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Table 5 Summary of studies examining risk of nephrocalcinosis/nephrolithiasis (NC/NL) 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 Summary
Hufnagle (1982) [30] cohort 10 premature infants with NC RUS during NICU admission • All infants received furosemide of at least 2 mg/kg/day for at least 12 days prior to NC.
Woolfield (1988) [31] cohort 36 infants with BW ≤ 1500 g RUS at 12 months of age • 3/32 (9%) infants had NC on RUS and had received chronic furosemide with doses ranging from 2 to 8 mg/kg/day. • NC resolved in 2/3 (67%) cases; 1 died of unrelated causes.
Jacinto (1988) [32] cohort 31 infants with BW < 1500 g RUS in third week of life and every 3 week thereafter until NICU discharge • NC was diagnosed in 20/31 (64%) of infants. • Exposure to furosemide was more common in NC group (65% vs 9%; p < 0.001).
Ezzedeen (1988) [33] cohort 17 premature infants with NC treated with furosemide; 3 premature infants treated with furosemide without NC (control group) RUS during NICU admission • No difference in average daily dose or duration of furosemide in NC group compared to control group.
Short (1991) [34] cohort 79 infants with GA < 32 weeks Serial RUS • 21/79 (27%) of infants diagnosed with NC. • No difference in mean total dose of furosemide.
Downing (1991) [35] cohort 117 infants with BW < 1750 g and BPD treated with furosemide RUS prior to discharge and in 3–6 month intervals for positive findings of NC/NL • 20/117 (17%) had evidence of NC/NL on RUS prior to discharge. • Infants maintained on furosemide were more likely to have persistent NC/NL compared to those for whom furosemide was stopped (p < 0.001).
Downing (1992) [36] cohort 27 infants with BW < 1500 g enrolled into 3 groups: 1) not exposed to furosemide (n = 7); 2) received furosemide without NC (n = 10); and 3) received furosemide with NC (n = 10) RUS and laboratory testing for glomerular and tubular kidney function • Infants in group 3 had lower creatinine clearance (reduced glomerular function) and higher tubular dysfunction compared to infants in group 1 and 2.
Stafstrom (1992) [37] cohort 11 premature infants with post-hemorrhagic hydrocephalus treated with furosemide and acetazolamide Serial RUS • 5/11 (45%) infants with evidence of NC. • No correlation between duration of treatment, total dosage of medications, and development of renal calculi.
Pope (1996) [38] cohort 13 premature infants with NC and exposed to furosemide divided into 2 groups: resolution of NC (n = 6) and persistent NC (n = 7). Serial RUS • No difference in duration of or cumulative dose of furosemide in infants with resolution of NC compared to those with persistence of NC.
Saarela (1999) [39] cohort 129 infants with BW < 1500 g RUS at 2 weeks, 6 weeks, and 3 months of life • 26/129 (20%) of infants diagnosed with NC. • The mean cumulative doses of furosemide were significantly higher in infants with NC compared to those without NC (19 mg vs 5 mg; p < 0.001).
Schell-Feith (2000) [40] cohort 215 infants with GA < 32 weeks RUS at 4 weeks of life and at term • NC diagnosed in 50/150 (33%) of infants at 4 weeks of life and 83/201 (41%) at term (NS). • At term, furosemide exposure was higher in those with NC (32%) compared to those without NC (18%) (p < 0.001).
Narendra (2001) [41] cohort 101 infants with GA < 32 weeks or BW < 1500 g RUS at 1 month of age and at term or NICU discharge • 16/101 (16%) diagnosed with NC. • The median total dose of furosemide was not significantly different before detection of NC on term RUS and in infants without NC (p = 0.75).
Hoppe (2002) [42] cohort 16 infants with GA < 37 weeks and diagnosed with NC RUS during NICU admission and every 3–6 months following discharge • NC persisted in 4/12 (33%) infants who received follow-up. • Infants with resolution of NC received lower dosages of furosemide compared to those with persistent NC (p < 0.05).
Hein (2004) [43] cohort 114 infants with BW < 1500 g divided into 2 groups: 1) NC (n = 20); 2) without NC (n = 94). 20 infants from control group matched to NC group based on BW and GA. RUS every 2 weeks during NICU admission • No difference in duration of furosemide therapy between groups.
Ketkeaw (2004) [44] cohort 36 infants with GA < 32 weeks and BW < 1250 g RUS prior to NICU discharge • 14/36 (39%) were diagnosed with NC. • The mean cumulative dose and mean duration of furosemide was higher in infants with NC compared to those without NC (102 mg vs 32 mg; p = 0.001 and 39 vs 7 days; p = 0.001).
Cranefield (2004) [45] cohort Cohort of infants enrolled in randomized trial of two regimens of dexamethasone for the prevention of BPD. RUS on study entry, day of life 28, and at discharge or 36 weeks postmenstrual age • 15/18 (83%) of infants for whom complete data were available were diagnosed with NC prior to discharge or 36 weeks postmenstrual age. • Furosemide was used infrequently in the trial. 7/8 (88%) of the infants who never received furosemide developed NC.
Gimpel (2010) [46] cohort 55 infants with GA < 32 weeks and BW < 1500 g RUS obtained after the first month of life • 15/55 (27%) of infants were diagnosed with NC. • The strongest independent risk factor for NC was furosemide therapy with cumulative dose > 10 mg/kg (OR 48.1 (95% CI 4.0–585); p < 0.01).
Chang (2011) [47] cohort 102 infants with GA < 34 weeks and BW < 1500 g RUS at term or prior to NICU discharge • 6/102 (6%) of infants were diagnosed with NC. • Exposure to furosemide was more common in the NC group compared to the group without NC (33% vs 3%; p = 0.027).
Lee (2014) [48] cohort 52 infants with BW < 1500 g RUS at 4 and 8 weeks of life • Exposure to furosemide did not differ significantly between infants with NC and those without NC.
Mohamed (2014) [49] cohort 97 infants with GA ≤ 34 weeks RUS at first week of life, at term, and at one year corrected age • Exposure to furosemide was more common in the NC group compared to the group without NC (50% vs 16%; p = 0.003).
  1. Legend: BW Birth weight, GA Gestational age, OR Odds ratio, CI Confidence interval, BPD Bronchopulmonary dysplasia