한빛사논문
Ahhyung Choi, PharmD1; Yunha Noh, PharmD, PhD1,2; Han Eol Jeong, MPH, PhD1,2; Eun-Young Choi, PharmD1; Kenneth K. C. Man, PhD3,4,5; Jung Yeol Han, MD, PhD6; Hyun-Soo Kim, MD, PhD7; Dong Keon Yon, MD8; Ju-Young Shin, PhD1,2,9
1School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
2Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
3Research Department of Practice and Policy, University College London School of Pharmacy, London, United Kingdom
4Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, United Kingdom
5Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong
6Korean Mothersafe Counselling Center, Department of Obstetrics and Gynecology, Inje University Ilsan Paik Hospital, Goyang, South Korea
7Division of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea
8Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea
9Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea
Corresponding Author: Ju-Young Shin, PhD, ; Dong Keon Yon, MD
Abstract
Importance: Proton pump inhibitors (PPIs) are increasingly used during pregnancy; however, several observational studies have raised concerns about an increased risk of specific types of congenital malformations.
Objective: To examine the association between PPI exposure during early pregnancy and the risk of congenital malformations.
Design, setting, and participants: This population-based cohort study used data from the National Health Insurance Service-National Health Information Database of South Korea (2010-2020); sibling-controlled analyses were conducted to account for familial factors. A total of 2 696 216 pregnancies in women aged 19 to 44 years between June 1, 2011, and December 31, 2019, and their live-born infants were identified. Pregnant women who were exposed to known teratogens or who delivered infants with chromosomal abnormalities or genetic syndromes were excluded. Data on participant race and ethnicity were not collected because the National Health Information Database does not report this information.
Exposures: Proton pump inhibitor use during the first trimester.
Main outcomes and measures: Primary outcomes were major congenital malformations, congenital heart defects, cleft palate, hydrocephalus, and hypospadias. The subtypes of major congenital malformations and congenital heart defects were evaluated as exploratory outcomes. Propensity score fine stratification was used to control for potential confounders, and a weighted generalized linear model was used to estimate relative risks with 95% CIs.
Results: Of 2 696 216 pregnancies (mean [SD] maternal age, 32.1 [4.2] years), 40 540 (1.5%; mean [SD] age, 32.4 [4.6] years) were exposed to PPIs during the first trimester. The absolute risk of major congenital malformations was 396.7 per 10 000 infants in PPI-exposed pregnancies and 323.4 per 10 000 infants in unexposed pregnancies. The propensity score-adjusted relative risks were 1.07 (95% CI, 1.02-1.13) for major congenital malformations, 1.09 (95% CI, 1.01-1.17) for congenital heart defects, 1.02 (95% CI, 0.72-1.43) for cleft palate, 0.94 (95% CI, 0.54-1.63) for hydrocephalus, and 0.77 (95% CI, 0.51-1.17) for hypospadias. In the sibling-controlled analyses, no associations were observed between PPI use and primary outcomes, including major congenital malformations (odds ratio, 1.05; 95% CI, 0.91-1.22) and congenital heart defects (odds ratio, 1.07; 95% CI, 0.88-1.30). A range of sensitivity analyses revealed results that were similar to the main findings.
Conclusions and relevance: In this cohort study, the use of PPIs during early pregnancy was not associated with a substantial increase in the risk of congenital malformations, although small increased risks were observed for major congenital malformations and congenital heart defects; findings from sibling-controlled analyses revealed that PPIs were unlikely to be major teratogens. These findings may help guide clinicians and patients in decision-making about PPI use in the first trimester.
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