Late Enteral Feedings Are Associated with Intestinal Inflammation and Adverse Neonatal Outcomes

Konnikova, Liza; Zaman, Munir M.; Makda, Meher; D'Onofrio, D; Freedman, Steven D.; Martin, Camilia R.

doi:10.1371/journal.pone.0132924

Cited by 35 publications

(28 citation statements)

References 32 publications

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“…This finding supports the concept that the inflammatory response in the gut can be a “motor” for systemic inflammation [16]. Neonatal brain injury from HIE may occur in the setting of pathologic cytokine and chemokine production via neuroinflammatory pathways [24].…”

Section: Discussionsupporting

confidence: 79%

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Enteral Feeding as an Adjunct to Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy

et al. 2018

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Background: Withholding enteral feedings during hypothermia lacks supporting evidence. Objectives: We aimed to determine if minimal enteral nutrition (MEN) during hypothermia in patients with hypoxic-ischemic encephalopathy was associated with a reduced duration of parenteral nutrition, time to full oral feeds, and length of stay, but would not be associated with increased systemic inflammation or feeding complications. Methods: We performed a pilot, retrospective, matched case-control study within the Florida Neonatal Neurologic Network from December 2012 to May 2016 of patients who received MEN during hypothermia (n = 17) versus those who were not fed (n = 17). Length of stay, feeding-related outcomes, and brain injury identified by MRI were compared. Serum inflammatory mediators were measured at 0–6, 24, and 96 h of life by multiplex assay. MRI were scored using the Barkovich system. Results: MEN subjects had a reduced length of hospital stay (mean 15 ± 11 vs. 24 ± 19 days, p < 0.05), days receiving parenteral nutrition (7 ± 2 vs. 11 ± 6, p < 0.05), and time to full oral feeds (8 ± 5 vs. 18 ± 18, p < 0.05). MEN was associated with a significantly reduced serum IL-12p70 at 24 and 96 h (p < 0.05). Brain MRI scores were not significantly different between groups. Conclusion: MEN during hypothermia was associated with a reduced length of stay and time to full feeds, but did not increase feeding complications or systemic inflammation.

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Section: Discussionsupporting

confidence: 79%

“…However, the absence of enteral feeding may exacerbate gut inflammation [15]. In preterm infants, delayed enteral feeding is associated with inflammation and increased morbidity [16]. …”

Section: Introductionmentioning

confidence: 99%

Enteral Feeding as an Adjunct to Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy

et al. 2018

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“…Early initiation of breast milk feeding signi cantly reduced the duration of regaining birth weight more than three days in the intervention group when compared to the controls. This nding demonstrates the bene t of early enteral feeding in the prevention of postnatal growth failure and is consistent with studies from Uganda [13], Iran [26] and India [12,30]. However, this did not correspond with a shortened hospital stay as shown in previous studies [12,26] and may be explained by other factors such as neonatal sepsis which may impact on the early stabilization of the neonates.…”

Section: Discussionsupporting

confidence: 90%

Enhancing early initiation of breast milk for sick and preterm neonates admitted at regional referral hospitals in Dar es Salaam, Tanzania

Hyera¹,

Assenga²,

Kazimoto³

et al. 2020

Preprint

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Background: Feeding is the cornerstone in the management of sick or preterm neonates and early initiation of breastfeeding is the single most effective intervention associated with reduced neonatal mortality. Alternative routes for early breast milk administration are either oropharyngeal colostrum or minimal enteral nutrition. However, enteral feeding is often delayed due to haemodynamic instability and the perceived risk of necrotizing enterocolitis (NEC). One strategy to overcome delays in enteral feeds is the implementation of standardized feeding guidelines.Methods: This study was conducted in three regional hospitals in Dar es Salaam, consisting of a historical control group at baseline and an intervention group after implementation of co-created and locally adapted feeding guidelines. Neonates were consecutively recruited and followed to a maximum of 28 days of life. The controls received routine standard care, while the intervention group received early enteral feeding. The outcomes measured were NEC, time to regain birth weight and neonatal mortality. Odds ratio was used to determine the association between feeding and outcomes, statistical significance was considered when p-value ≤0.05.Results: 292 neonates were enrolled in this study, 163 (55.8%) controls at baseline and 129 (44.2%) after the intervention. Study participants comprised of 130 (44.5%) neonates with very low birth weight and 162 (55.5%) with hypoxic ischemic encephalopathy. The mean age of initiating feeding was 45.34 ± 21.58 SD hours amongst the controls and was significantly reduced to 8.43 ± 3.02 SD hours in the intervention group. Overall, 1.4% (4 cases) of the neonates were diagnosed with NEC, 1.8% (3 cases) in the control group and 0.8 % (1 case) in the intervention group (P=0.4; 95% CI: 0.25-23.3). The mean duration of regaining birth weight was significantly reduced from 11.26 ± 4.34 SD days among controls to 8.25 ± 2.96 SD days in the intervention group (p=0.000; 95% CI: 1.61 - 4.41, n = 110). Mortality in these high-risk groups of neonates remained high (40.8%, n = 119), without significant difference between the control (41.7%) and intervention group (39.5%). Conclusions: After implementation of co-created and contextualized feeding guidelines the mean duration of initiating mother’s milk was significantly reduced. Neonates in the intervention group who received early breast milk feeding significantly regained birth weight earlier. However, the study was underpowered to detect a small difference in important outcomes, including NEC and mortality. A randomized study with a large sample size and high power is recommended to further confirm the safety of early provision of mother’s milk among high-risk neonates in a low resource setting.Trial registration: The study was registered on October 3, 2018 to the Pan African Clinical Trial Registry (www.pactr.org) under the identification number PACTR201810856025709.

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“…Accumulating data suggest that feeding initiation in the first 3 days is protective against intestinal and other prematurity-associated morbidities. 7,33 Feedings were initiated at a median age of 4 days in both groups, which is outside that protective window. And although the risk of NEC is heavily influenced by human milk exposure, the etiology of NEC is multifactorial and a portion of disease risk at any single center may be unrelated to the composition of feedings.…”

Section: Discussionmentioning

confidence: 99%

Growth and Development in Extremely Low Birth Weight Infants After the Introduction of Exclusive Human Milk Feedings

et al. 2016

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To estimate associations of exclusive human milk (EHM) feedings with growth and neurodevelopment through 18 months corrected age (CA) in extremely low birth weight (ELBW) infants. ELBW infants admitted from July 2011 to June 2013 who survived were reviewed. Infants managed from July 2011 to June 2012 were fed with bovine milk-based fortifiers and formula (BOV). Beginning in July 2012, initial feedings used a human milk-based fortifier to provide EHM feedings. Infants were grouped on the basis of feeding regimen. Primary outcomes were the Bayley-III cognitive scores at 6, 12, and 18 months and growth. Infants ( = 85; 46% received EHM) were born at 26 ± 1.9 weeks ( = 0.92 between groups) weighing 776 ± 139 g ( = 0.67 between groups). Cognitive domain scores were similar at 6 months (BOV: 96 ± 7; EHM: 95 ± 14; = 0.70), 12 months (BOV: 97 ± 10; EHM: 98 ± 9; = 0.86), and 18 months (BOV: 97 ± 16; EHM: 98 ± 14; = 0.71) CA. Growth velocity prior to discharge (BOV: 12.1 ± 5.2 g/kg/day; EHM: 13.1 ± 4.0 g/kg/day; = 0.33) and subsequent growth was similar between groups. EHM feedings appear to support similar growth and neurodevelopment in ELBW infants as compared with feedings containing primarily bovine milk-based products.

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Late Enteral Feedings Are Associated with Intestinal Inflammation and Adverse Neonatal Outcomes

Cited by 35 publications

References 32 publications

Enteral Feeding as an Adjunct to Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy

Enteral Feeding as an Adjunct to Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy

Enhancing early initiation of breast milk for sick and preterm neonates admitted at regional referral hospitals in Dar es Salaam, Tanzania

Growth and Development in Extremely Low Birth Weight Infants After the Introduction of Exclusive Human Milk Feedings

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