Safety of ACE-inhibitors in Pregnancy and Lactation:

First trimester exposure

• A 2006 epidemiologic study first suggested that ACE inhibitors are not safe in early pregnancy
• Although recent researches has questioned the association between first trimester ACE inhibitor use and congenital (particularly cardiac) abnormalities, given the proven risks of exposure in second and third trimester, they continue to recommend that these drugs be avoided throughout pregnancy
• Although there is less information about the risk of congenital malformations associated with first trimester exposure to ARBs , the available literature suggests that these agents have the same risks as ACE inhibitors

Second and third trimester exposure

• systematic review and meta-analysis provides good evidence that second and third trimester exposure to ACE inhibitors and ARBs is associated with serious adverse fetal/neonatal effects
• The use of drugs that act directly on the renin-angiotensin system has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death
• The most common problems are related to impaired fetal/neonatal renal function, which results in oligohydramnios during pregnancy (amniotic fluid is largely derived from the fetal kidneys), and anuria and renal failure after delivery
• Oligohydramnios increases the risk of umbilical cord compression and, in turn, fetal death.
• Severe oligohydramnios can lead to poor pulmonary development (pulmonary hypoplasia) and development of limb contractures and skeletal deformations
• Hypocalvaria, retinopathy, and prolonged neonatal hypotension have also been observed with second or third trimester ACE inhibitor exposure

Lactation

• ACE inhibitors are transferred into breast milk, but have very low levels in the milk.
• ACE inhibitors and angiotensin II receptor antagonists are generally not recommended for use by breastfeeding mothers, they are not absolutely contraindicated.
• Healthcare professionals may prescribe these medicines during breastfeeding if they consider that this treatment is essential for the lactating mother
• Captopril and enalapril have been reviewed by the American Academy of Pediatrics and are claimed compatible for use in lactation.
• However, newborns may be more susceptible to the hemodynamic effects of these drugs, such as hypotension, and sequelae, such as oliguria and seizures.
• hemodynamic status of the infant should be taken into account when deciding whether women taking these drugs should breastfeed
•  There is no information on the use of ARBs during breastfeeding.

 Risk Categories and Available ACE Inhibitors in Hospital

	Pregnancy Risk	Lactation
Captopril	D	NR	Because of the low levels of enalapril in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants
Enalapril	D	NR
Perindopril	D	NR	Because of the low reported levels in milk with similar drugs, it is unlikely that any of the ACE inhibitors reach clinically important levels in breastmilk. However, use of an ACE inhibitor that has been studied is preferred.
Ramipril (not available)	D	NR	Because no information is available on the use of ramipril during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant

Pregnancy risk factor D = Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage

NR= Not recommended 

References:

1. www.uptodate.com
2. https://www.gov.uk/drug-safety-update/clarification-ace-inhibitors-and-angiotensin-ii-receptor-antagonists
3. http://www.aafp.org/afp/2001/0701/p119.html
4. www.drugs.com
5. http://www.bmj.com/content/343/bmj.d5931
6. http://www.australianprescriber.com/magazine/35/2/47/50