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The risk of congenital heart defects associated with corticosteroids use during the first trimester of pregnancy: a systematic review and meta-analysis

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A Correction to this article was published on 22 November 2022

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Abstract

Background

Prior studies have suggested that maternal corticosteroids exposure during the first trimester may be associated with an increased risk of congenital heart defects (CHDs) in offspring. However, the findings are discrepant. Moreover, a complete overview of the existing data in the literature is lacking. Our objective was to identify whether such an association exists.

Methods and results

Relevant studies were identified via searching PubMed, Web of Science, Embase, Chinese databases, and the Cochrane Library databases (search date July 15, 2021) and through checking the reference lists of retrieved articles. The overall pooled risk estimate was calculated using random-effect models. We used the GRADE approach to assess the overall strength of the evidence and the Newcastle–Ottawa Scale to assess study quality. Subgroup analyses were performed to evaluate the association within studies or samples with different characteristics. Sensitivity analyses were performed to assess the robustness of the results. Nine studies involving 1,901,599 participants were included in the final analysis. All studies were evaluated as high quality. In the meta-analysis, no statistically significant association was found between maternal corticosteroids exposure during the first trimester and increased risk of CHDs in offspring (OR = 1.06, 95% CI: 1.00–1.13, P = 0.06, low certainty of evidence). Additionally, we also did not find significant differences in subgroup analyses of corticosteroids exposure patterns, including oral corticosteroids exposure (OR = 1.23, 95% CI: 1.00–1.52), ointment corticosteroids exposure (OR = 1.03, 95% CI: 0.90–1.19), inhalation corticosteroids exposure (OR = 1.06, 95% CI: 0.96–1.17), topical corticosteroids or systemic corticosteroids exposure (OR = 0.95, 95% CI: 0.79–1.15), and nasal corticosteroids exposure (OR = 1.12, 95% CI: 0.80–1.57).

Conclusions

Our study does not find an association between maternal corticosteroids exposure during the first trimester and offspring CHDs. However, the existing evidence is of low quality; thus, long-term prospective cohort studies are warranted to verify the safety of corticosteroids in this population, with adequate adjustments for confounding variables.

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All data generated or analyzed during this study are included in this published article.

Change history

Abbreviations

CHDs:

Congenital heart defects

CI:

Confidence interval

GRADE:

The Grading of Recommendations, Assessment, Development, and Evaluations recommendations

HR:

Hazard ratio

OR:

Odds ratio

PR:

Prevalence ratio

NOS:

Newcastle-Ottawa Scale

RR:

Risk ratio

SLE:

Systemic lupus erythematosus

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Acknowledgements

We thank everyone who has provided advice and help with this article.

Funding

This study was funded by the National Natural Science Foundation Program of China (no. 81973137 and 82173608 to Lizhang Chen) and the Project of Hunan Provincial Maternal and Child Health Care Hospital (2021RX26). The funding bodies had no role in the design of this study, the collection, analysis, and interpretation of the data, or in writing the manuscript.

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Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China

    Jiehua Wei, Fan Xia, Junxiang Miao, Tingting Wang & Lizhang Chen

  2. NHC Key Laboratory for Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China

    Tingting Wang

  3. Department of Internal Medicine, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, 410008, Hunan, China

    Xuemei Yan

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  1. Jiehua Wei
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  5. Lizhang Chen
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Contributions

Lizhang Chen and Tingting Wang contributed to the conception and study design. Jiehua Wei performed a search strategy and searched the literature. Jiehua Wei, Fang Xia, and Junxiang Miao selected the studies, extracted the data, and analyzed and interpreted the data. Jiehua Wei drafted the manuscript. Lizhang Chen, Xuemei Yan, and Jiehua Wei revised the article critically for important intellectual content and interpreted the results. All authors read and approved the final manuscript.

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Correspondence to Lizhang Chen or Xuemei Yan.

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Wei, J., Xia, F., Miao, J. et al. The risk of congenital heart defects associated with corticosteroids use during the first trimester of pregnancy: a systematic review and meta-analysis. Eur J Clin Pharmacol 79, 1–11 (2023). https://doi.org/10.1007/s00228-022-03416-w

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