The adverse renal effects of prostaglandin-synthesis inhibition in the fetus and the newborn.

OBJECTIVES

To summarize experimental animal data and to provide a limited literature review on the adverse renal effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the developing fetus and the maturing newborn.

DATA

The experimental data were obtained from anesthetized, ventilated, six- to eight-day-old rabbits that received an intravenous bolus of either acetylsalicylic acid (ASA), ibuprofen (IBU) or indomethacin (INDO). In one set of experiments, ASA was also tested in 12-week-old (young adult) rabbits. Renal function was monitored with inulin and para-aminohippuric acid clearances measuring glomerular filtration rate (GFR) and renal blood flow. The renal vascular resistance was calculated. All three nonspecific cyclo-oxygenase-1 or -2 (COX-1/2) inhibitors caused remarkably similar reversible, oliguric, acute renal failure (ARF). In young adult animals, the side effects were attenuated. The underlying pathophysiology is related to the carefully maintained low GFR of the fetus and the newborn, dependent on a delicate interplay between vasoconstriction (angiotensin II) and vasodilation (prostaglandins [PGs]). When PG-synthesis is inhibited, the vasoconstriction is relatively unopposed, causing ARF.

LITERATURE REVIEW

The renal effects of fetal exposure to NSAIDs are discussed, as are new insights into the role of COX-1/2 for a normal nephrogenesis. COX-nil or COX-inhibited animals have long lasting renal structural injury. Fetuses exposed in utero to significant amounts of NSAIDs have at birth various degrees of renal insufficiency and structural renal defects with a very high mortality.

CONCLUSIONS

All NSAIDs, both specific and nonspecific COX inhibitors, have renal side effects in the immediate post-natal period and should, therefore, be given with the utmost caution. NSAIDs given during pregnancy for the prevention of toxemia, polyhydramnios and premature labour may affect fetal renal function and structure. In animal experiments, IBU was not less nephrotoxic than INDO, as suggested recently by human premature neonates.