Table 2.
Late-onset sepsis (LOS) and secondary outcomes
| Outcomesa | Lactoferrin (n=209) | Placebo (n=205) | |
|---|---|---|---|
| Sepsis outcomes | No. (%) | No. (%) | Hazard Ratio (95% CI) |
| Primary composite outcome, No. (%) | 22 (10.5) | 30 (14.6) | 0.73 (0.42 – 1.26) |
| First culture-proven LOS, No. (%) | 17 (8.1) | 22 (10.7) | |
| Sepsis-related deaths, No. (%) | 5 (2.6) | 8 (4.4) | |
| Primary composite outcome by birth weight group, n/N (%) | |||
| 500g - 1000g | 7/39 (17.9) | 15/38 (39.5) | 0.45 (0.18 – 1.10)b |
| 1001g - 1500g | 12/91 (13.6) | 12/88 (13.8) | 0.99 (0.45 – 2.21) |
| 1501g - 2000g | 3/79 (3.8) | 3/79(3.8) | 1.04 (0.21 – 5.16) |
| First culture-proven or probable LOS, No. (%) | 34 (16.3) | 44 (21.5) | 0.76 (0.48 – 1.19) |
| All culture-proven and probable LOSc, No. (%) | 43 (43.1) | 54 (53.6) | 0.82 (0.55 – 1.23) |
| Isolated pathogens (all culture-proven and probable sepsis), No. | 29 | 38 | |
| Gram negative bacteriad | 8 | 12 | |
| Gram positive bacteria (excluding CoNS)e | 5 | 3 | |
| CoNS | 15 | 19 | |
| Candida | 1 | 4 | |
| Secondary outcomes | No. (IR/104)f | No. (IR/104)f | Rate ratio (95% CI) |
| NEC Bell’s stage ≥2 | 5 (0.5) | 11 (11) | 0.46 (0.16 – 1.31) |
| ROP requiring surgery | 8 (8.4) | 11 (11.4) | 0.74 (0.30 – 1.83) |
| Intraventricular hemorrhage III-IV (3–4week)c | 3 (1.9) | 7 (4.6) | 0.42 (0.17 – 1.02) |
| Periventricular leukomalacia (3–4weeks)c | 2 (1.3) | 4 (2.6) | 0.48 (0.23 – 1.01) |
| Bronchopulmonary dysplasiac | 25 (12.0) | 26 (12.7) | 0.94 (0.85 – 1.05) |
| Serious infections prior to discharge | |||
| Pneumonia | 24 (40.3) | 25 (40.1) | 1.01 (0.58 – 1.78) |
| Meningitis / encephalitis | 4 (6.4) | 6 (9.5) | 0.64 (0.18 – 2.27) |
| UTI | 7 (11.2) | 4 (6.3) | 0.50 (0.05 – 5.52) |
| Conditions requiring re-hospitalization | |||
| Pneumonia | 20 (1.6) | 21 (1.6) | 1.00 (0.54 – 1.84) |
| Meningitis/encephalitis | 1 (0.1) | 2 (0.2) | 0.51 (0.05 – 5.62) |
| UTI | 1 (0.1) | 2 (0.2) | 0.50 (0.55 – 5.52) |
| Bronchiolitis | 6 (0.5) | 18 (1.4) | 0.34 (0.14 – 0.86)g |
| Wheezing | 7 (0.6) | 3 (0.2) | 2.49 (0.64 – 9.64) |
| Pertussis-like syndrome | 3 (0.2) | 3 (0.2) | 1.04 (0.21 – 5.15) |
| Mortality | |||
| Mortality in the first 8 weeks | 29 (29.8) | 24 (24.5) | 1.23 (0.72 – 2.11) |
| In-hospital mortality | 30 (48.1) | 26 (40.7) | 1.13 (0.67 – 1.91) |
| Overall 24-month mortality | 37 (2.6) | 29 (2.1) | 1.32 (0.81 – 2.15) |
| Infection-associated mortalityh | 17 (1.3) | 16 (1.2) | 1.13 (0.57 – 2.24) |
Abbreviations: LOS, late-onset sepsis; CoNS, coagulase-negative staphylococci; NEC; necrotizing enterocolitis; ROP, retinopathy of prematurity; UTI, urinary tract infection.
Adjusted for hospital and weight category (≤1000 g, 1001–1500 g, 1501–2000 g), considering follow up from day 3 to day 56 or death for all neonatal outcomes for all infants.
p=0.08
Cumulative incidences/100 cases and cumulative incidence ratio (95% CI).
Klebsiella (4 and 3), E. coli (3 and 3), Enterobacter (1 and 2), Pseudomona (0 and 2), Acinetobacter (0 and 1) and Empedobacter (0 and 1) among BLF and placebo groups respectively.
Enterococcus (3 and 1), Staphylococcus aureus (1 and 2) and Streptococcus (1 and 0) among BLF and placebo groups respectively.
IR/104, Incidence rate per 10,000 child-days.
p=0.02
Mortality associated with sepsis and pneumonia, excluding early-onset sepsis. No infant died of meningitis/encephalitis, UTI or diarrhea.