CALIFORNIA trial, registered under trial number NTR4153 in the Dutch Trial Registry.

Background:Little is known about the perinatal development of Paneth cells (PCs) during gestation and the relation with necrotizing enterocolitis (NEC). We aimed to investigate when PCs arise and when they become immune competent during gestation. Methods: We included 57 samples of ileum tissue of fetuses/ infants with a gestional age (GA) between 9 and 40 wk taken as part of a standard autopsy procedure. Hematoxylin-eosin staining and anti-human defensin 5 immunohistochemistry were performed. We performed a semi-quantitative assessment of (immune-competent) PC numbers per 10 crypts per tissue section per GA. results: The number of PCs and the number of immunecompetent PCs increased with increasing GA (Spearman's ρ = 0.41, P = 0.002 and ρ = 0.61, P < 0.001, respectively). Whereas significantly higher PC numbers were observed after 37 wk gestation (median 7, range 0-12) compared to preterm infants (median 0, range 0-15; P = 0.002), we counted higher numbers of immune-competent PCs already in infants with GA above 29 wk (median 6, range 0-18) compared to infants with GA under 29 wk (median 2, range 0-9; P < 0.001). conclusion: The significant increase of immune-competent PCs starting from a GA of 29 wk mimics the rise in incidence of NEC during a similar postmenstrual age in preterm infants.P aneth cells (PCs) are specialized epithelial immune cells located in the base of the crypts of Lieberkühn located in the small intestine (1,2). PCs can be seen in the gut by the first trimester and are thought to mature during gestation (1,2). PCs protect the intestinal stem cells from pathogens by stimulating stem cell differentiation, shaping the intestinal microbiota, and assist in reparation of the gut (2). To this end, they secrete (among other things) human α-defensins (HD5/HD6) (3). These defensins protect the intestinal mucosa against bacterial invasion, and are thought to be associated with initiating and adapting immunity (3). How PCs develop after the first trimester and when PCs become immune competent remains uncertain.PCs are thought to play a role in the development of NEC, a common and devastating disease most commonly observed in preterm infants (4-6). NEC involves the preterm intestine and has a complex pathophysiology in which bacterial invasion and an excessive inflammatory response is an important contributing factor (5,6). Unfortunately, the exact pathophysiology is incompletely understood.It has been hypothesized that maturation of immune-competent PCs is crucial for NEC development (4,(6)(7)(8). In the preterm gut, PCs secrete defensins that might contribute to an excessive inflammatory response as observed in NEC (4). This hypothesis is derived from the observation that extremely-low-birth-weight human infants generally have the longest interval before the onset of NEC-with a peak incidence at the postmenstrual age of 29-33 wk (4,6-8). Despite the possible role for PC-maturation in the pathophysiology of NEC, little is known about PC-maturation and functioning in the immature intestine. Therefore, we ...

NTR3239.