The 10th Annual Bowman Symposium did not disappoint! World class presenters gathered to provide a top to bottom update on a variety of topics spanning from the nervous system to Genetics. After a day and a half of presentations though I was left with some concerning (scary) thoughts and it seemed Halloween was the perfect time to share them with you!
How Much Oxygen is Just Right?
Dr. Ola Saugstad provided a wonderful history of the use of oxygen in Neonatology. After his talk it was clear that oxygen is most definitely a drug with its most concerning side effect being the production of oxygen free radicals in the body. If we are too restrictive aiming for saturations of 85 – 89% we spare our infants ROP but put them at greater risk of death. Too high at 91 – 95% and they may survive but with more ROP (BOOST and SUPPORT). If we resuscitate with 100% oxygen that is associated with worse outcomes but so too is 21% in our newborns < 28 weeks. The NRP would advise us to use 21 – 30% to start in this group for resuscitating but he recommends 30%. Certainly the recent publication by Jack Rabi out of Calgary suggests room air may in fact be harmful in this group as a starting point! After 50 years of research we still don’t know what to give newborns to help them start their life outside the womb. Scary.
It’s All In The Name
Next up is Dr. Aviva Goldberg who raised a very important point that I had not considered before. In every researchers quest to come up with a catchy name for their study that people will remember, the connotation is equally important. The SUPPORT study came under heavy fire (commentary here) after a surprising increase in mortality was found in the arm randomized to 85 – 89% saturations. Families sued the investigators and in their complaints they were angry about being misled. How could a study that was named the SUPPORT study do anything other than help their children? The title in and of itself they argued misled them as they never would have thought increased mortality could be a risk. Researchers make sure you test out your clever names with parents before finalizing your studies. The decision otherwise could come back to haunt you…
Jury Still Out on Bevicizumab (Avastin) for ROP
Dr. Ian Clark provided an overvue of the current state of thinking on treating ROP. For central disease in Zone 1 Avastin is preferred but for more peripheral disease laser seems to still be recommended due to its decisiveness in eliminating the disease without affecting future vision. Concerns continue though with respect to potential systemic effects of putting an anti-VEGF medication in the eye. Can it leak out and cause disruption to angiogenesis in other organs and in particular the brain? A recent poster at the CPS meeting in Toronto entitled Neurodevelopmental outcomes of extremely preterm infants treated with bevacizumab for severe retinopathy of prematurity indicates that there may be greater impairment in those receiving injections. There are several flaws in this paper though including greater numbers of males (we always do worse), more sepsis and worse SNAP-II scores in the injection group but the results have been making it into discussions leaving Ophthalmologists wondering if they are doing the right thing…very scary.
Cow’s Milk Human Milk Fortifier Is Safe For Premature Infants… Or is it?
Next up was Dr. Bill Diehl Jones who presented in vitro data on the effect of these supplements with respect to their contribution to oxidative stress. Such stress has been associated with BPD, NEC and ROP to name a few disorders in preemies. A paper published this week in which intestinal cells were exposed to human milk with HMF experienced significantly increased intracellular oxidation, cell damage, and cell death compared to those exposed to just breast milk. A paper from 2013 indicates that premature infants fed HMF experience increasing levels of urinary isoprostanes (a measure of oxidative stress). We know that infants receiving these products experience better growth and bone density than those without exposure but is there a cost? Will further research in this area drive us towards exclusive human milk based diets? The seed that has been planted in my head now questioning the safety of this product I use every day…a little frightening.
Curtailing Antibiotic Use And The Coming Black Swan
John Baier spoke about practice variation between Neonatologists in terms of the decision to prolong antibiotics or not in the face of negative cultures. While we do have variation, the good news is that we overall have cut down our tendency to prolong past 48 hours in the face of negative cultures. If we practice long enough though, the Black Swan will eventually rear its ugly head. The Black Swan is an exceptionally unusual event but one that has dramatic impact. How will we respond when a patient becomes septic after 48 hours and the antibiotics were stopped? Will we panic and change our practice entirely to avoid the internal pain again of feeling like we made a mistake or remember that we have saved countless infants from the long-term effects of indiscriminate use such as NEC, atopic disease and obesity in childhood just to name a few. It is this nagging doubt I have about how we will react that gives me cause to worry!
Finishing With a Miracle
It doesn’t seem right to end on a down note so I thought it would be worth celebrating that a cure has been found for something very scary. Hypophosphatasia is a rare disorder of the bone which was previously lethal in many cases. Thanks to research that our own Dr. Cheryl Greenberg led here in Canada we are able to successfully treat these children now. The Bowman symposium showed us incredible videos of such treated children and to end this post I found this video from Youtube of Gideon who was one of these patients treated with FDA Okays Asfotase Alfa (Strensiq). If you would like to leave this post with a smile on your face until next Halloween have a look at the video!
Will that be q2h, q3h or q4h feeding? When I started my residency in Pediatrics that was the question I needed to ask before writing an order to start oral feeding in a preterm infant. At the time it seemed perfectly reasonable but I have to admit the question for me was “What if they aren’t ready?”. Does a baby who won’t take the breast or bottle at the 3 hour mark clearly show they aren’t able to feed or that they really are just not ready to feed? We commonly say that children are not small adults. Hospitalized adults commonly will utter the words “I’m not hungry” when their food tray is brought to them. This may be a reflection of what has been put before them rather than whether hunger exists or not but they seem to be able to be ready to eat so why not children and by extension preterm infants in the NICU.
My approach to feeding premature infants was fairly consistent until about 10 years ago when nurses in Edmonton, Alberta (in a level II unit) introduced me to “semi-demand” feeding. What I find interesting about this, is the paucity of evidence that existed on the subject. At the time, the evidence really centred around one paper but the impact of the approach was undeniable. In 2001 McCain et al published the randomized controlled trial involving 81 infants A feeding protocol for healthy preterm infants shortens time to oral feeding. The concept of semi-demand feeding was to assess each infant (once preterms reached 32-34 weeks CGA) before a feed for signs “of feeding readiness”. This was accomplished through offering non-nutritive sucking every three hours before a scheduled feed. If the infant was found to be in a wakeful state, the oral feeding was commenced but otherwise the infant was left for 30 minutes with NNS attempted again. If the infant was still not ready then a gavage would be given. The key here is that the infants were monitored for signs of feeding readiness rather than insisting upon an arbitrary time for their next feed. The study findings were a halving of the time it took to reach full feeds (10 days in control vs. 5 days in semi-demand) with no difference in weight gain observed between groups. The latter point is worth emphasizing, as the concern with semi-demand has been from some that in a worst case scenario where feeds took place every 3.5 hours a baby would miss one feed compared to another infant on a q3h schedule. This fear though does not bear out in the study.
The experience in the centre I currently work at has been so positive that it is hard to find a patient that is not fed in such a way whether a physician orders the approach or not! What is truly fascinating to me is how effective the approach seemingly is and has been adopted again with very little evidence compared to that traditionally needed to change a practice in the neonatal world. Interestingly, although we can’t say for sure we have noticed year over year declines in length of stay for infants born with a birthweight of 1500 – 2000g since the introduction of semi-demand feeding. This could be a coincidence as this has not been the only practice change in our units but it certainly is interesting.
I was delighted to see a paper published this week on the topic by Wellington and Perlman. This was a Quality Improvement project entitled Infant Driven Feeding in Premature Infants: A Quality Improvement Project. This study compared three periods. The first was one in which physicians set the feeding schedule (PDF), the second a training period for a new system and the last the infant driven period (IDP). In the PDF phase, the physicians would order one oral feed a day, then two, three and so on when the full feed was attained at each prescribed level. In the IDF period an assessment sheet for feeding readiness would be completed before each attempt and the decision to offer an oral feed based on the perceived ability to feed at that time.
While this study was not an RCT it is a much larger group of patients than the study by McCain. This comparison was between 153 PDF vs 101 IDF patients. Feeding readiness assessments would start at 32 weeks CGA but feedings would not be offered by either approach until 33 weeks CGA similar to our own approach to feeding for the most part. The use of IDF made no difference to timing of first attempt at nipple feeding. The time to attain full nipple feeding was where significant differences in approach became apparent.
Time to reach full nipple feeding by gestational age at birth:
<28 weeks: IDF versus PDF group reached full NF 17 days sooner (374/7 vs 40 weeks; p=0.03)
28–316/7: IDF versus PDF group reached full NF 11 days sooner (35 4/7 vs 37 1/7 weeks; p<0.001)
≥32 weeks: IDF versus PDF group reached full NF 3 days sooner (354/7 vs 351/7 weeks; p=0.04).
Affect on discharge
<28 weeks GA, no difference between the IDF versus PDF group (41 3/7 vs 39 4/7 weeks; p=0.10).
28–316/7 weeks GA, IDF group were discharged 9 days earlier (366/7 vs 381/7 weeks; p<0.001).
≥32 weeks GA, the IDF group were discharged 3 days earlier (36 weeks vs 363/7 weeks;
Although the findings are clear there does need to be the usual acknowledgement that this is not the gold standard RCT but the practice change in the unit was done pretty carefully. The concept is one that makes a great deal of sense regardless. The lack of difference in discharge for the smallest infants makes some sense as it may well be apnea of prematurity that is the last to resolve. There is no disputing however the benefit in earlier discharge for the 28 – 31 6/7 week group. They achieve feeding earlier and go home faster. From a family centred approach this is the best of both worlds. One should not write off the use of this technique in the smallest infants either as they will have their care normalized much earlier with the NG tube being removed and the parents getting to participate and practice feeding much earlier in their course. Although not measured in this study, it would be intriguing to look at the number of patients who were admitted to hospital post discharge with failure to thrive.
Imagine the impact as well on hospital length of stay data if you multiple the reductions in length of stay by the total number of patients seen in these gestational age categories each year. This almost certainly can represent over a year of patient days for many hospitals.
As I see it the direction is clear. We should not force our premature infants to follow a schedule that works for us. Rather use the cues that only they can provide to tell us when and how much milk they desire. Both the parents, infants and our hospitals will benefit.
There is the potential for a very significant issue to arise in the NICU environment in the coming years. As I was preparing the last blog piece following the decision by SCOTUS to allow same-sex marriage in all 50 states I began to think about the so-called ripple effect. In other words, now that the law has been changed, what impacts could this have that might have been unforeseen. The first thought that crept into my mind was that as male same-sex parents they would read the same literature that promotes breast milk feeding in the NICU and no doubt want the best for their infant in the NICU or for that matter any baby. In many NICUs however there are weight or gestational age restrictions indicating who will receive donor breast milk if the mother is not able or not willing to produce her own. In our unit for example we given DBM to all babies currently under 1250g and those recovering from NEC or other bowel surgery. Might men in a same-sex marriage who have adopted a child or used a surrogate who is not willing to breastfeed demand the same?
In looking into this I came across a very strange story from 2013 in which a nurse in the UK offered to “rent her breasts” to gay parents. The story at the time caused a fairly big stir as it raised a number of questions as to safety and the morality of it all. In some ways it was ahead of its time as there have been a number of articles recently addressing the very issue of safety of milk (will be addressed further in the article obtained outside of HMBANA approved breast milk banks.
As same-sex couples increase and many then choose to have children of their own to raise what demands will be made of access to breast milk? There is no question “breast is best” and I have either written or posted to Facebook many articles suggesting decreased incidence of allergy, necrotizing enterocolitis, improvements in the microbiome and many other benefits as well. What do we do in the situation of the same-sex family who declares that they want to provide breast milk to their infant in hospital as it is the best source of nutrition for their infant. If we say for example that their 2 kg, 34 week infant is too big to qualify for DBM is this fair given that they have no option for producing their own milk in the setting of male same-sex partners? Could we as health care providers be labelled as discriminating?
One option is to allow such parents to bring in their own milk but then where do they source it from? Milk purchased online or from the community may be contaminated with bacteria, viruses or contain some cow’s milk as some recent publications have demonstrated. Can we knowingly allow families to bring such milk into the hospital to feed their infant? Perhaps, but only if we have medical legal safeguards in place that protect the hospital from knowingly allowing patients to bring in milk which could be contaminated. Waivers of liability would need to be in place in each hospital permitting such sourcing of milk. If however we strongly discourage such practice will we direct them to the milk bank supplying our local hospital. Herein lies the challenge though. If availability of volume was not an issue, we could provide to all infants in the unit but the reality is there is simply not enough to go around. Furthermore, the larger the infant, the more donor milk they utilize and the more depleted the supply becomes for those of our smallest infants who are most in need of avoiding formula. Finally, who should pay for this milk if the family cannot produce any as in this situation. This is not a case of a mother who could produce but chooses not to but rather a family who is desperate to use what they have read is best but physically is incapable of producing. The same of course could be said for those women who try and cannot or due to prior surgery are unable to produce milk. I believe this is an issue that will come up across the US and Canada and I will be interested to see how it plays out and what role Bioethics may play in helping to resolve some of these questions.
This will be a slippery slope. If male same-sex parents are provided with free access to donor milk I don’t see how donor milk will not be made available to all families who cannot provide their own. Why would the male parents who biologically be unable to provide milk be given this “liquid gold” while other mothers who are pumping round the clock, taking domperidone and seeing a lactation consultant and getting only drops be denied as their newborn is 1600g and above the weight cutoff. I hope you can see the issue of equity popping up in this discussion.
Finally why not allow those parents who are male same-sex partners to simply pay for the milk they need if they don’t qualify for “free” milk under a unit’s program? Sadly the issue then becomes one of equity again. Do we want to care for infants in an environment where the wealthy who can afford to pay for the donor milk from an HMBANA milk bank get it and the poor are only offered formula? I have to admit I realize there are health care systems where this is the case but in Canada where we have a socialized medical system this kind of two tiered system would cause many to become nauseated.
I fear that this issue will come up as the number of people marrying and choosing to have children in same-sex relationships increases. If it leads to a 100% human milk diet for infants in the NICU I would say that is a good thing but I think the road like Winnipeg will be paved with many potholes that we will have to do our best to navigate around.
This is a lengthier piece than normal but the message at the end is critical to disseminate so I would encourage you to share this if you wish with others to prevent misinformation from being propagated in the media by the sensationalism of a claim by a group of Pediatricians.
My Facebook page became awash in rainbow overlaid posts on Friday. Very quickly I realized as did most of the developed world, that the US Supreme Court ruled in favour of same-sex marriage and just so no one thinks that this will turn into a homophobic piece, I celebrated the change along with many friends and fellow Social Media colleagues.
After the initial excitement began to wane I came across a press release that I found a little shocking given that I belong to the group of people (as a Pediatrician not a member of the organization) that released the statement shown below. The statement is from the American College of Pediatricians
Dr. Michelle Cretella, President of the American College of Pediatricians in response to the SCOTUS decision today stated, “[T]his is a tragic day for America’s children. The SCOTUS has just undermined the single greatest pro-child institution in the history of mankind: the natural family. Just as it did in the joint Roe v Wade and Doe v Bolton decisions, the SCOTUS has elevated and enshrined the wants of adults over the needs of children.“
Although it is disappointing only 4 of the 9 justices heeded the scientific findings in the College Brief, the College will continue to proclaim the important unique contributions of both mothers and fathers to the optimal nurturing of all children.
As I went to their website and read about this organization it became clear that this group is mixing Church and State so to speak. Their mission statement states:
Mission of the College
The Mission of the American College of Pediatricians is to enable all children to reach their optimal physical and emotional health and well-being. To this end, we recognize the basic father-mother family unit, within the context of marriage, to be the optimal setting for childhood development, but pledge our support to all children, regardless of their circumstances.
Who are these people and why are they speaking out in such contrast to the American Academy of Pediatrics who in 2013 published their technical report in support of same-sex couple raising children. The AAP which has about 64000 members dwarfs the membership of possibly 200 Pediatricians that comprise the American College of Pediatricians. The smaller group was formed when a group of Pediatricians became upset in 2002 of the AAPs position that endorsed same-sex couples adopting children. The trouble of course with an organization such as this is that their name implies some degree of credibility but in looking at their track record on this issue they have little to none. They are a group that seems to ignore the literature discussed below in favour of quasi-scientific religious literature suggesting harm from such family units. The support of the AAP, the dominant organization in the field was made clear June 26th with this statement. I particularly like the quote from the president of the AAP.
“Every child needs stable, nurturing relationships to thrive, and marriage is one way to support and recognize those relationships,” said Sandra G. Hassink, MD, FAAP, AAP president. “Today’s historic decision by the U.S. Supreme Court supports children in families with same-gender parents. If a child has two loving and capable parents who choose to create a permanent bond, it’s in the best interest of their children that legal institutions allow them to do so.”
Putting aside my natural suspicion of the American College of Pediatricians, it did lead me to ask an important question. Are kids truly better off being raised in a heterosexual marriage? Perhaps there is evidence to show that indeed this is something that we as Pediatricians should be promoting. Looking at the evidence though would suggest otherwise or at least that there is no difference. In 2014 the largest study to date was published by Australian researcher Crouch et al involving 315 parents representing 500 children from same-sex marriages (complete study here). The study involved a questionnaire that would then be compared against population data to see if differences exist between parental units. A little over two-thirds of the parental units were Lesbian. The results demonstrated that in virtually all measures of child health the parental units were equivalent. Curiously, sense of stronger family cohesion was present with the same-sex groups. Possible reasons for this may be related to the way in which children are brought into this world in the two parental unit types. Given that people of the same-sex must plan (there are exceptions no doubt) to procreate there is little chance of the unexpected pregnancy occurring. These are almost all “wanted or chosen” children as opposed to the situation encountered in many pregnancies that are not planned. That is not to say that these children can’t or won’t be loved but the likelihood seems much lower in a LGBT parenting situation due to the planning that is generally required. While the research did not go on to elaborate on why the cohesion might be enhanced this is just my speculation.
Adding to this piece of evidence that these children are likely to have equivalent health to the traditional family rearing model is a well-timed report that surfaced the same week as the Supreme Court Ruling. The report from the Huffington Post challenges that after reviewing 19000 studies on same-sex parenting there can be no conclusion that the children of such families are worse off in any measure of health. Where the above group derives their mission statement from then is certainly not based on science but rather perception.
Back to the American College of Pediatricians (ACOP). I mentioned earlier that I was suspicious of the ACOP and what they portray as advocating for a child’s best health. As a writer of a blog I firmly believe that the buck stops at me with respect to content. If I have a guest writer I am responsible for their content as well as my own. I took the liberty of reviewing a recent piece from their blog and what I saw both shocked me and left me with the certainty that this group is not so much advocating for the health of children as condemning those lifestyles that they do not believe fit the mother-father mold. On June 5th the group released the following piece entitled “P” is for Pedophile. Please click on the link if you have the stomach for it but to give you a taste of what they are talking about here is the quote from the first line of the entry.
“Driving in this morning I began to wonder. Why isn’t the movement of LGBT not the PGBT movement: “P” for pedophile?”
If this group had any credibility by having a professional sounding name, my hope is that this post will spread wide and far to help discredit this organization. The evidence suggests that members of the LGBT community raise just as healthy kids as any of us and any attempts to smear people simply for who they happen to bond with for life amounts to hate and there should be no room in Pediatrics or any other field of medicine for that.
The picture looks ridiculous. Why does this seem so unnatural yet we feed babies this same product around the world. Granted they don’t drink it from the source as this man is but the liquid is in essence the same. As the saying goes, “Cow’s milk is for baby cows”. When you put it that way it helps put in context the question posed as the title of this post. Should we be surprised that the consumption of a milk meant for another species might have some side effects at a population level if fed to enough infants; especially those with fragile bowel due to prematurity or other high risk condition compromising blood flow to the gut.
The following piece was written by Kari Bonnar with contributions from Sharla Fast both Registered Dieticians in our NICUs. It has been recognized for some time now that the use of donor milk in our highest risk premature infants is associated with less NEC and based on a previous review of the evidence we have been using DBM for the past several years. What this post explores though is the potential for further benefit by taking the next step. That is to ask the question; what additional benefit may be gained by replacing all sources of Cow’s Milk protein in this population. I am delighted to present their review of the literature here as I am sure you will find it as informative and thought provoking as I have.
The health benefits of human milk for all infants, including those born extremely premature, have been increasingly recognized and published.1 The American Academy of Pediatrics policy statement on breastfeeding and the use of human milk recommends that all preterm infants receive human milk including donor human milk if mother’s own milk is unavailable.2 When compared with a diet of preterm formula, premature infants have improved feeding tolerance and a lower incidence of late onset sepsis and necrotizing enterocolitis (NEC) when fed their mothers’ own milk.3 For mothers of extremely premature infants, providing sufficient milk to meet their infant’s needs is a common challenge. Pasteurized donor human milk has been made available to this population in WRHA since 2011 as it has been found to be well tolerated and is also associated with a significantly lower incidence of NEC.4
However, as the sole nutritive substance, human milk does not meet the macronutrient and micronutrient requirements of preterm infants. Multi-nutrient fortifiers are required to provide additional protein, minerals and vitamins to ensure optimal nutrient intake and neurodevelopmental growth.5Prolacta Bioscience has recently launched in Canada with their human milk-based fortifiers, which are gaining popularity due to the ongoing research and success with these products in the United States, Austria, and now Canada.6 It is a new and novel approach that is proving to be most beneficial in reducing neonatal morbidity and mortality rates.7
In infants fed an exclusive human milk diet, Sullivan et al. found a reduction in medical NEC of 50% and surgical NEC of almost 90% compared to a diet containing cow’s milk-based products.7 To date, there is no other intervention that has had such a marked effect on the incidence of NEC.8 Abrams et al. found that for every 10% increase in intake of anything other than an exclusive human milk diet, the risk of NEC increases by 11.8% and the risk of surgical NEC increases by 21%, both with a 95% confidence interval.9
Patel et al. found that for every dose increase of 10ml/kg/day of human milk over the first 28 days post birth, the odds of sepsis decreased by 19%.10 Further to this, they found that overall NICU costs were lowest in very low birth weight (VLBW) infants who received the highest daily dose of human milk. Similarly, Abrams et al. reported that for each 10% increase in the intake of other than exclusive human milk diet, there was an 18% increase in risk for sepsis.9 In addition to predisposing the infant to other morbidities in the preterm population, and subsequent neurodevelopmental disability, sepsis significantly increases NICU costs by 31%. This translates into higher societal and educational costs for VLBW infants who survive sepsis with neurodevelopmental disability.10,11
A reduction in the number of days on total parenteral nutrition (TPN) was found by Cristofalo at al. with the use of an exclusive human milk based diet, in addition to reduction in sepsis and NEC.12 These same findings have been documented by Ghandehari et al. which reflect that an exclusive human milk diet leads to improved feeding tolerance and therefore, a decrease in total TPN days.13 Given that TPN is often the cause of late onset sepsis, the reduction of TPN days is imperative and almost always translates into decreased length of stay.14 Abrams et al. found that duration of TPN was 8 days less in infants receiving a diet containing <10% cow’s milk-based protein versus ≥ 10%, another recognizable dose related finding.9
It is well documented that increased growth leads to a decreased incidence of cerebral palsy and poor neurodevelopmental scores at 18-22 months corrected age, therefore adequate growth (weight, head circumference and length) is crucial in this population.15 The study by Hair et al. followed a standardized feeding protocol with early and rapid advancement of fortification with donor human milk derived fortifier and found that growth standards were being met and resulted in a marked decrease in extrauterine growth restriction.14 Cristofalo et al. study also compared growth rates, which were found to be slightly slower in the human milk fortified versus cow’s milk fortified arm of this study. However, it was mentioned that the small differences could be prevented with further adjustments in fortifier to improve rates of growth, as shown by Hair et al.12, 14 Abrams et al. confirms in their findings that growth rates were similar among human milk-based and cow’s milk-based fortification.9 This is a popular area of ongoing research with many abstracts also showing adequate growth rates with use of human milk-based fortifiers.
In closing, the review of current evidence clearly indicates that a diet of exclusive human milk is associated with lower mortality and morbidity in extremely premature infants without compromising growth and should be considered as an approach to nutritional care for these infants. Further research is needed to fully capture the extent to which using exclusive human milk diets actually reduce overall healthcare costs via improving the short and long term outcomes of extremely premature infants. Research to date only explores the financial impact for the first few years of life; therefore the true costs of these major morbidities are vastly underestimated and underreported. There are many unpublished trials and abstracts that are currently in process that will only strengthen the shift toward exclusive human milk-based diets, ideally making this common practice among Canadian centres in the very near future.
1 American Academy of Pediatrics. Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics 2005; 115:496-506
2 American Academy of Pediatrics. Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics 2012; 129:3;e827-41
3 Schanler RJ, Shulman RJ, Lau C. Feeding strategies for premature infants: Beneficial outcomes of feeding fortified human milk vs preterm formula. Pediatrics 1999;103:1150-7
4 Boyd CA, Quigley MA, Brocklehurst P, Donor Breast milk versus infant formula for preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2007;92:F169-75
5 Agostini C et al. Enteral nutrition supply for preterm infants: commentary from the European society for pediatric gastroenterology, hepatology, and nutrition committee on nutrition. JPGN 2010;50:1:85-91
7 Sillivan S, et al. An Exclusively Human Milk-Based Diet is Associated with a Lower Rate of necrotizing Enterocolitis than a Diet of Human Milk and Bovine Milk-Based Products. J Pediatr 2010:156;562-7
8 Bell EF. Preventing necrotizing enterocolitis: what works and how safe? Pediatrics 2005:115;173-4
9 Abrams SA, Schanler RJ, Lee ML, Rechtman DJ. Greater Mortality and Morbidity in Extremely Preterm Infants fed a diet containing cow milk protein products. Breastfeed Med. 2014:9;1-8
10 Patel AL, Johnson TJ, Engstrom JL, Fogg LF, Jegier BJ et al. Impact of early human milk on sepsis and health-care costs in very low birth weight infants. J Perinatology 2013:33:514-19
11 Ganapathy V, Hay JW, Kim JH. Cost of necrotizing enterocolitis and cost-effectiveness of exclusively human milk-based products in feeding extremely premature infants. Breastfeed Med. 2012:7;29-37
12 Cristofalo EA, Schanler RJ, Blanco CL, Sullivan S, Trawoeger R, et al. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. J Pediatr. 2013;1-4
13 Ghandehari H, Lee ML, Rechtman DJ. An exclusive human milk based diet in extremely premature infants reduces the probability of remaining on total parenteral nutrition: a reanalysis of the data. BMC. 2012:5;188
14 Hair AB, Hawthorne KM, Chetta KE, Abrams, SA. Human milk feeding supports adequate growth in infants ≤1250 grams birth weight. BMC. 2013:6;459
15 Ehrankranz RA, Dusiuk AM, Vohr BR, Wright LL, Wrage LA, et al. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics. 2006.117:4; 1253-61