Placental and fetal growth restriction, size at birth and neonatal growth alter cognitive function and behaviour in sheep in an age- and sex-specific manner.
Intrauterine growth restriction and slow neonatal growth in humans are each associated with poorer learning, memory and cognitive flexibility in childhood and adulthood. The relative contributions of pre- and post-natal growth to cognitive outcomes are unclear, however. We therefore compared performance in learning, memory and reversal tasks using a modified Y-maze at 18 and 40 weeks of age in offspring of placentally-restricted (PR: 10 M, 13 F) and control (23 M, 17 F) ovine pregnancies. We also investigated relationships between size at birth, neonatal growth rates and cognitive outcomes. PR had limited effects on cognitive outcomes, with PR males requiring more trials to solve the initial learning task than controls (P=0.037) but faster completion of reversal tasks in both sexes at 18 weeks of age. In males, neonatal growth rate correlated inversely with numbers of trials and total time required to solve memory tasks at 40 weeks of age. In females, bleat frequency in the first reversal task at 18 weeks of age correlated positively with birth weight (r=0.734, P<0.05) and neonatal growth rate (r=0.563, P<0.05). We conclude that PR induces limited effects on cognitive outcomes in sheep, with some evidence of impaired learning in males, but little effect on memory or cognitive flexibility in either sex. Rapid neonatal growth predicted improved memory task performance in males, suggesting that strategies to optimize neonatal growth may have long-term cognitive benefits but that these may be sex-specific.
Robinson Research Institute, University of Adelaide, South Australia, Australia; School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia; School of Animal and Veterinary Sciences, University of Adelaide, South Australia, Australia.
Damien S
DS
Hunter
School of Animal and Veterinary Sciences, University of Adelaide, South Australia, Australia.
Susan J
SJ
Hazel
Robinson Research Institute, University of Adelaide, South Australia, Australia; School of Animal and Veterinary Sciences, University of Adelaide, South Australia, Australia.
Karen L
KL
Kind
Robinson Research Institute, University of Adelaide, South Australia, Australia; School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia.
Hong
H
Liu
School of Animal and Veterinary Sciences, University of Adelaide, South Australia, Australia.
Danila
D
Marini
Robinson Research Institute, University of Adelaide, South Australia, Australia; School of Population Heath, University of Adelaide, South Australia, Australia.
Lynne C
LC
Giles
Robinson Research Institute, University of Adelaide, South Australia, Australia; School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia.
Miles J
MJ
De Blasio
Robinson Research Institute, University of Adelaide, South Australia, Australia; School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia.
Julie A
JA
Owens
Robinson Research Institute, University of Adelaide, South Australia, Australia; School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia.
Julia B
JB
Pitcher
Robinson Research Institute, University of Adelaide, South Australia, Australia; School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia. Electronic address: kathy.gatford@adelaide.edu.au.
Kathryn L
KL
Gatford
D000375:Aging / Q000523:psychology*; D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight / Q000502:physiology; D003071:Cognition / Q000502:physiology; D005260:Female; D047109:Fetal Development / Q000502:physiology; D005317:Fetal Growth Retardation / Q000503:physiopathology* / Q000523:psychology*; D006128:Growth; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D012193:Reversal Learning / Q000502:physiology; D012727:Sex Characteristics; D034561:Sheep, Domestic; D014828:Vocalization, Animal
Birth weight; Cognition; IUGR; Maze; Neonatal growth; Sheep