The number of pregnant women receiving immunosuppressants for anti-rejection therapy or autoimmune diseases is increasing. All immunosuppressive drugs cross the placenta, raising questions about the long-term outcome of the children exposed in utero. There is no higher risk of congenital anomalies. However, an increased incidence of prematurity, intrauterine growth retardation (IUGR) and generally low birth weight has been reported, as well as maternal hypertension and preeclampsia. The most frequent neonatal complications are those associated with prematurity and IUGR, as well as adrenal insufficiency with corticosteroids, immunological disturbances with azathioprine and cyclosporine, and hyperkalemia with tacrolimus. The long-term follow-up of infants exposed to immunosuppressants in utero is still limited and experimental studies raise the question whether there could be an increased incidence at adult age of some pathologies including renal insufficiency, hypertension and diabetes.

Tocolysis with nonsteroidal anti-inflammatory drugs (NSAIDs) has been widely accepted for several years. Recently, the use of the cyclooxygenase-2 (COX2) preferential NSAID nimesulide has been proposed. However, data reporting neonatal acute renal failure or irreversible end-stage renal failure after maternal ingestion of nimesulide question the safety of this drug for the fetus and the neonate. Therefore, this study was designed to define the renal effects of nimesulide in newborn rabbits. Experiments were performed in 28 newborn rabbits. Renal function and hemodynamic parameters were measured using inulin and para-aminohippuric acid clearances as markers of GFR and renal blood flow, respectively. After a control period, nimesulide 2, 20, or 200 g/kg was given as an i.v. bolus, followed by a 0.05, 0.5, or 5 g · kg Ϫ1 · min Ϫ1 infusion. Nimesulide administration induced a significant dose-dependent increase in renal vascular resistance (29, 37, and 92%, respectively), with a concomitant decrease in diuresis (Ϫ5, Ϫ23, and Ϫ44%), GFR (Ϫ12, Ϫ23, and Ϫ47%), and renal blood flow (Ϫ23, Ϫ23, and Ϫ48%). These results are in contrast with recent reports claiming that selective COX2 inhibition could be safer for the kidney than nonselective NSAIDs. These experiments confirm that prostaglandins, by maintaining renal vasodilation, play a key role in the delicate balance regulating neonatal GFR. We conclude that COX2-selective/preferential inhibitors thus should be prescribed with the same caution as nonselective NSAIDs during pregnancy and in the neonatal period. Because of the role of prostaglandins (PGs) in the genesis of labor (term or preterm), nonselective nonsteroidal antiinflammatory drugs (NSAIDs) have been used as tocolytic drugs for several decades. Meanwhile, the use of NSAIDs during pregnancy to treat toxemia, polyhydramnios, or preterm labor and in the immediate postnatal period to induce closure of a symptomatic patent ductus arteriosus is increasing (1-4). However, side effects that affect mainly the cerebral, mesenteric, and renal microcirculations have been reported in fetuses and neonates (5-10), and NSAID-associated pulmonary hypoperfusion and persistence of fetal circulation may also compromise the newborn renal function (4, 11).It has been claimed that selective cyclooxygenase-2 (COX2) inhibitors could have the same curative effects as nonselective NSAIDs without the deleterious side effects attributed to COX1 inhibition. Therefore, the use of the COX2-preferential NSAID nimesulide (12, 13) has been proposed for tocolysis in humans (14). In a case report, Sawdy et al. (14) found no effect of nimesulide administered from the 16th to the 34th week of gestation on the renal and ductal functions of the fetus. Doppler flow indices for the ductus arteriosus and amniotic fluid index remained normal, and the infant was born with no congenital abnormalities and an uncomplicated neonatal course (14). However, recent data reporting severe oligohydramnios (15)

No abstract