How Human Milk Can Reduce the Devastating Impact of NEC

 

Premature babies and compromised neonates are at risk for many issues, including a devastating disease known as necrotizing enterocolitis (NEC).

Over the years there have been vast improvements in care provided to the smallest patients. And yet we continue to ask:

• What more can be done to reduce the increasing morbidities associated with babies born prematurely?
• Have we looked too far for something that can provide miraculous medicine?
• Have we looked beyond what nature intended as the best medicine (a mother’s own milk)?

Thankfully, an increasing amount of research has been done on the effects of human milk, and how it can impact and reduce morbidities associated with being a severely ill/premature neonate.

Epidermal growth factor and protein

How, specifically, does human milk (HM) impact NEC?

A team of scientists from Johns Hopkins conducted research with mice to reveal how breast milk works to ward off NEC.¹ They focused on epidermal growth factor (EGF) and a specific protein.

You might ask, “why mice for testing?” The answer is that rodents most resemble humans with their genetic and biological makeup. Many symptoms in humans can be replicated in mice.²

EGF, a substance found in animal and human breast milk, blocks the activation of the protein TLR4. This can instigate intestinal damage. This is how: TLR4 is a protein that regulates the body’s immune response to bacteria under normal conditions. In a premature infant, though, it regulates cell differentiation and intestinal growth.

After a baby is born, the intestines become colonized with bacteria to adapt to the new environment. If an infant is born premature, TLR4 is immature and reacts completely out of control. It starts to shut down the oxygen supply to the intestines, which causes the cell death seen in NEC.

Now enter the human milk factor. A study showed how human milk reduced TLR4 signaling in premature infants with the pretreatment of HM. “Taken together, our findings show that epidermal growth factor (EGF) is a key factor present in breast milk that prevents the onset of NEC in two ways:  EGF prevents intestinal cells from dying while at the same time restoring the cell growth that promotes gut healing,” says study author Misty Good, M.D., a neonatologist at Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center.¹˒³

Human milk preferences

The American Academy of Pediatrics (AAP) states that a mother’s own milk is always preferred, and that donor human milk (DHM), is an effective alternative when maternal milk isn’t available, or falls short of the infant’s needs.⁴

An exclusive human milk (EHM) diet is associated with decreased mortality, improved neurodevelopmental outcomes, decreased sepsis, and NEC, compared with infants who receive preterm formula (PTF).⁵˒⁶

Human milk and NEC rates

NEC affects about 5-10% of premature infants weighing less than 1500 grams, according to the NEC society.⁷

In a study done by Sullivan, et al, infants who were fed an EHM diet had a decreased rate of NEC by 50%, and a decreased surgical NEC rate of 90%.8

HM has been shown to have the greatest impact on NEC rates compared to any other intervention. A 50% reduction in NEC would prevent 1300-1850 cases annually. As we know, NEC is associated with death and a high mortality rate. The cost associated with each case of NEC is between $138K and $238K.⁸  Reducing NEC by 50% of cases/year still leaves an astronomical amount of dollars on the table treating NEC. For example, if you take an average number of cases and multiply that by the average cost of NEC, that is over $296,000,000/year spent treating NEC!!

Parental support and NEC

The NEC Society is committed to reducing the incidence of NEC. In a study administered to parents who were associated with the NEC Society, it was determined that partnering with parents for NEC prevention is sadly not common.

Areas for further quality improvement included, but were not limited to, advocacy for standardization of HM practices, and universal access to DHM.⁹ The surgeon general has advocated for expanding the use of DHM that is pasteurized and safely provided to such infants.⁶˒ 10

Human milk as medicine

When we think of HM as medicine to help prevent a devastating illness, why wouldn’t any hospital do whatever it takes to increase the amount of HM provided to their most vulnerable patients?

That includes early initiation of lactation within one hour of delivery, access to DHM, and a supportive team of doctors, nurses, and lactation consultants who are armed with expertise and knowledge to support a lactating mother and the most vulnerable patients (kindly referred to as “preemies”). It is not optional, it is vital!

The latest and greatest technology works to enable a mother and a hospital to provide an exclusive HM diet with human milk-based fortification to help reduce the morbidities associated with this terrible disease process.

Data suggest that the use of an exclusive human milk-based diet to include an appropriate human milk-based fortifier should be considered for all VLBW infants. The American Academy of Pediatrics (AAP) firmly adheres to the position that breastfeeding ensures the best possible health as well as the best developmental and psychosocial outcomes for infants.¹¹

 

Looking for more information on NEC? Read Dr. Jae Kim’s blog post, “Achieving Break-NEC Speed in the NICU: Is Zero NEC Coming?”

 

References

1. “Scientists reveal how breast milk prevents necrotizing enterocolitis in premature babies.” News Medical Lifesciences, https://www.news-medical.net/news/20150423/Scientists-reveal-how-breast-milk-prevents-necrotizing-enterocolitis-in-premature-babies.aspx.  Accessed 1 October 2017.
2. Melina, R. “Why do medical researchers use mice?”.  Live Science,    https://www.livescience.com/32860-why-do-medical-researchers-use-mice.html.  Accessed 28 September 2017.
3. De Curtis M, Terrin G. Necrotizing enterocolitis (NEC): what’s going on. Journal of Pediatric and Neonatal Individualized Medicine, 2013, 2-3.
4. New American Academy of Pediatrics Recommendations Aim to Ensure Safe Donor Human Milk Available for High Risk Infants Who Need It. (2016).  https://www.aap.org/en-us/about-the-aap/aap-press-room/Pages/New-American-Academy-of-Pediatrics-Recommendations-Aim-to-Ensure-Safe-Donor-Human-Milk-Available-for-High-Risk-Infants-Who.aspx.  Accessed 8 October 2017.
5. Huston, R., Markell, A., McCulley, E., Pathak, M., Rogers, S., Sweeney, S., Dolphin, N., and Gardiner, S. (2014).  Decreasing Necrotizing Enterocolitis and Gastrointestinal Bleeding in the Neonatal Intensive Care Unit.  ICAN:  Infant, Child, & Adolescent Nutrition, 6, 86-93.
6. Abrams, S., Schanler, R., Lee, M., Rechtman, D., and The Prolacta Study Group. (2014).  Greater Mortality and Morbidity in Extremely Preterm Infants Fed a Diet Containing Cow Milk Protein Products.  Academy of Breastfeeding Medicine, 9, 281-285.
7. NEC Society – Protecting Preemies from Necrotizing Enterocolitis. https://necsociety.org/.  Accessed 28 September 2017.
8. Sullivan, S., Schanler, R., Kim, J., Patel, A., Trawoger, R., Kiechl-Kohlendorfer, U.,… Lucas, A. (2010).  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.  The Journal of Pediatrics, 156, 562-567.
9. Canvasser, J., Gadepalli, S., Gephart, S., and Kim, J. “Perspectives from parents of infants impacted by NEC:  NEC communication in the NICU.” http://www.vtoxford.org/meetings/AMQC/Handouts2014/LearningFair/NECSociety_PerspectivesfromParentsimpactedbyNEC.pdf.  Accessed 6 October 2017.
10. The Surgeon General’s Call to Action to Support Breastfeeding. (2011).  https://www.surgeongeneral.gov/library/calls/breastfeeding/calltoactiontosupportbreastfeeding.pdf.  Accessed 6 October 2017.
11. Breastfeeding and the Use of Human Milk.  Pediatrics:  Official Journal of the American Academy of Pediatrics.  115(2):  496-506, 2005 Feb.