NIHR Signal Fortified donor breast milk led to similar development for very-low-birthweight babies compared with formula milk

Published on 18 April 2017

Providing very-low-birthweight babies with fortified human donor breast milk made no difference to their developmental neurological outcomes at 18 months compared with giving formula.

This randomised controlled trial looked at 363 babies with birth weights of less than 1500g in neonatal intensive care units in Canada. When the mother’s own milk supply was limited, the babies were given either nutrient-enriched donor breast milk or formula developed for premature babies. There was no difference in their understanding, language, or ability to manipulate objects at 18 months.

This finding might help to reduce anxiety about providing formula in areas where donor breast milk is difficult to obtain. However, the research was focussed on developmental outcomes rather than potential effects of donor breast milk on other risks of prematurity, such as immunity or gastrointestinal complications.

This trial will continue to collect data to re-assess developmental outcomes when the children reach five years of age.

Fortified donor breast milk led to similar development for very-low-birthweight babies compared with formula milk

Why was this study needed?

Mothers of very-low-birthweight babies are often unable to produce enough breast milk. The babies’ feeds need to be supplemented to ensure they get enough nutrients and calories. This can be done with either formula milk made especially for premature babies, or with donor human milk. The donor milk is pasteurised and then enriched with added nutrients needed by premature babies.

There are 17 milk bank services in the UK, but access to donor milk varies depending on location and in some places it is hard to come by. The use of donor milk has been increasing each year; the total volume of donor milk in the UK increased from 5,000 litres in 2012 to 7,000 litres in 2014.  There is still uncertainty over the best milk, the optimum time for introducing milk feeds and the best feeding regimen.

The aim of this trial was to see if nutrient-enriched donor milk, compared to formula, improved the brain development of very-low-birthweight babies.

What did this study do?

This randomised controlled trial included 363 babies with birthweight less than 1500g, recruited from four neonatal intensive care units in Ontario, Canada. Babies were fed their own mother’s milk whenever possible. If not available, they were assigned to receive nutrient-enriched donor milk or formula as a supplement for 90 days or until hospital discharge.

Babies were tested for brain development at 18 months using the Bayley Scales of Infant and Toddler Development Third Edition. The test looks at three skill areas: attention, engagement and understanding (cognitive skills); responsiveness and engagement with language (language skills); and ability to grasp and manipulate objects (fine motor skills).

The study has several strengths. Families and assessors were unaware of which group a particular baby was in, and very few babies dropped out of the study before the 18 months assessment. Sufficient participants were recruited to detect a five point difference in the composite score, if it existed. This was considered a clinically important difference.

What did it find?

Human donor milk had no effect on any developmental outcomes at 18 months compared with formula:

  • There was no difference between groups in cognitive skills. Mean score was 92.9 in the donor milk group, versus 94.5 in the formula group (adjusted mean difference −2.0, 95% confidence interval [CI] −5.8 to 1.8).
  • There was no difference between groups in language skills. Mean score was 87.3 in the donor milk group, versus 90.3 in the formula group (adjusted mean difference −3.1, 95% CI −7.5 to 1.3).
  • There was no difference between groups in motor skills. Mean score 91.8 in the donor milk group, and 94.0 in the formula group (adjusted mean difference −3.7, 95% CI −7.4 to 0.09).

What does current guidance say on this issue?

The 2010 NICE guideline on donor milk banks only covers how such services should be run.  It does not consider when donor milk should be used, or what the benefits may be.

In July 2016 the British Association of Perinatal Medicine published a framework for practice on the use of donor human milk for newborn infants. It suggests that there is not currently enough evidence to make firm recommendations, and that individual networks and hospitals should continue to develop their own policies and procedures for the use of donor milk until further research is carried out. These policies vary around the country.

What are the implications?

The advantages of breast feeding are promoted across the NHS. If a mother’s own breast milk is in short supply, there may be reservations around the temporary use of alternatives and their potential effects. This study provides reassurance that either formula or human donor milk will give comparable developmental outcomes. 

This study looked only at developmental outcomes and there may well be different effects on other complications of prematurity and low birthweight. Maternal views will also be a key factor. 

The use of donor breast milk in the NHS is growing but access varies greatly around the country because of supply.

Citation and Funding

O'Connor DL, Gibbins S, Kiss A, et al. Effect of supplemental donor human milk compared with preterm formula on neurodevelopment of very low-birth-weight infants at 18 months: a randomized clinical trial. JAMA. 2016;316(18):1897-1905.

This project was funded by the Canadian Institutes of Health Research and the Ontario Ministry of Health and Long-Term Care.

Bibliography

British Association of Perinatal Medicine. The use of donor human expressed breast milk in newborn infants: a framework for practice. London: British Association of Perinatal Medicine; 2016.

NHS Choices. Breastfeeding your premature baby. London: Department of Health; updated 2016

NICE. Donor milk banks: service operation. CG93. London: National Institute for Health and Care Excellence; 2010.

Why was this study needed?

Mothers of very-low-birthweight babies are often unable to produce enough breast milk. The babies’ feeds need to be supplemented to ensure they get enough nutrients and calories. This can be done with either formula milk made especially for premature babies, or with donor human milk. The donor milk is pasteurised and then enriched with added nutrients needed by premature babies.

There are 17 milk bank services in the UK, but access to donor milk varies depending on location and in some places it is hard to come by. The use of donor milk has been increasing each year; the total volume of donor milk in the UK increased from 5,000 litres in 2012 to 7,000 litres in 2014.  There is still uncertainty over the best milk, the optimum time for introducing milk feeds and the best feeding regimen.

The aim of this trial was to see if nutrient-enriched donor milk, compared to formula, improved the brain development of very-low-birthweight babies.

What did this study do?

This randomised controlled trial included 363 babies with birthweight less than 1500g, recruited from four neonatal intensive care units in Ontario, Canada. Babies were fed their own mother’s milk whenever possible. If not available, they were assigned to receive nutrient-enriched donor milk or formula as a supplement for 90 days or until hospital discharge.

Babies were tested for brain development at 18 months using the Bayley Scales of Infant and Toddler Development Third Edition. The test looks at three skill areas: attention, engagement and understanding (cognitive skills); responsiveness and engagement with language (language skills); and ability to grasp and manipulate objects (fine motor skills).

The study has several strengths. Families and assessors were unaware of which group a particular baby was in, and very few babies dropped out of the study before the 18 months assessment. Sufficient participants were recruited to detect a five point difference in the composite score, if it existed. This was considered a clinically important difference.

What did it find?

Human donor milk had no effect on any developmental outcomes at 18 months compared with formula:

  • There was no difference between groups in cognitive skills. Mean score was 92.9 in the donor milk group, versus 94.5 in the formula group (adjusted mean difference −2.0, 95% confidence interval [CI] −5.8 to 1.8).
  • There was no difference between groups in language skills. Mean score was 87.3 in the donor milk group, versus 90.3 in the formula group (adjusted mean difference −3.1, 95% CI −7.5 to 1.3).
  • There was no difference between groups in motor skills. Mean score 91.8 in the donor milk group, and 94.0 in the formula group (adjusted mean difference −3.7, 95% CI −7.4 to 0.09).

What does current guidance say on this issue?

The 2010 NICE guideline on donor milk banks only covers how such services should be run.  It does not consider when donor milk should be used, or what the benefits may be.

In July 2016 the British Association of Perinatal Medicine published a framework for practice on the use of donor human milk for newborn infants. It suggests that there is not currently enough evidence to make firm recommendations, and that individual networks and hospitals should continue to develop their own policies and procedures for the use of donor milk until further research is carried out. These policies vary around the country.

What are the implications?

The advantages of breast feeding are promoted across the NHS. If a mother’s own breast milk is in short supply, there may be reservations around the temporary use of alternatives and their potential effects. This study provides reassurance that either formula or human donor milk will give comparable developmental outcomes. 

This study looked only at developmental outcomes and there may well be different effects on other complications of prematurity and low birthweight. Maternal views will also be a key factor. 

The use of donor breast milk in the NHS is growing but access varies greatly around the country because of supply.

Citation and Funding

O'Connor DL, Gibbins S, Kiss A, et al. Effect of supplemental donor human milk compared with preterm formula on neurodevelopment of very low-birth-weight infants at 18 months: a randomized clinical trial. JAMA. 2016;316(18):1897-1905.

This project was funded by the Canadian Institutes of Health Research and the Ontario Ministry of Health and Long-Term Care.

Bibliography

British Association of Perinatal Medicine. The use of donor human expressed breast milk in newborn infants: a framework for practice. London: British Association of Perinatal Medicine; 2016.

NHS Choices. Breastfeeding your premature baby. London: Department of Health; updated 2016

NICE. Donor milk banks: service operation. CG93. London: National Institute for Health and Care Excellence; 2010.

Effect of Supplemental Donor Human Milk Compared With Preterm Formula on Neurodevelopment of Very Low-Birth-Weight Infants at 18 Months: A Randomized Clinical Trial

Published on 9 November 2016

O'Connor, D. L.,Gibbins, S.,Kiss, A.,Bando, N.,Brennan-Donnan, J.,Ng, E.,Campbell, D. M.,Vaz, S.,Fusch, C.,Asztalos, E.,Church, P.,Kelly, E.,Ly, L.,Daneman, A.,Unger, S.

Jama Volume 316 Issue 18 , 2016

For many very low-birth-weight (VLBW) infants, there is insufficient mother's milk, and a supplement of pasteurized donor human milk or preterm formula is required. Awareness of the benefits of mother's milk has led to an increase in use of donor milk, despite limited data evaluating its efficacy. To determine if nutrient-enriched donor milk compared with formula, as a supplement to mother's milk, reduces neonatal morbidity, supports growth, and improves neurodevelopment in VLBW infants. In this pragmatic, double-blind, randomized trial, VLBW infants were recruited from 4 neonatal units in Ontario, Canada, within 96 hours of birth between October 2010 and December 2012. Follow-up was completed in July 2015. Infants were fed either donor milk or formula for 90 days or to discharge when mother's milk was unavailable. The primary outcome was the cognitive composite score on the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 18 months' corrected age (standardized mean, 100 [SD, 15]; minimal clinically important difference, 5 points). Secondary outcomes included Bayley-III language and motor composite scores, growth, and a dichotomous mortality and morbidity index. Of 840 eligible infants, 363 (43.2%) were randomized (181 to donor milk and 182 to preterm formula); of survivors, 299 (92%) had neurodevelopment assessed. Mean birth weight and gestational age of infants was 996 (SD, 272) g and 27.7 (2.6) weeks, respectively, and 195 (53.7%) were male. No statistically significant differences in mean Bayley-III cognitive composite score (adjusted scores, 92.9 in donor milk group vs 94.5 in formula group; fully adjusted mean difference, -2.0 [95% CI, -5.8 to 1.8]), language composite score (adjusted scores, 87.3 in donor milk group vs 90.3 in formula group; fully adjusted mean difference, -3.1 [95% CI, -7.5 to 1.3]), or motor composite score (adjusted scores, 91.8 in donor milk group vs 94.0 in formula group; fully adjusted mean difference, -3.7 [95% CI, -7.4 to 0.09]) were observed between groups. There was no statistically significant difference in infants positive for the mortality and morbidity index (43% in donor milk group, 40% in formula group) or changes in growth z scores. Among VLBW infants, use of supplemental donor milk compared with formula did not improve neurodevelopment at 18 months' corrected age. If donor milk is used in settings with high provision of mother's milk, this outcome should not be considered a treatment goal. isrctn.org Identifier: ISRCTN35317141.

The Bayley-III tests measure the development of infants and toddlers aged 1-42 months by asking them to complete a series of tasks. There are three sets of scores taken from the tests – cognitive, language and motor. The cognitive score reflects attention, engagement and understanding. The language score assesses understanding and expression of language. The motor score looks at both fine and gross motor skills, such as grasping, stacking blocks, sitting and climbing stairs. Completed tasks are scored, and the scores are converted to composite scores. These composite scores are used to compare a child’s progress against average scores taken from typically developing children of the same age.A difference of 5 points is seen as clinically important.

Expert commentary

Whether to make up the shortfall in mother’s own milk in extremely preterm infants with human pasteurised donor milk or preterm formula is a hotly debated topic as the evidence for the use of either is inconclusive and out of date. Donor milk is expensive and lower in nutrient content but may reduce the occurrence of severe intestinal inflammation called necrotising enterocolitis. This paper, showing no impact on later development of preterm infants fed bovine nutrient fortified donor milk versus formula, adds to the emerging evidence questioning the routine use of donor milk. Further adequately powered studies on outcomes such as necrotising enterocolitis and cost-benefit analyses are needed before recommendations can be made for clinical practice.

Dr Sabita Uthaya, Clinical Senior Lecturer and Consultant in Neonatal Medicine, Chelsea and Westminster Hospital / Imperial College London

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