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Table 2 Summary of studies examining risk of hearing loss in premature infants

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

Study (Year) Design Population and Sample Size Outcome Measure Results
Mjoen (1982) [19] cohort 60 high-risk infants 27–44 weeks GA ABR testing in NICU and follow-up visits • 4 infants with evidence of SNHL. • 3/4 infants exposed to ototoxic medications (furosemide and/or aminoglycoside).
McCann (1985) [18] randomized controlled 17 premature infants with BPD (7 infants received furosemide and 10 infants received placebo) Audiology screen at discharge and follow-up visits • Normal hearing in all infants.
Salamy (1989) [20] cohort GA 24–34 weeks ABR in NICU and follow-up; behavioral audiometry from 3 months to 4 years • Infants with SNHL received greater amounts of furosemide for longer durations, in combination with aminoglycoside or vancomycin therapy (p < 0.001 for all factors).
Brown (1991) [21] case-control 35 infants with SNHL and 70 matched hearing-intact controls BAER testing prior to discharge from NICU • 17/35 (49%) infants with SNHL and 6/70 (9%) controls were exposed to furosemide (p < 0.0001).
Borradori (1997) [22] case-control 8 children with progressive bilateral deafness born preterm (GA ≤ 34 weeks) with 16 controls matched on GA and BW and 15 controls matched on perinatal complications ABR at NICU discharge and follow-up • 8/8 (100%) infants with SNHL and 13/15 (87%) controls received furosemide (NS). • Mean duration (p < 0.001), total cumulative dose (p < 0.001), and maximum daily dose (p = 0.05) were higher in SNHL group.
Ertl (2001) [23] case-control 22 premature infants with SNHL and 25 controls matched on GA, BW, and perinatal factors associated with hearing loss OAE test and ABR if failed OAE • 4/22 (18%) infants with SNHL and 1/25 (4%) controls received furosemide (p < 0.01).
Rais-Bahrami (2004) [24] cohort 57 infants who received furosemide and 207 infants who did not receive furosemide OAE, ABR, or both prior to NICU discharge • No difference in abnormal hearing screen in furosemide and non-furosemide groups (16% vs. 16%; p = 0.95).
Xoinis (2007) [25] case-control 71 infants with SNHL, 24 with auditory neuropathy,and 95 controls matched on GA, BW, and birth year ABR and OAE • Higher exposure to furosemide in SNHL group (51%) and AN group (96%) compared to control group (32.6%) (p < 0.05) for both comparisons.
Coenraad (2011) [26] case-control 9 infants with hearing loss and 36 controls matched on GA, gender, and birth year ABR screening prior to NICU discharge and repeat ABR and OAE at follow-up visit for failed screening. • No differences in furosemide exposure between groups (44% vs. 25%; p = 0.56).
Martinez-Cruz (2012) [27] case-control 6 children with SNHL and 87 normal-hearing controls with birth weights < 750 g BAER screening and OAE at follow-up visits for failed initial screening • 6/6 (100%) infants with SNHL and 45/87 (52%) control infants received furosemide (p = 0.002). • Longer average duration of furosemide in SNHL infants who received furosemide compared with controls (18 days vs. 7 days).
Rastogi (2013) [28] cohort Infants with BW < 1500 g. ABR prior to NICU discharge; Follow-up at 2 years for failed screening to determine hearing status • No association with furosemide and hearing loss when adjusting for BW, GA, and other perinatal risk factors (OR 1.18; p = 0.3).
Wang (2017) [29] cohort Included all infants with BW ≤ 1500 g. 297 infants with normal hearing and 12 infants with hearing loss OAE before discharge and BAER at 3 months corrected age if failed initial screen • Exposure to ototoxins (furosemide and/or gentamicin) was associated with hearing loss (OR 3.62; 95% CI 1.67–7.82).
  1. Legend: GA Gestational Age, ABR Auditory brainstem response, BPD Bronchopulmonary dysplasia, SNHL Sensorineural hearing loss, BAER Brainstem auditory evoked response, NICU Neonatal Intensive Care Unit, BW Birthweight, NS Non-significant, OAE Otoacoustic emission, AN Auditory neuropathy, ANSD Auditory neuropathy spectrum disorder, OR Odds ratio, CI Confidence Interval