Neonatal Updates: Recent Nutritional Publications part 2.

Breast Milk and how to use it

Colacci M, et al. Growth and Development in Extremely Low Birth Weight Infants After the Introduction of Exclusive Human Milk Feedings. American journal of perinatology. 2016(EFirst). This is a before and after study from a center where they changed to “exclusive” human milk feedings. About 40 babies before and after the switch are included, all with a birth weight under 1 kg. In fact the group with “exclusive” human milk feeds were exclusive for at least 4 weeks and then had bovine products introduced when they reached 1500 g or 34 weeks, whichever occurred first. Why that was done is not described, maybe it was a cost issue, human milk based fortifier was used up until the switch over (or at least it was started when the babies were receiving 100 mL/kg/day of milk). The introduction of bovine fortifier (or cows milk based formula) may have been because as the babies get bigger it becomes more expensive to provide human milk-based products. More than 90% of the babies in each group received some maternal breast milk, but most (about 80%) got at least some formula.

The authors report growth outcomes, some clinical short-term outcomes, and long-term neurologic and developmental outcomes. Macronutrient intakes were not different between groups, and were not very good during the first week at least, 3 g/kg/d of protein, and 82 kcal/kg/d, feeds were started on average on the 4th day of life, on average. Of interest, the incidence of NEC was identical between the groups, at 10%.Growth outcomes were also not different, with the loss of about 1.5 weight z-scores between birth and discharge, finally all the scores on developmental assessment were just about identical between the groups.

Belfort MB, et al. Breast Milk Feeding, Brain Development, and Neurocognitive Outcomes: A 7-Year Longitudinal Study in Infants Born at Less Than 30 Weeks’ Gestation. The Journal of pediatrics. 2016. This is a cohort study from Melbourne of babies under 30 weeks gestation, for whom donor breast milk was not available. They analyzed breast milk intake during the first 28 days of life, and correlated the number of days that more than 50% of the intake was breast milk, and the daily breast milk intake, to outcomes at 2 years and 7 years and MRI brain volumes at term and at 7 years of age. 180 babies were in the study, and the more days you get more breast milk the more deep nuclear gray matter you have when you reach term.

At 7 years of age the babies who had more days with more than 50% breast milk had better performance on “IQ (0.5 points/d; 95% CI, 0.2-0.8), mathematics (0.5; 95% CI, 0.1-0.9), working memory (0.5; 95% CI, 0.1-0.9), and motor function (0.1; 95% CI, 0.0-0.2) tests.”

At 7 years of age the total brain size was somewhat bigger (about 2 cc for every day of breast milk >50%) which sounds like a lot to me, but it wasn’t significant when adjusted for covariates, in fact at 7 years none of the MRI volumes were significant after adjustment.

 Bharwani SK, et al. Systematic review and meta-analysis of human milk intake and retinopathy of prematurity: a significant update. J Perinatol. 2016. A systematic review and meta-analysis of observational studies of the effects of maternal milk (in this review studies were excluded if they were only examining the effects of donor milk, but 2 were included that used some maternal and some donor milk) on the development of RoP and of severe RoP. Despite the major limitations of these kinds of studies, and the difficulties in trying to meta-analyze them, there does seem to be a real association between receiving any amount of human milk and a reduced risk of retinopathy.

Rosas R, et al. Experimental study showed that adding fortifier and extra-hydrolysed proteins to preterm infant mothers’ milk increased osmolality. Acta Paediatrica. 2016. The authors here took breast milk from mothers who had delivered preterm and added a commercial fortifier (from Nestlé) at the usual concentration, recommended by the manufacturer, and then at a slightly higher concentration, and then with added oligopeptides at 2 different concentrations. They refrigerated the mixture and then measured the osmolality at intervals for 23 hours. Osmolality increased progressively, being around 296 for the unfortified breast milk, with standard fortification this increased immediately to 380 and then continued to increase more slowly up to about 450. With higher concentrations of fortifier, the immediate increase was to over 450, with not much difference when protein was added, and then continued to increase to about 530.

The composition of the Nestlé fortifier is somewhat different to the Enfamil and Similac that we use in Canada. There is an error in the publication, but I think that the fortifier is supposed to have 400 kcal/100 g (and not 4 as it says in the table!), the additional calories are mostly as carbohydrate (66g/100g) with very little fat (0.4g/100g). When you add the fortifier at the recommended concentration you supposedly add 20 kcal per 100 mL of milk, 1 g of protein, and 3.5 g of carbohydrate, and 0.02 g of fat; I can’t make that add up to 20 kcal, I think it is more like 18 kcal. Enfamil powdered fortifier in contrast has very little carbohydrate, so when you use at the recommended concentration you add 1 g of fat, 1.1 g of protein and almost no carbohydrate, per 100 ml. The Similac fortifier in contrast has a bit less protein (1g additional per 100 mL of breast milk) and 1.8 g of carbohydrate and about 1/3 g of fat. The Similac carbohydrates are “corn-syrup  solids” which is mostly glucose, whereas in the Nestlé FM 85 they are malodextrins, which are less osmotically active.

You clearly can’t extrapolate these new data to the other fortifiers, or to using higher concentrations of the other fortifiers with or without added protein, how important these numbers are is difficult to know, but osmolality closest to human milk is probably best. Currently it looks like the Enfamil fortifier increases osmolality the least, by about 24 just after it is added, but what happens to that over the next 24 hours I don’t know.

McLeod G, et al. Comparing different methods of human breast milk fortification using measured v. assumed macronutrient composition to target reference growth: a randomised controlled trial. The British journal of nutrition. 2016;115(3):431-9.

In this randomized trial 40 infants under 30 weeks were assigned to either get standardized nutritional management, or an individualized approach which required a weekly analysis of  a pooled milk sample from that week, and then adjustment of the fortification to achieve, I think, between 3.8 and 4.4 g/kg/d of protein and between 545 and 629 kJ/kg/d (that’s 130 to 150 kcal/kg/d), I say “I think” because that is only mentioned in the introduction and not in the methods, where they say they planned to target the upper range of those recommendations.

The study required the analysis of over 1,800 samples of breast milk. An enormous work load for just 40 babies. However they didn’t achieve any increase in nutritional intakes in the intervention group, and intakes in the intervention group were well below the targets. The reason for which seems to be that they arbitrarily limited fortifiers to maximum allowable concentrations (Standard fortifier powder (Wyeth): maximum 4 g/100 ml;
protein supplement: maximum 0·5 g/100 ml; and an extra calorie supplement: maximum 3·0 g/100 ml) As a result, and with the low power of this small study, they showed no improvement in any growth outcome with the intervention. With almost identical nutritional intakes in the 2 groups, this is hardly surprising. There are a couple of other surprising things, fortification was not started at all until the babies were on full feeds, so not until 20 days of age on average. The babies were discharged a 38 weeks, and only weighed 2.3 to 2.5 kg on average at discharge.

I think this idea still has a lot of merit, whether it is viable with the workload involved is questionable, but targeting substantially higher protein intakes than these achieved here, will likely improve growth, and fat-free growth at discharge, individualizing the supplementation of breast milk should be further investigated, in similar RCTs, but aiming for over 4 g/kg/d of protein. Perhaps the best model would be to enroll and study only infants with sub-optimal growth; those who have good growth (not just weight gain) on standard fortification, and here are many, will probably have little benefit from individual adjustments of fortification.

About Keith Barrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
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