Gut development following insulin-like growth factor-1 supplementation to preterm pigs

Authors: RASMUSSEN, MARTIN BO - University Of Copenhagen; HOLGERSEN, KRISTINE - University Of Copenhagen; PANKRATOVA, STANISLAVA - University Of Copenhagen; BÆK, OLE - University Of Copenhagen; Burrin, Douglas - Doug; THYMANN, THOMAS - University Of Copenhagen; SANGILD, PER TORP - University Of Copenhagen

Submitted to: Pediatric Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2023
Publication Date: 12/12/2023
Citation: Rasmussen, M., Holgersen, K., Pankratova, S., Baek, O., Burrin, D.G., Thymann, T., Sangild, P. 2023. Gut development following insulin-like growth factor-1 supplementation to preterm pigs. Pediatric Research. 95:1528-1535. https://doi.org/10.1038/s41390-023-02949-9.
DOI: https://doi.org/10.1038/s41390-023-02949-9

Interpretive Summary: The survival rates of very premature infants are increasing but many of these infants experience poor growth in the months after birth. Insulin-like growth factor-1 (IGF-1) is a key hormone involved in the regulation of infant growth and organ development. Premature infants have low plasma IGF-1 levels after birth and these low levels may be linked to their poor growth. Premature infants are also at higher risk for intestinal diseases, like necrotizing enterocolitis, because of immature gut growth. The aim of this study was test whether intravenous administration of IGF-1 fused with a binding protein (IGFBP-3) for 19 days after birth would restore normal IGF-1 blood levels and promote growth and function of the gut in premature newborn pigs. We also compared control and IGF-1 treated preterm pigs with term pigs reared on the sow and fed their mother’s milk. Our results showed that sow-reared term pigs has larger intestines with a thicker mucosa compared to preterm pigs. Treatment with IGF-1 did not increase intestinal growth but did increase the activity of key enzymes that digest dietary carbohydrate. IGF-1 also resulted in larger kidney and spleens compared to untreated preterm pigs. Supplementing IGF-1 to preterm pigs had a modest benefit on intestinal function but increased growth of select organs in the first few weeks after preterm birth.

Technical Abstract: Reduced insulin-like growth factor-1 (IGF-1) levels may contribute to impaired organ development in preterm infants. Using preterm pigs as models, we hypothesized that IGF-1 supplementation improves health and gut development during the first three weeks of life. First, clinical and organ endpoints were compared between artificially-reared, caesarean-delivered preterm pigs and vaginally-delivered, sow-reared term pigs at 5, 9 and 19 days. Next, preterm pigs were treated with recombinant human IGF-1 for 19 days (2.25 mg/kg/day, systemically). Relative to term pigs, preterm pigs had lower body weight, fat, bone contents, relative weights of liver and spleen and a longer and thinner intestine at 19 days. Preterm birth reduced intestinal villi heights and peptidase activities, but only at 5 and 9 days. In preterm pigs, clinical complications and mortality were reduced after IGF-1 treatment. It also increased spleen and kidney weights, without affecting growth or gut development until 19 days, except for increased maltase to lactase activity (reflecting gut maturation). Preterm birth affects body composition and gut maturation in the first 1-2 weeks, but differences are marginal thereafter. Supplemental IGF-1 may improve clinical and gut health in pigs and infants in the first few weeks after preterm birth.