This article originally posted 24 March, 2012 and appeared in Issue 416
Test Your Knowledge Answer #416
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Answer and Critique (Correct Answer =B)
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), important medications in the management of diabetes, are known to delay the progression of nephropathy in type 1 and type 2 diabetes; however, both types of drugs are teratogenic and contraindicated during pregnancy. ACE inhibitors increase the risk of fetal injury and fetal loss. Previous studies indicated that ACE inhibitors should not be used during the second and third trimesters but could be used safely during the first trimester; however, a recent study showed that ACE inhibitors increase the risk of major congenital malformations in a fetus exposed to the drug during the first trimester. ACE inhibitors should thus be stopped before conception. ARBs should also be stopped before conception because no safety data are available during the first trimester of pregnancy. Insulin pump use can continue throughout pregnancy.
Key Point:
A comprehensive evaluation for the presence of complications of diabetes and the safety of medications should be carried out in a patient with diabetes who is pregnant or who desires pregnancy.
Patients who have diabetes and plan a pregnancy should have a comprehensive ophthalmic evaluation and counseling regarding the possibility of the development and/or worsening of retinopathy during pregnancy. Untreated proliferative retinopathy is a contraindication for conception, but treated and stable retinopathy is not. Although microalbuminuria is not a contraindication to conception, proteinuria of 190 mg/24 hours (or more) before or during pregnancy is associated with a 3-times higher risk of hypertensive disorder in the second half of pregnancy. The increased risk of hypertension and a long duration of diabetes do not predict adverse outcomes in pregnancy, however, and should not be considered contraindications. Counseling about pregnancy-induced hypertension, the increased risk of mortality from untreated cardiovascular diseases, and the increased risk of renal complications is recommended before conception.
Bibliography
Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861-9. [PMID: 11565518] [PubMed]
Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006;354:2443-51. [PMID: 16760444] [PubMed]
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD.The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy [published erratum in N Engl J Med. 1993;330:152]. The Collaborative Study Group. N Engl J Med. 1993;329:1456-62. [PMID: 8413456] [PubMed]
Lip GY, Churchill D, Beevers M, Auckett A, Beevers DG. Angiotensin-converting-enzyme inhibitors in early pregnancy [Letter]. Lancet. 1997;350:1446-7. [PMID: 9371172] [PubMed]
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