%0 Journal Article
%T Probiotics, Prebiotics, Lactoferrin, and Combination Products for Prevention of Mortality and Morbidity in Preterm Infants: A Systematic Review and Network Meta-Analysis.
%A Wang Y
%A Florez ID
%A Morgan RL
%A Foroutan F
%A Chang Y
%A Crandon HN
%A Zeraatkar D
%A Bala MM
%A Mao RQ
%A Tao B
%A Shahid S
%A Wang X
%A Beyene J
%A Offringa M
%A Sherman PM
%A El Gouhary E
%A Guyatt GH
%A Sadeghirad B
%J JAMA Pediatr
%V 177
%N 11
%D 2023 11 1
%M 37782505
%F 26.796
%R 10.1001/jamapediatrics.2023.3849
%X Modulation of intestinal microbiome by administering probiotics, prebiotics, or both may prevent morbidity and mortality in premature infants.<BR>To assess the comparative effectiveness of alternative prophylactic strategies through a network meta-analysis (NMA) of randomized clinical trials.<BR>MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, and Google Scholar from inception until May 10, 2023.<BR>Eligible trials tested probiotics, prebiotics, lactoferrin, and combination products for prevention of morbidity or mortality in preterm infants.<BR>A frequentist random-effects model was used for the NMA, and the certainty of evidence and inferences regarding relative effectiveness were assessed using the GRADE approach.<BR>All-cause mortality, severe necrotizing enterocolitis, culture-proven sepsis, feeding intolerance, time to reach full enteral feeding, and duration of hospitalization.<BR>A total of 106 trials involving 25 840 preterm infants were included. Only multiple-strain probiotics were associated with reduced all-cause mortality compared with placebo (risk ratio [RR], 0.69; 95% CI, 0.56 to 0.86; risk difference [RD], -1.7%; 95% CI, -2.4% to -0.8%). Multiple-strain probiotics alone (vs placebo: RR, 0.38; 95% CI, 0.30 to 0.50; RD, -3.7%; 95% CI, -4.1% to -2.9%) or in combination with oligosaccharides (vs placebo: RR, 0.13; 95% CI, 0.05 to 0.37; RD, -5.1%; 95% CI, -5.6% to -3.7%) were among the most effective interventions reducing severe necrotizing enterocolitis. Single-strain probiotics in combination with lactoferrin (vs placebo RR, 0.33; 95% CI, 0.14 to 0.78; RD, -10.7%; 95% CI, -13.7% to -3.5%) were the most effective intervention for reducing sepsis. Multiple-strain probiotics alone (RR, 0.61; 95% CI, 0.46 to 0.80; RD, -10.0%; 95% CI, -13.9% to -5.1%) or in combination with oligosaccharides (RR, 0.45; 95% CI, 0.29 to 0.67; RD, -14.1%; 95% CI, -18.3% to -8.5%) and single-strain probiotics (RR, 0.61; 95% CI, 0.51 to 0.72; RD, -10.0%; 95% CI, -12.6% to -7.2%) proved of best effectiveness in reduction of feeding intolerance vs placebo. Single-strain probiotics (MD, -1.94 days; 95% CI, -2.96 to -0.92) and multistrain probiotics (MD, -2.03 days; 95% CI, -3.04 to -1.02) proved the most effective in reducing the time to reach full enteral feeding compared with placebo. Only single-strain and multistrain probiotics were associated with greater effectiveness compared with placebo in reducing duration of hospitalization (MD, -3.31 days; 95% CI, -5.05 to -1.58; and MD, -2.20 days; 95% CI, -4.08 to -0.31, respectively).<BR>In this systematic review and NMA, moderate- to high-certainty evidence demonstrated an association between multistrain probiotics and reduction in all-cause mortality; these interventions were also associated with the best effectiveness for other key outcomes. Combination products, including single- and multiple-strain probiotics combined with prebiotics or lactoferrin, were associated with the largest reduction in morbidity and mortality.