Sex-specific effects of neonatal oral sucrose treatment on growth and liver choline and glucocorticoid metabolism in adulthood

Am J Physiol Regul Integr Comp Physiol. 2021 Nov 1;321(5):R802-R811. doi: 10.1152/ajpregu.00091.2021. Epub 2021 Oct 6.


Hospitalized preterm infants experience painful medical procedures. Oral sucrose is the nonpharmacological standard of care for minor procedural pain relief. Infants are treated with numerous doses of sucrose, raising concerns about potential long-term effects. The objective of this study was to determine the long-term effects of neonatal oral sucrose treatment on growth and liver metabolism in a mouse model. Neonatal female and male mice were randomly assigned to one of two oral treatments (n = 7-10 mice/group/sex): sterile water or sucrose. Pups were treated 10 times/day for the first 6 days of life with 0.2 mg/g body wt of respective treatments (24% solution; 1-4 μL/dose) to mimic what is given to preterm infants. Mice were weaned at age 3 wk onto a control diet and fed until age 16 wk. Sucrose-treated female and male mice gained less weight during the treatment period and were smaller at weaning than water-treated mice (P ≤ 0.05); no effect of sucrose treatment on body weight was observed at adulthood. However, adult sucrose-treated female mice had smaller tibias and lower serum insulin-like growth factor-1 than adult water-treated female mice (P ≤ 0.05); these effects were not observed in males. Lower liver S-adenosylmethionine, phosphocholine, and glycerophosphocholine were observed in adult sucrose-treated compared with water-treated female and male mice (P ≤ 0.05). Sucrose-treated female, but not male, mice had lower liver free choline and higher liver betaine compared with water-treated female mice (P < 0.01). Our findings suggest that repeated neonatal sucrose treatment has long-term sex-specific effects on growth and liver methionine and choline metabolism.

Keywords: corticosterone; development; insulin-like growth factor 1; neonatal pain; tibia length.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Age Factors
  • Analgesics / administration & dosage
  • Analgesics / toxicity*
  • Animals
  • Animals, Newborn
  • Betaine / metabolism
  • Choline / metabolism*
  • Female
  • Glucocorticoids / metabolism*
  • Glycerylphosphorylcholine / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Mice, Inbred C57BL
  • Phosphorylcholine / metabolism
  • S-Adenosylmethionine / metabolism
  • Sex Factors
  • Sucrose / administration & dosage
  • Sucrose / toxicity*
  • Tibia / drug effects*
  • Tibia / growth & development
  • Weight Gain / drug effects*


  • Analgesics
  • Glucocorticoids
  • insulin-like growth factor-1, mouse
  • Phosphorylcholine
  • Betaine
  • Sucrose
  • Glycerylphosphorylcholine
  • Insulin-Like Growth Factor I
  • S-Adenosylmethionine
  • Choline

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