The Influence of Maternal-Foetal Parameters on Concentrations of Zonulin and Calprotectin in the Blood and Stool of Healthy Newborns during the First Seven Days of Life. An Observational Prospective Cohort Study

Abstract

Background: It can be hypothetically assumed that maternal and perinatal factors influence the intestinal barrier. Methods: The study was conducted with 100 healthy, full-term newborns breastfed in the first week of life, with similar analyses for their mothers. Zonulin and calprotectin levels were used as intestinal permeability markers. Results: The median (range) zonulin concentrations (ng/mL) were in mothers: serum, 21.39 (6.39–57.54); stool, 82.23 (42.52–225.74); and newborns: serum cord blood, 11.14 (5.82–52.34); meconium, 54.15 (1.36–700.65); and stool at age seven days, 114.41 (29.38–593.72). Calprotectin median (range) concentrations (µg/mL) in mothers were: stool, 74.79 (3.89–211.77); and newborns: meconium, 154.76 (6.93–8884.11); and stool at age seven days 139.12 (11.89–627.35). The use of antibiotics during pregnancy resulted in higher zonulin concentrations in umbilical-cord serum and calprotectin concentrations in newborn stool at seven days, while antibiotic therapy during labour resulted in higher zonulin concentrations in the stool of newborns at seven days. Zonulin concentrations in the stool of newborns (at seven days) who were born via caesarean section were higher compared to with vaginal birth. With further analyses, caesarean section was found to have a greater effect on zonulin concentrations than prophylactic administration of antibiotics in the perinatal period. Pregnancy mass gain >18 kg was associated with higher calprotectin concentrations in maternal stool. Body Mass Index (BMI) increase >5.7 during pregnancy was associated with decreased zonulin concentrations in maternal stool and increased calprotectin concentrations in stool of mothers and newborns at seven days. There was also a negative correlation between higher BMI increase in pregnancy and maternal zonulin stool concentrations and a positive correlation between BMI increase in pregnancy and maternal calprotectin stool concentrations. Conclusion: Maternal-foetal factors such as caesarean section, antibiotic therapy during pregnancy, as well as change in mother’s BMI during pregnancy may increase intestinal permeability in newborns. Changes in body mass during pregnancy can also affect intestinal permeability in mothers. However, health consequences associated with increased intestinal permeability during the first days of life are unknown. Additionally, before the zonulin and calprotectin tests can be adopted as universal diagnostic applications to assess increased intestinal permeability, validation of these tests is necessary.

Analysis of Faecal Zonulin and Calprotectin Concentrations in Healthy Children During the First Two Years of Life. An Observational Prospective Cohort Study

“…In our clinic, a previous study [29] found that maternal-foetal factors, such as caesarean section, antibiotic therapy during pregnancy and body mass index (BMI) increase > 5.7 during pregnancy may have impacted on increases in intestinal barrier permeability in newborn children up to seven days of age.…”

“…In the previous stage, the intestinal-barrier status was assessed in mothers before delivery and in newborns in the first week of life. In the presented second stage of the study, based on the same cohort, the state of the intestinal barrier in children between one and twenty-four months of age was assessed [29].…”

“…The study included 100 healthy, full-term newborns born in the Department of Obstetrics, Gynaecology and Neonatology at the Independent Public Clinical Hospital No. The purpose of this study was to evaluate stool zonulin and calprotectin concentrations as markers of intestinal barrier permeability in the first two years of life (one month to 24 months) in children from the cohort previously described [29] to verify two hypotheses. The first is that factors that affect intestinal barrier permeability in the neonatal period (until the seventh day of life) correlate with intestinal-barrier permeability factors in the first two years; the second, a claim that factors, such as children's body mass, type of feeding (breast or formula) and antibiotic therapy can affect intestinal-barrier permeability factors in children.…”

The Effect of Probiotics on Symptoms, Gut Microbiota and Inflammatory Markers in Infantile Colic: A Systematic Review, Meta-Analysis and Meta-Regression of Randomized Controlled Trials

“…These observations are backed by studies assessing immunological markers such as calprotectin in this group of patients [81,82]. In addition, these markers are dependent on maternal-fetal factors, such as antibiotic therapy or BMI changes during pregnancy, mode of delivery, and feeding patterns [75]. For this reason, in order to fully assess the causal relationship between the microbiota and the function of the immune system with relation to symptoms of infantile colic, a multifactorial analysis should be performed, which was not performed in the works described in this systematic review.…”

“…On the other hand, if breast milk microbiota are affected by intrapartum antibiotics, in some cases, the beneficial effect of breast milk on the gut microbiome may be unfavourably altered [74]. Importantly, most authors did not report variables that may shape gut microbiota and intestinal permeability in newborns, e.g., mode of delivery, weight gain during pregnancy, antibiotic therapy during pregnancy and labor [75], which all may affect colicky behaviour. In addition, a body of evidence exists that links infantile colic with caffeine consumption [76] and smoking [77,78], as well as consumption of allergenic products [79].…”