Association between furosemide in premature infants and sensorineural hearing loss and nephrocalcinosis: a systematic review.

Furosemide is a potent loop diuretic commonly and variably used by neonatologists to improve oxygenation and lung compliance in premature infants. There are several safety concerns with use of furosemide in premature infants, specifically the risk of sensorineural hearing loss (SNHL), and nephrocalcinosis/nephrolithiasis (NC/NL). We conducted a systematic review of all trials and observational studies examining the association between these outcomes with exposure to furosemide in premature infants. We searched MEDLINE, EMBASE, CINAHL, and clinicaltrials.gov. We included studies reporting either SNHL or NC/NL in premature infants (< 37 weeks completed gestational age) who received at least one dose of enteral or intravenous furosemide. Thirty-two studies met full inclusion criteria for the review, including 12 studies examining SNHL and 20 studies examining NC/NL. Only one randomized controlled trial was identified in this review. We found no evidence that furosemide exposure increases the risk of SNHL or NC/NL in premature infants, with varying quality of studies and found the strength of evidence for both outcomes to be low. The most common limitation in these studies was the lack of control for confounding factors. The evidence for the risk of SNHL and NC/NL in premature infants exposed to furosemide is low. Further randomized controlled trials of furosemide in premature infants are urgently needed to adequately assess the risk of SNHL and NC/NL, provide evidence for improved FDA labeling, and promote safer prescribing practices.