We thank Dr Vlachadis and colleagues for their interest in our work and their comments. The results of our study, which showed no significant increase in the risk of major birth defects after statin exposure during the first trimester of pregnancy, incited them to argue in favour of the future use of statins in the prevention of pre-eclampsia and other obstetric complications.
We agree upon theoretical considerations and experimental data possibly supporting the idea that statins could be useful in the prevention of pre-eclampsia; however, these mechanistic arguments have, as yet, not been supported by clinical evidence. A clinical trial aimed at studying pravastatin for the prevention of pre-eclampsia in high-risk women, and a second randomised, placebo-controlled, double-blind study on pravastatin use in severe early-onset pre-eclampsia, are under way. However, even preliminary results from these trials are unavailable to date, and there are currently no human data suggesting significant efficacy of statins in this indication. Of note, several previous attempts to find a treatment for pre-eclampsia based on pathophysiologic pathways have failed.[4, 5]
Our study assessed the risk associated with inadvertent exposure to statins during pregnancy. Therefore, a great majority of the patients in our cohort (86%) discontinued treatment during the first trimester of pregnancy. The use of statins in the prevention of pre-eclampsia would require the prolonged use of these drugs; however, the effects of long-term statin use on fetal and neonatal health in humans remain largely unknown. Among early teratogenic potential mechanisms hypothesised for this class of drugs is the involvement of a continuing alteration of cellular metabolism and regulation. Thus, it cannot be ruled out that most available exposures, lim-ited to the (early) first trimester, may not have covered the most sensitive period or a sufficient duration of exposure to reveal teratogenic or fetotoxic effects.
The safe use of statins beyond the first trimester of pregnancy or for a prolonged duration cannot be extrapolated from our results, and further research is certainly required to better assess the risk/benefit ratio of these drugs during pregnancy.