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February ADCES Blog Post - Clinical Refresher: Statin Use in Pregnancy

By Courtney Cameron posted 02-13-2023 08:00


Clinical Refresher: Statin Use in Pregnancy

In July 2021, the FDA Issued an update requesting the removal of the pregnancy contraindication to statins.1 The FDA amended this contraindication so that providers for patients at very high risk for ASCVD events may consider continuing statin therapy through pregnancy.1 Very high risk patients include those with familial hypercholesterolemia and established cardiovascular disease.1 The FDA continues to recommend holding statin therapy for primary prevention in pregnant patients due to the slow, chronic atherosclerosis disease process and possible risk for fetal harm.1 Additionally, women who are not pregnant but could become pregnant may continue statin therapy.1 Lastly, the FDA continues to recommend that women taking statin therapy avoid breastfeeding. 

The primary driver for concern over statin use in pregnancy is due to the understanding that cholesterol is critical to fetal development of cell membranes and steroidogenesis.2,3 Additionally, early animal studies demonstrated that statin exposure was associated with skeletal malformations, gastroschisis, and low birth weight in newborns.2 There has been one case study demonstrating the development of congenital abnormalities following exposure to lovastatin.4 No data is available to prove statins are safe to use in pregnancy.2 However, recent data has not established a clear link between statin exposure and spontaneous abortion, specific congenital abnormalities, or congenital abnormalities collectively.1,2 A brief compilation of recent data to support this safety update is below. 

Table of recent evidence for statin use in pregnancy.
Citation Study and Population Exposure Findings Comments
5 Pollack PS, et al. Birth Defects Res A Clin Mol Teratol. 2005;73(11):888-896.

Review of worldwide pharmacovigilance reporting system through 12/31/2002. Retrospective and prospective cases included. 477 reports reviewed (386 prospective, 91 retrospective).

Most reports of exposure to simvastatin. In 90% of cases, statin was discontinued in the first trimester.

simvastatin and/or lovastatin

Congenital anomalies were reported in 6 cases (3.8% of reports - similar to 3.2% of background US population rate). No specific pattern of anomalies could be determined. 

One report of statin exposure during the entire duration of pregnancy with no negative outcomes reported.

Prospective reports found 4 cases of fetal death associated with statin exposure (2.5%). This percentage is higher than the US background rate of 0.7%.

Pregnancy outcomes (congenital abnormalities, abortion, live birth) after exposure to statins, largely in the first trimester, were similar to outcomes in the background US population.
6 Taguchi N, et al. Reprod Toxicol. 2008;26(2):175-177. Prospective cohort study of 64 women with hypercholesterolemia exposed to statin therapy in the first trimester between 1998-2005. atorvastatin (n=46), simvastatin (n=9), pravastatin (n=6), rosuvastatin (n=3).

No statistically significant differences in live births, stillbirths, spontaneous abortions, or therapeutic abortions (pregnancy outcomes). 

No statistically significant  difference in birth defects or neonatal health problems (neonatal outcomes). 

Statin exposure was associated with lower gestational age at birth (38.4 weeks vs 39.3 weeks; p=0.04) and birth weight (3.14kg vs 3.45kg; p=0.01).

Cannot prove causality. Statins were not shown to alter pregnancy outcomes and did not increase teratogenic effects. Statins were associated with a statistically significant lower gestational age at birth and birth weight, which may be attributed to maternal disease processes.
7 Petersen EE, et al. Am J Med Genet A. 2008;146A(20):2701-2705. A case series using two US national databases. Any statin. Neonatal defect identified.

First data set identified 13 cases. 11 cases exposed to lipophilic statins. Anomalies were congenital heart defects (7), cleft lip with or without cleft palate (2), neural tube defects (2), and prenatal diagnosis of anencephaly leading to termination of pregnancy (2). 

Second data set identified 9 cases. 8 cases exposed to lipophilic statins. Anomalies were congenital heart defects (5), cleft lip (2), hypospadias (1), trisomy 21 (1).

Casualty cannot be determined. Recall bias cannot be ruled out. This data supports further study into risk differences of hydrophilic vs lipophilic statins.
8 Toleikyte I, et al. Circulation. 2011;124(15):1606-1614.

Review of Norwegian medical birth registry for women with familial hypercholesterolemia exposed to lipid lowering drugs. 

Included were 1093 women with 2319 births. Results were compared to the general population 1967-2006.

0.8% of the cases reviewed were using lipid-lowering drugs, most commonly statins and/or bile acid sequestrants.

No differences in frequency of prematurity, congenital malformations, or low birth weight regardless of maternal cholesterol levels. 

Highest risks for prematurity were due to pregnancy-induced hypertension and maternal age. Highest risks for low birth weight or congenital malformations were due to pregnancy-induced hypertension. 

No difference in birth weight regardless of maternal statin use.

Women with familial hypercholesterolemia are not at an inherent increased risk of negative neonatal outcomes based on their diagnosis alone.
9 Zarek J, et al. Expert Review of Obstetrics & Gynecology. 2013;8(6):513-524. Meta-analysis of 6 studies published through 01/28/2013. Any statin. Most common exposures in the first trimester.

No statistically significant difference in birth defects (RR 1.15, 95% CI 0.75-1.76).

Increased risk of spontaneous abortions with statin exposure (RR 1.35, 95% CI 1.04 - 1.75). Possibly driven by maternal morbidity.

Increased risk of therapeutic abortions (RR 2.56, 95% CI 1.71 - 3.84). Possibly driven by maternal morbidity and fear associated with fetal statin exposure.

Statins not associated with increased risk of congenital anomalies and no pattern to anomalies can be determined. 

Small increased risk of spontaneous abortion - unclear confounders to determine correlation with statin exposure.

10 Winterfeld U, et al. BJOG. 2013;120(4):463-471.

Prospective observational controlled study of women exposed to statins in their first trimester between 1990 - 2009. 

249 pregnancies reviewed and matched.

Simvastatin (n=124), atorvastatin (n=67), pravastatin (n=32), rosuvastatin (n=18), fluvastatin (n=7), cerivastatin (n=1).

6% of women continued statin therapy into the second trimester. Median duration of exposure was 6 weeks. 

No difference in major birth defects (odds ratio 1.5, 95% CI 0.5-4.5).

No difference in rates of elective pregnancy termination (hazard ratio 1.96, 95% CI 0.60-6.44). 

No difference in risk of miscarriage (hazard ratio 1.36, 95% 0.63-2.93).

Higher risk for miscarriage among older women (hazard ratio 1.14, 95% CI 1.08-1.21).

Statin use increased risk of prematurity (odds ratio 2.1, 95% CI 1.1-3.8).

No difference in outcomes between hydrophilic and lipophilic statins.

Again demonstrates higher rates (though not statistically significant) of elective termination of pregnancy.

No difference in congenital anomalies and no pattern to anomalies identified. 

Data does not support the hypothesis that lipophilic statins pose a higher risk.

11 Bateman BT, et al. BMJ. 2015;350:h1035. Cohort study of Medicaid database births 2000-2007. 45% of women who received a statin had pre-existing diabetes. First trimester. atorvastatin (n=538); simvastatin (n=319); lovastatin (n=132); pravastatin, fluvastatin, cerivastatin, or rosuvastatin (n=163). After adjustment for confounders, propensity score matched analysis revealed increased congenital malformations (RR 1.04, 95% CI 0.79-1.37). Pre-existing diabetes was a driver for increased risk (RR 1.34 (95% CI 1.07-1.68). Statins are not likely to increase risk of congenital malformations when women are exposed inadvertently in the first trimester. Therefore, continuing statin therapy in a woman of childbearing potential is unlikely to increase harm.
12 Chang JC, et al. JAMA Netw Open. 2021;4(12):e2141321. Retrospective cohort study of Taiwan Health Insurance Database for births 01/01/2004 - 12/31/2014. 469 women were included and matched to 4690 controls. atorvastatin (n=132), rosuvastatin n=82), lovastatin (n=49), simvastatin (n=31), fluvastatin (n=25) pravastatin (n=8), any other statin (n=142).

Statin exposure was associated with lower birth weight (RR 1.51, 95% CI 1.05-2.16), higher chance of preterm birth (RR 1.99, 95% CI 1.46-2.71), and lower 1-minute Apgar score (RR 1.83, 95% CI 1.04-3.20).

Pregestational diabetes diagnosis was a driver for higher risks of congenital anomalies (RR 2.29, 95% CI 1.38-3.80). No difference in development of congenital anomalies after adjusted analysis. 

Lipophilic statins were associated with a significant increase in risk of low birth weight compared to hydrophilic statins (RR 1.52, 95% CI 1.04-2.22 vs RR 1.47, 95% CI 0.84-2.55).

Hydrophilic statins associated with low 1-min apgar score compared to lipophilic statins (RR 2.20, 95% CI 1.06-4.55 vs RR 1.72, 95% CI 0.96-3.09) 

No increased risks seen for women exposed to statins before pregnancy. 

Supports the use of statins in women of child bearing potential. 

Statin use itself was not associated with a risk of congenital anomalies. 

Statin use did result in lower birth weight, preterm birth, and lower 1-min Apgar scores.

Takeaways for CDCES colleagues:

  1. The choice to continue statin therapy in pregnancy should follow a risks/benefits discussion with high risk patients (familial hypercholesterolemia or established ASCVD). Note that most available evidence evaluates statin use in the first trimester only. 

  2. Available evidence does not strongly link statin use with teratogenicity, however, evidence also does not prove the safe use of statins in pregnancy. 

  3. Statin therapy should be continued in patients who can become pregnant but are not currently. 

  4. Statin therapy should be held for those breastfeeding or for primary prevention in pregnant patients. 



  1. FDA requests removal of strongest warning against using cholesterol-lowering statins during pregnancy; still advises most pregnant patients should stop taking statins. FDA. Available at: Accessed 5 February 2023. 

  2. Newman CB, Preiss D, Tobert JA, et al. Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association [published correction appears in Arterioscler Thromb Vasc Biol. 2019 May;39(5):e158]. Arterioscler Thromb Vasc Biol. 2019;39(2):e38-e81. doi:10.1161/ATV.0000000000000073

  3. Mauricio R, Khera A. Statin Use in Pregnancy: Is It Time For a Paradigm Shift?. Circulation. 2022;145(7):496-498. doi:10.1161/CIRCULATIONAHA.121.058983

  4. Ghidini A, Sicherer S, Willner J. Congenital abnormalities (VATER) in baby born to mother using lovastatin. Lancet. 1992;339(8806):1416-1417. doi:10.1016/0140-6736(92)91237-3

  5. Pollack PS, Shields KE, Burnett DM, Osborne MJ, Cunningham ML, Stepanavage ME. Pregnancy outcomes after maternal exposure to simvastatin and lovastatin. Birth Defects Res A Clin Mol Teratol. 2005;73(11):888-896. doi:10.1002/bdra.20181

  6. Taguchi N, Rubin ET, Hosokawa A, et al. Prenatal exposure to HMG-CoA reductase inhibitors: effects on fetal and neonatal outcomes. Reprod Toxicol. 2008;26(2):175-177. doi:10.1016/j.reprotox.2008.06.009

  7. Petersen EE, Mitchell AA, Carey JC, et al. Maternal exposure to statins and risk for birth defects: a case-series approach. Am J Med Genet A. 2008;146A(20):2701-2705. doi:10.1002/ajmg.a.32493

  8. Toleikyte I, Retterstøl K, Leren TP, Iversen PO. Pregnancy outcomes in familial hypercholesterolemia: a registry-based study. Circulation. 2011;124(15):1606-1614. doi:10.1161/CIRCULATIONAHA.110.990929

  9. Zarek J, Delano KE, Nickel C, Laskin CA, Koren G. Are statins teratogenic in humans? addressing the safety of statins in light of potential benefits during pregnancy. Expert Review of Obstetrics & Gynecology. 2013;8(6):513-524. doi:10.1586/17474108.2013.842684.

  10. Winterfeld U, Allignol A, Panchaud A, et al. Pregnancy outcome following maternal exposure to statins: a multicentre prospective study. BJOG. 2013;120(4):463-471. doi:10.1111/1471-0528.12066

  11. Bateman BT, Hernandez-Diaz S, Fischer MA, et al. Statins and congenital malformations: cohort study. BMJ. 2015;350:h1035. Published 2015 Mar 17. doi:10.1136/bmj.h1035

  12. Chang JC, Chen YJ, Chen IC, Lin WS, Chen YM, Lin CH. Perinatal Outcomes After Statin Exposure During Pregnancy. JAMA Netw Open. 2021;4(12):e2141321. Published 2021 Dec 1. doi:10.1001/jamanetworkopen.2021.41321

Thank you ADCES Pharmacy COI Members for reading! Was this information surprising to you? How might you use this information in your practice? 

1 comment



02-13-2023 18:01

Great first blog post, Courtney! Thanks for this write up - it was relevant to a patient I saw in clinic today trying to conceive! Her PCP stopped her statin 4 months ago as part of a preconception visit - I think this is a great education point that it is ok to remain on statin therapy, for this patient of mine, while trying to get pregnant and only stop when she is pregnant. (on for primary prevention). Appreciate your time in putting this together, thank you.