TY - JOUR
T1 - The effect of statins exposure during pregnancy on congenital anomalies and spontaneous abortions
T2 - A systematic review and meta-analysis
AU - Hirsch, Ayala
AU - Ternovsky, Natali
AU - Zwas, Donna R.
AU - Rotem, Reut
AU - Amir, Offer
AU - Hirsh Raccah, Bruria
N1 - Publisher Copyright:
Copyright © 2022 Hirsch, Ternovsky, Zwas, Rotem, Amir and Hirsh Raccah.
PY - 2022/9/29
Y1 - 2022/9/29
N2 - Objective: To assess the effect of statin exposure during pregnancy on congenital anomalies and spontaneous abortions. Data sources: Electronic databases were searched from inception to January 2022. Study Eligibility Criteria: Cohort studies and randomized controlled trials (RCTs) evaluate the effect of treatment with statins on congenital anomalies in general and cardiac malformations in particular. Studies evaluating spontaneous abortions were included as a secondary outcome. Study appraisal and synthesis methods: Pooled odds ratio was calculated using a random-effects model and meta-regression was utilized when applicable. Results: Twelve cohort studies and RCTs were included in the analysis. Pregnancy outcomes of 2,447 women that received statins during pregnancy were compared to 897,280 pregnant women who did not. Treatment with statins was not associated with a higher risk of overall congenital anomalies (Odd Ratio = 1.1, CI (0.9–1.3), p = 0.33, I2 = 0%). Yet, cardiac malformations were more prevalent among neonates born to statins users (OR = 1.4, CI (1.1–1.8), p = 0.02, I2 = 0%). The risk was higher when exposure occurred during the first trimester. This finding was statistically significant in cohort studies, but not in RCTs. Statin treatment was also associated with a higher rate of spontaneous abortions (OR = 1.5, CI (1.1–2.0), p = 0.005, I2 = 0%). In meta-regression analysis, no significant association between lipophilic statins and the rate of congenital anomalies was found. Conclusion: Overall, treatment with statins during pregnancy was not associated with an increased risk of congenital anomalies. A slight risk elevation for cardiac malformation and spontaneous abortions was seen in cohort studies but not in RCTs. Systematic Review Registration: clinicaltrials.gov, identifier [CRD42020165804 17/2/2020] The meta-analysis was presented online at 42nd annual meeting of SMFM. January 31-5 February 2022.
AB - Objective: To assess the effect of statin exposure during pregnancy on congenital anomalies and spontaneous abortions. Data sources: Electronic databases were searched from inception to January 2022. Study Eligibility Criteria: Cohort studies and randomized controlled trials (RCTs) evaluate the effect of treatment with statins on congenital anomalies in general and cardiac malformations in particular. Studies evaluating spontaneous abortions were included as a secondary outcome. Study appraisal and synthesis methods: Pooled odds ratio was calculated using a random-effects model and meta-regression was utilized when applicable. Results: Twelve cohort studies and RCTs were included in the analysis. Pregnancy outcomes of 2,447 women that received statins during pregnancy were compared to 897,280 pregnant women who did not. Treatment with statins was not associated with a higher risk of overall congenital anomalies (Odd Ratio = 1.1, CI (0.9–1.3), p = 0.33, I2 = 0%). Yet, cardiac malformations were more prevalent among neonates born to statins users (OR = 1.4, CI (1.1–1.8), p = 0.02, I2 = 0%). The risk was higher when exposure occurred during the first trimester. This finding was statistically significant in cohort studies, but not in RCTs. Statin treatment was also associated with a higher rate of spontaneous abortions (OR = 1.5, CI (1.1–2.0), p = 0.005, I2 = 0%). In meta-regression analysis, no significant association between lipophilic statins and the rate of congenital anomalies was found. Conclusion: Overall, treatment with statins during pregnancy was not associated with an increased risk of congenital anomalies. A slight risk elevation for cardiac malformation and spontaneous abortions was seen in cohort studies but not in RCTs. Systematic Review Registration: clinicaltrials.gov, identifier [CRD42020165804 17/2/2020] The meta-analysis was presented online at 42nd annual meeting of SMFM. January 31-5 February 2022.
KW - cardiac anomalies
KW - congenital anomalies
KW - hydroxymethylglutaryl-coenzyme a (HMG-CoA) reductase inhibitors
KW - spontaneous abortion
KW - statins
UR - http://www.scopus.com/inward/record.url?scp=85140111744&partnerID=8YFLogxK
U2 - 10.3389/fphar.2022.1003060
DO - 10.3389/fphar.2022.1003060
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C2 - 36249743
AN - SCOPUS:85140111744
SN - 1663-9812
VL - 13
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 1003060
ER -