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.

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.

Background Aberrant gut microbiota composition in preterm neonates is linked to adverse health consequences. Little is known about the impact of perinatal factors or maternal gut microbiota on initial preterm gut colonization. Methods Fecal samples were collected from 55 preterm neonates (<35 gestational weeks), 51 mothers, and 25 full-term neonates during the first 3–4 postpartum days. Gut microbiota composition was assessed using 16S ribosomal RNA gene sequencing. Results Preterm neonates exhibited significantly lower gut microbiota alpha diversity and distinct beta diversity clustering compared to term neonates. Spontaneous preterm birth was associated with distinct initial gut microbiota beta diversity as compared to iatrogenic delivery. Gestational age or delivery mode had no impact on the preterm gut microbiota composition. The cause of preterm delivery was also reflected in the maternal gut microbiota composition. The contribution of maternal gut microbiota to initial preterm gut colonization was more pronounced after spontaneous delivery than iatrogenic delivery and not dependent on delivery mode. Conclusions The initial preterm gut microbiota is distinct from term microbiota. Spontaneous preterm birth is reflected in the early neonatal and maternal gut microbiota. Transmission of gut microbes from mother to neonate is determined by spontaneous preterm delivery, but not by mode of birth. Impact The initial gut microbiota in preterm neonates is distinct from those born full term. Spontaneous preterm birth is associated with changes in the gut microbiota composition of both preterm neonates and their mothers. The contribution of the maternal gut microbiota to initial neonatal gut colonization was more pronounced after spontaneous preterm delivery as compared to iatrogenic preterm delivery and not dependent on delivery mode. Our study provides new evidence regarding the early gut colonization patterns in preterm infants. Altered preterm gut microbiota has been linked to adverse health consequences and may provide a target for early intervention.

Context Longitudinal data on levels of hypothalamic-pituitary-gonadal axis hormones and insulin-like growth factor I (IGF-I) during puberty in boys with a history of cryptorchidism are largely missing. Objective To compare pubertal hormone levels between boys with a history of congenital cryptorchidism who experienced spontaneous testicular descent or underwent orchiopexy and boys without a history of cryptorchidism. Design Prospective, longitudinal pubertal follow-up every 6 months (2005 to 2019) Setting A nested case control study within a population-based birth cohort Participants 109 Finnish boys, including boys with a history of unilateral cryptorchidism who underwent orchiopexy (n = 15), unilateral cryptorchidism who had spontaneous testicular descent (n = 15), bilateral cryptorchidism who underwent orchiopexy (n = 9), bilateral cryptorchidism who had spontaneous testicular descent (n = 7), and controls (n = 63) Main Outcome Measures Serum reproductive hormone levels and testicular volume Results From around onset of puberty, boys with bilateral cryptorchidism who underwent orchiopexy had significantly higher follicle-stimulating hormone (FSH) and lower inhibin B levels than controls. Boys with unilateral cryptorchidism who underwent orchiopexy had significantly higher FSH than controls, whereas inhibin B levels were similar. Testosterone, luteinizing hormone, insulin-like factor 3, and IGF-I were generally similar between groups. Testicular volume of boys with unilateral or bilateral cryptorchidism who underwent orchiopexy was smaller than that of the controls from one year after pubertal onset (p &lt; 0.05). Conclusions Cryptorchid boys, in particular those with bilateral cryptorchidism who underwent orchiopexy, had altered levels of serum biomarkers of Sertoli cells and germ cells and smaller testicular volumes compared with controls.

Background/Objectives Obesity in early childhood is associated with increased risk of chronic diseases, but studies of body composition at preschool ages are sparse. Therefore, we examined differences in body composition by sex and obesity status in Finnish preschool aged children and within-individual changes in body composition in normal and overweight children.Subject/Methods Body composition was measured using segmental multifrequency bioimpedance analysis (BIA) in 476 children and in 781 children at age 3 and 5 years, respectively. Of those, 308 had repeated BIA measurements at both ages. BMI-SDS was used for classification of normal weight and overweight children. ResultsSex difference in the amount of lean mass (LM) was already seen at 3 years of age (boys 11.7 kg, girls 11.3 kg; p<0.001). At 5 years of age, boys had lower fat mass (FM; 3.6kg vs 3.9 kg, p<0.001), lower percent fat mass (%FM; 17.2 % vs. 19.1 %; p<0.001), and higher LM (16.0 kg vs. 15.2 kg; p<0.001) than girls. Overweight children had higher values in FM, %FM and LM compared to normal weight peers at both ages. Among normal weight children, the increase of LM by age was associated with only minor changes in FM whereas children who were or became overweight both LM and FM was substantially increased between 3 and 5 years of age.Conclusions BIA-assessed body composition differs by sex and obesity status already at age of 3 years.For children who are or become overweight at very young age, the patterns for the changes in LM and FM by age are different than for normal weight children.

Purpose Recent studies have reported alarming appendiceal tumor rates associated with complicated acute appendicitis, especially in patients presenting with a periappendicular abscess. However, the data on histology of appendiceal tumors among acute appendicitis patients is limited, especially in patient cohorts differentiating between uncomplicated and complicated acute appendicitis. We have previously reported the association of increased appendiceal tumor prevalence with complicated acute appendicitis in this population-based study. The objective of this secondary analysis was to evaluate the association of both appendicitis severity and patient age with appendiceal tumor histology. Methods This nationwide population-based registry study (The Finnish Cancer Registry) was conducted from 2007 to 2013. All appendiceal tumors (n = 840) and available medical reports (n = 504) of these patients at eight study hospitals were previously evaluated, identifying altogether 250 patients with both acute appendicitis and appendiceal tumor. Results The severity of acute appendicitis was significantly associated with more malignant tumor histology. The risk of adenocarcinoma or pseudomyxoma was significantly higher among patients with periappendicular abscess (OR 15.05, CI 95% 6.98–32.49, p < 0.001) and patients presenting with perforated acute appendicitis (OR 4.09, CI 95% 1.69–9.90, p = 0.0018) compared to patients with uncomplicated acute appendicitis. Similarly, patient age over 40 years was significantly associated with the risk of adenocarcinoma and pseudomyxoma (OR 26.46, Cl 95% 7.95–88.09, p < 0.001). Patient sex was not associated with a more malignant appendiceal tumor histology (p = 0.67). Conclusion More malignant appendiceal tumor histology of adenocarcinoma or pseudomyxoma was significantly associated with patient age over 40 years and complicated acute appendicitis, especially periappendicular abscess.

Highlights  An effective way to decrease perinatal risks is to avoid multiple pregnancies  Elective single frozen embryo transfer may result in surplus thawed good embryos  Recryopreservation cycle with vitrification results in good embryo survival rates  Transfers of twice-frozen embryos result in favorable pregnancy outcomes  Perinatal outcome after recryopreservation with vitrification is uncompromised Pregnancy potential of embryos cryopreserved and thawed twice.

BackgroundProstate cancer (PC) is the most common cancer in men worldwide. The incidence of PC varies significantly geographically, which might result e.g. from genetic factors and local discrepancies in screening policies, but also from differences in lifestyle such as diet. Novel environmental factor, namely gut microbiota (GM) has been recently associated with many pathological processes including tumor progression within human body but its role in PC is disputable.MethodsWithin a clinical prospective single center trial, the GM profiles were assessed from 181 men with clinical suspicion of PC utilizing 16S rRNA gene sequencing (Illumina). Sequences were assigned to operational taxonomic units (OTUs) after which differential abundance analysis, α- and β-diversities, and predictive functional (PICRUST) analysis were performed. Further, plasma steroid hormone levels correlated to predicted microbiota functions.ResultsPC was diagnosed in 60% (108/181). Apart for less smoking among subjects with PC, there were no life-style differences between the groups. The GM profiles of men with PC differed significantly from those without cancer, e.g. Prevotella 9, members of family Erysipelotrichaceae and potentially pathogenic Escherichia-Shigella were increased, and e.g. Jonquetella, Moryella, Anaeroglobus, Corynebacterium and CAG-352 were reduced in PC cases. Predictive functional analyses revealed increased 5-α-reductase activity (5-AR), copper absorption and retinal metabolism as functional results of different microbiota. Plasma testosterone negatively correlated with predicted microbial 5-AR activity (Wilcoxon rank sum p=0.057) and in a subgroup of men taking 5-AR inhibitors (n=17), plasma estrone (p=0.027), and estradiol (p=0.054) levels were higher in men with predicted increased microbial 5-AR function.ConclusionsCertain bacterial and functional features within GM composition are associated with PC risk and altered androgen, copper and retinol metabolism are potential mechanisms. Findings could explain the previously reported association of life-style effects and geographical differences observed in PC.Trial registration numberNCT02241122