ACE Inhibitors and Pregnancy

“He had never turned his mind to the possibility of Mrs Brown becoming pregnant and whether enalapril would be a suitable anti-hypertensive during pregnancy.”

Dr A found that her blood pressure was raised and after a couple of reviews and investigations, he made a diagnosis of hypertension and commenced her on enalapril. This controlled her blood pressure very effectively. 

Sometime later Dr A was shocked and surprised to receive a letter of complaint from Mrs Brown. In the letter Mrs Brown explained that she had recently had a miscarriage. When she had a D and C at the local maternity hospital, the doctor there advised her that enalapril should not be used during pregnancy. She was angry that Dr A had never informed her of this.

Dr A vaguely recalled that Mrs Brown had told him that she attended a female GP at a different general practice for her Pap smears. He had never enquired of her as to whether she was using any contraception, or whether she wanted to have children. He had never turned his mind to the possibility of Mrs Brown becoming pregnant and whether enalapril would be a suitable anti-hypertensive during pregnancy.

He consulted Therapeutic Guidelines and was surprised to find that enalapril and all angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are category D in pregnancy¹.

What are the Risks Associated with use of ACE Inhibitors and ARBs in Pregnancy? 

Research first emerged in the early 1990s of the association of ACE inhibitors in pregnancy and the development of severe fetal abnormalities. A significantly increased incidence of oligohydramnios, neonatal renal failure, pulmonary hypoplasia, calvarial hypoplasia and fetal death was reported². The increased risk of fetal abnormalities was initially thought to be limited to women receiving ACE inhibitor therapy in the second and third trimesters of pregnancy. However, a more recent study suggested a significantly increased risk (>2.7) of major congenital malformations in women receiving ACE inhibitors therapy in the first trimester of pregnancy³. A higher incidence of fetal abnormalities in the offspring of women taking ARBs during pregnancy has also been noted.⁴

A recent study from the UK reviewed women aged 16–45 years who were referred to a tertiary Hypertension Clinic. The authors found that 47% of women in this age group
were taking an ACE inhibitor or an ARB or both and of these women, about 25% were using no contraception, or barrier methods. The authors of this study were concerned at the frequent usage of these drugs in this group of patients. 

With the increased incidence of obesity and its associated co-morbidities of hypertension, it is likely that it is going
to be increasingly common to see women of child bearing age who require antihypertensive treatment. There is some value in the old adage that ‘all women between the ages of 15 and 50 years should be assumed to be pregnant’. 

Doctors who are prescribing ACE inhibitors or ARBs to women of childbearing age should ensure that the patient is informed of the serious risks to a developing baby if the woman should become pregnant. The doctor should ensure that the woman is using reliable contraception, or if she desires pregnancy, reconsider the drug choice. 

Dr A consulted MDA National who assisted him to write a suitably apologetic letter to Mrs Brown and he heard no more from her.

References

1. Victorian Drug Usage Advisory Committee. Therapeutic guidelines. Cardiovascular. North Melbourne, Vic.: Therapeutic Guidelines; 1999. p. v.
2. Shotan A, Widerhorn J, Hurst A, Elkayam U. Risks of angiotensin-converting enzyme inhibition during pregnancy: experimental and clinical evidence, potential mechanisms and recommendations for use. Am J Med. 1994 May;96(5):451-6.
3. 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 Jun 8;354(23):2443-51.
4. Quan A. Fetopathy associated with exposure to angiotensin converting enzyme inhibitors and angiotensin receptor antagonists. Early Hum Dev. 2006 Jan;82(1):23-8.
5. Martin U, Foreman MA, Travis JC, Casson D, Coleman JJ. Use of ACE inhibitors and ARBs in hypertensive women of childbearing age. J Clin Pharm Ther. 2008 Oct;33(5):507-11.