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Aims: The contemporary prescription patterns of antidiabetic drugs following guideline changes recommending metformin as first‐line gestational diabetes (GDM) pharmacotherapy is underexplored. We aimed to examined use of metformin and insulin during pregnancy among women with GDM over 20 years in the United Kingdom. Methods: We conducted a population‐based cohort study using linked data from the Clinical Practice Research Datalink, its pregnancy register and Hospital Episode Statistics from 1998 to 2017. We included pregnancies of women without prior diabetes history who received GDM diagnosis or initiated an antidiabetic drug after 20 weeks gestation. Patient‐level and practice‐level characteristics were compared between metformin initiators and insulin initiators. We described trends of initiating metformin as first‐line treatment and described time to initiation of rescue insulin overall, and by body mass index among metformin initiators. Results: Our cohort included 5633 pregnancies from 5393 women with GDM, of whom 38.9% initiated pharmacotherapy (41% insulin, 59% metformin). Metformin prescriptions (as opposed to insulin) increased substantially, from <5% of pregnancies before 2007 to 42.5% in 2008. Over 85% of pregnancies that were prescribed pharmacotherapy were prescribed metformin as first‐line treatment in 2015. Among metformin initiators, 16% initiated rescue insulin, typically occurring within 40 days of metformin initiation. Choice of GDM pharmacotherapy varied by characteristics, including smoking, obesity, race/ethnicity and general practice regions. Conclusions: Metformin was the most prescribed medication for GDM, with large increases over the past 2 decades. The increasing use of oral‐antidiabetic drugs during pregnancy, consistent with other regions, highlights the need for future studies examining effectiveness and safety of antidiabetic drug use during pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: Inversed probability weighted (IPW) estimators are commonly used to adjust for time-fixed or time-varying confounders. However, in high-dimensional settings, including all identified confounders may result in unstable weights leading to higher variance. We aimed to develop a visualization tool demonstrating the impact of each confounder on the bias and variance of IPW estimates, as well as the propensity score overlap.Methods: A SAS macro was developed for this visualization tool and we demonstrate how this tool can be used to identify potentially problematic confounders of the association of statin use after myocardial infarction on one-year mortality in a plasmode simulation study using a cohort of 39,792 patients from the UK (1998-2012).Results: Through the tool's output, we can identify problematic confounders (two instrumental variables) and important confounders by comparing the estimated psuedo MSE with that from the fully adjusted model and propensity score overlap plot.Conclusion: Our results suggest that the analytic impact of all confounders should be considered carefully when fitting IPW estimators. [ABSTRACT FROM AUTHOR]

Aims: Metformin is increasingly used off-label as the treatment of gestational diabetes (GDM). Our objective was to determine if metformin versus insulin initiation is associated with the adverse pregnancy outcomes., Materials and Methods: We conducted a retrospective cohort study using data from the Clinical Practice Research Datalink, its pregnancy register, and Hospital Episode Statistics from 1998 to 2018. We included pregnancies of women who initiated metformin or insulin between 20 weeks gestation and pregnancy end. The primary outcome was a composite outcome of large for gestational age (LGA) and macrosomia. The secondary outcomes included small for gestational age (SGA), preterm birth, caesarean delivery, and hypertensive disorders during pregnancy (HDP). Inverse probability weighted-Cox proportional hazards models were to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CI), comparing those who initiated metformin versus insulin at cohort entry, accounting for baseline covariates., Results: Our cohort included pregnancies of 1297 women initiating metformin and of 895 women initiating insulin. Compared to insulin initiation, metformin initiation was associated with a decreased risk of LGA or macrosomia (HR 0.64, 95% CI 0.49, 0.78), Caesarean delivery (HR 0.83, 95% CI 0.69, 0.98), and preterm birth (HR 0.83, 95% CI 0.58, 1.08). The HRs for HDP and SGA were 0.92 (95% CI 0.57, 1.27) and 1.33 (95% CI 0.67, 2.00), respectively., Conclusions: Our study suggests that, compared to initiating insulin, initiating metformin is associated with decreased risks of adverse pregnancy outcomes among women with GDM. These findings provide important real-world evidence regarding the use of metformin for GDM., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: While the benefits of levothyroxine are well-established for overt hypothyroidism, they are unclear for subclinical hypothyroidism (SCH) among pregnant women., Objective: To estimate the effect of initiation of levothyroxine on pregnancy loss among women with SCH with an emulated target trial using observational data., Methods: We emulated a target trial using the United Kingdom's Clinical Practice Research Datalink to account for the staggered timing of diagnosis and treatment of SCH and the time of entry of women into prenatal care. We emulated multiple nested trials (at each gestational week) and used an intention-to-treat approach to define levothyroxine use (≥1 prescription in the 7 days prior to trial entry), with eligible users matched to non-users (1:4) on time of diagnosis, gestational week of the first eligible trial and high-dimensional propensity score. Pregnancy losses included spontaneous abortion and stillbirth. A pooled logistic regression model with bootstrap resampling was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI)., Results: Based on 159,177 eligible person-trials (5781 women), the matched cohort included 181 initiators and 640 non-initiators of levothyroxine, with 57 pregnancy losses occurring during follow-up. Overall, the mean age of women was 32.2 years (SD 5.4), 25% were obese, 8% had type 2 diabetes and about 50% were nulliparous. After matching, women who initiated levothyroxine versus not had higher thyroid-stimulating levels during pregnancy and were more likely to have a history of hypothyroidism. The cumulative incidence of pregnancy loss was lower in initiators versus non-initiators of levothyroxine. The adjusted HR for pregnancy loss was 0.87 (95% CI 0.22, 1.56)., Conclusions: Although our assessment of the effect of initiation of levothyroxine for SCH in pregnancy precludes any definitive conclusions due to wide confidence intervals, this study illustrates the feasibility of using the target trial emulation framework to examine the effectiveness of medication use in pregnancy., (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Our study aimed to describe levothyroxine prescription patterns and trends over time among pregnant women with subclinical hypothyroidism (SCH) in the United Kingdom. We used data from the Clinical Practice Research Datalink linked to its Pregnancy Register and the Hospital Episode Statistics database from 1998 to 2017. The study population included women with a diagnosis of SCH or an abnormal thyroid-simulated hormone (TSH) level one year prior to or during pregnancy. We compared characteristics between women who received a prescription for levothyroxine during pregnancy and those who did not. We further described the timing, dose, duration, and temporal trends of levothyroxine prescriptions. Our cohort included 6,757 pregnancies from 6,287 women with SCH, of whom 10% received levothyroxine during pregnancy. Among women who received levothyroxine, most received their first prescription during the first trimester (median gestational age: 7 weeks; interquartile range [IQR]: 0, 16) with a median daily dosage of 50 mcg (IQR: 50, 73). Levothyroxine prescription varied over time, decreasing from 23% of pregnant women in 1998 to 7.5% in 2003, remaining stable until 2014, and increasing to 12.5% in 2016. Smoking, diabetes, polycystic ovary syndrome, infertility, timing of SCH diagnosis, age, TSH level at diagnosis, and general practice regions were associated with prescription. Few women with SCH received levothyroxine during pregnancy, and treatment varied by patient characteristics and geographical regions. These results highlight the need to increase awareness among healthcare providers and will guide future studies that explore barriers to initiating levothyroxine treatment for women with SCH during pregnancy., (© 2021 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)