Objective We applied propensity score matching method at scale on patient records to confirm signals of known drug effects on preterm birth and detect previously unidentified potential drug effects. Materials and Methods This was a retrospective study on women who had continuity of care at Providence St. Joseph Health (PSJH) both before and after pregnancy and delivered live births between 2013/01/01 and 2022/12/31 (n=365,075). Our exposures of interest were all outpatient medications prescribed during pregnancy. We limited our analyses to medication that met the minimal sample size (n=600). The primary outcome of interest was preterm birth. Secondary outcomes of interest were small for gestational age and low birth weight. We used propensity score matching at scale to evaluate the risk of these adverse pregnancy outcomes associated with drug exposure after adjusting for demographics, pregnancy characteristics, and comorbidities. Results The total medication prescription rate increased from 58.5% to 75.3% (P<0.0001) from 2013 to 2022. The prevalence rate of preterm birth was 7.7%. 175 out of 1329 prenatally prescribed outpatient medications met the minimum sample size. We identified 58 medications statistically significantly associated with the risk of preterm birth (P≤ 0.1; decreased: 12, increased: 46). Discussion We narrowed down from 1329 medications to 58 medications that showed statistically significant association with the risk of preterm birth even after addressing numerous covariates through propensity score matching. Conclusion This data-driven approach demonstrated that multiple testable hypotheses in pregnancy pharmacology can be prioritized at scale, laying the foundation for application in other pregnancy outcomes.

YH and SNP declare no conflict of interest. JJH has received research funding (paid to the institute) from Pfizer, Novartis, Janssen, Gilead and Bristol Myers Squibb. QW has been funded in part by Pfizer, Novartis, and Janssen (paid to the institute). LH and NDP are scientific advisors for Sera Prognostics, a pregnancy diagnostics company and NDP holds stock options. Sera Prognostics is not associated with this study or any of the findings.

Support was provided in part by the United States National Institute of Child Health and Human Development under Grant HD091527; Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

All procedures were reviewed and approved by the Institutional Review Board at the PSJH through expedited review on 11-04-2020 (study number STUDY2020000196). Consent was waived because disclosure of protected health information for the study involved no more than minimal risk to the privacy of individuals.

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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All clinical logic has been shared and available online at https://github.com/Hadlock-Lab/PSM_Maternity_at_scale. Results have been aggregated and reported within this paper to the extent possible while maintaining privacy from personal health information (PHI) as required by law. All data is archived within PSJH systems in a HIPAA-secure audited compute environment to facilitate verification of study conclusions.

https://github.com/Hadlock-Lab/PSM_Maternity_at_scale