title: Postnatal amniotic fluid intake reduces gut inflammatory responses and necrotizing enterocolitis in preterm neonates.
abstract: Preterm neonates are susceptible to gastrointestinal disorders such as necrotizing enterocolitis (NEC). Maternal milk and colostrum protects against NEC via growth promoting, immunomodulatory, and antimicrobial factors. The fetal enteral diet amniotic fluid (AF), contains similar components, and we hypothesized that postnatal AF administration reduces inflammatory responses and NEC in preterm neonates. Preterm pigs (92% gestation) were delivered by caesarean section and fed parental nutrition (2 days) followed by enteral (2 days) porcine colostrum (COLOS, n = 7), infant formula (FORM, n = 13), or AF supplied before and after introduction of formula (AF, n = 10) in experiment 1, and supplied only during the enteral feeding period in experiment 2 (FORM, n = 16; AF, n = 14). The NEC score was reduced in both AF and COLOS pigs, relative to FORM, when AF was provided prior to full enteral feeding (9.9 and 7.7 compared with 17.3, P < 0.05). There was no effect of AF when provided only during enteral feeding. AF pigs showed decreased bacterial abundance in colon and intestinal inflammation-related genes (e.g., TNF-α, IL-1α, IL-6, NOS) were downregulated, relative to FORM pigs with NEC. Anti-inflammatory properties of AF were supported by delayed maturation and decreased TNF-α production in murine dendritic cells, as well as increased proliferation and migration, and downregulation of IL-6 expression in intestinal cells (IEC-6, IPEC-J2). Like colostrum, AF may reduce NEC development in preterm neonates by suppressing the proinflammatory responses to enteral formula feeding and gut colonization when provided before the onset of NEC.
authors.affiliation: Dept. of Nutrition, Exercise and Sports, 30 Rolighedsvej, DK-1958 Frederiksberg C, Denmark.
authors.forename: Jayda
authors.initials: J
authors.lastname: Siggers
authors.forename: Mette V
authors.initials: MV
authors.lastname: Ostergaard
authors.forename: Richard H
authors.initials: RH
authors.lastname: Siggers
authors.forename: Kerstin
authors.initials: K
authors.lastname: Skovgaard
authors.forename: Lars
authors.initials: L
authors.lastname: Mølbak
authors.forename: Thomas
authors.initials: T
authors.lastname: Thymann
authors.forename: Mette
authors.initials: M
authors.lastname: Schmidt
authors.forename: Hanne K
authors.initials: HK
authors.lastname: Møller
authors.forename: Stig
authors.initials: S
authors.lastname: Purup
authors.forename: Lisbeth N
authors.initials: LN
authors.lastname: Fink
authors.forename: Hanne
authors.initials: H
authors.lastname: Frøkiær
authors.forename: Mette
authors.initials: M
authors.lastname: Boye
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
authors.forename: Stine B
authors.initials: SB
authors.lastname: Bering
mesh_terms: D000653:Amniotic Fluid / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D003126:Colostrum / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D004750:Enteral Nutrition; D020345:Enterocolitis, Necrotizing / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D020895:Enterocytes / Q000378:metabolism; D005260:Female; D005759:Gastroenteritis / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007408:Intestinal Absorption; D007422:Intestines / Q000382:microbiology; D046228:Microarray Analysis; D010289:Parenteral Nutrition, Total; D010539:Permeability; D011247:Pregnancy; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013552:Swine
chemical_list: D016207:Cytokines; D012313:RNA
keywords: amniotic fluid; colostrum; formula; inflammation; preterm