Exposure to furosemide as the strongest risk factor for nephrocalcinosis in preterm infants

The objective of this study was to determine which of the many risk factors for nephrocalcinosis (NC) in preterm infants are most relevant.

In 55 neonates born before 32 completed weeks of gestation, parameters relevant to NC were analyzed. Median birthweight was 1010 g (range 500-2070 g). Fifteen (27%) asymptomatic children had ultrasonographic NC.

In multivariate analysis the strongest independent risk factor was furosemide therapy above 10 mg per kg bodyweight cumulative dose, with a 48-fold increased risk of NC (odds ratio confidence interval 4.0-585, P < 0.01). The risk of NC was 1.65-fold higher per 100 g lower weight (1.07-2.56, P= 0.02) and 4.5-fold higher per mmol/l of urinary calcium concentration (1.14-17.7, P= 0.03). Many other risk factors were only significant in univariate analysis (gestational age, mechanical ventilation, infection, broncho-pulmonary dysplasia, blood transfusions, intraventricular hemorrhage, surfactant therapy, vasopressors, phenobarbital or caffeine, duration of hospital stay), indicating an indirect effect only. Other parameters of calcium and phosphate homeostasis were not significant, possibly due to standardized supplementation.

We suggest that in preterm infants, furosemide should be prescribed with caution and close monitoring of calcium excretions is advisable. Some guidelines for infant respiratory distress syndrome now favor calcium-sparing thiazides if diuretics are considered.