Date of Award

January 2025

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Audrey A. Merriam

Abstract

The objective of this study is 1) to understand the effect of GLP-1 receptor agonist (GLP-1RA) use in the year prior to conception on risk of developing hypertensive disorders of pregnancy (HDP) and on gestational weight gain (GWG), and 2) to analyze important ethical considerations relevant to research in pregnancy and specifically related to GLP-1RAs.All patients delivering between 2014-2024 with evidence of GLP-1RA exposure in the year prior to conception were identified through electronic medical record (EMR) query with hand review to confirm exposure. GLP-1RA exposed patients were classified according to GLP-1RA indication for use: 1) pregestational diabetes mellitus (PGDM) or 2) weight management (WM) for increased body mass index (BMI). Control groups for each indication cohort were identified from 2021-2022 delivery EMR data. PGDM controls were patients with pregestational type 1 or type 2 diabetes mellitus managed with medication other than GLP-1RA in the year prior to conception. WM controls were a stratified random sample of patients without PGDM not on antihyperglycemic medication in the year prior to conception with BMIs between 30<40 kg/m2 and ≥40 kg/m2. Demographic and clinical characteristics and obstetrical outcomes were compared. Logistic regression was employed to assess the crude (OR) and adjusted odds ratios (aOR) for HDP controlling for covariates significant in bivariate tests at <0.05. Multinomial logistic regression was employed to assess the crude (OR) and adjusted odds ratios (aOR) for GWG controlling for covariates significant in bivariate tests at <0.05. 243 patients had GLP-1RA exposure in the year prior to conception. Of these, 103 were exposed for PGDM and 140 for WM. For the PGDM cohort, 175 controls were identified from the two years of EMR data interrogated. For the WM cohort, random sampling yielded 200 controls, with half (n=100) having BMI between 30<40 kg/m2 and the other half (n=100) BMI ≥40 kg/m2. Bivariate tests for race/ethnicity, pre-pregnancy BMI, and chronic hypertension identified significant differences between exposed and unexposed patients in the PGDM cohort. For the WM cohort, exposed and unexposed patients had significant differences in PCOS diagnosis, gestational weight gain, and HDP. Within the PGDM group, GLP-1RA exposure did not significantly affect GWG. Those exposed to a GLP-1RA in the WM cohort had significantly decreased risk of GWG below recommendations (aOR1=0.42 (0.18-0.80)). This effect was driven by post-conception GLP-1RA exposure as it significantly decreased risk of GWG below recommendations (aOR=0.32 (0.14-0.77)). For both the PGDM and WM cohort, exposed patients were half as likely to develop HDP compared to unexposed counterparts (PGDM aOR=0.52 (0.30-0.90); WM aOR=0.49 (0.30-0.81)). This effect was driven by post-conception GLP-1RA exposure as it significantly decreased risk of HDP in PGDM (aOR=0.52 (0.28-0.96)) and WM (aOR=0.47 (0.25-0.89)) cohorts. GLP-1RA use in the year prior to conception decreases risk of GWG under recommendations, which may reflect rebound weight gain during pregnancy after GLP-1RA cessation. GLP-1RA use in the year prior to conception significantly reduced the likelihood of developing HDP for patients with PGDM and undergoing WM. Both of these effects appear to be driven by post-conception exposure. There are large evidence gaps for pregnant people, and research in pregnancy should be prioritized to ensure strong evidence to guide safe clinical practice. Several considerations are more complicated in pregnancy, including risk, potential maternal and fetal benefit, and study design, but strong ethical analyses are critical to informing clinical science in pregnant humans to narrow the evidence gaps. Reproductive justice as an organizing theoretical framework offers many important insights into critically evaluating research, pregnancy, and GLP-1RAs and should be centered throughout research in pregnancy efforts.

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This is an Open Access Thesis.

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