Impact of obesity treatments on subsequent pregnancy outcomes

Harvard University D/B/A Harvard School Of Public Health, Boston MA

Investigators

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Abstract

PROJECT SUMMARY Obesity continues to increase in the United States and anti-obesity drugs are being heavily promoted. As a result, even though treatment guidelines recommend lifestyle interventions as a first-line treatment, and despite the safety and efficacy concerns around some anti-obesity drugs, prescription of these agents is on the rise. The obesity epidemic affects young women and spills into pregnancy. In fact, obesity is one of the most common medical complications in pregnancy, known to increase the risk of multiple adverse perinatal outcomes. Although anti-obesity drugs are not recommended to women planning pregnancy, pregnant women are exposed because half of pregnancies are unplanned, and those already using a drug may have no time to discontinue before organogenesis. Yet, little is known about the current utilization of anti-obesity treatments around conception or about their effects on the pregnant mother and the developing fetus. Data is needed to inform the risk-benefit trade-offs and facilitate evidence-based decision-making in obese women with reproductive potential. Since randomized trials to define the impact of these agents in pregnancy are not realistic, we need timely information based on carefully conducted large observational studies. Our primary objective is to quantify the effectiveness of specific anti-obesity drugs on reducing obesity- related pregnancy complications when used before conception; and their safety when used during pregnancy intentionally or unintentionally. By harnessing the power of real-world data, we aim to quantify the relative risk of a broad spectrum of obstetric and neonatal outcomes in relation to specific anti-obesity treatment strategies. We have established a cohort of 1.3 million pregnancies linked to infants with longitudinal information on prescriptions and clinical conditions within a population-based health care database (MarketScan). The study population will include over 100,000 obese women with a pregnancy in 2011-2025. Drug exposure will be determined based on pharmacy dispensing records, and outcomes will be based on in- and outpatient diagnoses and procedures, adhering to validated definitions. The study protocols will emulate hypothetical target trials, which restrict the population to those eligible for the intervention and incorporate active reference groups. Rigorous measures will be employed to further mitigate confounding, including propensity score weighting. Absolute risk differences and their 95% confidence intervals will be estimated through generalized linear models, with innovative quantitative bias analyses conducted to test the findings' robustness. Our proposal benefits from the collective experience and established track record of a multidisciplinary team, and our prior work and preliminary results attest to the project's feasibility. Ultimately, completion of this research will contribute information to our understanding of the risks and benefits of anti-obesity medications in women with reproductive potential, inform clinical guidelines and pregnancy safety narratives in drug labels, and potentially provide reassuring evidence to patients accidentally exposed during pregnancy.