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Background: Leveraging a large nationwide study of Icelandic women, we aimed to narrow the evidence gap around female attention-deficit/hyperactivity disorder (ADHD) and cardiometabolic comorbidities by determining the prevalence of obesity, hypertension, type 2 diabetes, and cardiovascular diseases among women with ADHD and examine the association between cardiometabolic conditions and co-occurring ADHD with anxiety and mood disorders, alcoholism/substance use disorder (SUD), self-harm, and suicide attempts., Methods: We conducted a cross-sectional analysis of the nationwide, all-female, population-based SAGA Cohort Study (n = 26,668). To ascertain diagnoses and symptoms, we used self-reported history of ADHD diagnoses, selected cardiometabolic conditions and psychiatric disorders, and measured current depressive, anxiety, and PTSD symptoms through appropriate questionnaires (PHQ-9, GAD-7, and PCL-5). We calculated age-adjusted prevalences of cardiometabolic conditions by women's ADHD status and estimated adjusted prevalence ratios (PR) and 95% confidence intervals (CI), using modified Poisson regression models. Similarly, we assessed the association of cardiometabolic conditions and co-occurring ADHD with current psychiatric symptoms and psychiatric disorders, using adjusted PRs and 95% CIs., Results: We identified 2299 (8.6%) women with a history of ADHD diagnosis. The age-adjusted prevalence of having at least one cardiometabolic condition was higher among women with ADHD (49.5%) than those without (41.7%), (PR = 1.19, 95% CI 1.14-1.25), with higher prevalence of all measured cardiometabolic conditions (myocardial infarctions (PR = 2.53, 95% CI 1.83--3.49), type 2 diabetes (PR = 2.08, 95% CI 1.66-2.61), hypertension (PR = 1.23, 95% CI 1.12-1.34), and obesity (PR = 1.18, 95% CI 1.11-1.25)). Women with cardiometabolic conditions and co-occurring ADHD had, compared with those without ADHD, substantially increased prevalence of (a) all measured mood and anxiety disorders, e.g., depression (PR = 2.38, 95% CI 2.19-2.58), bipolar disorder (PR = 4.81, 95% CI 3.65-6.35), posttraumatic stress disorder (PR = 2.78, 95% CI 2.52-3.07), social phobia (PR = 2.96, 95% CI 2.64-3.32); (b) moderate/severe depressive, anxiety, and PTSD symptoms with PR = 1.76 (95% CI 1.67-1.85), PR = 1.97 (95% CI 1.82-2.12), and PR = 2.01 (95% CI 1.88-2.15), respectively; (c) alcoholism/SUD, PR = 4.79 (95% CI 3.90-5.89); and (d) self-harm, PR = 1.47 (95% CI 1.29-1.67) and suicide attempts, PR = 2.37 (95% CI 2.05-2.73)., Conclusions: ADHD is overrepresented among women with cardiometabolic conditions and contributes substantially to other psychiatric comorbidities among women with cardiometabolic conditions., (© 2023. The Author(s).)

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.

Objective: Previous research reported greater risk of adverse perinatal outcomes associated with first trimester exposure to angiotensin converting enzyme inhibitors (ACEIs) in comparison to unexposed pregnancies among non-hypertensive women. We examined the relationship between first trimester exposure to ACEIs and angiotensin receptor blockers (ARBs), and maternal and perinatal outcomes, whilst controlling for the underlying hypertension., Study Design: We performed a population-based cohort study among 130,061 pregnancies resulting in birth in NSW, Australia between 2005 and 2012. Birth data were linked to hospital discharge and pharmaceutical dispensing records. After restricting to women with chronic hypertension, 67 and 73 pregnancies exposed to ACEIs and ARBs respectively during the first trimester were compared with 316 pregnancies exposed to methyldopa., Study Outcomes: Preterm delivery, caesarean section, low birth weight, small for gestational age and Apgar score <7., Results: Compared to pregnancies exposed to methyldopa, the adjusted odds ratio (aOR) for ACEI exposure was 0.5 (95% CI: 0.2-1.1) for preterm delivery, 1.6 (0.8-3.1) for caesarean section, 0.6 (0.2-1.3) for LBW and 0.8 (0.4-1.9) for SGA. The corresponding aORs and confidence intervals for ARB exposure were 0.7 (0.3-1.5), 1.2 (0.6-2.6), 1.3 (0.7-2.6), and 1.2 (0.6-2.4)., Conclusion: No association between early pregnancy exposure to ACEIs and ARBs and perinatal outcomes was observed, however, the possibility of an association cannot be ruled out due to limited power. Nonetheless, this study suggests that the magnitude of risk is smaller than that reported previously., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Although smoking during pregnancy may lead to many adverse outcomes, numerous studies have reported a paradoxical inverse association between maternal cigarette smoking during pregnancy and preeclampsia. Using a counterfactual framework we aimed to explore the structure of this paradox as being a consequence of selection bias. Using a case-control study nested in the Icelandic Birth Registry (1309 women), we show how this selection bias can be explored and corrected for. Cases were defined as any case of pregnancy induced hypertension or preeclampsia occurring after 20 weeks' gestation and controls as normotensive mothers who gave birth in the same year. First, we used directed acyclic graphs to illustrate the common bias structure. Second, we used classical logistic regression and mediation analytic methods for dichotomous outcomes to explore the structure of the bias. Lastly, we performed both deterministic and probabilistic sensitivity analysis to estimate the amount of bias due to an uncontrolled confounder and corrected for it. The biased effect of smoking was estimated to reduce the odds of preeclampsia by 28 % (OR 0.72, 95 %CI 0.52, 0.99) and after stratification by gestational age at delivery (<37 vs. ≥37 gestation weeks) by 75 % (OR 0.25, 95 %CI 0.10, 0.68). In a mediation analysis, the natural indirect effect showed and OR > 1, revealing the structure of the paradox. The bias-adjusted estimation of the smoking effect on preeclampsia showed an OR of 1.22 (95 %CI 0.41, 6.53). The smoking-preeclampsia paradox appears to be an example of (1) selection bias most likely caused by studying cases prevalent at birth rather than all incident cases from conception in a pregnancy cohort, (2) omitting important confounders associated with both smoking and preeclampsia (preventing the outcome to develop) and (3) controlling for a collider (gestation weeks at delivery). Future studies need to consider these aspects when studying and interpreting the association between smoking and pregnancy outcomes.

While obesity is an indicated risk factor for hypertensive disorders of pregnancy, smoking during pregnancy has been shown to be inversely associated with the development of preeclampsia and gestational hypertension. The purpose of this study was to investigate the combined effects of high body mass index and smoking on hypertensive disorders during pregnancy. This was a case-control study based on national registers, nested within all pregnancies in Iceland 1989-2004, resulting in birth at the Landspitali University Hospital. Cases (n = 500) were matched 1:2 with women without a hypertensive diagnosis who gave birth in the same year. Body mass index (kg/m2) was based on height and weight at 10-15 weeks of pregnancy. We used logistic regression models to calculate odds ratios and corresponding 95% confidence intervals as measures of association, adjusting for potential confounders and tested for additive and multiplicative interactions of body mass index and smoking. Women's body mass index during early pregnancy was positively associated with each hypertensive outcome. Compared with normal weight women, the multivariable adjusted odds ratio for any hypertensive disorder was 1.8 (95% confidence interval, 1.3-2.3) for overweight women and 3.1 (95% confidence interval, 2.2-4.3) for obese women. The odds ratio for any hypertensive disorder with obesity was 3.9 (95% confidence interval 1.8-8.6) among smokers and 3.0 (95% confidence interval 2.1-4.3) among non-smokers. The effect estimates for hypertensive disorders with high body mass index appeared more pronounced among smokers than non-smokers, although the observed difference was not statistically significant. Our findings may help elucidate the complicated interplay of these lifestyle-related factors with the hypertensive disorders during pregnancy.

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. [ABSTRACT FROM AUTHOR]

Background: Hypertensive disorders complicate up to 10% of pregnancies. Evidence suggests a potential association between maternal hypertensive disorders during pregnancy, particularly preeclampsia, and adverse neurodevelopment in the offspring, but existing studies are subject to limitations. We aimed to assess whether in-utero exposure to preeclampsia/eclampsia negatively impacts academic performance at ages 9, 12 and 15 years. Methods: Using individually linked, nationwide data from the Icelandic registries we followed all children born in 1989–2004 (N = 68,580), from birth until the end of 2014, thereof 63,014 (91.9%) took at least one standardized test. Using a stepwise, mixed-effects approach, we modelled the hypothesized relationship while adjusting for maternal, perinatal and childhood variables of interest. We compared test scores, measured on a normalized scale ranging from 0–60 with a mean of 30 and a standard deviation of 10, in the 4th, 7th, and 10th grades, between children exposed to preeclampsia or eclampsia in-utero versus children from normotensive pregnancies in the population. Results: Children exposed to preeclampsia/eclampsia scored lower than those unexposed in mathematics across all grade levels, corresponding to a difference of 0.44 points (95% CI: 0.00, 0.89), 0.59 points (95% CI: 0.13, 1.06) and 0.59 points (95% CI: 0.08, 1.10), respectively. No differences were observed in the language arts. Conclusions: Our findings suggest a minimal effect of maternal preeclampsia/eclampsia on children’s academic performance at ages 9, 12 and 15 years. The differences observed in mathematic scores between exposed and unexposed children were minimal, less than one tenth of a standard deviation per measurement occasion. [ABSTRACT FROM AUTHOR]