Methods

1. Blinding of randomisation: Can't tell
2. Blinding of intervention: No
3. Complete follow up: Yes
4. Blinding of outcome measurement: No

Participants

68 preterm infants: 28‐36 weeks in two strata.
Exclusions: multiple births, congenital abnormalities and chromosomal disorders, congenital infection. Growth restricted infants (<5th percentile) may also have been excluded.
Department of Child Health, University Hospital of Wales, Cardiff.
1972‐ 73.

Interventions

Term formula milk (N= 34 ) versus unfortified, Pasteurised donor breast milk (N= 34). Assigned from birth for 2 months.

Outcomes

Rates of weight gain, increase in head circumference and length from birth until 1 month and from 1 month until 2 months.

Notes

Infants of mothers who wished to breastfeed were initially given expressed breast milk if unable to feed naturally. There were only two such infants, their feeding group was not specified and the results for these infants are not presented separately in the paper. Given that this applies to only two out of 68 infants, we have included this study in the review.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

1. Blinding of randomisation: Yes
2. Blinding of intervention: No
3. Complete follow up: No
4. Blinding of outcome measurement: Can't tell

Participants

67 preterm infants (27‐33 weeks).
Birth weight <1600g. Excluded if "congenital anomaly or major disease".
Dept of Pediatrics, Duke University, USA.
1980‐ 82.

Interventions

Term formula milk (N= 26) versus unfortified, Pasteurised donor breast milk (N=41). Feeds were assigned until the infant reached a weight of 1800g or until withdrawn from the study because of feed intolerance or necrotising enterocolitis.

Outcomes

Time to regain birth weight.
Mean daily gain in weight, length and head circumference, from regaining birth weight until reaching 1800g.
Data on adverse events can be determined although these were not primary end‐points of the study.

Notes

Although the report gave information on adverse outcomes, the seven affected infants were withdrawn from the study and not included in the analyses of growth rates. Therefore, growth data are reported for 20 infants in each arm of the trial.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

1. Blinding of randomisation: Yes
2. Blinding of intervention: No
3. Complete follow up: Yes
4. Blinding of outcome measurement: Can't tell

Participants

159 infants of birth weight <1850g. Stratified by birth weight <1200g and 1201‐ 1850g. Infants with congenital abnormalities excluded. Infants with intra‐uterine growth restriction not excluded.
Study undertaken in the early 1980's in neonatal units in Anglia region of the UK.

Interventions

Preterm formula milk (N= 76) versus donor (mainly "drip") breast milk (N= 83). The formula was intended to be delivered at 180 ml/kg/day versus the breast milk at 200 ml/kg/day. Feeds were assigned until the infant reached a weight of 2000 g or until discharge from the neonatal unit.

Outcomes

Short term outcomes:
Time to regain birth weight (62 infants). Rates of change in weight (58 infants), crown‐heel length (26 infants) and head circumference (48 infants) from the point of regained birth weight until discharge from the neonatal unit or reaching a weight of 2000 g.
Incidence of necrotising enterocolitis‐ suspected and confirmed reported on complete cohort of 159 infants.
Longer term outcomes:
Validated neurological assessment at 18 months in 122 (85%) of surviving infants.
Bayley mental development index and psychomotor development index at 18 months, corrected for preterm gestation, in 114 (94%) of surviving infants suitable for the assessment.
Growth performance in surviving infants (weight, length and head circumference) at 9 months (110 infants), 18 months (136 infants), and 7.5‐ 8 years (130 infants) post term.

Notes

The first "interim" report provided data on short term growth outcomes in a pre‐defined subset of the total cohort recruited.
Follow‐up at 18 months was achieved for more than 80% of surviving infants. Developmental assessments (Bayley Psychomotor and Mental Development Indices) at 18 months post term were reported for 114 of the 159 children originally enrolled in the study. 16 children had died and 7 had been lost to follow‐up. 12 surviving children had cerebral palsy affecting fine motor skills, and these children were not assessed. A further 10 children were not assessed due to severe visual or hearing impairment or because follow up data were obtained by telephone for geographical reasons.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

1. Blinding of randomisation: Yes
2. Blinding of intervention: No
3. Complete follow up: Yes
4. Blinding of outcome measurement: Can't tell

Participants

343 infants of birth weight <1850 g. Stratified by birth weight <1200g and 1201‐ 1850g. Infants with congenital abnormalities excluded. Infants with intra‐uterine growth restriction not excluded.
Study undertaken in the early 1980's in neonatal units in Anglia region of the UK.

Interventions

Preterm formula milk (N= 173) versus banked donor breast milk (N= 170 ) as a supplement to the mother's own breast milk.

Outcomes

Short term outcomes:Time to regain birth weight (132 infants). Rates of change in weight (115 infants), crown‐heel length (45 infants) and head circumference (97 infants) from the point of regained birth weight until discharge from the neonatal unit or reaching a weight of 2000 g.
Incidence of necrotising enterocolitis‐ suspected and confirmed reported on complete cohort of 343 infants.
Longer term outcomes: Validated neurological assessment, at 18 months, in 278 (88%) of surviving infants.
Bayley mental development index and psychomotor development index at 18 months, corrected for preterm gestation, in 273 (96%) of surviving infants suitable for the assessment.
Growth performance in surviving infants (weight, length and head circumference) at 9 months (259 infants), 18 months (302 infants), and 7.5‐ 8 years (290 infants) post term.

Notes

The first "interim" report provided data on short term growth outcomes in a pre‐defined subset of the total cohort recruited.
Developmental assessments (Bayley Psychomotor and Mental Development Indices) at 18 months post term were reported for 273 of 343 children originally enrolled in the study. 29 children had died and 12 lost to follow‐up. 24 surviving children had cerebral palsy affecting fine motor skills, and these children were not assessed. A further 5 children were not assessed due to severe visual or hearing impairment or because follow up data were obtained by telephone for geographical reasons.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

1. Blinding of randomisation: Yes (only for formula milk groups)
2. Blinding of intervention: No
3. Complete follow up: Yes
4. Blinding of outcome measurement: Can't tell

Participants

106 preterm infants of birth weight less than 2100g, but between 10th and 90th centiles for birth weight. Infants excluded if evidence of "physical abnormality or obvious disease". Premature Unit, Helsinki University Children's Hospital. 1972 to 1975.

Interventions

Term formula milk (N= 84) versus unfortified donor breast milk (N= 22). Feeds continued until a weight of 2.4 kg was attained or until infants were withdrawn from the study because of a "medical complication".

Outcomes

Time, from birth, to regain birth weight. Rate of weight change from birth and from point of regained birth weight.

Notes

Allocation to the formula milks was undertaken using a random sequence of four numbers, but every fifth infant was allocated to receive term human milk, so allocation concealment may have been sub‐optimal.
Donor breast milk was given at a 170 mL/kg/day, compared with formula at 150 mL/kg/day, "in order to achieve equivalent calorie inputs". Donor breast milk fed infants were also given supplemental vitamins.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

1. Blinding of randomisation: Yes
2. Blinding of intervention: No
3. Complete follow up: Yes
4. Blinding of outcome measurement: Can't tell

Participants

173 infants of gestational age less than 30 weeks', whose mothers intended to breastfeed but whose own milk became insufficient from birth until 90 days of age or hospital discharge.
North Shore University Hospital, New York, USA. 2000 to 2003.

Interventions

Preterm formula milk (N= 81) versus unfortified donor breast milk (N=92) given as a supplement to maternal breast milk.

Outcomes

Incidence of late‐onset invasive infection and/or necrotising enterocolitis, duration of hospitalisation and growth during the study period (weight gain, head circumference increment, and length increment).

Notes

Participating infants received small quantities (20 ml per kg per day) of their own mother's milk during the first week after birth and continued for 3‐5 days before the volume was advanced. Milk intake was increased by 20 ml per kg per day to 100 ml per kg at which time human milk fortifier was added. Subsequently the volume of fortified human milk was advanced by 20 m//kg per day until 160 mL/kg per day was achieved. If no mother's milk was available and the baby was assigned to donor breast milk then a similar advancement and fortification protocol was followed. For all infants, adjustments in milk intake between 160 and 200 mL/kg per day were recommended to ensure an average weekly weight gain of at least 15 g/kg per day.
17 enrolled infants were switched from donor breast milk to preterm formula because of poor weight gain but all of the analyses were by intention to treat. However, 7 infants who were never fed (3 in the donor milk group, 4 in the formula group) were excluded from the analyses.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

1. Blinding of randomisation: Can't tell
2. Blinding of intervention: No
3. Complete follow up: Yes
4. Blinding of outcome measurement: Can't tell

Participants

20 preterm or low birth weight infants; all infants to be "physically normal with no further signs of disease; no further details published.
Department of Paediatrics, University Medical School, Pecs, Hungary,
prior to 1980.

Interventions

Term formula milk (N= 10) versus donor breast milk (N= 10) for at least four weeks from birth.

Outcomes

Time, from birth, to regain birth weight (mean but no standard deviation reported).
Mean weight change from birth and from regaining birth weight calculable from graph but no SD.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

1. Blinding of randomisation: Yes
2. Blinding of intervention: No
3. Complete follow up: Yes
4. Blinding of outcome measurement: Can't tell for growth assessments, yes for Brazelton score.

Participants

81 very low birth weight infants, excluding infants with "any significant illness" or those who required ventilatory support at day 10.
Parklands memorial Hospital, Dallas, USA. Early 1980s.

Interventions

Preterm formula milk (N= 44) versus donor breast milk (N= 37). The donor breast milk was not Pasteurised. Feeds were allocated on the tenth day of life, and continued until the infant reached a weight of 2000 g or until withdrawn from the study because of "any illness requiring intravenous infusion of fat or protein".

Outcomes

Mean daily rates of change in weight, crown‐heel length and head circumference from the tenth until the thirtieth day of life were reported.

Notes

The feeds were not allocated until the tenth day after birth in order to avoid the use of protein‐enriched formula "when active growth was unlikely". In the first nine days of life the infants received a term formula or maternal expressed breast milk (if available). Although the report gave information on adverse outcomes, including necrotising enterocolitis, the five affected infants were withdrawn from the study and not included in the analyses of growth rates.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate