Journal of Reproductive Immunology 84 (2010) 206–207

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Journal of Reproductive Immunology

journa l homepage: www.e lsev ier .com/ locate / j repr imm

Letters to the Editor

Statins for the treatment of obstetric complications inantiphospholipid syndrome?

Keywords:StatinsAntiphospholipid syndromePregnancy Loss

In her paper, “Pravastatin prevents miscarriagesin antiphospholipid antibody-treated mice,” [J. Reprod.Immunol. 2009;82(November (2)):126–31] Dr. Girardi’sconclusions go well beyond her data when she recom-mends the use of statin drugs to prevent human pregnancyloss.

Pravastatin, and all statin drugs, are FDA Category Xfor pregnancy (contraindicated), because of teratogenic-ity, placental disruption (Kenis et al., 2005; Forbes et al.,2008), and theoretical long-term fetal neurological damage(Ponce et al., 2008). Statins may disrupt gonadal stem celldevelopment in fetuses, potentially leading to later infertil-ity or other problems (Ding et al., 2008). Dr. Girardi allegessafety of statins in pregnancy based on studies underpow-ered to detect teratogenicity, one of which explicitly statesthat “simvastatin and lovastatin remain contraindicatedduring pregnancy (Pollack et al., 2005).

Even if the mechanism described in the article doesaccount for a significant proportion of human pregnancylosses, a fact not yet established, a statin trial for pregnancyloss cannot take place without much stronger indication ofhuman safety, including primate trials, and IRB approvalsunder strictest conditions, including long-term follow-upof neurological development and perhaps fertility of theoffspring. Given the ubiquity of statins in the community,the desperation of couples who lose pregnancies, and thedifferences between mice and humans, a single experiencein mice is insufficient to suggest a clinical trial in pregnantwomen.

References

Ding, J., Jiang, D., Kurczy, M., Nalepka, J., Dudley, B., Merkel, E.I., Porter, F.D.,Evwin, A., Winograd, N., Burgess, J., Molyneaux, K., 2008. Inhibition of

HMG CoA reductase reveals an unexpected role for cholesterol duringPGC migration in the mouse. BMC Dev. Biol. 8, 120.

Forbes, K., Hurst, L.M., Aplin, J.D., Westwood, M., Gibson, J.M., 2008. Statinsare detrimental to human placental development and function; useof statins during early pregnancy is inadvisable. J. Cell. Mol. Med. 12,2295–2296.

0165-0378/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.

Kenis, I., Tartakover-Matalon, S., Cherepnin, N., Drucker, L., Fishman,A., Pomeranz, M., Lishner, M., 2005. Simvastatin has deleteriouseffects on human first trimester placental explants. Hum. Reprod. 20,2866–2872.

Ponce, J., de La Ossa, N.P., Hurtado, O., MIllan, M., Arenillas, J.F., Davalos, A.,Gasuli, T., 2008. Simvastatin reduces the association of NMDA recep-tors to lipid rafts: a cholesterol mediated effect in neuroprotection.Stroke 39, 1269–1275.

Pollack, P.S., Shields, K.E., Burnett, D.M., Osborne, M.J., Cunningham, M.K.,Stepanavage, M.E., 2005. Pregnancy outcomes after maternal expo-sure to simvastatin and lovastatin. Birth Defects Res. A Clin. Mol.Theratol. 73, 888–896.

Michael D. Lockshin a,b,c

a Barbara Volcker Center for Women andRheumatic Diseases, New York, United Statesb Mary Kirkland Center for Lupus Research at

the Hospital for Special Surgery, New York,United States

c Medicine and Obstetrics-Gynecology,Joan and Sanford Weill College of Medicine,

New York, United States

Silvia S. Pierangeli ∗

Antiphospholipid StandardizationLaboratory, University of Texas Medical

Branch, Galveston, TX, United States

∗ Corresponding author at: BrackenridgeHall 2.108, 301 University Boulevard,

Galveston, TX 77555-0883, United States.Tel.: +1 409 772 0222;fax: +1 409 772 0223.

E-mail address: sspieran@utmb.edu(S.S. Pierangeli)

11 October 2009doi:10.1016/j.jri.2009.11.007

Author’s response to ‘Statins for the treatment of obstet-ric complications in Antiphospholipid Syndrome?’

In my paper “Pravastatin prevents miscarriage inantiphospholipid antibody-treated mice” [J. Reprod.

Immunol. 82 (November (2)) (2009) 126–131], I do notrecommend the use of statin drugs to prevent humanpregnancy loss. The first sentence of the concludingparagraph of my review article reads “We recognize thatthese studies were conducted in mice and that clinical