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Journal List > J Korean Med Sci > v.40(2) > 1516089438

Oh, Cho, Han, Choi, and Shin: Real-World Utilization Patterns of Oral Corticosteroids During Pregnancy: A Nationwide Population-Based Study in Korea

Abstract

Oral corticosteroids (OCS) are frequently used during pregnancy, but patterns of their usage and indications are understudied. We described OCS utilization among pregnant women in South Korea using the Health Insurance Review and Assessment database, 2010–2021. Among 4,574,294 pregnancies, 6.2% (n = 283,001) were exposed to OCS, with the annual prevalence increasing from 4.98% in 2010 to 6.65% in 2021. Methylprednisolone and prednisolone accounted for 90% of OCS use during pregnancy, and the median duration of prescriptions was four days. Respiratory and skin diseases were the most common indications, and prescriptions for pregnancy-associated conditions increased notably after 2017, coinciding with insurance coverage for infertility treatments. OCS prescriptions declined during the first trimester and increased near delivery, suggesting discontinuation upon pregnancy recognition. Our findings highlight the common and increasing use of OCS during pregnancy, mainly for acute conditions, underscoring the need for further research on their safety in pregnant populations.

Graphical Abstract

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Oral corticosteroids (OCS) are used to control flares in various conditions such as allergic diseases or autoimmune diseases in pregnant women.1 OCS may also be considered for pregnant women as pregnancy can change immunological responses that could potentially aggravate pre-existing allergic conditions.1 Additionally, beyond their approved indications, OCS are frequently prescribed for off-label indications, such as supporting in vitro fertilization or preventing recurrent miscarriage in early pregnancy.23 OCS are therefore drugs with a high likelihood of exposure during pregnancy, even among women who did not have previously used OCS.
Yet, no studies to date have evaluated the patterns of OCS usage during pregnancy including the indications for which they are prescribed. Thus, we aimed to describe the OCS utilization patterns in pregnant women using a large nationwide database in South Korea.
We conducted a retrospective observational study using the Health Insurance Review and Assessment (HIRA) database of South Korea from 2009 to 2022. The HIRA database, which covers almost the entire South Korean population, contains data on patient’s demographics and healthcare claims record (e.g., diagnoses, prescription records, and medical procedures) from both in- and outpatient settings. Using this nationally representative database, we identified all pregnancies with delivery records defined based on HIRA procedure codes (Supplementary Table 1) between January 1, 2010, and December 31, 2021. Pregnancies resulting in non-live births were not included in the analysis. The last menstrual period (LMP) was estimated based on the delivery date and diagnoses of preterm birth, using a validated algorithm in administrative healthcare database.4 Specifically, LMP was estimated by subtracting 245 days from the delivery date if the mother had a diagnostic code for preterm delivery (O42, O60.1, O60.3), and by subtracting 273 days for otherwise full-term delivery.
We first described the baseline characteristics of the pregnancies according to OCS exposure during pregnancy. OCS exposed pregnancies were defined as pregnancies with ≥ 1 OCS prescription from LMP to the day before the delivery date and unexposed pregnancies were defined as those without OCS prescription from LMP to the day before the delivery date. In each pregnancy, we assessed maternal age, insurance type, and obstetric conditions (e.g., nulliparity, multifetal pregnancies) at delivery. We also evaluated the indication-related conditions (e.g., autoimmune inflammatory disease, skin disease, respiratory system disease), comorbidities, and comedications from 180 days before LMP to the day before the date of delivery and healthcare utilization within 180 days prior to LMP. Baseline characteristics are presented as frequencies and percentages for categorical variables and as means and standard deviations for continuous variables. Absolute standardized differences (aSD) were calculated to quantify the differences between the OCS-exposed and unexposed pregnancies.
In addition, we described the annual prevalence of OCS exposure during pregnancy from 2010 to 2021. We further analyzed the prevalence by individual OCS. As prednisolone and methylprednisolone accounted for majority of the OCS usage (> 90%), we grouped the OCS as: 1) prednisolone, 2) methylprednisolone, and 3) others (dexamethasone, betamethasone, deflazacort, hydrocortisone and triamcinolone). We also calculated the number of OCS prescriptions during five different assessment windows: 1) pre-pregnancy period (one year before the LMP), 2) first trimester (LMP to day 90 of gestation), 3) second trimester (day 90 to day 180), 4) third trimester (day 180 to delivery), and 5) postpartum period (1 year after delivery).
Lastly, we evaluated the annual proportion of individual indication among OCS exposed pregnancies. Indications were identified based on the primary International Classification of Diseases, Tenth Revision (ICD-10) diagnosis of OCS prescription and were categorized into six groups: autoimmune inflammatory disease, asthma, diseases of the skin, diseases of the respiratory system, pregnancy-associated condition, and others. Disease of the respiratory system included all subcodes of ICD-10 Chapter J, while pregnancy-associated conditions included in vitro fertilization, female infertility, threatened abortion, and subcodes of ICD-10 code “Z3,” which are health service encounters related to reproduction. A detailed list of indications and the corresponding diagnostic codes for each indication is provided in Supplementary Table 2. We also assessed the proportion of each OCS indication among OCS exposed pregnancies (or women) during pre-pregnancy, first trimester, second trimester, third trimester and postpartum period. All analyses were performed using SAS Enterprise Guide 7.1 software (SAS Institute, Cary, NC, USA).
We identified a total of 4,574,294 pregnancies, of which 283,001 (6.2%) have been exposed to OCS during pregnancy. The median (interquartile range) duration of OCS prescription during pregnancy was 4.0 (3.0–6.0) days. Compared with unexposed pregnancies, OCS exposed pregnancies were older, more likely to have comorbidities (e.g., gastrointestinal diseases and hypertension), and had a higher number of diagnoses (distinct 3-digit ICD-10 codes) recorded (6.79 vs. 4.84, aSD 0.46) (Table 1). As expected, the prevalence of indication-related conditions was significantly higher in the OCS-exposed group.
Table 1

Characteristics of pregnancies according to OCS exposure

jkms-40-e80-i001
Characteristics No. of pregnancies (%) Absolute standardized difference
OCS (n = 283,001) Unexposed (n = 4,291,174)
Maternal age at delivery, yr 0.10
< 25 15,671 (5.54) 226,115 (5.27)
25–29 62,418 (22.06) 1,018,228 (23.73)
30–34 126,442 (44.68) 2,023,823 (47.16)
35–39 67,036 (23.69) 892,993 (20.81)
40–44 11,078 (3.91) 126,740 (2.95)
> 44 356 (0.12) 3,375 (0.08)
Medical aid recipient 3,247 (1.15) 35,901 (0.84) 0.03
Comorbidities
Depression 2,158 (0.76) 17,185 (0.40) 0.05
Diabetes 6,909 (2.44) 80,159 (1.87) 0.04
Dyslipidemia 8,272 (2.92) 83,123 (1.94) 0.06
Endometriosis 2,232 (0.79) 24,783 (0.58) 0.03
Epilepsy/Seizures 4,342 (1.53) 40,451 (0.94) 0.05
Gastrointestinal diseases 96,927 (34.25) 709,403 (16.53) 0.42
Hypertension 31,749 (11.22) 325,089 (7.58) 0.13
Migraine/Headache 14,829 (5.24) 130,260 (3.04) 0.11
Polycystic ovarian syndrome 4,789 (1.69) 33,631 (0.78) 0.08
Renal disease 1,841 (0.65) 14,852 (0.35) 0.04
Thyroid disorders 37,769 (13.35) 515,058 (12.00) 0.04
Indication-related conditions
Autoimmune inflammatory disease
Ankylosing spondylitis 426 (0.15) 691 (0.02) 0.05
Inflammatory bowel disease 398 (0.14) 2,640 (0.06) 0.03
Psoriatic arthropathies 1,087 (0.38) 4,869 (0.11) 0.05
Rheumatoid arthritis 2,274 (0.80) 1,727 (0.04) 0.12
Systemic lupus erythematosus 1,847 (0.65) 1,060 (0.02) 0.11
Asthma 10,161 (3.59) 25,669 (0.60) 0.21
Diseases of the skin
Atopic dermatitis 7,070 (2.50) 27,426 (0.64) 0.15
Contact dermatitis 60,272 (21.30) 206,963 (4.82) 0.50
Urticaria 22,685 (8.02) 46,792 (1.09) 0.34
Other skin diseases 20,320 (7.18) 86,399 (2.01) 0.25
Diseases of the respiratory system
Acute upper respiratory infections 116,574 (41.19) 872,808 (20.34) 0.46
Acute lower respiratory infections 68,854 (24.33) 365,221 (8.51) 0.44
Non-infectious upper respiratory tract disease 71,878 (25.40) 350,116 (8.16) 0.47
Non-infectious bronchus disease 15,010 (5.30) 76,480 (1.78) 0.19
Pregnancy-associated conditions
Treatment of infertility 11,288 (3.99) 33,163 (0.77) 0.21
In vitro fertilization 27,016 (9.55) 279,528 (6.51) 0.11
Threatened abortion 31,071 (10.98) 393,103 (9.16) 0.06
Maternal medication use
Antidiabetics 6,749 (2.38) 62,473 (1.46) 0.07
Antihistamines 201,528 (71.21) 1,230,367 (28.67) 0.94
Fertility drug 19,359 (6.84) 116,508 (2.71) 0.19
Inhaled corticosteroids 8,555 (3.02) 22,250 (0.52) 0.19
NSAIDs 116,592 (41.20) 558,097 (13.01) 0.67
Paracetamol 160,426 (56.69) 1,423,675 (33.18) 0.49
Obstetric conditions
Nulliparity 128,482 (45.40) 2,295,582 (53.49) 0.16
Cesarean birth 141,408 (49.97) 1,795,756 (41.85) 0.16
Multifetal pregnancies 9,311 (3.29) 76,830 (1.79) 0.10
Healthcare utilization, mean ± SD
No. of distinct diagnoses 6.79 ± 4.57 4.84 ± 3.91 0.46
No. of prescription drugs other than OCS 14.15 ± 10.48 9.50 ± 8.76 0.48
No. of outpatient visits 8.19 ± 7.71 5.35 ± 5.73 0.42
No. of inpatient visits 0.11 ± 0.44 0.08 ± 0.37 0.08
Obstetric comorbidity index 0.38 ± 0.73 0.23 ± 0.57 0.22
NSAID = nonsteroidal anti-inflammatory drug, OCS = oral corticosteroids, SD = standard deviation.

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During the study period, the prevalence of OCS exposure notably increased from 4.98% in 2010 to 6.65% in 2021. Among individuals younger than 35 years, the prevalence rose from 4.89% in 2010 to 5.77% in 2021. In those aged 35 years and older, the prevalence increased from 5.48% in 2010 to 8.34% in 2021 (Supplementary Table 3). Methylprednisolone (45.2%) and prednisolone (45.0%) accounted for the majority of OCS usage (Fig. 1A). Across the pregnancy period, OCS prescriptions sharply declined during the first trimester and gradually increased during the third trimester, specifically near the delivery date (Fig. 1B). Among all pregnancies, 230,274 (5.03%) were exposed during the first trimester, followed by 37,861 (0.83%) in the second trimester and 35,130 (0.77%) in the third trimester.
Fig. 1

Trends of OCS prescriptions in pregnant women. Temporal trends in OCS prescription during pregnancy (A) and prescription patterns before, during and after pregnancy (B).

OCS = oral corticosteroids, LMP = last menstrual period.
aOther OCS include deflazacort, hydrocortisone and triamcinolone.
jkms-40-e80-g001

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Among OCS exposed pregnancies, respiratory (40.48%) and skin (22.17%) diseases were the most prevalent indications (Fig. 2A). The proportion of pregnancy-associated conditions showed a notable increase from 9.31% in 2017 to 34.87% in 2021. The proportion of OCS usage for diseases of respiratory system increased from 12.80% in 2010 to 21.88% in 2019, but subsequently declined, with 14.26% in 2021 (Fig. 2A). Rheumatoid arthritis (0.72%) and systemic lupus erythematosus (0.60%) were the most prevalent indication among autoimmune inflammatory diseases, and dermatitis (15.57%) and urticaria (5.70%) accounted the high proportions among diseases of the skin. Acute upper respiratory tract infections (15.74%) predominated among diseases of the respiratory system, and within the pregnancy associated conditions, treatment of infertility (5.94%) had high proportions. Majority of the OCS prescriptions were used for acute conditions such as skin and respiratory diseases both during pregnancy and pre-pregnancy (Fig. 2B). The proportions of autoimmune diseases and asthma were relatively low but increased after gestation (Fig. 2B).
Fig. 2

Indications of OCS prescriptions in pregnant women. Temporal trends in indications of OCS during pregnancy (A) and OCS indications according to timing of exposure (B).

OCS = oral corticosteroids.
jkms-40-e80-g002

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In this nationwide population-based study that comprises all pregnancies with live births from 2010 to 2021, the prevalence of OCS exposure during pregnancy was 6.2%. This proportion was higher than that reported in previous studies conducted in the United States and Australia.56 Throughout the study period, methylprednisolone and prednisolone were the most frequently used OCS during pregnancy, possibly due to their limited placenta transfer.7 We also observed a large decrease in OCS prescriptions after the time of gestation. This finding would indicate that many women tend to discontinue OCS after recognizing that they are pregnant, which would also be attributed to concerns on the safety of prenatal OCS use. Of note, most of the OCS prescriptions were used for acute conditions during pregnancy and the median duration of prescription was relatively short (4 days). In South Korea, OCS prescriptions for infertility treatment have been covered by health insurance from 2017, which coincides with the increase in OCS prescriptions for pregnancy-associated conditions after 2017.8 The prevalence of OCS prescriptions during pregnancy generally increased over the study period, with a more pronounced rise in older women. However, there was a slight decrease in 2021, likely driven by fewer prescriptions for respiratory system diseases. This coincides with the implementation of social distancing measures during the coronavirus disease 2019 pandemic, which resulted in reduced respiratory infection rates.910
This study has several limitations. We defined the OCS usage based on prescriptions, which may not accurately reflect actual exposure. In addition, although we identified the indications via the primary diagnoses of OCS prescriptions, it may not align with the actual indications. Lastly, because the HIRA database does not contain information on the start of pregnancy or LMP, we estimated these based on delivery dates and preterm birth diagnostic codes. While the algorithm we used has demonstrated a high positive predictive value for determining gestational age in administrative databases, there remains some potential for misclassification, and further validation of this algorithm is needed within the HIRA database.
Overall, our findings highlight the common usage of OCS during pregnancy for various indications. Further studies should be conducted to confirm the safety of OCS use in pregnant populations.

Ethics statement

This study was approved by the Institutional Review Board of Sungkyunkwan University (No. 2023-12-047), and the requirement for informed patient consent was waived as our study used deidentified claims data.

Notes

Funding: This research was supported by a grant (RS-2024-00332632) from Ministry of Food and Drug Safety in 2024–2028. The funder had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Disclosure: Ju-Young Shin received grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of South Korea, and pharmaceutical companies, including Pfizer, UCB, and LG Chem, outside the submitted work.

Data Sharing Statement: No additional data are available to the public.

Author Contributions:

  • Conceptualization: Oh J, Cho Y, Han JY, Choi A, Shin JY.

  • Data curation: Oh J, Cho Y.

  • Formal analysis: Oh J.

  • Funding acquisition: Shin JY.

  • Investigation: Oh J.

  • Methodology: Oh J, Cho Y, Han JY, Choi A, Shin JY.

  • Project administration: Han JY, Choi A, Shin JY.

  • Supervision: Choi A, Shin JY.

  • Validation: Choi A, Shin JY.

  • Visualization: Oh J, Cho Y.

  • Writing - original draft: Oh J, Cho Y, Choi A.

  • Writing - review & editing: Oh J, Cho Y, Han JY, Choi A, Shin JY.

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SUPPLEMENTARY MATERIALS

Supplementary Table 1

Procedure codes used to define the live birth deliveries
jkms-40-e80-s001.doc

Supplementary Table 2

Categorization of OCS indications using ICD-10 codes
jkms-40-e80-s002.doc

Supplementary Table 3

Time trend of oral corticosteroid prescription during pregnancy stratified by maternal age at delivery
jkms-40-e80-s003.doc
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