Soluvit

Nutrition support included enteral nutrition (EN) and parenteral nutrition (PN). Total parenteral nutrition (TPN) was provided during the first few days after ileostomy, jejunostomy, or anastomosis. The “all-in-one” solution contained lipids (Omegavan®, Fresenius Kabi or Lipofundin®, B. Braun Melsungen), amino acids (18AA-11; Treeful, Shanghai, China), a glucose solution, minerals, trace elements (Addamel; Fresenius Kabi, Wuxi, Jiangsu, China), water-soluble vitamins (Soluvit; Fresenius Kabi, Wuxi, Jiangsu, China), and fat-soluble vitamins (Vitalipid; Fresenius Kabi, Wuxi, Jiangsu, China) and was infused continuously via peripherally inserted central catheters (PICCs) or central venous catheters (CVCs) by infusion pumps (SN-1500H, Shenzhen, China). We replaced the medium chain triglyceride/long chain triglyceride (MCT/LCT)-based lipids with fish oil-based lipids (Omegavan; Fresenius Kabi, Jiangsu, China) when the levels of any three of the seven liver indicators were two times higher than normal. Enteral nutrition (breast milk, hydrolyzed formula, or amino acid-based formula) was introduced by pumping for 1–3 h through a nasal tube every 3 h, and advanced gradually based on intestinal tolerance. PN was decreased and weaned off when EN increased sufficiently to sustain adequate growth.

Piglets were delivered by cesarean section either pre-term on day 106 of gestation (n = 43, from 2 sows) or at full term on day 116 of gestation (n = 41, from 2 sows). Pancreatic tissue was collected from pre-term and term piglets euthanized either immediately after birth (TERM-d1 and PRE-TERM-d1, both n = 17) or after rearing in the intensive care unit until day 11 (TERM-d11, n = 24, and PRETEM-d11, n = 26), see Figure 1 top.
Pigs received continuous parenteral nutrition (PN) at 96 ml·kg⁻¹·day⁻¹ via the umbilical catheter. PN was adjusted from commercially available products (Kabiven, Soluvit, and Vitalipid; Fresenius Kabi, Bad Homburg, Germany), as previously presented in detail (35 (link)). PN was supplied from birth to post-natal day 5, when catheters were removed. Enteral nutrition (EN) was provided in increasing amounts with bovine colostrum until day 6, together with PN. From day 6 to 11, all pigs were given a diet with decreasing proportions of colostrum and increasing proportions of raw bovine milk as previously detailed (35 (link)).
At the end of the experiment, pigs were anesthetized with Zoletil (0.1 ml/kg i.m.), and then, euthanized with an intracardiac injection of 5 ml of 20% pentobarbital. The abdomen was opened and pancreatic samples were quickly collected and snap-frozen in liquid nitrogen and stored until further analysis.

The preterm pigs received continuous parental nutrition (PN, Kabiven, Fresenius Kabi, Uppsala, Sweden) via the umbilical catheter at PND1-7, with infusion rates of 3–6 mL/kg/h. The PN was modified with Vamin, Soluvit, Vitalipid, and Peditrace (all Fresenius Kabi). Enteral nutrition (EN) gradually increased (32–224 mL/kg/day) throughout the study. Pigs were fed through the orogastric tube until PND5 and drank independently from a trough from PND6-10. The EN consisted of bovine milk supplemented with vitamins and minerals, a diet that minimizes gut complications in long-term preterm pig studies.^{44 (link)} The PN and EN supplies were adjusted for metabolic body weight of pigs (Supplementary Table S1).