Effectiveness and safety of drugs in pregnancy: evidence from drug target Mendelian randomization

Abstract

Limited information exists regarding the impact of pharmacotherapy in pregnancy due to ethical concerns of unintended foetal harm. We investigate genetically proxied intrauterine antihypertensive exposure on offspring outcomes, including gestational age and birthweight, using two-sample multivariable Mendelian randomization. Higher levels of maternal protein targets for calcium channel blockers increased gestational age by 3.99 days (95%CI: 0.02, 7.96) per 10mmHg decrease in SBP. Genetically proxied maternal protein targets for beta-adrenoceptor blocking drugs, vasodilator antihypertensive drugs on the KNCJ11 gene, potassium-sparing diuretics and aldosterone antagonists demonstrated little evidence of increased risk to offspring. Both parental genetic protein targets for vasodilator antihypertensive drugs demonstrated similar effects on birthweight, suggesting detrimental offspring effects due to genetic perturbation of these pathways is unlikely. Little evidence for increased risk of adverse offspring outcomes due to maternal antihypertensive drug target perturbation was found. Triangulation of these findings with existing evidence may guide physicians and mothers during pregnancy.