Cow’s milk allergy in infancy and later development of juvenile idiopathic arthritis:a register-based case-control study

Abstract We examined the association between cow’s milk allergy (CMA) and juvenile idiopathic arthritis (JIA). The material for this case-control study was collected from national registers of all children born in Finland between 2000 and 2010 and diagnosed with JIA (n = 1,298) and age-, sex-, and place-matched controls (n = 5,179). We identified 235 children with CMA; 66 of these children also had JIA. A conditional logistic regression analysis was performed to evaluate the association between CMA and JIA and to test whether exposure to antibiotics would be a covariate for this association. In boys (but not in girls), a diagnosis of CMA and the use of hypoallergenic formula in infancy were associated with the later development of JIA (odds ratio = 2.4, 95% confidence interval: 1.6, 3.6). The association was most evident in boys who were diagnosed with JIA before age 3 years or diagnosed with CMA with predominantly gastrointestinal symptoms. There was no statistically significant additive interaction between CMA and antibiotic exposure in the later development of JIA. These associations may reflect impaired maturation of intestinal immunity and integrity in boys with a risk of JIA. Predisposing factors related to JIA pathogenesis seem to display a sex-linked disparity

The natural history of emerging diabetic retinopathy and microalbuminuria from prepuberty to early adulthood in Type 1 diabetes:a 19-year prospective clinical follow-up study

Abstract Objective: To evaluate the impact of long-term glycaemic control and glycaemic variability on microvascular complications in adolescents and young adults with childhood-onset Type 1 diabetes. Methods: Twenty-six participants took part in a prospective follow-up study. We used univariate generalised estimating equations (GEE) analysis with first-order autoregressive AR(1) covariance structure for repeated measurements to evaluate the relationship between emerging diabetic retinopathy (DR) and each single explanatory variable, namely age at developmental stages from late prepuberty until early adulthood, duration of diabetes and long-term HbA1c. Thereafter, the simultaneous effect of these three explanatory variables to DR was analysed in a multivariate model. Results: Twenty-five participants developed DR by early adulthood after a median diabetes duration of 16.2 years (range 6.3–24.0). No participants had DR during prepuberty. Each of the three variables was independently associated with emerging DR: age (OR 1.47, 95% CI to 1.25 to 1.74, p < 0.001) stronger than diabetes duration (OR 1.42, 95% CI 1.23 to 1.63, p < 0.001) and HbA1c (OR 1.02, 95% CI 1.001 to 1.05, p = 0.041) in this population. In the multivariate analysis of these three explanatory variables, only age was associated with DR (adjusted OR 1.52, 95% CI 1.10 to 2.10, p = 0.012). Conclusions: The emergence of DR during adolescence and early adulthood is not rare and increases with age in patients with deteriorating metabolic control during puberty and thereafter. This underpins the need to prevent deterioration of glycaemic control from taking place during puberty—seen again in this follow-up study—in children with diabetes

Impact of intrapartum and postnatal antibiotics on the gut microbiome and emergence of antimicrobial resistance in infants

Abstract Altogether, 20–30% of women receive intrapartum antibiotic prophylaxis (IAP) to prevent sepsis in infants and 2–5% of newborn infants receive antibiotics due to suspected sepsis. Caesarean section has a long-term impact on the intestinal microbiome but the effects of perinatal antibiotics on gut microbiome in vaginally delivered infants are not well known. We compared the impact of IAP, postnatal antibiotics, or their combination on the gut microbiome and emergence of antimicrobial resistance in a controlled study of 149 newborn infants recruited within 24 hours after birth. We collected 659 fecal samples, including 426 daily samples from infants before discharge from the hospital and 111 follow-up samples at six months. Penicillin was mostly used for IAP and the combination of penicillin and aminoglycoside for postnatal treatment. Postnatal antibiotic groups received Lactobacillus reuteri probiotic. Newborn gut colonization differed in both IAP and postnatal antibiotics groups as compared to that in control group. The effect size of IAP was comparable to that caused by postnatal antibiotics. The observed differences were still present at six months and not prevented by lactobacilli consumption. Given the present clinical results, the impact of perinatal antibiotics on the subsequent health of newborn infants should be further evaluated

Etiology of infectious diseases in acutely Ill children at a pediatric hospital in Finland

Abstract This is a brief report of the etiology of infectious diseases in a pediatric emergency department. Our cohort study of 4647 children demonstrated rhinovirus as the most common etiology in a pediatric emergency department (23%) and intensive care (48%). The population-based incidence of rhinovirus-related visits was 1796/100,000/yr in children <5 years. The most common bacterial pathogen was Escherichia coli (5%)

Microbiome of the first stool after birth and infantile colic

Abstract Background: Recent studies have shown a diverse microbiome in the first stool after birth. The clinical significance of the microbiome of the first stool is not known. Infantile colic has earlier been associated with the composition of the intestinal microbiome. Methods: We set out to test whether the microbiome of the first stool is associated with subsequent infantile colic in a prospective, population-based cohort study of 212 consecutive newborn infants. We used next-generation sequencing of the bacterial 16S rRNA gene. Results: The newborns who later developed infantile colic (n = 19) had a lower relative abundance of the genus Lactobacillus and the phylum Firmicutes in the first stool than those who remained healthy (n = 139). By using all microbiome data, random forest algorithm classified newborn with subsequent colic and those who remained healthy with area under the curve of 0.66 (SD 0.03) as compared to that of shuffled samples (P value <0.001). Conclusions: In this prospective, population-based study, the microbiome of the first-pass meconium was associated with subsequent infantile colic. Our results suggest that the pathogenesis of infantile colic is closely related to the intestinal microbiome at birth

Microbiota of the first-pass meconium and subsequent atopic and allergic disorders in children

Abstract Background: Some cohort studies have suggested that gut microbiota composition is associated with allergic diseases in children. The microbiota of the first-pass meconium, which forms before birth, represents the first gut microbiota that is easily available for research and little is known about any relationship with allergic disease development. Objective: We investigated whether the bacterial composition of the first-pass meconium is associated with the development of allergic diseases before 4 years of age. Methods: Prospective birth cohort study. Bacterial composition of first-pass meconium was analysed using bacterial 16S rRNA gene amplicon sequencing. Atopic and allergic diseases were evaluated via online survey or telephone to age 4 years, based on the International Study of Asthma and Allergies in Childhood questionnaire. Results: During a 6-week period in 2014, 312 children were born at the Central Finland Central Hospital. Meconium was collected from 212 at a mean of 8-hour age. Outcome data at 4 years were available for 177 (83%) children, and 159 of these had sufficient amplification of bacterial DNA in meconium. Meconium microbiota composition, including diversity indices and relative abundances of the main phyla and genera, was not associated with subsequent atopic eczema, wheezing or cow’s milk allergy. Principal components analysis did not identify any clustering of the meconium microbiomes of children with respect to wheezing or cow’s milk allergy. Conclusions: We found no evidence that gut microbiota composition of first-pass meconium is associated with atopic manifestations to age 4 years. However, larger studies are needed to fully exclude a relationship

Cranberry-lingonberry juice affects the gut and urinary microbiome in children:a randomized controlled trial

Abstract The mechanism by which cranberry-lingonberry juice (CLJ) prevents urinary tract infections (UTI) in children remains unknown. We hypothesized that it alters the composition of the gut or urinary microbiome. Altogether, 113 children with UTIs were randomly allocated to drink either CLJ or a placebo juice for 6 months. We collected urinary samples at 3 months and fecal samples at 3, 6 and 12 months and used next-generation sequencing of the bacterial 16S gene. The children who consumed CLJ had a lower abundance of Proteobacteria (p = 0.03) and a higher abundance of Firmicutes phylum (p = 0.04) in their urinary microbiome at 3 months than did those in the placebo group. The abundance of Escherichia coli in the urinary microbiome was 6% in the CLJ group and 13% in the placebo group (p = 0.42). In the gut microbiome the abundance of Actinobacteria at 3 and 12 months was higher in the children receiving CLJ. The diversity of the urinary and gut microbiome did not differ between the groups. The children drinking CLJ had a different urinary and gut microbiome from those receiving a placebo juice. A healthy urinary microbiome may be important in preventing UTIs in children