TY - JOUR

T1 - Delayed growth, motor function and learning in preterm pigs during early postnatal life

AU - Andersen, Anders D.

AU - Sangild, Per T.

AU - Munch, Sara L.

AU - van der Beek, Eline M.

AU - Renes, Ingrid B.

AU - Ginneken, Chris Van

AU - Greisen, Gorm O.

AU - Thymann, Thomas

N1 - Copyright © 2016 the American Physiological Society.

PY - 2016/3/15

Y1 - 2016/3/15

N2 - Preterm birth interrupts normal fetal growth with consequences for postnatal growth and organ development. In preterm infants, many physiological deficits adapt and disappear with advancing postnatal age, but some may persist into childhood. We hypothesized that preterm birth would induce impaired organ growth and function during the first postnatal week in pigs, while motor abilities and behavioral characteristics would show more persistent developmental delay. Cesarean-delivered preterm (n = 112, 90% gestation) or term (n = 56, 100% gestation) piglets were reared under identical conditions and euthanized for blood and organ collection on postnatal days 0, 5, or 26. Body weight gain remained lower in preterm vs. term pigs up to day 26 (25.5 ± 1.5 vs. 31.0 ± 0.5 g·kg(-1)·day(-1), P < 0.01) when relative weights were higher for brain and kidneys and reduced for liver and spleen. Neonatal preterm pigs had reduced values for blood pH, Po2, glucose, lactate, hematocrit, and cortisol, but at day 26, most values were normalized, although plasma serotonin and IGF 1 levels remained reduced. Preterm pigs showed delayed neonatal arousal and impaired physical activity, coordination, exploration, and learning, relative to term pigs (all P < 0.05). Supplementation of parenteral nutrition during the first 5 days with an enteral milk diet did not affect later outcomes. In preterm pigs, many physiological characteristics of immaturity disappeared by 4 wk, while some neurodevelopmental deficits remained. The preterm pig is a relevant animal model to study early dietary and pharmacological interventions that support postnatal maturation and neurodevelopment in preterm infants.

AB - Preterm birth interrupts normal fetal growth with consequences for postnatal growth and organ development. In preterm infants, many physiological deficits adapt and disappear with advancing postnatal age, but some may persist into childhood. We hypothesized that preterm birth would induce impaired organ growth and function during the first postnatal week in pigs, while motor abilities and behavioral characteristics would show more persistent developmental delay. Cesarean-delivered preterm (n = 112, 90% gestation) or term (n = 56, 100% gestation) piglets were reared under identical conditions and euthanized for blood and organ collection on postnatal days 0, 5, or 26. Body weight gain remained lower in preterm vs. term pigs up to day 26 (25.5 ± 1.5 vs. 31.0 ± 0.5 g·kg(-1)·day(-1), P < 0.01) when relative weights were higher for brain and kidneys and reduced for liver and spleen. Neonatal preterm pigs had reduced values for blood pH, Po2, glucose, lactate, hematocrit, and cortisol, but at day 26, most values were normalized, although plasma serotonin and IGF 1 levels remained reduced. Preterm pigs showed delayed neonatal arousal and impaired physical activity, coordination, exploration, and learning, relative to term pigs (all P < 0.05). Supplementation of parenteral nutrition during the first 5 days with an enteral milk diet did not affect later outcomes. In preterm pigs, many physiological characteristics of immaturity disappeared by 4 wk, while some neurodevelopmental deficits remained. The preterm pig is a relevant animal model to study early dietary and pharmacological interventions that support postnatal maturation and neurodevelopment in preterm infants.

KW - Animals

KW - Animals, Newborn

KW - Arousal

KW - Behavior, Animal

KW - Exploratory Behavior

KW - Female

KW - Gestational Age

KW - Growth Disorders

KW - Learning Disorders

KW - Male

KW - Motor Skills Disorders

KW - Movement Disorders

KW - Organ Size

KW - Parenteral Nutrition

KW - Pregnancy

KW - Sus scrofa

KW - Weight Gain

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1152/ajpregu.00349.2015

DO - 10.1152/ajpregu.00349.2015

M3 - Journal article

C2 - 26764054

VL - 310

SP - R481-R492

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6119

IS - 6

ER -