers in the first year following the collapse (1.9% vs.3.1%; aOR 1.43; 95% CI 1.07-1.90), which disappeared after adjusting for aggregate unemployment rate (aOR 1.05; 95% CI 0.72-1.54). No changes were observed for preeclampsia or use of calcium channel blockers between the pre- and post-collapse periods. CONCLUSIONS: Our data suggest a transient increased risk of gestational hypertension and use of ß-blockers among pregnant women in Iceland in the first and most severe year of the national economic recession.

Smoking and obesity among pregnant women in Iceland 2001-2010.

BACKGROUND: The prevalence of smoking during pregnancy in Western societies has decreased in the last decades, whereas prevalence of overweight and obesity has increased. Our objective was to study secular trends and patterns of smoking and body weight among pregnant women in Iceland, during a period of dramatic changes in the nation's economy. METHODS: On the basis of the Medical Birth Registry, we used a random sample of 1329 births between 1 January 2001 and 31 December 2010. Information on smoking, body mass index and background factors during pregnancy was retrieved from the Medical Birth Register and maternity records. Trends in smoking, overweight, obesity and body mass index were assessed using logistic and linear regression analyses. Logistic regression analysis was used to examine the annual odds of smoking and obesity and by socio-demographic characteristics. RESULTS: We found a decrease in the prevalence of continued smoking during pregnancy from 12.4% in 2001 to 7.9% in 2010 [odds ratio (OR) = 0.94, 95% confidence interval (CI) (0.88-1.00)], particularly among women with Icelandic citizenship [OR = 0.92, 95% CI (0.86-0.98)], whereas no changes in obesity [OR = 1.02, 95% CI (0.96-1.07)] were observed. The highest prevalence of maternal smoking and obesity was observed in 2005-06. CONCLUSION: Our results indicate that smoking during pregnancy decreased among Icelandic women in 2001-10, whereas an initial increase in obesity prevalence seemed to level off towards the end of the observation period. Interestingly, we found that both of these maternal risk factors reached their highest prevalence in 2005-06, which coincides with a flourishing period in the nation's economy.