Fetal toxic effects of angiotensin II receptor antagonists: case report and follow-up after birth.
OBJECTIVE
To report a child born with renal impairment following severe anhydramnios due to maternal exposure to an angiotensin II receptor type 1 (AT1) antagonist, valsartan, and hydrochlorothiazide during the first 28 weeks of pregnancy.


METHODS
A hypertensive woman treated with valsartan 80 mg/day, hydrochlorothiazide 12.5 mg/day, prazosin 10 mg/day, lysine acetylsalicylate 100 mg/day, and levothyroxine 250 microg/day became pregnant. At 28 weeks' gestational age, severe anhydramnios associated with high beta2-microglobulin levels in the fetal blood cord was observed. Upon discontinuation of valsartan, fetal renal prognosis improved. In this case, using the Naranjo probability scale, the renal insufficiency of the child was probably related to valsartan. At the age of 2.5 years, the child presented with only mild chronic renal insufficiency. Growth parameters were within the normal range, and there was no evidence of developmental delay.


CONCLUSIONS
Exposure to AT1 antagonists during the second part of pregnancy can lead to abnormalities similar to those observed after exposure to angiotensin-converting enzyme inhibitors, that is, reduced fetal kidney perfusion that may result in oligoamnios and neonatal renal insufficiency. Fourteen previous reports of maternal exposure to AT1 antagonists during this period have been published. In 6 cases, fetal or neonatal death occurred; in 2 cases, pregnancy was terminated because of complete anhydramnios or fetal abnormalities; in 1 case, renal insufficiency persisted at 8 months of age; in 2 cases, kidney function was fairly normal at birth; and in 4 cases, including the one described here, neonatal renal failure improved in the first year of life.


CONCLUSIONS
AT1 antagonists should be avoided throughout pregnancy. If these agents are prescribed accidentally to a pregnant woman, monitoring of amniotic fluid volume and beta2-microglobulin fetal blood levels after discontinuation of the AT1 antagonist can provide critical data for advising parents on pregnancy and fetal outcome.
Bos-Thompson
Marie-Andrée
MA
Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, Montpellier, France. ma-thompson@chu-montpellier.fr
Hillaire-Buys
Dominique
D
Muller
Françoise
F
Dechaud
Hervé
H
Mazurier
Evelyne
E
Boulot
Pierre
P
Morin
Denis
D
D000653:Amniotic Fluid; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects*; D000959:Antihypertensive Agents / Q000009:adverse effects*; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy; D011297:Prenatal Exposure Delayed Effects; D051437:Renal Insufficiency / Q000139:chemically induced*; D013777:Tetrazoles / Q000009:adverse effects*; D014633:Valine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D000068756:Valsartan; D001613:beta 2-Microglobulin / Q000097:blood
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D013777:Tetrazoles; D001613:beta 2-Microglobulin; D000068756:Valsartan; D014633:Valine