Angiotensin II-receptor-antagonists: further evidence of fetotoxicity but not teratogenicity.
BACKGROUND
Like angiotensin converting enzyme (ACE) inhibitors angiotensin II (AT II)-receptor-antagonists may cause persistent or even lethal fetotoxic defects when used during the late second or third trimester. There are insufficient data on first-trimester exposure to these substances in terms of teratogenicity. The two databases of the Berlin Teratology Information Service (TIS) were evaluated for pregnancy outcome following exposure to AT II-receptor-antagonists. One database covers case reports on newborns with congenital abnormalities identified after birth, in which drug-effect associations can be evaluated retrospectively. The other enrolls women prospectively according to exposure to particular drugs during pregnancy, with follow-up of pregnancy outcome.


METHODS
Five cases (four retrospective and one prospective) involving late-pregnancy use of AT II-receptor-antagonists were recently reported to us, each of which included one or more of the following abnormalities: oligohydramnios/anhydramnios, anuria, hypoplastic skull bones, limb contractions, lung hypoplasia, and neonatal death. Among 37 prospectively enrolled first-trimester-exposed pregnancies there were 30 live births including one with a major malformation (cleft palate). One pregnancy was electively terminated after exencephaly had been diagnosed.


CONCLUSIONS
AT II-receptor-antagonists may induce fetotoxic effects when used in the second and third trimesters. The available data on first-trimester use do not strongly support a teratogenic potential. AT II-receptor-antagonists should not be used by pregnant women. In case of inadvertent exposure, therapy should be changed to the known antihypertensives of choice (e.g., metoprolol, methyldopa, and hydralazine) and fetotoxic effects should be ruled out by ultrasound. Treatment with AT II-receptor-antagonists during early pregnancy is not in itself an indication for termination of a wanted pregnancy.
Schaefer
Christof
C
Fachbereich Embryonaltoxikologie (Department of Embryotoxicology), Berliner Betrieb für Zentrale Gesundheitliche Aufgaben, Berlin, Germany. schaefer@embryotox.de
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D012189:Retrospective Studies
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II