Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019
Authors: Subramanian Anuradhaa , Azcoaga-Lorenzo Amaya , Anand Astha , Phillips Katherine , Lee Siang Ing , Cockburn Neil , Fagbamigbe Adeniyi Francis , Damase-Michel Christine , Yau Christopher , McCowan Colin , O’Reilly Dermot , Santorelli Gillian , Hope Holly , Kennedy Jonathan I. , Abel Kathryn M. , Eastwood Kelly-Ann , Locock Louise , Black Mairead , Loane Maria , Moss Ngawai , Plachcinski Rachel , Thangaratinam Shakila , Brophy Sinead , Agrawal Utkarsh , Vowles Zoe , Brocklehurst Peter , Dolk Helen , Nelson-Piercy Catherine , Nirantharakumar Krishnarajah ,   on behalf of the MuM-PreDiCT Group
Published: January 2023

Abstract
Background
The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.

Methods
A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register.
Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period.
Logistic regression models were performed to identify risk factors for polypharmacy.

Results
During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%.
Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs).
Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14–1.18) and 1.55 (1.53–1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33–2.47), 1.71 (1.65–1.76), 1.41 (1.35–1.47) and 1.39 (1.30–1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18–1.20) and 1.05 (1.03–1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.

Conclusions
The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.