Intestinal Goblet Cell Loss during Chorioamnionitis in Fetal Lambs: Mechanistic Insights and Postnatal Implications.

Chorioamnionitis, an important cause of preterm birth, is linked to necrotizing enterocolitis (NEC). NEC is characterized by a disrupted mucus barrier, goblet cell loss, and endoplasmic reticulum (ER) stress of the intestinal epithelium. These findings prompted us to investigate the mechanisms underlying goblet cell alterations over time in an ovine chorioamnionitis model. Fetal lambs were intra-amniotically (IA) exposed to lipopolysaccharides (LPS) for 5, 12, or 24 h, or 2, 4, 8, or 15 d before premature delivery at 125 d gestational age (GA). Gut inflammation, the number, distribution, and differentiation of goblet cells, ER stress, and apoptosis were measured. We found a biphasic reduction in goblet cell numbers 24 h-2 d after, and 15 d after IA LPS exposure. The second decrease of goblet cell numbers was preceded by intestinal inflammation, apoptosis, and crypt ER stress, and increased SAM-pointed domain-containing ETS transcription factor (SPDEF)-positive cell counts. Our combined findings indicated that ER stress drives apoptosis of maturating goblet cells during chorioamnionitis, ultimately reducing goblet cell numbers. As similar changes have been described in patients suffering from NEC, these findings are considered to be clinically important for understanding the predecessors of NEC, and targeting ER stress in this context is interesting for future therapeutics.

Use of extensively hydrolysed formula for refeeding neonates postnecrotising enterocolitis: a nationwide survey-based, cross-sectional study.

OBJECTIVE: To evaluate the prevalence of and reasons for using extensively hydrolysed formulas (EHFs) of cow's milk proteins in the French neonatal units as well as the modality of their prescription for refeeding infants recovering from necrotising enterocolitis (NEC). METHODS: A multicentre nationwide cross-sectional study using a questionnaire to address the prevalence of use and the reasons for prescribing EHF in hospitalised neonates and to examine the protocols and the actual reasons for their use for refeeding infants in recovery from NEC. The questionnaire was sent to only 1 senior neonatologist in each neonatal unit included in the study. RESULTS: More than half of the French neonatal units participated in the survey. 91% of the surveyed units used EHF. Of 1969 infants hospitalised on the day the survey was run, 12% were fed on an EHF. 11% of the EHF prescriptions were due to previous NEC. The main reasons for using an EHF to feed infants post-NEC were the absence of human milk (75%) and surgical management of NEC (17%). When given, EHF was mainly prescribed for a period varying between 15 days and 3 months. None of the involved units continued using the EHF after 6 months of age. More than half of the surveyed units acknowledged hospitalising infants for the initiation of weaning EHF but only 21% of them tested these infants for cow's milk allergy. CONCLUSIONS: The prevalence of EHF use in the French neonatal units is high. Refeeding infants post-NEC is one of the main reasons for such a high prevalence. The main incentive for using an EHF is the absence of human breast milk, either maternal or donor.

Intestinal failure following necrotizing enterocolitis: A clinical approach.

Intestinal failure is a recognized complication of surgically-managed necrotizing enterocolitis (NEC). Functional adaptation of remaining bowel means that many children are eventually able to achieve enteral autonomy. Integrated multidisciplinary care in the early post-operative phase is key to long-term success. The objective of this review is to outline a clinical approach to management of intestinal and nutritional complications experienced by children following intestinal resection for NEC.