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Assessing the benefits and risks to mothers and offspring of continuing treatment for maternal hypertension and hypothyroidism: an observational cohort study in the UK Clinical Practice Research Datalink

Barry, C.-J. S.; Walker, V. M.; Burden, C.; Davey Smith, G.; Davies, N. M.

2024-08-09 epidemiology
10.1101/2024.08.09.24311727 medRxiv
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AJOG at a glanceA. Why was this study conducted? This study aimed to evaluate the risks and benefits of discontinuing maternal prescriptions for chronic hypertension and hypothyroidism during pregnancy. B. What are the key findings? Discontinuing beta-blockers and thyroid hormones was associated with some improved maternal outcomes, such as a reduced risk of miscarriage. We found limited evidence of an association between the discontinuation of multiple drugs subclasses such as renin-angiotensin system drugs and differential risk of maternal or neonatal outcomes. C. What does this study add to what is already known? This study provides observational evidence that discontinuing certain medications may not be strongly associated with differential risk of maternal or neonatal outcomes and highlights the need for further research due to limitations such as confounding by indication and potential data misclassification. Exclusion of pregnant women from clinical trials, due to ethical concerns, has limited evidence on medication safety during pregnancy, resulting in conservative guidance. Yet, rising prevalence of chronic conditions in reproductive-age women has increased medication use. This study evaluates risks and benefits of discontinuing drug prescriptions for chronic hypertension, and hypothyroidism during pregnancy using linked primary care records from a longitudinal intergenerational database. Using UK Clinical Practice Research Datalink (CPRD) GOLD, we conducted multivariable regression models, adjusted for covariates, to assess maternal treatment discontinuation on various outcomes. Cohorts of 3,232 and 3,334 pregnancies with chronic hypertension and hypothyroidism respectively were derived from the CPRD. Discontinuing vasodilator antihypertensive drugs for hypertension was associated with increased gestational age (mean difference: 3.98 weeks, 95% CI: 1.61, 6.35). Estimated associations between other antihypertensives (calcium-channel blockers, diuretics or renin-angiotensin system drugs) and any study outcome crossed the null. Discontinuing thyroid hormones for hypothyroidism were associated with reduced the odds of miscarriage (OR: 0.29, 95% CI: 0.15, 0.54) and increased gestational age (mean difference 1.84 weeks, 95% CI: 0.12, 3.57). Results were robust in sensitivity analysis. This study reports a reassuring lack of association between many drug subclasses and adverse offspring outcomes. This evidence of potential risk associated with treatment discontinuation may guide clinical decision-making for treating chronic hypertension and hypothyroidism during pregnancy in similar populations.

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