Appendix 1. 'Risk of bias' tool

1. Sequence generation (checking for possible selection bias). Was the allocation sequence adequately generated?

For each included study, we categorised the method used to generate the allocation sequence as:

• low risk (any truly random process, e.g. random number table; computer random number generator);

• high risk (any non‐random process, e.g. odd or even date of birth; hospital or clinic record number); or

• unclear risk.

2. Allocation concealment (checking for possible selection bias). Was allocation adequately concealed?

For each included study, we categorised the method used to conceal the allocation sequence as:

• low risk (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);

• high risk (open random allocation; unsealed or non‐opaque envelopes, alternation; date of birth); or

• unclear risk.

3. Blinding of participants and personnel (checking for possible performance bias). Was knowledge of the allocated intervention adequately prevented during the study?

For each included study, we categorised the methods used to blind study participants and personnel from knowledge of which intervention a participant received. Blinding was assessed separately for different outcomes or class of outcomes. We categorised the methods as:

• low risk, high risk or unclear risk for participants; and

• low risk, high risk or unclear risk for personnel.

4. Blinding of outcome assessment (checking for possible detection bias). Was knowledge of the allocated intervention adequately prevented at the time of outcome assessment?

For each included study, we categorised the methods used to blind outcome assessment. Blinding was assessed separately for different outcomes or class of outcomes. We categorised the methods as:

• low risk for outcome assessors;

• high risk for outcome assessors; or

• unclear risk for outcome assessors.

5. Incomplete outcome data (checking for possible attrition bias through withdrawals, dropouts, protocol deviations). Were incomplete outcome data adequately addressed?

For each included study and for each outcome, we described the completeness of data including attrition and exclusions from the analysis. We noted whether attrition and exclusions were reported, the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. Where sufficient information was reported or supplied by the trial authors, we re‐included missing data in the analyses. We categorised the methods as:

• low risk (< 20% missing data);

• high risk (≥ 20% missing data); or

• unclear risk.

6. Selective reporting bias. Are reports of the study free of suggestion of selective outcome reporting?

For each included study, we described how we investigated the possibility of selective outcome reporting bias and what we found. For studies in which study protocols were published in advance, we compared prespecified outcomes versus outcomes eventually reported in the published results. If the study protocol was not published in advance, we contacted study authors to gain access to the study protocol. We assessed the methods as:

• low risk (where it is clear that all of the study's prespecified outcomes and all expected outcomes of interest to the review have been reported);

• high risk (where not all the study's prespecified outcomes have been reported; one or more reported primary outcomes were not prespecified outcomes of interest and are reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported); or

• unclear risk.

7. Other sources of bias. Was the study apparently free of other problems that could put it at a high risk of bias?

For each included study, we described any important concerns we had about other possible sources of bias (for example, whether there was a potential source of bias related to the specific study design or whether the trial was stopped early due to some data‐dependent process). We assessed whether each study was free of other problems that could put it at risk of bias as:

• low risk;

• high risk;

• unclear risk.

If needed, we explored the impact of the level of bias through undertaking sensitivity analyses.

Appendix 2. GRADE

GRADE considers that evidence from randomised controlled trials is high quality, but that assessment may be downgraded based on consideration of any of five areas.

• Design (risk of bias).

• Consistency across studies.

• Directness of the evidence.

• Precision of estimates.

• Presence of publication bias.

This results in an assessment of the quality of a body of evidence in one of four grades.

1. High: we are very confident that the true effect lies close to that of the estimate of the effect.

2. Moderate: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

3. Low: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.

4. Very low: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Appendix 3. Electronic search strategy

Milk or formula search strategies

MEDLINE(R) and Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations and Daily

via Ovid (ovidsp.ovid.com)

1946 to 28 September 2018

Searched on: 1 October 2018

Records retrieved: 2537

1 exp Infant, Premature/ (51111)

2 exp Infant, Low Birth Weight/ (31685)

3 Premature Birth/ (11274)

4 (preterm or preterms or pre term or pre terms).ti,ab. (65706)

5 (preemie$ or premie or premies).ti,ab. (150)

6 prematur$.ti,ab. (131848)

7 (low adj3 (birthweight$ or birth weight$)).ti,ab. (31674)

8 (lbw or vlbw or elbw).ti,ab. (7485)

9 or/1‐8 (219368)

10 Infant Formula/ (3933)

11 formula$.ti,ab. (277253)

12 10 or 11 (278195)

13 9 and 12 (4365)

14 Milk, Human/ (17874)

15 Milk Banks/ (422)

16 (breastmilk$ or milk$).ti,ab. (116057)

17 or/14‐16 (119637)

18 9 and 17 (5756)

19 13 or 18 (8298)

20 randomized controlled trial.pt. (468895)

21 controlled clinical trial.pt. (92668)

22 randomized.ab. (422504)

23 placebo.ab. (192035)

24 drug therapy.fs. (2050146)

25 randomly.ab. (297839)

26 trial.ab. (440111)

27 groups.ab. (1836626)

28 or/20‐27 (4287670)

29 exp animals/ not humans/ (4499073)

30 28 not 29 (3706627)

31 19 and 30 (2537)

Embase

via Ovid (ovidsp.ovid.com)

1974 to 28 September 2018

Searched on: 1 October 2018

Records retrieved: 2947

1 prematurity/ (89190)

2 exp low birth weight/ (54784)

3 (preterm or preterms or pre term or pre terms).ti,ab. (90499)

4 (preemie$ or premie or premies).ti,ab. (224)

5 prematur$.ti,ab. (168322)

6 (low adj3 (birthweight$ or birth weight$)).ti,ab. (39175)

7 (lbw or vlbw or elbw).ti,ab. (10058)

8 1 or 2 or 3 or 4 or 5 or 6 or 7 (288691)

9 artificial milk/ (12531)

10 formula$.ti,ab. (344884)

11 9 or 10 (348727)

12 8 and 11 (6305)

13 breast milk/ (24259)

14 milk bank/ (110)

15 (breastmilk$ or milk$).ti,ab. (125678)

16 or/13‐15 (130935)

17 8 and 16 (7348)

18 12 or 17 (11077)

19 randomized controlled trial/ (513947)

20 controlled clinical trial/ (457995)

21 Random$.ti,ab. (1330412)

22 randomization/ (79416)

23 intermethod comparison/ (238126)

24 placebo.ti,ab. (275734)

25 (compare or compared or comparison).ti. (459192)

26 ((evaluated or evaluate or evaluating or assessed or assess) and (compare or compared or comparing or comparison)).ab. (1792923)

27 (open adj label).ti,ab. (65919)

28 ((double or single or doubly or singly) adj (blind or blinded or blindly)).ti,ab. (209762)

29 double blind procedure/ (153064)

30 parallel group$1.ti,ab. (22153)

31 (crossover or cross over).ti,ab. (93846)

32 ((assign$ or match or matched or allocation) adj5 (alternate or group$1 or intervention$1 or patient$1 or subject$1 or participant$1)).ti,ab. (287519)

33 (assigned or allocated).ti,ab. (337932)

34 (controlled adj7 (study or design or trial)).ti,ab. (299382)

35 (volunteer or volunteers).ti,ab. (225794)

36 human experiment/ (413882)

37 trial.ti. (251429)

38 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 (4358702)

39 (rat or rats or mouse or mice or rodent or rodents or swine or porcine or murine or sheep or lamb or lambs or ewe or ewes or pig or pigs or piglet or piglets or sow or sows or rabbit or rabbits or cat or cats or kitten or kittens or dog or dogs or puppy or puppies or monkey or monkeys or horse or horses or foal or foals or equine or calf or calves or cattle or heifer or heifers or hamster or hamsters or chicken or chickens or livestock or panda or pandas or buffalo$ or baboon$).ti. (2142499)

40 38 not 39 (4076303)

41 18 and 40 (2947)

Maternity & Infant Care Database (MIDIRS)

via Ovid (ovidsp.ovid.com)

1971 to August 2018

Searched on: 1 October 2018

Records retrieved: 2336

1 (preterm or preterms or pre term or pre terms).mp. (24799)

2 (preemie$ or premie or premies).mp. (52)

3 prematur$.mp. (22144)

4 (low adj3 (birthweight$ or birth weight$)).mp. (11391)

5 (lbw or vlbw or elbw).mp. (2911)

6 1 or 2 or 3 or 4 or 5 (39839)

7 formula$.mp. (6112)

8 6 and 7 (1052)

9 (breastmilk$ or milk$).mp. (8742)

10 6 and 9 (1857)

11 8 or 10 (2336)

CINAHL Complete

via Ebsco (www.ebsco.com/products/research-databases)

Inception to 20180919

Searched on: 21 September 2018

Records retrieved: 2770

S1 (MH "Infant, Premature") 18,840

S2 (MH "Infant, Low Birth Weight+") 11,604

S3 TI ( preterm or preterms or pre‐term or pre‐terms ) OR AB ( preterm or preterms or pre‐term or pre‐terms) 24,932

S4 TI ( preemie* or premie or premies ) OR AB ( preemie* or premie or premies ) 254

S5 TI prematur* OR AB prematur* 23,780

S6 TI ( low N3 (birthweight* or birth‐weight*) ) OR AB ( low N3 (birthweight* or birth‐weight*) ) 9,526

S7 TI ( lbw or vlbw or elbw ) OR AB ( lbw or vlbw or elbw ) 2,560

S8 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 57,624

S9 (MH "Infant Formula") 3,535

S10 TI formula* OR AB formula* 36,707

S11 S9 OR S10 38,406

S12 S8 AND S11 1,355

S13 (MH "Milk, Human+") 4,886

S14 (MH "Milk Banks") 434

S15 TI ( breastmilk* or milk* ) OR AB ( breastmilk* or milk* ) 13,874

S16 S13 OR S14 OR S15 15,557

S17 S8 AND S16 2,069

S18 S12 OR S17 2,817

S19 TI (rat or rats or mouse or mice or hamster or hamsters or dog or dogs or cat or cats or sheep or lamb or lambs or pig or pigs or baboon*) 64,810

S20 S18 not S19 2,770

CENTRAL

via Wiley (www.wiley.com)

Issue 9 of 12, September 2018

Searched on: 1 October 2018

Records retrieved: 1875

#1 MeSH descriptor: [Infant, Premature] explode all trees 3387

#2 MeSH descriptor: [Infant, Low Birth Weight] explode all trees 2036

#3 MeSH descriptor: [Premature Birth] this term only 1028

#4 (preterm or preterms or pre next term or pre next terms):ti,ab,kw 10114

#5 (preemie* or premie or premies):ti,ab,kw 34

#6 prematur*:ti,ab,kw 18080

#7 (low near/3 (birthweight* or birth next weight*)):ti,ab,kw 4473

#8 (lbw or vlbw or elbw):ti,ab,kw 1377

#9 {OR #1‐#8} 23404

#10 MeSH descriptor: [Infant Formula] this term only 531

#11 formula*:ti,ab,kw 30754

#12 #10 or #11 30754

#13 #9 and #12 1252

#14 MeSH descriptor: [Milk, Human] this term only 926

#15 MeSH descriptor: [Milk Banks] this term only 5

#16 (breastmilk* or milk*):ti,ab,kw 8086

#17 #14 or #15 or #16 8086

#18 #9 and #17 1339

#19 #13 or #18 2017

#20 #13 or #18 in Trials 1875

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