Prevention of necrotizing enterocolitis in premature infants – an updated review

Table 1 Summary of five randomized controlled trials of human milk feeding on the risk of necrotizing enterocolitis

Ref.	Yr	GA	BW	N	Study	Control	NEC ≥ stage II, %			Mortality, %			LOS, %
							Study	Control	P < 0.05	Study	Control	P < 0.05	Study	Control	P < 0.05
Corpeleijn et al[8]	2016	-	< 1500	373	DM	PF	9.3	8.9	No	13.7	12.7	No	36.6	34.7	No
Cristofalo et al[9]	2013	-	500-1250	53	HM	PF	3	21	Yes	0	8	No	55	79	No
Sullivan et al[10]	2010	-	500-1250	207	HM	Bovine milk	5.8	15.9	Yes	-	-	-	19	13	No
Schanler et al[11]	2005	< 30	-	243	DM	PF	6	9	No	3	3.6	No	1	4.8	No
Schanler et al[12]	1999	26-30	-	108	HM	PF	1.6	13	Yes	-	-	-	31	48	Yes

BW: Birth weight; LOS: Late onset sepsis; NEC: Necrotizing enterocolitis.

Table 2 Summary of 23 randomized controlled trials of probiotics on the risk of necrotizing enterocolitis

Ref.	Yr	GA	BW	N	Study	NEC ≥ stage II, %			Mortality, %			LOS, %
						Study	Control	P < 0.05	Study	Control	P < 0.05	Study	Control	P < 0.05
Shashidhar et al[25]	2017	-	750-1499	104	L. acidophilus, L. rhamnosus, B. longum and S. boulardii	4.1	12.5	No	1.9	5.7	No	-	-	-
Güney-Varal et al[26]	2017	≤ 32	≤ 1500	110	L. rhamnosus, L. casei, L. plantorum and B. animalis	0	10	Yes	1.4	22.5	Yes	17.1	35	No
Xu et al[27]	2016	30-37	1500-2500	125	S. boulardii	0	0	No	-	-	-	7.8	12.2	No
Hays et al[28]	2016	25-31	700-1600	199	B. lactis, B. longum, B. lactis and B. longum.	5.5	5.8	No	-	-	-	-	-	-
Costeloe et al[29]	2016	23-30	-	1310	B. breve	9.4	10.0	No	8.3	8.5	No	11.2	11.7	No
Patole et al[30]	2014	< 33	-	159	B. breve	0	1.3	No	0	0	No	22	16	No
Totsu et al[31]	2014	-	< 1500	283	B. bifidum	0	0	No	1.3	0	No	8.5	13.1	No
Benor et al[32]	2014	-	≤ 1500	58	L. acidophilus and B. lactis	4	18.2	No	1	2	NO	24	18	No
Oncel et al[33]	2014	≤ 32	≤ 1500	454	L. reuteri	4.0	5.0	No	7.5	10	No	6.5	12.5	Yes
Jacobs et al[34]	2013	< 32	< 1500	1099	B. infantis, S. thermophilus, and B. lactis	2.0	4.4	Yes	4.9	5.1	No	14.2	16.5	No
Serce et al[35]	2013	≤ 32	≤ 1500	208	S. boulardii	6.7	6.7	No	3.8	4.8	No	24.3	18.3	No
Fernández-Carrocera et al[36]	2013	-	< 1500	150	L. acidophilus, L. rhamnosus, L. casei, L. plantarum, B. infantis and S. thermophillus	8.0	16.0	No	1.3	9.3	No	-	-	-
Demirel et al[37]	2013	≤ 32	≤ 1500	271	S. boulardii	4.4	5.1	No	3.7	3.6	No	14.9	15.4	No
Rojas et al[38]	2012		≤ 2000	750	L. reuteri	2.4	4.0	No	5.9	7.4	No	9.1	10.6	No
Al-Hosni et al[39]	2012	-	501-1000	101	L. rhamnosus and B. infantis	6.0	7.8	No	6	7.8	No	26.0	31.4	No
Braga et al[40]	2011	-	750-1499	231	B. breve and L. casei	0	3.6	Yes	21.8	24.1	No	33.6	37.5	No
Sari et al[41]	2011	< 33	< 1500	221	L. sporogenes	6.5	9	No	2.7	3.6	No	26.4	23.4	No
Mihatsch et al[18]	2010	< 30	< 1500	183	B. lactis	2.2	4.5	No	2.2	1.1	No	-	-	-
Samanta et al[42]	2009	< 32	< 1500	274	B. infantis, B. bifidum, B. longum and L. acidophilus	5.5	15.8	Yes	4.4	14.7	Yes	14.3	19.5	Yes
Lin et al[43]	2008	< 34	< 1500	434	B. bifidum and L. acidophilus	1.8	6.5	Yes	0.9	4.1	No	19.8	11.5	No
Lin et al[44]	2005	-	< 1500	367	L. acidophilus and B. infantis	1.1	5.3	Yes	3.9	10.7	Yes	12.3	19.3	Yes
Bin-Nun et al[45]	2005	-	≤ 1500	145	B. infantis, S. thermophilus, and B. bifidus	4	16.4	Yes	0	20.5	Yes	-	-	-
Dani et al[46]	2002	< 33	< 1500	585	L. rhamnosus	1.4	2.8	No	-	-	-	4.7	4.1	No

BW: Birth weight; LOS: Late onset sepsis; NEC: Necrotizing enterocolitis.

Table 3 Summary of five randomized controlled trials of prophylactic antibiotics on the risk of necrotizing enterocolitis

Ref.	Yr	GA	BW	N	Study	NEC ≥ stage II, %			Mortality, %			LOS, (%)
						Study	Control	P < 0.05	Study	Control	P < 0.05	Study	Control	P < 0.05
Tagare et al[47]	2010	< 37	-	140	Amoxicillin clavulanic acid and amikacin	13.0	4.2	Yes	2.9	2.8	No	1.4	14.1	Yes
Kenyon et al[48]	2002	< 37	-	4809	Co-amoxiclav	1.6	0.3	Yes	5.7	6.2	No	6.2	7.9	No
Oei et al[49]	2001	≤ 32	-	43	Erythromycin	4.5	4.8	No	4.5	4.8	No	-	-	-
Siu et al[50]	1998	-	< 1500	140	Vancomycin	12.7	27.5	Yes	15.5	18.8	No	-	-	-
Owen et al[51]	1993	24-33	-	117	Ampicillin	14	3.5	Yes	6.8	12	No	3.4	10	No

BW: Birth weight; LOS: Late onset sepsis; NEC: Necrotizing enterocolitis.