Statins and pregnancy

• no controlled studies demonstrate teratogenic effects in humans; however, case reports have documented congenital anomalies, including vertebral, anal, cardiac, tracheal, esophageal, renal, and limb deficiency (VACTERL association), intrauterine growth retardation (IUGR), and demise in fetuses exposed during pregnancy, especially in the first trimester. It is thought that adverse events are under-reported and likely biased toward severe outcomes, thereby limiting actual reported exposures
  • overall birth prevalence of any isolated lower-limb defect or VACTERL anomaly is estimated as 1:100,000 and ranges from 1:50,000 for simvastatin (Zocor) to 1:500,000 for lovastatin (Mevacor)
  • these congenital anomaly frequencies do not exceed general population rates (2)
• highly lipophilic statins (such as simvastatin, atorvastatin) achieve embryoplacental concentrations similar to those of maternal plasma
  • therefore if statin therapy is needed, these agents should be avoided. Pravastatin is the most hydrophilic statin and has no reports of abnormal pregnancy outcomes, even in animal research (2)
• a review concerning statin use in pregnancy states that (3):
  • women of child-bearing age are rarely treated with cholesterol-lowering drugs, so there are few data on the use of statins during pregnancy
  • central nervous system and limb defects have been reported in newborns exposed to statins in utero. Several case reports describe similar malformations that are very rare in the general population
  • animal toxicity studies also suggest that statins are teratogenic
  • the data are not conclusive, but they suggest that statins should be avoided during pregnancy and that pregnant women exposed to cholesterol-lowering drugs should be monitored very closely
• it seems prudent to recommend that a woman should have stopped statin therapy for at least three months before trying to conceive (4,5)
  • this view has now been produced in NICE guidance (6):
    • statins are contraindicated in pregnancy:
      • advise women of childbearing potential of the potential teratogenic risk of statins and to stop taking them if pregnancy is a possibility
      • advise women planning pregnancy to stop taking statins 3 months before they attempt to conceive and to not restart them until breastfeeding is finished

Notes:

• a review of 6 studies found no significant increased risk of major congenital malformations with prenatal exposure to statins vs controls, though rate of spontaneous abortion was higher (OR 1.36, 95%CI 1.06-1.75), which authors suggest may be associated with maternal comorbidity (7)

Reference:

1. Edison RJ, Muenke M. Mechanistic and epidemiologic considerations in the evaluation of adverse birth outcomes following gestational exposure to statins. Am J Med Genet A 2004;131:287-298.
2. Patel C et al. Clinical inquiries. What precautions should we use with statins for women of childbearing age? J Fam Pract. 2006 Jan;55(1):75-7.
3. Statins: beware during pregnancy. Prescrire Int. 2006 Feb;15(81):18-9.
4. British Heart Foundation Factfile (January 2009). Familial Hypercholesterolaemia (FH).
5. Personal Communication (March 20th 2006), Dr Mike Khan, Consultant Endrocrinologist. University Hospitals Coventry and Warwickshire.
6. NICE (July 2014). Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease
7. Karadas, B, Uysal, N, Erol, H, et al. Pregnancy outcomes following maternal exposure to statins: A systematic review and meta-analysis. Br J Clin Pharmacol. 2022. https://doi.org/10.1111/bcp.15423