Running head: QUALITY IMPROVEMENT INITIATIVES IN NEONATAL
Quality Improvement Initiatives in Neonatology and Proposals for Prevention of Necrotizing
Enterocolitis.
Durbin, L. RN, FNP-BC, Jnah, A., APRN, DNP(c), NNP-BC, Newberry, D., DNP, NNP-BC
(authors names will not be included upon submission to journal)
Conflicts of Interest and Source of Funding: none declared
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QUALITY IMPROVEMENT INITIATIVES IN NEONATAL
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Quality Improvement Initiatives in Neonatal Medicine and Suggestions for Research Related to
Prevention of Necrotizing Enterocolitis.
ABSTRACT
Quality Improvement (QI) initiatives optimize explorative ideas in order to uncover and
implement the best practices for patient care and outcome improvement. Medical institutions
such as the Vermont Oxford Network (VON), the National Association of Neonatal Nurses
(NANN), and the National Association of Neonatal Nurse Practitioners (NANNP) have been
instrumental in developing QI initiatives, publishing outcomes, and remaining active in
healthcare policy and politics for the very purpose of benefiting the neonate. Neonates are
unique in their makeup and more so in their response to the external environment. One such area
of concern for this population, in abundant need of QI exploration, is with regards to the disease
process necrotizing enterocolitis (NEC). The use of human milk feedings and probiotic
supplementation are two highly investigated approaches demonstrating promise in reducing the
incidence of NEC. Implementation into practice combining these approaches is the suggestion
of this manuscript. The Advanced Practice Nurse (APN) is in a position to make an impact by
way of active participation in the development of such initiatives, for it is through APN
leadership that evidence based practice and interpretation of research findings enhance neonatal
results and work toward illness prevention.
Key words: Necrotizing Enterocolitis, Probiotics, Quality Improvement, Advanced Practice
Nurse
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Quality Improvement Initiatives in the Neonatal Intensive Care Unit.
Advanced practice nursing (APN) inspired quality improvement (QI) initiatives in the
neonatal intensive care unit (NICU) are executed with the premise of enhancing care for
neonates and their families. QI allows for the distribution of newly developed, evidence driven
therapies reasoned to be the best recognized management strategies for the neonate. Quality
improvement, based on inter-institutional collaboration, may be the superior method for
furthering the quality and value of healthcare,1 much in the manner that we have acknowledged a
multidisciplinary, inter professional team approach as the preferred approach to patient care.
Agencies such as the National Association of Neonatal Nurses (NANN), and the American
Academy of Pediatrics (AAP) have contributed to initiatives corroborating the use of breast milk
as best practice for neonatal feeding regimins.4,6 The Vermont Oxford Network (VON) has more
recently investigated the use of probiotic supplements as a means for NEC prevention,3 which is
essentially in need of further QI endeavors.
The Vermont Oxford Network is an ideal model of QI in the neonatal arena, consisting of
over 950 Neonatal Intensive Care Units (NICU) around the world whose mission is to improve
the quality and safety of neonatal care through research, education and QI endeavors. 2 The
VON has been instrumental in establishing outcomes for the purpose of refining present
standards of neonatal care. The network incorporates various disciplines in the development
and management of its outcomes, including that of the APN.
VON was involved in a study which examined the effect of probiotic supplements on the
growth percentage of extremely low birth weight (ELBW) infants.3 Although this study failed to
denote a lower percentage of infants with weight below the 10th percentile at 34 weeks post
menstrual age, the linear growth trajectory during the first 28 days after the start of feedings was
QUALITY IMPROVEMENT INITIATIVES IN NEONATAL
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accelerated in the probiotic group .3 It is not evident, however, whether this accelerated growth
during the first 28 days of study was due to differences in institutional feeding and nutrition
practice.3 What this study did indicate is that the utilization of probiotic supplements was not
associated with any apparent adverse effects, nor increases in the incidence of NEC and sepsis,3
thus suggesting a reassuring safety profile for the application of probiotic supplements in the
field of neonatology.
NANN has composed several position statements with regards to areas of neonatal
interest and importance. Established through evidence based research, NANN recognizes human
milk and breastfeeding as a vital component in reducing infant mortality, and encourages
neonatal nurses to promote education of this topic to mothers.4 NANN is furthermore influential
in their provision of a research institute agenda based on health promotion, safety, and disease
prevention, aimed at enhancing patient outcomes and delivery of care.5
The American Academy of Pediatrics (AAP) likewise provisions the use of human milk
feedings as the optimal form of nutrition for use in the preterm infant and states that all preterm
infants should receive human milk or pasteurized donor milk if the mother’s milk is unavailable.6
The AAP endorses the beneficial short and long term effects of human milk, including lower
rates of sepsis and NEC, as well as the improvement of the preterm infant’s immature host
defense.6, Furthermore, the AAP claims the incidence of NEC is notably reduced from 83% to
58% with the use of human milk, even when prepared with cow milk–based human milk
fortifiers.6
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Community of Interest.
Neonates are unique in the manner that they transition to the environment and in the way
that a negative consequence may be precisely related to this transition. What is more, neonatal
outcomes may be related to intrauterine factors known to alter their growth and development or
result in a premature birth. The preterm neonate encompasses a set of diagnoses, illnesses and
challenges that are the absolute result of immature organ systems, not entirely prepared for
extrauterine life.
Necrotizing enterocolitis is one such diagnosis posing as an impediment to neonates.
NEC is a primary cause of death in the neonatal intensive care unit.7 The overall incidence of
NEC is approximately 1 in 1000 live births, but may transpire in up to 7% of very low birth
weight infants.8 NEC is almost entirely a disease of prematurity, and term infants who develop
NEC are likely to encompass predisposing risk factors such as congenital heart disease, sepsis, or
hypotension.9 There are approximately 4,500 hospitalizations associated with NEC annually in
the United States, with the highest incidence occurring among male, non-Hispanic, black, very
low birth weight infants.7 Hospital costs related with this disease are estimated between $500
million and $1 billion annually in the United States.10 The mean additional healthcare costs for
surgical NEC infants when compared to matched controls between the ages of 6-12, 12-24 and
24-36 months were $18,274, $14,067 and $8,501 per infant for each respective six month
period.11
Intestinal immaturity, labile microvascular tone and atypical microbial intestinal flora
may provide explanation as to the gastrointestinal related diseases specific to this population.12
An exceedingly abnormal immunoreactive intestinal mucosa leaves the neonate increasingly
susceptible to pathology.12 Additionally, abnormal intestinal microflora, leaning toward gram-
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negative bacteria, has been realized to be associated with the early stages of NEC.12 A study by
Carlisle et al. was executed so as to observe the variety of bacteria expressed in early NEC.12
Researchers discovered an increase in Citrobacter, Klebsiella, and Tatumella bacterium in the
intestinal flora of rat pups with NEC, whereas animals without NEC demonstrated more
Streptococcus and Enterococcus in their microbiota.12
Identifying the Problem.
NEC is a disease process that remains specific to the neonate and persists as one of the
most frequently encountered illnesses in this population. NEC has proven to be of utmost
challenge to eliminate, and therefore remains a topic of priority for research. The mean
prevalence of NEC is about 7% amongst infants with a birth weight between 500 and 1500
grams,13 and the mortality rate associated with this illness has been demonstrated to be about
28%, with a 14% increase amid those infants requiring surgery.14
The increasing survival rate of the smallest infants has respectively prompted an increase
in the occurrence of NEC.13 Fitzgibbons et al. performed an analysis of neonates weighing
between 500 and 1500 g, and born between 2005 to 2006, with the objective to establish birth
weight-based points of reference for in-patient mortality rates amongst infants with NEC.
Infants weighing 501 to 750 g developed NEC at a rate of 12%.13 This rate decreased to 3.3% in
those infants weighing 1251 to 1500 g,13 thus denoting the significance of birth weight as a
predictive risk factor for NEC (p < .001).13
By and large, strategies regarding nutritional management of premature infants and NEC
have been those of prevention. One of the few standardized approaches to NEC prevention has
been the allotment of gradual human milk enteral feeds to premature infants, as this practice has
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currently been established as decreasing, but not eliminating, the incidence of NEC.15 It is now
known that delaying enteral feeds can lead to atrophy of the intestinal mucosa and hindered
development of absorptive function.15 Consequently, withholding feedings for prolonged
periods of time has since become an eliminated method of practice. Earlier studies theorized an
increase in incidence of NEC with rapid volume feeding advancements. As such, it is postulated
by Martin et al. that cautious volume increases may be the safest approach in reducing the
occurrence of disease,15 although quantification of volume increases was not specifically
defined. Hay outlines a common approach to advancing enteral feeding as employing a
“minimal enteral feeding” strategy.16 Minimal enteral feeding denotes small amounts of
feedings of formula or breast milk at advancements of 5 to 25 ml/kg/day.16 Subsequently, there
seems to be no increased incidence of NEC in infants who obtain minimal enteral feedings,
predominantly when human milk is used.16 Despite the proven benefits of human milk feedings
and likely benefit of probiotics, NEC continues to be a substantial challenge. QI initiatives
exercising the use of probiotics together with breast milk feeds is required so as to ensure
optimal defensive strategy against this overwhelming illness.
Interventional Solution to the Problem.
A resolution to the matter of NEC is apt to be a multifactorial one, and will likely require
several additional research trials before an entirely preventative solution is realized. In light of
this, and many other research opportunities focused on the neonate, the APN is in a position to
move forth with QI initiatives directed toward positive outcomes. The leadership role of the
APN allows the opportunity for promoting evidence based practice and interpretation of research
findings into improved patient care.
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Neonatologists and Neonatal Nurse practitioners (NNP) alike, have formed an increased
understanding involving the pathophysiology of the neonatal gastrointestinal system with regards
to NEC, and have assembled information related to the microbiota and inflammatory effects
likely to be implicated in its diagnosis. For instance, the intestinal flora of infants who develop
NEC has been established to be unlike that of infants who do not acquire the disease, in that
there is an abundance of gram negative bacteria.17 Furthermore, the preterm infant’s gut flora
differs from that of term infants in the nature of the bacteria alone that populates their intestinal
tract.17 These variances of type may well be the effect of increased antibiotic exposure,
immaturity of the immune system, differences in feeding regimens and lack of proximity to
family.17 With this said, it is reasonable to proceed with QI initiatives formulated with the intent
of altering the preterm neonatal intestinal milieu towards a more favorable and less pathologic
state. A prospective option for practice is through the addition of probiotic supplements to breast
milk, as this has been presented as a protective strategy against NEC.
An already established, partial resolution to NEC is through the use of early human milk
feedings. Research has established an association between human milk feedings and an overall
decreased incidence of NEC.18, 19, 22 This has prompted preferentiality toward human milk and
donor milk feedings for neonates, especially premature and VLBW infants, who are at greatest
risk for developing the disease. Infants fed breast milk have a discernible reduction in the
incidence of NEC compared to those who are formula fed.19 This reduction may be associated
with the bioactive components in human milk that are thought to stimulate gut development and
optimize bowel colonization.20 Moreover, neonates who received breast milk were reported to
have enhanced intestinal flora over those fed formula, which may be attributable to the presence
of lactic acid bacteria in human milk.21 This practice has been expanded to likewise include the
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use of donor human milk as an enteral feeding option amongst NICUs. A meta-analysis by
Quigley et al. established a decreased incidence of NEC in infants fed donor milk versus
formula.22 Of added note, the pasteurization process of donor milk does not affect its content of
oligosaccharides, known to function indirectly as prebiotics, providing nourishment to probiotic
bacteria, and thus enhancing the promotion of favorable gut bacteria.20
A solution for decreasing rates of NEC involves the use of probiotics as a means of
restoring the gut to a less pathologic environment or an environment for promoting wellness, as
probiotic bacteria may prevent more pathologic bacteria from dominating receptor sites and
using nutrients in the gastrointestinal mucosa, ultimately assisting the infant in establishing
boundaries against a toxic environment.23 The most commonly used probiotics to date are
nonpathologic, lactic acid producing, gram negative bacteria such as Lactobacillus and
Bifidobacterium species.23
A 2013 study by Underwood et al. revealed a promising correlation for infants
supplemented with the probiotic bacteria Bifidobacterium longum ssp infantis in combination
with human milk, in that infants were demonstrated as having over-all lower gram negative
bacteria in stool.17 Furthermore, no infants who received this probiotic supplement developed
NEC.17 An additional analysis by Hunter et al. assessed the impact of routine Lactobacillus
reuteri supplementation on NEC in infants weighing less than 1000 g.24 The incidence of NEC
was significantly lower in the probiotic-treated group and was deemed to prevent one case of
NEC for every eight infants given the probiotic supplement.24 Furthermore, data from 25
randomized controlled trials, and the earlier mentioned study by the VON on routine use of
probiotics, indicate that significant adverse effects of probiotics are uncommon or do not occur.25
Based on these outcomes, it is reasonable to employ the probiotic species Bifidobacterium and
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Lactobacillus in future QI initiatives, as these specific probiotics have been proven as
nonthreatening therapies for prevention of NEC in an area of medicine where side effect profiles
run high.
A 2007 article published in the British Journal of Nutrition described the benefits of
probiotic bacteria isolated from breast milk. One reported advantage of probiotics observed in
human milk is the improvement in barrier function and reduction in permeability of the
intestine.22 This is of great significance when NEC is a concern, and may be an instrumental
factor in decreasing the incidence and severity of the disease. Moreover, neonates who received
breast milk were reported to have enhanced intestinal flora over those fed formula, perhaps
attributable to the presence of lactic acid bacteria in human milk.22 Many of the benefits
reported from probiotic isolates in human milk include an improvement in immune response, the
ability to control overgrowth of pathologic bacteria, and an overall decrease in inflammation.22
Barriers regarding the use of probiotics in the prevention of NEC include uncertainties
regarding the ideal strains, how much bacteria to employ, and the length of time for probiotic
treatment to ensue.26 Nevertheless, probiotics have proven to be worthy and effective
preventative practice, and practitioners and researchers alike should be the responsible parties
involved in establishing parameters for use.
Given what we know regarding the preterm gut, theories related to NEC development,
and the benefits of human milk feeds, QI initiatives may be based on the addition of specific
probiotic supplements to human and donor milk feeds. Furthermore, probiotic strains which have
been suggested to be of benefit and have demonstrated a positive safety profile should be
employed. Considering their previously cited potential, Bifidobacterium and Lactobacillus
species would be realistic probiotic species to consider in such initiatives.
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The APNs Role in Answering QI Neonatal Barriers.
In light of what appears to be an ever rising and complex neonatal population, the NNP
performs a vital role in the delivery and promotion of quality health care. Concentrated on
common goals for enhancing patient outcomes, the NNP is in the position to make an impact by
way of active participation in the development and practice of research and quality improvement.
Timoney and Sansoucie 27 recommend that ANPs be encouraged to enhance their scope of
practice by partnering with physicians in the expansion of outcomes-based research, education,
and QI initiatives.27 All the more, the motivation of the APN should be focused on promotion of
translational research, which allocates for the transformation of scientific findings into the
advancement of patient care at the bedside.28 Even such disease processes as complex and
elusive as NEC are within the realm of the APN to yield modifications and proposals for QI
initiatives. In doing so, the APN remains in parallel with the intents of the Institute of Medicine
(IOM), to provide reliable evidence for which to make well informed, research based decisions.29
What is more, the NNP remains unique in that they encompass an evolved understanding of
neonatal pathophysiology, assessment, nursing theory and innovation.
With the onset of the Patient Protection and Affordability Care Act (PPACA), medicine
is in the process of transitioning to a state in which disease prevention and quality health care for
everyone are the ultimate goals.30 Quality health care can be further defined as care that is
evidence based and proven to be of benefit to the patient for which it is directed. In keeping with
this theme, prevention of complex neonatal diseases, most notably NEC, should be at the
forefront of the minds of neonatologists and neonatal NNPs alike. Consequently, the NNP has an
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obligation to actively participate in this transitional process so as to substantiate APNs as more
than just “midlevels” but as change makers within the neonatal arena.
Conclusion
The next phase toward prevention of complex neonatal diseases such as NEC is to
examine the evidence and create standardized QI initiatives focused on providing high quality
neonatal care. Although we may still be years away from eradicating this devastating illness,
recent studies have presented the use of human milk feeds and probiotic supplementation as
advantageous to the at risk neonate. A reasonable suggestion for future practice is to implement
the combination of probiotic supplements with human and donor milk feeds. QI initiative
alliances are designed to be of influence in unveiling the best known practices for patient care
and outcome improvement, while accepting the viewpoint of benefiting neonates worldwide.
Furthermore, neonatal NNPs are in the position to make an impact by way of contribution to the
development of and implementation of quality research, and through interpretation of research
findings intended for improved neonatal outcomes.
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