Abstract
For infants born moderately/late preterm (32-37 weeks of gestation), immaturity of the intestine has the potential to impact both short- and long-term gastrointestinal function. The aim of this study conducted in sheep was to compare the morphology and smooth muscle contractility of the ileum in term and late preterm lambs. Lambs delivered preterm (132 days gestation; n = 7) or term (147 days gestation; n = 9) were milk-fed after birth and euthanased at 2 days of age. A segment of distal ileum was collected for analysis of the length and cellular composition of the villi and crypts, smooth muscle width and contractility, and mRNA expression of the cell markers Ki67, lysozyme, mucin 2, synaptophysin, chromogranin A, olfactomedin 4, axis inhibition protein 2, and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5). There was no difference in the proportion of inflammatory, proliferating, apoptotic, enterocyte, or goblet cells between groups, but preterm lambs exhibited a significant upregulation of the stem cell marker LGR5 (p = 0.01). Absolute villus height (term: 1,032 ± 147 µm, preterm: 651 ± 52 µm; p < 0.0001) and crypt depth (term: 153 ± 11 µm, preterm: 133 ± 17 µm; p = 0.01) were significantly shorter in the preterm ileums, with a trend (p = 0.06) for a reduction in muscularis externa width. There was no difference between groups in the contractile response to acetylcholine, but peak contractility in response to bradykinin (p = 0.02) and angiotensin II (p = 0.03) was significantly greater in the preterm lambs. Findings demonstrate that the crypt-villus units are shorter in the ileum of late preterm offspring, but functionally mature with an equivalent cellular composition and normal contractile response to acetylcholine compared with term offspring. The exaggerated contractility to inflammatory mediators evident in the preterm ileum, however, may be of concern.
Highlights
Preterm birth, defined as birth occurring before 37 completed weeks of gestation, affects approximately 10% of all live births worldwide, with the majority (~80%) classified as moderately or late preterm [1, 2]
There was no difference between groups in the peak contractile responses to acetylcholine (Figure 3A) or histamine (Figure 3B)
Infants that are born late preterm do not usually exhibit overt gastrointestinal dysfunction, the findings of this study clearly demonstrate differences in the contractility, gene expression, and cellular structure of the ileum, with a heightened contractile response to inflammatory mediators
Summary
Preterm birth, defined as birth occurring before 37 completed weeks of gestation, affects approximately 10% of all live births worldwide, with the majority (~80%) classified as moderately or late preterm (birth between 32 and 37 weeks of gestation) [1, 2]. As gestational age at birth increases, enteral feeding is implemented and in infants born only a few weeks early (late preterm) bottle feeding is undertaken (preferably expressed breast milk) [11] as suck–swallow coordination becomes established [12]. In these late preterm infants, intestinal cellular differentiation is sufficient to perform the functions of digestion and absorption [6], they are born during a period of rapid intestinal growth, with a 34% increase in small intestine length observed to occur between 32 and 40 weeks of gestation [5]. The aim of this study conducted in sheep was to compare the morphology and smooth muscle contractility of the ileum in term and late preterm lambs
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