BackgroundResults of some studies suggest that prenatal antidepressant exposure increases the risk of autism spectrum disorder (ASD) in offspring, while other studies suggest that depression independently increases the risk of having a child with ASD. Thus, confounding by indication is a concern.ObjectiveThe aim of this study was to estimate the risk of ASD in offspring of women who were exposed to antidepressants and/or had depression during pregnancy compared to unexposed women.Materials and methodsWe conducted a cohort study with nested sibling case–control analysis. Using the UK Clinical Practice Research Datalink (CPRD), we identified mother– baby pairs where the mother had ≥12 months of history before the delivery date and the child had ≥3 years of follow-up. Exposures during pregnancy were classified as 1) depression treated with antidepressants, 2) untreated depression, 3) other indications for antidepressant use, and 4) 4:1 match of unexposed women with no history of depression or antidepressant use. We calculated the prevalence of ASD and relative risk (RR) with 95% CI. In the sibling analysis, we compared exposure among ASD cases to that of non-ASD siblings born to the same mother. We calculated ORs and 95% CIs for women with treated and untreated depression, compared to unexposed.ResultsWe identified 2,154 offspring with ASD among 194,494 mother–baby pairs. Compared to unexposed, the RR of ASD was 1.72 (95% CI 1.54–1.93) for treated depression and 1.50 (95% CI 1.28–1.75) for untreated depression, while the RR was not elevated in women who received antidepressants for other indications (RR =0.73, 95% CI 0.41–1.29). Additional analyses to assess the effects of severity of depression suggest that the risk of ASD in offspring increases with increasing severity, not with the antidepressant treatment. The results of the sibling analysis were similar to the main analysis.ConclusionWomen with depression during pregnancy have an increased risk of having a child with ASD, regardless of antidepressant use.

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BackgroundAlthough there is a growing body of literature about the impact of asthma exacerbations during pregnancy on adverse perinatal outcomes, it is still unclear whether asthma exacerbations themselves or asthma severity are the driving factor for negative outcomes. This study aimed to estimate the associations between maternal asthma exacerbations and perinatal outcomes; and whether this differed by asthma treatment regime as a proxy for severity.MethodsWe included births of women with asthma in Sweden from July 2006-November 2013 (N=33 829). Asthma exacerbations were defined as unplanned emergency visits/hospitalisations, or a short course of oral corticosteroids. Adjusted odds ratios (aOR) were estimated for the associations between exacerbations during pregnancy and perinatal outcomes (small for gestational age (SGA), preterm birth, birth weight and mode of delivery), stratified by pre-conception treatment regime.ResultsExacerbations occurred in 1430 (4.2%) pregnancies. Exacerbations were associated with reduced birth weight (aOR 1.45, 95%CI 1.24–1.70), and elective (aOR 1.50, 95%CI 1.25–1.79) and emergency caesarean section (aOR 1.35, 95%CI 1.13–1.61). Multiple exacerbations were associated with a 2.6-fold increased odds of SGA (95%CI 1.38–4.82). Amongst women treated pre-pregnancy with combination therapy (proxy for moderate-severe asthma), exacerbators were at increased odds of elective (aOR 1.69, 95%CI 1.30–2.2) and emergency (aOR 1.62, 95%CI 1.26–2.08) caesarean section; and SGA (aOR 1.74, 95%CI 1.18–2.57) versus non-exacerbators.ConclusionMaternal asthma exacerbations increase the risk of SGA and caesarean sections, particularly in women with multiple exacerbations or moderate-severe asthma. Adequate antenatal asthma care is needed to reduce exacerbations and reduce risks of poor outcomes.

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There was a high prevalence of non-adherence and poor self-management skills in all cohorts. More awareness of the importance of optimal asthma management during pregnancy is warranted, since no improvements were observed over the past decade.

This article aimed to assess the clinical effectiveness of non-hormonal targeted therapies (TTs) in terms of increase of median progression-free survival (PFS) and overall survival (OS) in receptor-positive metastatic breast cancer (MBC) patients by performing a systematic review and meta-analysis. We systematically searched relevant randomized controlled trials and extracted data about number of patients on targeted and comparator therapy, receptor status, line of treatment, median PFS and OS, p values, hazard ratios (HRs) and 95% confidence intervals (CI). Inverse variance was used to estimate pooled HRs, chi-square test for heterogeneity and Jadad scale for quality were applied. Thirty-eight studies (n=17,192 patients) were eligible for inclusion. TTs added 3.3months to the median PFS [0.7-9.6; HRs 0.74, 95% CI 0.71-0.77] of receptor-positive MBC patients and prolonged their median OS with 3.5months [0-4.7; HRs 0.90, 95% CI 0.82-0.98]. The highest increase in median PFS of 3.6months was found in HER2-/hormone receptor(HR)+ patients, while the highest increase in median OS of 7.2months was observed in HER2+/HRmixed status patients. First-line TTs were most effective in increasing the median PFS in the HR+/HER2- group with 2.0months, and in the HER2+/HRmixed group by adding 4.7months to the median OS. Second-line TTs were most effective for HER2-/HR+ patients by adding 2.6months to their PFS, and for HER2+/HRmixed patients by adding 3.1months to their median OS. Albeit small, the gain in months of median PFS and median OS was significant. Importantly, the results reported show large variation, and thus routinely applying a personalized approach seems warranted.

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Background Studies demonstrate the prescription rate for inhaled corticosteroids (ICS) decreases in early pregnancy, possibly increasing exacerbation risk. This could be related to non‐adherence to prescribed asthma medication or medication cessation by the patient or doctor. ICS use during pregnancy has not previously been summarized in a systematic review. Objective The aim of this systematic review and meta‐analysis was to evaluate the use of ICS during pregnancy among asthmatic women, specifically: (1) the prevalence of use, (2) changes of use during pregnancy compared with pre‐pregnancy and (3) medication adherence among ICS users. Methods We systematically searched literature in Embase, MEDLINE, CINAL and Cochrane, using terms related to asthma, pregnancy and medication use. All English articles reporting ICS among pregnant women with asthma were included. Prevalence, changes in ICS use during pregnancy and ICS adherence were pooled using STATA (version 15.0, StataCorp USA). Results A total of 4237 references were retrieved in the initial search. Screening and review led to the inclusion of 52 articles for one or more aims (Aim 1: N = 45; Aim 2, N = 13; and Aim 3, N = 5). The pooled prevalence of ICS use during pregnancy was 41% (95%CI 36%‐45%); 49% (95%CI 44%‐55%) in Europe, 39% (95%CI 32%‐47%) in Australia and 34% (95%CI 27%‐41%) in North America. In eight prescription databases, ICS prescription rates lowered in the first trimester of pregnancy, compared with pre‐pregnancy, increased in the second trimester and decreased in the third trimester. Five studies reported ICS adherence among pregnant women, using four measures of self‐reported non‐adherence. In two comparable studies, pooled ICS non‐adherence was 40% (95%CI 36%‐44%). Conclusions The prevalence of ICS use among pregnant women with asthma is 41% and varies widely between countries and continents, and prescription rates for ICS change throughout pregnancy. More studies are needed to investigate ICS adherence during pregnancy in women with asthma.