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MS WordPerinatologist Corner - C.E.U/C.M.E. Modules
Preconception Counseling for Women with Diabetes and Hypertension
Sponsored by The Indian Health Service Clinical Support Center
Step 3. Hypertension Medication: What you can’t use
Case Scenario #1
AD is a 25 y/o nullipara with newly diagnosed type 2 diabetes mellitus and moderate essential hypertension. She also has been trying to become pregnant. Her blood sugars have been fairly well controlled with diet and exercise, but her blood pressure is persistently greater than 140/90. What are the categories of risk for drugs in pregnancy? Because of her dual problem, would it be appropriate to start an angiotensin converting enzyme (ACE) inhibitor? Could we then discontinue it when she becomes pregnant? Or would it be safer to start another medication that would be safer in pregnancy since she is not using any form of contraception?
Discussion
The FDA uses a scale of A, B, C, D, and X for its current categories for drug use in pregnancy.
The angiotensin converting enzyme inhibitors (ACE)
are preferred agents in non-pregnant hypertensive diabetic patients. Their benefit is derived from the fact that they relax the glomerular afferent arteriole, they enhance glomerular blood flow and thus reduce the incidence and severity of proteinuria and hypertension.
All ACE inhibitors are contraindicated in the 2nd and 3rd trimesters (category D). Some are still labeled category C in the 1st trimester, e. g., lisinopril, enalapril, and captopril. One must interpret this carefully as the findings from the New England Journal of Medicine in June 2006 article below show that exposure to ACE inhibitors even during the first trimester can not be considered safe and should be avoided
.
However, in the fetus, they can create a situation of such persistent glomerular high flow that destruction of the delicate fetal glomerular capillary network may result. This can then result in fetal renal failure and oligohydramnios.
Findings from an observational study published in The New England Journal of Medicine in June 2006 revealed that infants exposed to ACE inhibitors during the first trimester of the gestational period had an increased overall relative risk (RR) for congenital malformations compared with those not exposed (RR, 2.71; 95% confidence interval [CI], 1.72 - 4.27). Half of these defects were various cardiac septal defects, and the remainder included some defects of the central nervous, urologic, or other systems. Women receiving ACE inhibitor therapy were generally older and more likely to have other chronic conditions compared with those not receiving therapy.
This may be seen during the latter half of pregnancy, or in the newborn period. While this situation may be reversible if the ACE is stopped, that cannot be assured.
Angiotensin receptor blockers
Angiotensin receptor blockers (ARBs) appear to have the lowest risk of any antihypertensive of precipitating diabetes, according to a network meta-analysis. (Elliott 2007) Elliott W J and Meyer P M. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet 2007; 369: 201–207. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17240286
The same teratogenic effects above have unfortunately also been described with the angiotensin receptor blockers (ARB), such as candesartan. ACEs are also first trimester teratogens, and are associated with congenital defects of the cardiovascular (atrial and ventricular septal defects) and central nervous system and skeleton (spina bifida, microcephaly, calvarial hypoplasia). Their use in the peri-conceptional period is therefore no longer recommended.
Breastfeeding
ACE inhibitors also appear in small quantities in breast milk. The American Academy of Pediatrics Committee on Drugs considers captopril, enalapril, and other ACE inhibitors compatible with breastfeeding. While we could not find any evidence of adverse neonatal effects in breastfed infants whose mothers were on ACE inhibitors, we could likewise not find any pediatricians who were comfortable with that situation….
Categories for Drug Use in Pregnancy
CATEGORY | INTERPRETATION* |
|---|---|
A |
Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities to the fetus in any trimester of pregnancy. |
B |
Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate and well-controlled studies in pregnant women. |
C |
Animal studies have shown an adverse effect and there are no adequate and well-controlled studies in pregnant women. |
D |
Adequate well-controlled or observational studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective. |
X |
Adequate well-controlled or observational studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities or risks. The use of the product is contraindicated in women who are or may become pregnant. |
*Sources:
FDA Use-in-Pregnancy Ratings, perinatology.com
Current Categories for Drug Use in Pregnancy, FDA/Office of Public Affairs
