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July 2013

Greetings from the Prolacta Team

LATCH… "to acquire understanding of, to comprehend"

I have been attending multiple Advanced Practice Nurses (APN) educational conferences recently in order to obtain needed pharmacology continuing education credits to meet the maintenance requirements for my advanced practice licenses. Over the past two months I have attended three such educational programs – one on the east coast, one on the west coast and most recently one in the midwest. All three conferences were designated for "pharmacology" education hours and all three had at least half of the day’s content devoted to the use of human milk – including the use of mother’s own milk (MOM), donor milk (DM), and human milk fortifiers.

I have 35 years of neonatal experience with 27 of those years as a Neonatal Nurse Practitioner. Over my long career I have been regularly exposed to academic and research findings demonstrating the benefits of human milk feeding for the low birth-weight infant. But of late we seem to be approaching a different and exciting shift or a clinical “tipping point” in the use of a human milk diet not only in this at-risk population but for all newborns.

Certainly the most recent revised policy on “Breastfeeding and the Use of Human Milk” from the Section on Breastfeeding of the American Academy of Pediatrics is helping lead this practice globally. But just as importantly is the emerging evidence from numerous clinical sites and practitioners on the benefits of human milk feeding. And that is driving the change in practice locally. The Pediatric Academic Society meeting held in Washington DC this year provides a prime example of this phenomena with over 30 presentations on breastfeeding and human milk and 4 specifically on extremely premature infants who received a 100% human milk based diet.

We at Prolacta Bioscience are dedicated to the use of human milk, including an exclusive human milk-derived human milk fortifier, in the nutritional management of very low birth weight infants (VLBW). We are proud to contribute to the evolving science, research and clinical evidence supporting human milk diets for all newborns. And we are equally as proud to be affiliated with the many healthcare professionals and clinical sites that champion and drive this change in practice every day.

Terry S. Johnson, APN, NNP-BC, MN, CLEC
Neonatal Nurse Practitioner
Editor, Prolacta eNewsletter

Prolacta Bioscience's eNewsletter serves to extend our mission of "making a meaningful difference in the lives of thousands of the most helpless infants through world class research and innovative products". One of the ways we accomplish this is by providing the health care professional with a brief overview of evolving research, current clinical issues and emerging practice strategies relevant to the care of the sick premature infant and newborn.

Feeding Practices and Necrotizing Enterocolitis

Numerous studies have documented the increased risk of necrotizing enterocolitis (NEC) in the absence or lack of adherence to feeding protocols for low birth-weight infants. A recent review article (Ramani M & Ambalavanan N Clin Perinatol 40(2013) 1-10 noted that “there is no consensus among health care professionals on feeding practices in preterm infants and there are wide variations in such practices across NICUs in the United States” and that “some of these feeding practices are not evidence based but based on personal experience or unit culture.” (p.2). The authors review the current data on various feeding practices and their impact on the risk of NEC, mortality, and other morbidities in preterm infants. The evidence was evaluated to determine the quality of evidence indicated based on the US Preventative Services Task Force hierarchy of research design available at and recommendations offered based on the US Preventative Services Task Force definitions (

Role of Absent or Reversed End-Diastolic Flow in the Development of NEC

Blood flow through the umbilical artery (UA) can become compromised in high risk pregnancies with abnormal placentation. Infants who have Absent or Reversed End-Diastolic Flow (AREDF) in utero experience decreased blood flow through the superior mesenteric artery (SMA) and may be at an increased risk of developing necrotizing enterocolitis (NEC). Doppler ultrasound (US) is used clinically to access placental vascular function and patterns of fetal growth and it is recommended that pregnancies complicated by maternal preeclampsia or intrauterine growth restriction (IUGR) be monitored by Doppler US. The placental vascular bed expands throughout a normal pregnancy producing a decrease in UA blood flow resistance as gestation age proceeds. This expansion results in an increase in end-diastolic blood flow which ensures adequate fetoplacental perfusion throughout the cardiac cycle (Sankaran S & Kyle PM. Best Pract Res Clin Obstet Gynaecol. 2009;23(6):765-777. In AREDF, a decrease in end-diastolic velocity can be observed when 30 percent of the placental villous vasculature is injured. Absence or reversal of flow corresponds to 60 to 70 percent of the placenta being damaged. Effects of AREDF include fetal hypoxia and acidosis resulting in intrauterine growth restriction (IUGR). Redistribution of blood flow to the developing brain results in decreased intestinal blood flow and increased mesenteric vascular resistance that may predispose the infant to intestinal ischemic injury and increased risk of NEC.

A recent thorough presentation, the Risk of Necrotizing Enterocolitis and Feeding Interventions for Preterm Infants with Abnormal Umbilical Artery Doppler appeared in the literature (Geary E Neonatal Netw. 2013 Jan-Feb;32(1):5-15. The article provides an extensive review of the evolving literature regarding the link between SMA flow and the development of NEC. The author reviews research on enteral feeding interventions and protocols for infants with AREDF. Results from the Abnormal Doppler Enteral Prescription Trial (ADEPT) examined effects of early versus delayed feedings in infants born after exposure to AREDF in utero (Leaf A et al. ADEPT- abnormal Doppler enteral prescription trial. BMC Pediatr.2009;9:63. ). Outcomes measured included the incidence of NEC and sepsis, time taken to establish full enteral feedings, and postnatal growth effects of early verses delayed feedings in infants. Infants in the early feeding group established full feedings earlier than the late group and had a lower incidence of cholestatic jaundice, as well as improved weight gain at discharge. There were no differences in the incidence of NEC or sepsis between the two groups. The protective immunobiologic benefits of human milk and the associated decrease in NEC of exclusive human milk feedings were not evaluated in this trial.

Role of Changes in the Microbiome as a Predictor for Late Onset NEC

Intestinal colonization has remained an important target of investigation in the etiology of NEC. Early colonizing organisms interact with the intestinal mucosa to shape the developing immune system towards homeostasis or dysregulation. A multi-center publication appearing in Microbiome 2013, 1:13 doi:10.1186/2049-2618-1-13 suggests that the microbial community of preterm infants, compared to healthy, term infants, consists of dramatically fewer beneficial species, lower bacterial diversity, and more pathogens. The authors note that NEC does not occur in germ-free animals, lending credence to the importance of intestinal colonization to the development of NEC. They report that several epidemiologic studies in preterm infants report an association between early empirical antibiotic use and subsequently increased risk of NEC, while randomized, controlled trials in preterm infants suggest that probiotic agents may reduce the risk of NEC.

Banked stool and urine samples collected prior to disease onset from infants <29 weeks gestational age, including 11 infants who developed NEC and 21 matched controls who survived free of NEC were analyzed. Stool bacterial communities were profiled by 16S rRNA gene sequencing and urinary metabolomic profiles were assessed by NMR.

During postnatal days 4 to 9, samples from infants who later developed NEC lacked Propionibacterium (P = 0.009) compared to controls. Furthermore, NEC was preceded by distinct forms of dysbiosis. During days 4 to 9, samples from four NEC cases were dominated by members of the Firmicutes (median relative abundance >99% versus <17% in the remaining NEC and controls, P < 0.001). During postnatal days 10 to 16, samples from the remaining NEC cases were dominated by Proteobacteria, specifically Enterobacteriaceae (median relative abundance >99% versus 38% in the other NEC cases and 84% in controls, P = 0.01). NEC preceded by Firmicutes dysbiosis occurred earlier (onset, days 7 to 21) than NEC preceded by Proteobacteria dysbiosis (onset, days 19 to 39). All NEC cases lacked Propionibacterium and were preceded by either Firmicutes (≥98% relative abundance, days 4 to 9) or Proteobacteria (≥90% relative abundance, days 10 to 16) dysbiosis, while only 25% of controls had this phenotype (predictive value 88%, P = 0.001). Early dysbiosis is strongly involved in the pathobiology of NEC. These striking findings support that early dysbiosis is strongly involved in the pathobiology of NEC and indicate that early microbial and metabolomic signatures may provide highly predictive biomarkers of NEC.

Lipid and Calorie Loss from Donor Human Milk with Gavage Feedings

Numerous studies using various measuring methods have shown that continuous gavage feedings using different styles of feeding pumps can result in a loss of lipid and caloric content in mother’s own milk (MOM) and donor human milk (DHM) as compared with gravity feeds. The inverse relationship between the infusion time and lipid content has been postulated to be secondary to the loss of fat associated with an adherence to the lumen of the plastic tubing that connects the milk container to the feeding tube. A recent publication by Brooks S, Vickers AM & Aryal S. compared the lipid and calorie loss from DHM among 3 methods of simulated gavage feedings commonly used in the NICU in Adv Neonatal Care. 2013 Apr;13(2):131-8. DOI: The study was performed at the Mother’s Milk Bank of North Texas and only DHM from this facility was utilized. None of the dDHM in the study was fortified. The sample milk ranged from 2.38 g/dL (17.8 kcal/oz) to 4.39 g/dL of fat (23.5 kcal/oz). The mean fat content of the 24 samples was 3.31 g/L (20.05 kcal/oz). Twenty-four samples of 8 oz of DHM were divided into four 60-mL aliquots. Timed feedings were given with syringes connected to narrow-lumened extension tubing designed for enteral feedings and connected to standard silastic feeding tubes. Gravity feedings were given using identical syringes and silastic feeding tubes. All aliquots were analyzed using the York Dairy Analyzer.

The univariate repeated measures analysis of variance for overall differences between feeding methods showed a significant difference between the methods (P<.0001). There was a significant difference in fat content between the control sample and the 1-hour and 2-hour feeding methods (P<.0001). There was no significant difference in fat content between the control and the gravity feeding methods (P=.3296).Pairwise comparison revealed a significant difference between both gravity and 1-hour feeding methods (P<.0001), and gravity and 2-hour feeding method (p<.0001). There was no significant difference in lipid content between the 1-hour and 2-hour feeding methods (P=.2729).

Continuous infusion of enteral feedings is used to minimize the most frequent signs of feeding intolerance in low birth-weight infants: emesis, increased work of breathing, use of continuous positive pressure ventilation, and addition of fortification. These data suggest a loss of nutrients that require further evaluation of current feeding practices in the NICU.

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