title: Neonatal milk supplementation in lambs has persistent effects on growth and metabolic function that differ by sex and gestational age.
abstract: The perinatal environment has a major influence on long-term health and disease risk. Preterm birth alters early-life environment and is associated with altered metabolic function in adulthood. Whether preterm birth per se or the early nutritional interventions used to support growth in preterm infants underpins this association is unknown. Lambs born preterm, following dexamethasone induction of labour, or spontaneously at term were randomised to receive nutrient supplementation, analogous to the milk fortifier used clinically or water as a control for the first 2 weeks after birth. Thereafter, nutrition was not different between groups. Growth was monitored, and the glucose-insulin axis function was assessed in juvenile (4 months) and adult life (14 months). Early nutrition influenced adult metabolic function and body composition to a greater extent than preterm birth. In supplemented females, arginine-stimulated insulin secretion was increased in preterm but reduced in term-born juveniles compared with controls (repeated-measures ANOVA P<0·01). In supplemented preterm males, adult weight, ponderal index (PI) and fasting insulin concentrations were elevated compared with preterm controls (weight, 75 (sem 3) v. 69 (sem 2) kg; PI, 48·0 (sem 2·1) v. 43·7 (sem 1·7) kg/m3; fasting insulin, 0·19 (sem 0·02) v. 0·10 (sem 0·02) ng/ml). Conversely, supplemented term-born males had reduced adult weight, PI and fasting insulin concentrations compared with term-born controls (weight, 64 (sem 2) v. 70 (sem 2) kg; PI, 44·4 (sem 1·8) v. 48·2 (sem 1·7) kg/m3; fasting insulin, 0·09 (sem 0·02) v. 0·14 (sem 0·02) ng/ml; all group×supplement interactions P<0·05). Adult metabolic health may reflect both gestational age at birth and early nutrition. Human studies are urgently needed to investigate the adult sex-specific health implications of neonatal nutritional strategies.
authors.affiliation: 1Department of Paediatrics and Child Health,University of Otago,PO Box 7343, Wellington South, 6242,New Zealand.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Berry
authors.affiliation: 2Liggins Institute,University of Auckland,Private Bag 92019, Auckland, 1142,New Zealand.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Jaquiery
authors.affiliation: 2Liggins Institute,University of Auckland,Private Bag 92019, Auckland, 1142,New Zealand.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Oliver
authors.affiliation: 3Department of Paediatrics: Child and Youth Health,University of Auckland,Private Bag 92019, Auckland, 1142,New Zealand.
authors.forename: Jane E
authors.identifier: http://orcid.org/0000-0003-2697-1422
authors.initials: JE
authors.lastname: Harding
authors.affiliation: 2Liggins Institute,University of Auckland,Private Bag 92019, Auckland, 1142,New Zealand.
authors.forename: Frank H
authors.identifier: http://orcid.org/0000-0001-6424-6577
authors.initials: FH
authors.lastname: Bloomfield
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001823:Body Composition; D003907:Dexamethasone; D004195:Disease Models, Animal; D005260:Female; D005527:Food, Fortified / Q000009:adverse effects / Q000032:analysis; D005865:Gestational Age; D044882:Glucose Metabolism Disorders / Q000209:etiology / Q000517:prevention & control*; D006130:Growth Disorders / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008892:Milk / Q000009:adverse effects / Q000737:chemistry; D050177:Overweight / Q000209:etiology / Q000517:prevention & control*; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D011897:Random Allocation; D012727:Sex Characteristics; D034561:Sheep, Domestic; D015430:Weight Gain
chemical_list: D003907:Dexamethasone
keywords:  CIDR controlled internal drug release;  CRL crown–rump length;  DO deuterium oxide;  HGC hyperglycaemic clamps;  IVGTT intravenous glucose tolerance test;  PI;  ponderal index; Developmental origins; Neonatal nutrition; Preterm birth; Sex differences