Effect of Formula Containing Lactobacillus reuteri DSM 17938 on Fecal Microbiota of Infants Born by Cesarean-Section.

OBJECTIVES: Microbiota modulation by probiotics in infants born by cesarean (C)-section is poorly understood. We aimed at assessing the response of C-section-delivered infant microbiota to a formula containing Lactobacillus reuteri Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSM) 17938 and comparing it with that of vaginally delivered infants. METHODS: Infants delivered by C-section (C) and vaginally (V) were randomized to receive either control formula (CCt, n = 10; VCt, n = 10) or the same formula containing L reuteri (CLr, n = 11; VLr, n = 9) within 72 hours following birth. Stool samples were collected at 2 weeks and 4 months of age. Microbial DNA was extracted, amplified, and pyrosequenced. RESULTS: The phylogenetic profiles of the CLr, VCt, and VLr microbiota were not significantly different at any age but diverged from that of CCt at 2 weeks. Compared with VCt, CCt displayed lower Bifidobacterium and higher Enterobacter, unclassified Enterobacteriaceae, Enterococcus, Clostridium, and unclassified Clostridiaceae relative abundance at 2 weeks, as well as lower Collinsella and higher Enterococcus and Coprococcus abundance at 4 months. The level of most of these taxa was not significantly different between the CLr and the vaginal-delivery groups. Compared with VCt, the only difference observed in VLr microbiota was higher Lactobacillus at the 2 study ages and Coprococcus at 4 months. CONCLUSIONS: Our results show that a formula containing L reuteri DSM 17938 does not essentially alter the microbiota in vaginally born infants. In C-section-delivered infants, however, this strain seems to play the role of keystone species by modulating the early development of the microbiota toward the composition found after vaginal delivery.

The Real-World Routine Use of Caffeine Citrate in Preterm Infants: A European Postauthorization Safety Study.

BACKGROUND: Caffeine citrate is the treatment of choice for apnea of prematurity (AOP). Regulatory agencies have requested real-world data on drug utilization and safety, a postauthorization safety study, of a pharmaceutical-grade caffeine citrate, Peyona, to confirm its benefit for preterm infants. OBJECTIVES: To investigate the clinical use, outcomes, and safety profile of this pharmaceutical-grade caffeine citrate in the routine treatment of preterm infants with a gestational age (GA) <37 weeks. METHODS: We conducted a multicenter, noninterventional, prospective study in five European countries. Patients eligible for study enrollment were <37-week GA neonates who received treatment with the pharmaceutical-grade caffeine citrate and whose parents had given informed consent. RESULTS: A total of 506 preterm infants were enrolled from 21 institutions. The pharmaceutical-grade caffeine citrate doses were administered intravenously, orally, or via both routes. The main indication of use was AOP treatment (58%) followed by AOP prophylaxis (37%). Median treatment duration was 21 days. The primary cause of study termination was AOP resolution (n = 407; 80%). Hundred and six patients (21%) required supplemental oxygen on day 28; 48 patients (9.5%) had bronchopulmonary dysplasia at 36 weeks' postmenstrual age. Twenty-three adverse drug reactions were observed in 21 neonates (4.2%); the most frequent was tachycardia (2.3%) and only one (seizures) was considered serious. Thirty-one patients (8.1%) had hepatic or renal functional impairment; the side effects were manageable, and these patients also benefitted from treatment. CONCLUSIONS: The use of this caffeine citrate is safe for the management of AOP in a real-world setting.

Parental stress management using relaxation techniques in a neonatal intensive care unit: A randomised controlled trial.

OBJECTIVE: The objective of this study was to investigate the effect of relaxation techniques on the stress/anxiety of parents with hospitalised premature infants, three months following discharge from the neonatal intensive care unit. STUDY DESIGN: A randomised controlled trial was conducted in the neonatal intensive care unit of a tertiary maternity hospital including 59 parents, who were randomised into two groups: 31 in the intervention group and 28 in the control group. Parents in the intervention group practiced three different relaxation techniques, in addition to undergoing the same information-based training courses as did the parents of the control group. DATA COLLECTION: Data were collected 10-15 days post delivery and three months post discharge. The assessment measures included the Perceived Stress Scale, the State and Trait Anxiety Inventory 1 and 2 and salivary cortisol levels. RESULTS: The psychometric assessment at baseline was comparable between the two groups. The intervention group showed a significant reduction in trait anxiety (p=0.02) compared with the control group three months post discharge. The perceived stress decreased in both groups (p=0.699). No difference in salivary cortisol levels was detected. The multivariate analysis revealed that higher initial stress levels (p<0.001) and university/college education (p=0.003) were associated with higher parental stress, whereas moderate-to-high income satisfaction was associated with lower parental stress (p=0.003). CONCLUSION: Further long-term follow-up of families with a neonatal intensive care unit experience could assess more delayed effects of stress management by relaxation techniques.

A Randomized Double Blind Controlled Safety Trial Evaluating d-Lactic Acid Production in Healthy Infants Fed a Lactobacillus reuteri-containing Formula.

BACKGROUND: d-Lactic acidosis in infants fed lactic acid bacteria-containing products is a concern. METHODS: The primary objective of this non-inferiority trial was to compare urinary d-lactic acid concentrations during the first 28 days of life in infants fed formula containing Lactobacillus reuteri (1.2 × 10(6) colony forming units (CFU)/ml) with those fed a control formula. The non-inferiority margin was set at a two-fold increase in d-lactic acid (0.7 mmol/mol creatinine, log-transformed). Healthy term infants in Greece were enrolled between birth and 72 hours of age, and block randomized to a probiotic (N = 44) or control (N = 44) group. They were exclusively fed their formulae until 28 days of age and followed up at 7, 14, 28, 112, and 168 ± 3 days. Anthropometric measurements were taken at each visit and tolerance recorded until 112 days. Urine was collected before study formula intake and at all visits up to 112 days and blood at 14 days. RESULTS: d-Lactic acid concentration in the probiotic group was below the non-inferiority margin at 28 days: treatment effect -0.03 (95% confidence interval [CI]: [-0.48 to 0.41]) mmol/mol creatinine but was above the non-inferiority margin at 7 and 14 days-treatment effect 0.50 (95% CI: [0.05-0.96]) mmol/mol creatinine and 0.45 (95% CI: [0.00-0.90]) mmol/mol creatinine, respectively. Blood acid excess and pH, anthropometry, tolerance, and adverse events (AEs) were not significantly different between groups. CONCLUSION: Intake of L. reuteri-containing formula was safe and did not cause an increase in d-lactic acid beyond two weeks.