Neonatal and early infancy antibiotic exposure is associated with childhood atopic dermatitis, wheeze and asthma.

Antibiotics are frequently administered in the neonatal period and early infancy. Little is known about the long-term health consequences of early life antibiotic exposure. The objective is to investigate the association between neonatal and early life (0-6 months) antibiotic treatment and the development of atopic dermatitis, asthma and the use of inhaled corticosteroid medication later in childhood. We analyzed data obtained from hospital records and national registers in a cohort of 11,255 children. The association between early antibiotic exposure and the outcomes were analyzed using logistic regression. Confounding factors were included in the model. Neonatal antibiotic therapy for confirmed infection was associated with childhood atopic dermatitis (adjusted odds ratio 1.49; 95% confidence interval 1.15-1.94). Antibiotic therapy by six months of age was more common in children developing atopic dermatitis (adjusted odds ratio 1.38; 95% confidence interval 1.15-1.64), asthma (adjusted odds ratio 1.56; 95% confidence interval 1.32- 1.85) and inhaled corticosteroid medication use (adjusted odds ratio 1.88; 95% confidence interval 1.66-2.13).  Conclusions: Neonatal antibiotic therapy for confirmed or clinically diagnosed infection is associated with increased risk of atopic dermatitis later in childhood. Antibiotic treatment before six months of age is associated with atopic dermatitis, asthma and inhaled corticosteroid use. What is known: • The use of antibiotics early in life has been associated with an increased risk of developing atopic dermatitis or asthma. • Confounding by indication or reverse causation may underlie the observed associations. What is new: • Our results demonstrate that neonatal antibiotic therapy for confirmed or clinically diagnosed infection was associated with increased risk of atopic dermatitis and antibiotic treatment before six months of age was associated with atopic dermatitis, asthma and inhaled corticosteroid use in analyses adjusted for confounding factors.

Early life exposures and development of allergic disease in infants with familial risk: Results from ongoing probiotic intervention trials.

AIM: We search revision of risk determinants of the ongoing allergy epidemic. METHODS: Children numbering 433 born to mothers with allergic disease or sensitisation were selected from the three ongoing probiotic intervention trials for this case-control study. Children who developed atopic eczema or food allergy, had positive skinprick test results or had been prescribed inhaled corticosteroids by the age of 2 years were identified as cases (n = 231), while children without allergic manifestations were the healthy controls (n = 202). The data on early environmental exposures were collected from prospectively documented study records. The statistical analyses were adjusted for potential confounders. RESULTS: Determinants associated with the increased risk of atopic eczema were lower maternal prepregnancy BMI (aOR 0.15, 95% CI: 0.037-0.54) and maternal intrapartum antibiotic treatment (aOR 2.21, 95% CI 1.20-4.10), the latter also linked to obstructive respiratory symptoms (aOR 3.87, 95% CI 1.07-14.06). The risk of allergic sensitisation was associated with lower maternal prepegnancy BMI (aOR 0.18, 95% CI 0.43-0.79) and intrapartum antibiotic treatment (aOR 2.13, 95% CI 1.07-4.22). CONCLUSION: Based on our demonstrations, interventions such as personalised diets, can be optimised for specific subgroups and definite risk periods.

Neighborhood Socioeconomic Disadvantage and Childhood Body Mass Index Trajectories From Birth to 7 Years of Age.

BACKGROUND: The epidemic of increasing childhood overweight and obesity is a major global health concern, with local contextual factors identified as possible contributors. Robust research is needed to establish an evidence base supporting health policy decisions to reverse the trend. We aimed to examine the association between neighborhood socioeconomic disadvantage and trajectories of body mass index (BMI) from birth to age 7. METHODS: The present study included 11,023 children born within the Southwest Finland Birth Cohort who were free of severe conditions affecting growth with adequate exposure and growth data. We obtained child growth data until school age from municipal follow-up clinics. We based cumulative childhood neighborhood socioeconomic disadvantage on the average annual income, unemployment, and level of education in a residential area defined using a geographic grid at a spatial resolution of 250 m by 250 m. RESULTS: Cumulative neighborhood socioeconomic disadvantage was associated with distinct childhood BMI z score trajectories from birth to age 7. Despite being born in the lowest BMI z scores, children growing up in disadvantaged neighborhoods subsequently exhibited a trajectory of increasing BMI z scores starting at 4 years of age, ending up with a higher risk of overweight at the end of the follow-up (30%) as compared with children living in more affluent neighborhoods (22%). The corresponding risk of obesity was 5 % for those in affluent neighborhoods and 9 % and those in disadvantaged neighborhoods. CONCLUSION: Cumulative exposure to neighborhood socioeconomic disadvantage is independently associated with unfavorable BMI development and obesity in childhood.

Antibiotics, obesity and the link to microbes - what are we doing to our children?

BACKGROUND: Childhood obesity and overweight are among the greatest health challenges in the pediatric population. Obese individuals exhibit marked differences in the composition of the intestinal microbial community as compared to lean subjects. These changes in the gut microbiota precede the clinical manifestation of overweight. Convincing experimental data suggest a causal role for intestinal microbes in the development of obesity and associated metabolic disorders. DISCUSSION: Exposure to antibiotics exerts a devastating impact on the intestinal microbial community. Epidemiological studies have provided evidence indicating that early or repeated childhood exposure to antibiotics is associated with increased risk of overweight later in childhood but the causal role of this exposure in obesity development is not clear. However, data from studies conducted using experimental animal models indicate that antibiotic-induced changes in the gut microbiota influence host metabolism and lead to fat accumulation. The intestinal microbiota perturbation caused by antibiotic exposure in the perinatal period appears to program the host to an obesity-prone metabolic phenotype, which persists after the antibiotics have been discontinued and the gut microbiota has recovered. These observations may have serious implications in the clinical setting, since a substantial number of human infants are subjected to antibiotic treatment through the mother during delivery or directly in the immediate neonatal period. The clinical significance of these exposures remains unknown. Prudent use of antibiotics is paramount not only to reduce the propagation of antibiotic-resistant organisms but also to minimize the potentially detrimental long-term metabolic consequences of early antibiotic exposure. Improved means of reliably detecting neonates with bacterial infection would reduce the need for empirical antibiotic exposure initiated based on nonspecific symptoms and signs or risk factors. Finally, means to support healthy microbial contact in neonates and infants requiring antibiotic treatment are needed.

Ascites in newborns - a diagnostic challenge.

Isolated fetal ascites is a rare finding in prenatal ultrasound examination. The finding is always aberrant and requires further exploration. More than half of fetal ascites findings are associated with structural anomalies. Other causes include prenatal infections and genetic disorders. The cause and time of detection of ascites have an influence on the baby's prognosis. In spite of careful examinations the cause of ascites frequently remains open during pregnancy. During the first hours of life the baby needs intensive care, and when necessary, etiologic exploration will be simultaneously continued.

The Role of Infant Gut Microbiota Modulation by Perinatal Maternal Probiotic Intervention in Atopic Eczema Risk Reduction.

INTRODUCTION: Probiotics have shown potential in reducing the occurrence of atopic eczema in high-risk infants. We aimed here to assess whether the preventive effect of maternal probiotic administration stems from compositional changes in early gut microbiota. METHODS: This study included 46 mother-infant pairs from an original randomized controlled trial assessing the impact of maternal probiotic intervention with either the combinations of Lacticaseibacillus rhamnosus LPR and Bifidobacterium longum BL999, or Lacticaseibacillus paracasei ST11 and Bifidobacterium longum BL999, or placebo beginning 2 months before expected delivery and ending 2 months after birth. All children were vaginally delivered, full term and breastfed. During the 2-year follow-up period, the children were clinically evaluated by physicians for atopic eczema, and their gut microbiota was profiled at 1 and 6 months of age by 16S rRNA gene sequencing using an Illumina sequencing platform. RESULTS: Altogether, 19 of 46 children developed atopic eczema by the age of 2 years. At 1 and 6 months of age, gut microbial diversity was similar between children who developed atopic eczema and their healthy controls, but at the age of 6 months, children who developed atopic eczema manifested with significantly higher relative abundance of Clostridia. Probiotic intervention did not significantly influence microbial diversity, and the effects on microbial composition were not consistent with the changes associated with the development of atopic eczema. CONCLUSION: The reduction of the risk of atopic eczema achieved by perinatal maternal probiotic intervention does not seem to require substantial gut microbiota modulation.

Maternal Intrapartum Antibiotic Treatment and Gut Microbiota Development in Healthy Term Infants.

OBJECTIVE: The aim of the study was to investigate the impact of intrapartum antibiotic treatment (IAT) on the compositional development of gut microbiota in healthy term infants. STUDY DESIGN: A case-control study of 24 infants exposed to and 24 matched infants not exposed to IAT was conducted. All subjects were born by vaginal delivery at term and breastfed. None of the infants received antibiotics during the immediate neonatal period. Fecal samples were obtained at the ages of 1 and 6 months. The composition of the intestinal microbiota was assessed by 16S rRNA gene sequencing. RESULTS: IAT was associated with reduced microbial richness but not diversity at 1 month of age. Furthermore, the relative abundances of Clostridiaceae and Erysipelotrichaceae were significantly altered in infants exposed to IAT as compared to nonexposed infants at 1 month of age. The observed deviations in gut microbiota composition between infants exposed and not exposed to IAT diminished by the age of 6 months. CONCLUSIONS: IAT is associated with short-term perturbations in the gut microbiota development in healthy term, vaginally delivered, breastfed infants. The composition of the gut microbiota is mostly restored by the age of 6 months.

Neonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonization.

Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. Here, we investigate the long-term impact of antibiotic treatment in the neonatal period and early childhood on child growth in an unselected birth cohort of 12,422 children born at full term. We find significant attenuation of weight and height gain during the first 6 years of life after neonatal antibiotic exposure in boys, but not in girls, after adjusting for potential confounders. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with significantly higher body mass index throughout the study period in both boys and girls. Neonatal antibiotic exposure is associated with significant differences in the gut microbiome, particularly in decreased abundance and diversity of fecal Bifidobacteria until 2 years of age. Finally, we demonstrate that fecal microbiota transplant from antibiotic-exposed children to germ-free male, but not female, mice results in significant growth impairment. Thus, we conclude that neonatal antibiotic exposure is associated with a long-term gut microbiome perturbation and may result in reduced growth in boys during the first six years of life while antibiotic use later in childhood is associated with increased body mass index.

Associations between human milk oligosaccharides and growth in infancy and early childhood.

BACKGROUND: Breastfeeding modulates infant growth and protects against the development of obesity. However, whether or not maternal variation in human milk components, such as human milk oligosaccharides (HMOs), is associated with programming of child growth remains unknown. OBJECTIVE: Our objective was to determine the association between maternal HMO composition and child growth during the first 5 y of life. In addition, the association between maternal prepregnancy BMI and HMO composition was assessed. METHODS: Human milk samples from 802 mothers were obtained from a prospective population-based birth cohort study, Steps to healthy development of Children (STEPS), conducted in Turku, Finland. HMO composition in these milk samples was analyzed by HPLC. Child growth data from 3 mo to 5 y were collected from municipal well-baby clinics and linked to maternal HMO composition data to test for associations. RESULTS: Maternal HMO composition 3 mo after delivery was associated with height and weight during the first 5 y of life in children of secretor mothers. Specifically, HMO diversity and the concentration of lacto-N-neo-tetraose (LNnT) were inversely associated and that of 2'-fucosyllactose (2'FL) was directly associated with child height and weight z scores in a model adjusted for maternal prepregnancy BMI, mode of delivery, birthweight z score, sex, and time. Maternal prepregnancy BMI was associated with HMO composition. CONCLUSIONS: The association between maternal HMO composition and childhood growth may imply a causal relation, which warrants additional testing in preclinical and clinical studies, especially since 2'FL and LNnT are among the HMOs now being added to infant formula. Furthermore, altered HMO composition may mediate the impact of maternal prepregnancy BMI on childhood obesity, which warrants further investigation to establish the cause-and-effect relation.

C-11 acetate has excellent reproducibility for quantification of myocardial oxidative metabolism.

AIMS: C-11 acetate PET imaging allows quantification of myocardial oxidative metabolism. We sought to assess the reproducibility of such analysis with the Carimas software. METHODS AND RESULTS: The myocardial oxygen consumption rate was assessed via a kmono index--the clearance rate constant of a mono-exponential function fitted to a C-11 acetate clearance curve. Two observers of different experience levels--a novice and an expert--analysed 53 C-11 acetate PET studies--each study twice. These results were compared using Bland-Altman (BA) plots with the global kmono-s obtained earlier with a validated reference method. We also assessed intra- and interobserver reproducibility on global, regional, and segmental [17-segment model (AHA)] levels--a linear mixed model for the repeated measures was fitted to our data--using intraclass correlation coefficients (ICCs) and differences between repeats and the observers. Carimas kmono values were lower than the reference--by 10.7% in the novice and by 9.6% in the expert, and were in substantial agreement with it--R(2) values were 0.944 and 0.943 correspondingly; the coefficients of repeatability--1.96 SD of biases in BA plots--were 11.2% in both the observers. The intra- and interobserver ICCs were high on global and regional levels--above 0.99 in the novice and 0.96 in the expert. The intra- and interobserver differences were low on global and regional levels, the most pronounced being the left anterior descending artery (LAD) interobserver difference of 2.2%. CONCLUSION: The study showed extremely good reproducibility-both intra- and interobserver-for C-11 acetate PET analysis of myocardial oxidative metabolism.

Relationship between obstructive coronary artery disease and abnormal stress testing in patients with paroxysmal or persistent atrial fibrillation.

Atrial fibrillation (AF) has been linked to the presence of underlying coronary artery disease (CAD). However, whether the higher burden of CAD observed in AF patients translates into higher burden of myocardial ischemia is unknown. In 87 patients (71% male, mean age 61 ± 10 years) with paroxysmal or persistent AF and without history of CAD, MSCT coronary angiography and stress testing (exercise ECG test or myocardial perfusion imaging) were performed. CAD was classified as obstructive (≥50% luminal narrowing) or not. Stress tests were classified as normal or abnormal. A population of 122 patients without history of AF, similar to the AF group as to age, gender, symptomatic status and pre-test likelihood, served as a control group. Based on MSCT, 17% of AF patients were classified as having no CAD, whereas 43% showed non-obstructive CAD and the remaining 40% had obstructive CAD. A positive stress test was observed in 49% of AF patients with obstructive CAD. Among non-AF patients, 34% were classified as having no CAD, while 41% showed non-obstructive CAD and 25% had obstructive CAD (P = 0.013 compared to AF patients). A positive stress test was observed in 48% of non-AF patients with obstructive CAD. In conclusion, the higher burden of CAD observed in AF patients is not associated to higher burden of myocardial ischemia.

Prevalence of coronary artery disease assessed by multislice computed tomography coronary angiography in patients with paroxysmal or persistent atrial fibrillation.

BACKGROUND: Although atrial fibrillation (AF) has been linked to underlying coronary artery disease (CAD), data supporting this association have been based on ECG and clinical history for the definition of CAD rather than direct visualization of atherosclerosis. METHODS AND RESULTS: The prevalence of CAD among patients with paroxysmal or persistent AF and without history of CAD was evaluated using multislice computed tomography. Multislice computed tomography was performed in 150 patients with AF (61+/-11 years, 67% males, 58% asymptomatic) with predominantly low (59%) or intermediate (25%) pretest likelihood of CAD. CAD was classified as obstructive (> or =50% luminal narrowing) or not. A population of 148 patients without history of AF, similar to the AF group as to age, gender, symptomatic status, and pretest likelihood, served as a control group. Logistic regression analysis was applied to evaluate the relationship between demographic and clinical data and the presence of obstructive CAD. On the basis of multislice computed tomography, 18% of patients with AF were classified as having no CAD, whereas 41% showed nonobstructive CAD and the remaining 41% had obstructive CAD. Among patients without AF, 32% were classified as having no CAD, whereas 41% showed nonobstructive CAD and 27% had obstructive CAD (P=0.010 compared with patients with AF). At logistic regression analysis, age, male gender, and the presence of AF were significantly related to obstructive CAD. CONCLUSIONS: A higher prevalence of obstructive CAD was observed among patients with AF, confirming the hypothesis that AF could be a marker of advanced coronary atherosclerosis.