Maternal breast milk is what we should be giving to every preterm infant as much as possible. But we know that there are cases of transmission of cytomegalovirus (CMV) and reports of transmission of other pathogens to babies from breast milk. Transmission of CMV is probably very common, with some reports stating that as many as 37% of extremely low birth weight infants of seropositive mothers may acquire the virus from mothers milk.
I introduced universal freezing of breast milk (in 2001 I think) to our NICU when I was at the Royal Victoria Hospital following 2 serious cases of breast milk acquired CMV disease, we did that to try and reduce CMV transmission, but with the full knowledge that the evidence base was limited.
An overview of the literature I think shows that not much has changed since then. CMV acquisition by extremely preterm infants from maternal breast milk is common, most cases are asymptomatic, but there is an increase in BPD among babies who acquire CMV postnatally and there are occasional serious infections with hepatic dysfunction, persistent thrombocytopenia and pneumonitis. The most serious complications appear to be in the most immature infants, and in those who already have some liver or pulmonary injury. I reviewed some of the recent studies last year. Long term follow-up doesn’t show much neurodevelopmental impact, and also does not reveal an increase in deafness.
Freezing breast milk reduces CMV activity in breast milk, even 3 hours of freezing has an effect, but 72 is probably preferable, and, after freezing many samples will no longer contain viable, culturable CMV, and others have reduced activity.
However, there is no good prospective evidence that this reduces CMV acquisition, or prevents serious disease. It seems likely that if you reduce the viral load there will be fewer cases, and fewer cases of symptomatic disease, but that is not proven, and it may be that the overall reduction in viral viability is not enough to prevent transmission.
Also, a policy that all breast milk will be frozen prior to giving it to the babies will have an impact especially during the first few days of life, when a victorious mother arrives in the NICU with 3 mL of colostrum. If we then freeze and later re-thaw the precious liquid that will delay the infant receiving all the goodies, and it might also potentially harm transmission of infection protecting components even while reducing CMV load.
Our NICU at Sainte Justine until recently froze most breast milk brought to the NICU by parents, but did not routinely freeze during the first days when the volumes were low, so most babies received some non-frozen milk in any case. Later on, as stores increased, it was usual for the milk technicians to unfreeze a stored sample for the day’s feeds, newly arriving milk was frozen for later use.
Changes in our NICU milk kitchen have made us re-evaluate the practice.
Some recent articles about breast milk storage and handling have shown the following (many reviewed in Peters MDJ, et al. Safe management of expressed breast milk: A systematic review. Women and Birth. 2016;29(6):473-81):
Lactoferrin concentrations are much higher in human milk than in bovine milk (and almost absent in bovine milk based preparations), they are high in milk from preterm delivering mothers, and stay high for a couple of months. (Turin CG, et al. Lactoferrin concentration in breast milk of mothers of low-birth-weight newborns. J Perinatol. 2017. Albenzio M, et al. Lactoferrin Levels in Human Milk after Preterm and Term Delivery. American journal of perinatology. 2016;33(11):1085-9.) Storage of EBM at usual freezer temperatures, -20 degrees, substantially lowers activity of lactoperoxidase, and immunoglobulin A, with a smaller impact on lactoferrin, and lysozyme. (Akinbi H, et al. Alterations in the host defense properties of human milk following prolonged storage or pasteurization. Journal of pediatric gastroenterology and nutrition. 2010;51(3):347-52.) But the impact on lactoferrin concentrations is still important (Raoof NA, et al. Comparison of lactoferrin activity in fresh and stored human milk. J Perinatol. 2015;36(3):207-9) prolonged storage leading to about a 50% drop in lactoferrin.
An observational study from Spain including 22 neonatal intensive care units suggested that freezing breast milk might be effective in reducing postnatally acquired CMV (Balcells C, et al. Vertically transmitted cytomegalovirus infection in newborn preterm infants. Journal of perinatal medicine. 2016. p. 485.)
We now know that breast milk contains probiotic organisms, as well as potential pathogens. In one study freezing at -20 for 2 weeks did not clearly affect bacterial CFUs, (Marin ML, et al. Cold Storage of Human Milk: Effect on Its Bacterial Composition. Journal of Pediatric Gastroenterology & Nutrition 2009;49.) and the probiotic organisms were still present after thawing, but the data I can find are limited, you can certainly imagine that the precise way the milk is frozen and thawed might have an impact on bacterial contamination. One study showed that freezing the thawing and rewarming breast milk led to lower bacterial counts, and the same group showed that bacterial colony counts continued to fall during 9 months of freezing.
One study showed that antioxidant activity of breast milk decreases during storage at -20, but not at -80, (Aksu T, et al. The effects of breast milk storage and freezing procedure on interleukine-10 levels and total antioxidant activity. The journal of maternal-fetal & neonatal medicine : 2015;28(15):1799-802) but another study contradicted that and found a reduction at -80 also.
Milk has bactericidal capacity, which decreases during storage and is better maintained after freezing than after refrigeration, especially after 48 hours.
What we need, of course is a randomized controlled trial, and lo and behold, there is one! Omarsdottir S, et al. Cytomegalovirus Infection and Neonatal Outcome in Extremely Preterm Infants After Freezing of Maternal Milk. Pediatric Infectious Disease Journal. 2015;34(5):482-9. In this study 140 babies less than 28 weeks gestation whose mothers were intending to breast feed were randomized to receive only frozen maternal milk, (at -20 for at least 72 hours) with pasteurized donor milk used during the first days until thawed breast milk was available. The control group received fresh breast milk as soon as possible, and did get some donor milk, they also received some frozen milk, as milk was kept refrigerated for a maximum of 72 hours, and then frozen for later use if necessary. There were 66 of the mothers who had detectable CMV in their breast milk. Of those there was a transmission rate of 8% (minor different between groups could have been due to chance, 9% frozen, 6% fresh). Of note, the intervention period lasted 6 weeks, and 2 of the CMV transmissions in the frozen breast milk group were detected after that period, when the babies had been receiving fresh milk, leaving only 1 (3%) who is known to have developed CMV during the frozen breast milk phase. None of the CMV cases appeared to be symptomatic. What this means, unfortunately is that the study is underpowered to detect a major potential impact on CMV transmission, but there was no evidence of protection found from freezing breast milk for the 1st 6 weeks of life on transmission of CMV during the entire neonatal ICU stay. The study did find that the only cases of fungal sepsis were in the fresh breast milk group, from a secondary analysis of their data. Candida may be inactivated by freezing, according to the authors, but I can’t find the original data.
It may be that freezing to inactivate CMV is not as effective as previously thought, using very sensitive techniques one group found that samples were often still infective even after freezing. (Hamprecht K, et al. Cytomegalovirus (CMV) Inactivation in Breast Milk: Reassessment of Pasteurization and Freeze-Thawing. Pediatr Res. 2004;56(4):529-35.) Which may account for several case reports of babies who only ever received frozen-thawed milk, and still acquired CMV, apparently from the milk. To be certain what we should do we really need a much larger randomized trial, probably including only seropositive mothers.
At present I think that the evidence of protection from acquisition of symptomatic CMV infection by freezing and thawing of breast milk is lacking. There are potential adverse effects on immunologic components of breast milk, so we probably shouldn’t routinely freeze all maternal breast milk prior to giving it to extremely preterm infants.
Some countries recommend pasteurization of stored maternal breast milk (in France, for example). Holder pasteurization, heating the milk to 62.5 degrees for 30 minutes is the usual method (also used for milk banks in general). Holder pasteurization has major impacts on protein content of the milk severely degrading lactoferrin, lysozyme, immunoglobulins, reducing erythropoietin levels and cytokines, as well as epidermal growth factor and transforming growth factor. (for a complete review see ; Peila C, et al. The Effect of Holder Pasteurization on Nutrients and Biologically-Active Components in Donor Human Milk: A Review. Nutrients. 2016;8(8).)
Holder pasteurization does do what it is supposed to though, it does inactivate viruses, fungi, and bacteria. CMV is comprehensively inactivated by Holder pasteurization. Other pasteurization techniques (high temperature short duration) also inactivate the virus, and seem to have less impact on the immune characteristics of human milk, but aren’t widely used.
I have previously posted about the randomized controlled trial of pasteurization of mother’s breast milk, which actually showed a slight increase (potentially due to chance) in late onset sepsis compared to feeding fresh breast milk.
A new observational study from France, as part of Epipage2 (Dicky O, et al. Policy of feeding very preterm infants with their mother’s own fresh expressed milk was associated with a reduced risk of bronchopulmonary dysplasia. Acta Paediatrica. 2017.) showed that those NICUs that followed the national recommendation and pasteurized the milk of mothers of very preterm babies had more bronchopulmonary dysplasia. This was only shown on the adjusted analysis, whereas a possibly higher rate of NEC with raw milk from the univariate data disappeared on the adjusted analysis. They also did not show an effect on late onset sepsis.
With all of the major impact on human milk immune functions, I think that routinely pasteurizing maternal breast milk is not warranted, particularly in view of the lack of evidence of a benefit.
Final message, breast is best, and fresh is probably the best breast.
Thank you for such a great report. Very interesting.
in my the unit where I work we are giving frozen EBM. I just want to ask how do you thaw breast milk in your unit. In my unit we cannot do slow thawing due to the fact that our milk kitchen staff will prepare the milk feed the next day after it is being thawed. And I am aware that slow thawed EBM will only be use within 24 hours. Since we have a high census, we are thawing a lot of frozen EBM. Can we thaw EBM on a clean basin with cool water prior to preparing milk feeds for 24 hours?
I don’t know any actual data about this issue. We thaw frozen milk in a water bath at room temperature, and use what is thawed within 24 hours. Important to ensure that mothers freeze milk in small batches at first, to avoid throwing away milk not used that day.
Thank you for your excellent post.
I wondered if you saw this JAMA article-
Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study. Josephson CD, Caliendo AM, Easley KA, Knezevic A, Shenvi N, Hinkes MT, Patel RM, Hillyer CD, Roback JD. JAMA Pediatr. 2014 Nov;168(11):1054-62.
We were part of this study and routinely freeze mom’s milk for 48 hours till babies are 32 weeks of gestation.
As described in this study, we are concerned that the CMV disease burden may be under-reported in the literature and that risk-benefit analysis may not be clearly in favor of feeding fresh breast milk. We do however allow fresh colostrum swabbing of cheeks as soon it is available.
Are you aware of any practice survey data from US/ Canada regarding freezing of breast milk? What is the standard of care as far as this issue is concerned?
Hi Dr. Barrington,
You may be interested to see this recent study on microwaves eradicating CMV in breast milk: