Ontogeny of alkaline phosphatase activity in infant intestines and breast milk

Ye Yang, Emilee Rader, Michele Peters-Carr, Rebecca C Bent, Jennifer T Smilowitz, Karen Guillemin, Bethany Rader, Ye Yang, Emilee Rader, Michele Peters-Carr, Rebecca C Bent, Jennifer T Smilowitz, Karen Guillemin, Bethany Rader

Abstract

Background: Necrotizing enterocolitis (NEC) is a devastating disease of intestinal inflammation that primarily affects premature infants. A potential risk factor for necrotizing enterocolitis is exposure of the premature neonatal intestine to environmental bacteria and their proinflammatory products such as lipopolysaccharide. The metalloenzyme alkaline phosphatase (ALP) has been shown to reduce lipopolysaccharide-mediated inflammation. Additionally, premature rat pups have reduced alkaline phosphatase activity and expression as compared to full term pups. To explore the possibility that the human premature neonatal intestine has a paucity of alkaline phosphatase activity, we measured endogenously produced intestinal alkaline phosphatase activity in meconium as a function of gestational age. To test whether breast milk could serve as a source of exogenous alkaline phosphatase to the neonatal intestine through ingestion, we measured alkaline phosphatase activity in breast milk across a range of time points post-birth.

Methods: Alkaline phosphatase activity was quantified in 122 meconium samples from infants of gestational ages ranging from 24 to 40 weeks and in 289 breast milk samples collected from 78 individual mothers between days 2-49 post-birth.

Results: We observed a strong positive correlation between the meconium alkaline phosphatase activity and gestational age, with preterm infants having lower meconium alkaline phosphatase activities than early term or term infants. Breast milk alkaline phosphatase activity was highest in the first week post-birth, with peak alkaline phosphatase activity at day 2 post-birth, followed by relatively low alkaline phosphatase activity in weeks 2-7.

Conclusions: Our results are consistent with the two major risk factors for necrotizing enterocolitis development, preterm birth and lack of breast milk feeding, both contributing to a paucity of alkaline phosphatase activity and impaired capacity to detoxify proinflammatory bacterial products such as lipopolysaccharide.

Keywords: Gestational age; LPS detoxification; Meconium; Necrotizing enterocolitis (NEC).

Conflict of interest statement

Consent for publication

The manuscript contains no details, images or videos of any individual person.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
(a) Meconium ALP activity increases with gestational age (P < 0.0001, R2 = 0.3416; one-way ANOVA and posttest for linear trend). (b) Meconium ALP activities are significantly lower in preterm (up to 36 weeks of gestation) infants than those in term (37–38 weeks) or term (39–40 weeks) infants. (***, P < 0.0001; one-way ANOVA followed by Bonferroni’s Multiple Comparison Test). Error bars represent standard deviations, n is sample size
Fig. 2
Fig. 2
Alkaline phosphatase activity of breast milk as a function of time. Average ALP units in breast milk samples obtained in postnatal days 2–5, week 2 (days 8–13), week 3–4 (days 17–22) and week 6–7 (days 40–49). Error bars represent standard deviation and n is sample size. All coefficients in the model are statistically significant at the p < 0.001 level using a mixed-effects regression model in which model coefficients represent the difference between the ALP activity in the first week and ALP activity in week 2, week 3–4, and week 6–7
Fig. 3
Fig. 3
Trends in alkaline phosphatase activity by individual. Lines represent trends in ALP activity in serial breast milk samples from the 56 individual donors for which 4 milk samples were available. Each dot represents ALP units from each of the 4 individual milk samples, one from postnatal week 1, week 2, week 3–4, or week 6–7. Sample sizes are as follows, day 2, n = 13; day 3, n = 7; day 4, n = 23; day 5, n = 13; day 10, n = 7; day 12, n = 47; day 13, n = 2; day 17, n = 2; day 19, n = 50; day 20, n = 2; day 21, n = 2; day 42, n = 53; day 43, n = 1; day 49, n = 1

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Source: PubMed

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