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Diabetologia
Published in: Diabetologia 6/2011

01-06-2011 | Article

Exposure to candesartan during the first trimester of pregnancy in type 1 diabetes: experience from the placebo-controlled diabetic retinopathy candesartan trials

Authors: M. Porta, J. W. Hainer, S.-O. Jansson, A. Malm, R. Bilous, N. Chaturvedi, J. H. Fuller, R. Klein, T. Orchard, H.-H. Parving, A.-K. Sjølie, on behalf of the DIRECT Study Group

Published in: Diabetologia | Issue 6/2011

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Abstract

Aims/hypothesis

The teratogenic consequences of angiotensin-converting enzyme inhibitors angiotensin receptor blockers (ARBs) during the second and third trimesters of pregnancy are well described. However, the consequences of exposure during the first trimester are unclear, especially in diabetes. We report the experience from DIRECT (DIabetic REtinopathy and Candesartan Trials), three placebo-controlled studies designed to examine the effects of an ARB, candesartan, on diabetic retinopathy.

Methods

Over 4 years or longer, 178 normotensive women with type 1 diabetes (86 randomised to candesartan, 32 mg once daily, and 92 assigned to placebo) became pregnant (total of 208 pregnancies).

Results

More than half of patients were exposed to candesartan or placebo prior to or in early pregnancy, but all discontinued it at an estimated 8 weeks from the last menstrual period. Full-term pregnancies (51 vs 50), premature deliveries (21 vs 27), spontaneous miscarriages (12 vs 15), elective terminations (15 vs 14) and other outcomes (1 vs 2) were similar in the candesartan and placebo groups. There were two stillbirths and two ‘sick babies’ in the candesartan group, and one stillbirth, eight ‘sick babies’ and one cardiac malformation in the placebo group.

Conclusions/interpretation

The risk for fetal consequences of ARBs in type 1 diabetes may not be high if exposure is clearly limited to the first trimester. Long-term studies in fertile women can be conducted with ARBs during pregnancy, provided investigators diligently stop their administration upon planning or detection of pregnancy.

Trial registration

ClinicalTrials.gov DIRECT-Prevent 1 NCT00252733; DIRECT-Protect 1 NCT00252720; DIRECT-Protect 2 NCT00252694.

Funding

The study was funded jointly by AstraZeneca and Takeda.
Appendix
Available only for authorised users
Literature
1.
Schjoedt KJ, Hansen HP, Tarnow L, Rossing P, Parving HH (2008) Long-term prevention of diabetic nephropathy: an audit. Diabetologia 51:956–961PubMedCrossRef
2.
Alwan S, Polifka JE, Friedman JM (2005) Angiotensin II receptor antagonist treatment during pregnancy. Birth Defects Research (Part A) 73:123–130CrossRef
3.
Quan A (2006) Fetopathy associated with exposure to angiotensin converting enzyme inhibitors and angiotensin receptor antagonists. Early Human Development 82:23–28PubMedCrossRef
4.
Cooper WO, Hernandez-Diaz S, Arbogast PG et al (2006) Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med 354:2443–2451PubMedCrossRef
5.
Lennestål R, Otterblad Olausson P, Källén B (2009) Maternal use of antihypertensive drugs in early pregnancy and delivery outcome, notably the presence of congenital heart defects in the infants. Eur J Clin Pharmacol 65:615–625PubMedCrossRef
6.
Caton AR, Bell EM, Druschel CM et al (2009) Antihypertensive medication use during pregnancy and the risk of cardiovascular malformations. Hypertension 54:63–70PubMedCrossRef
7.
Yoder SR, Thornburg LL, Bisognano JD (2009) Hypertension in pregnancy and women of childbearing age. Am J Med 122:890–895PubMedCrossRef
8.
Allen VM, Armson BA, Wilson RD et al (2007) Teratogenicity associated with pre-existing and gestational diabetes. J Obstet Gynaecol Can 29:927–944PubMedCrossRef
9.
Chaturvedi N, Porta M, Klein R et al (2008) Effect of candesartan on prevention (DIRECT–Prevent 1) and progression (DIRECT–Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials. Lancet 372:394–402CrossRef
10.
Sjølie AK, Klein R, Porta M et al (2008) Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT–Protect 2): a randomised placebo-controlled trial. Lancet 372:1385–1393PubMedCrossRef
11.
Food and Drug Administration (1992) Dangers of ACE inhibition during second and third trimesters of pregnancy. Med Bull 22:2
12.
American Diabetes Association (2010) Standards of medical care in diabetes—2010. Diabetes Care 33(Suppl 1):S11–S61CrossRef
13.
Schultz S, Moullec J-M, Corvol P, Gasic J-M (1996) Early expression of all the components of the renin–angiotensin system in human development. Am J Pathology 149:2067–2079
14.
Haaland K (2010) Angiotensin II receptor antagonists against migraine in pregnacny: fatal outcome. J Headache Pain 11:167–169PubMedCrossRef
Metadata
Title
Exposure to candesartan during the first trimester of pregnancy in type 1 diabetes: experience from the placebo-controlled diabetic retinopathy candesartan trials
Authors
M. Porta
J. W. Hainer
S.-O. Jansson
A. Malm
R. Bilous
N. Chaturvedi
J. H. Fuller
R. Klein
T. Orchard
H.-H. Parving
A.-K. Sjølie
on behalf of the DIRECT Study Group
Publication date
01-06-2011
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 6/2011
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-010-2040-1

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