ABSTRACT
BACKGROUND: Human milk oligosaccharides (HMOs) have important and diverse biological functions in early life. This study tested the safety and efficacy of a starter infant formula containing Limosilactobacillus (L.) reuteri DSM 17938 and supplemented with 2'-fucosyllactose (2'FL). METHODS: Healthy infants < 14 days old (n = 289) were randomly assigned to a bovine milk-based formula containing L. reuteri DSM 17938 at 1 × 107 CFU/g (control group; CG) or the same formula with added 1.0 g/L 2'FL (experimental group; EG) until 6 months of age. A non-randomized breastfed group served as reference (BF; n = 60). The primary endpoint was weight gain through 4 months of age in the formula-fed infants. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, stooling characteristics, adverse events (AEs), fecal microbiota and metabolism, and gut immunity and health biomarkers in all feeding groups. RESULTS: Weight gain in EG was non-inferior to CG as shown by a mean difference [95% CI] of 0.26 [-1.26, 1.79] g/day with the lower bound of the 95% CI above the non-inferiority margin (-3 g/day). Anthropometric Z-scores, parent-reported stooling characteristics, gastrointestinal symptoms and associated behaviors, and AEs were comparable between formula groups. Redundancy analysis indicated that the microbiota composition in EG was different from CG at age 2 (p = 0.050) and 3 months (p = 0.052), approaching BF. Similarly, between sample phylogenetic distance (weighted UniFrac) for BF vs EG was smaller than for BF vs CG at 3-month age (p = 0.045). At age 1 month, Clostridioides difficile counts were significantly lower in EG than CG. Bifidobacterium relative abundance in EG tracked towards that in BF. Fecal biomarkers and metabolic profile were comparable between CG and EG. CONCLUSION: L. reuteri-containing infant formula with 2'FL supports age-appropriate growth, is well-tolerated and may play a role in shifting the gut microbial pattern towards that of breastfed infants. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov ( NCT03090360 ) on 24/03/2017.
Subject(s)
Infant Formula , Probiotics , Double-Blind Method , Feces/microbiology , Humans , Infant , Milk, Human/chemistry , Oligosaccharides , Phylogeny , TrisaccharidesABSTRACT
AIM: We examined the effects on gastrointestinal (GI) tolerance of a novel infant formula that combined specific fermented formula (FERM) with short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS), with a 9:1 ratio and concentration of 0.8 g/100 mL. METHODS: This prospective, double-blind, randomised, controlled trial comprised 432 healthy, term infants aged 0-28 days whose parents decided to not start, or discontinued, breastfeeding. Infant formula with scGOS/lcFOS+50%FERM, scGOS/lcFOS+15%FERM, 50%FERM and scGOS/lcFOS were tested. Parents completed standardised seven-day diaries on GI symptoms, crying, sleeping and stool characteristics each month until the infants were 17 weeks. RESULTS: All the formulas were well tolerated. At four weeks, the overall incidence of infantile colic was significantly lower (8%) with scGOS/lcFOS+50%FERM than scGOS/lcFOS (20%, p = 0.034) or 50%FERM (20%, p = 0.036). Longitudinal modelling showed that scGOS/lcFOS+50%FERM-fed infants also displayed a persistently lower daily crying duration and showed a consistent stool-softening effect than infants who received formula without scGOS/lcFOS. CONCLUSION: The combination of fermented formula with scGOS/lcFOS was well tolerated and showed a lower overall crying time, a lower incidence of infantile colic and a stool-softening effect in healthy term infants. These findings suggest for the first time that a specific infant formula has a preventive effect on infantile colic in formula-fed infants.
Subject(s)
Colic/prevention & control , Cultured Milk Products , Infant Formula , Oligosaccharides/therapeutic use , Prebiotics , Crying , Double-Blind Method , Humans , Infant , Infant, Newborn , Prospective StudiesABSTRACT
Acute hyperammonemia has a variety of etiologies and clinical manifestations. If not treated early in neonates, it leads to irreversible brain damage or death. We present a 7-day-old female patient who was brought to the emergency department with drownsiness and vomiting. Metabolic work-up revealed a blood ammonia level of 290 µmol/L (normal <100 µmol/L in neonates) with a compensated respiratory alkalosis, normal glycaemia and lactate and absence of urinary ketones. Oral feeding was stopped, an infusion of 20 % glucose was started, and sodium benzoate and arginine hydrochloride were given. After a drop of ammonemia within 12 h of treatment, it started rising again. N-carbamylglutamate (NCG) was added resulting in a rapid normalisation of ammonemia. Feedings were progressively reintroduced, the ammonia levels remained low. The results of the metabolic work-up were compatible with carbamyl phosphate synthase 1 (CPS1) or N-acetyl glutamate synthase (NAGS) deficiency. Genetic analysis confirmed the latter diagnosis with a homozygous mutation c. 1450T > C (p.W484R) in exon 6 of the NAGS gene in the patient and a carrier state in both parents. At the age of 9 months, the child is growing well with normal neurological development, under treatment with NCG 100 mg/kg/day and a normal diet. Conclusion: This case highlights the importance of keeping a high index of suspicion and early testing for ammonia levels in neonates/children with unexplained encephalopathy. In neonates with congenital hyperammonemia, NCG should always be started together with the standard management of hyperammonemia until all laboratory investigations are complete or indicate another disease.
Subject(s)
Brain/physiopathology , Glutamates/therapeutic use , Urea Cycle Disorders, Inborn/drug therapy , Amino-Acid N-Acetyltransferase/blood , Female , Humans , Infant, Newborn , Time Factors , Urea Cycle Disorders, Inborn/blood , Urea Cycle Disorders, Inborn/physiopathologyABSTRACT
BACKGROUND: Human milk comprises large fat globules enveloped by a native phospholipid membrane, whereas infant formulas contain small, protein-coated lipid droplets. Previous experimental studies indicated that mimicking the architecture of human milk lipid droplets in infant milk formula (IMF) alters lipid metabolism with lasting beneficial impact on later metabolic health. OBJECTIVES: To evaluate in a follow-up (FU) study of a randomized, controlled trial whether a Concept IMF with large, milk phospholipid-coated lipid droplets enriched with dairy lipids beneficially impacts long-term body mass index (BMI in kg/m2) trajectories and blood pressure at school age. METHODS: Fully formula-fed infants were randomly assigned to Concept IMF (n = 115) or Control IMF with conventional, small lipid droplets containing vegetable oils (n = 108) for the first 4 mo of age. A group of 88 breastfed infants served as a reference. During FU, anthropometrics were collected at 1, 3, 4, and 5 y of age, and blood pressure only at the last visit. RESULTS: Compared to Control, Concept group children had consistently lower mean BMI values during FU, with the most marked difference at 1 y of age (difference in means -0.71 kg/m2, 95% confidence interval (CI): -1.13, -0.29; P = 0.001); mean values were close to the breastfed group (P > 0.05). Contrary, the mean BMI values of the Control group were higher compared with the breastfed group during FU from 1 to 5 y of age (differences in means from 0.59 to 0.96 kg/m2, respectively; P < 0.02). At 5 y of age, the Concept group had a lower mean diastolic and arterial blood pressure compared with the Control group; -4.3mm Hg (95% CI: -7.3, -1.3; P = 0.005) and -3.7 mm Hg (95% CI: -6.5, -0.9; P = 0.01), respectively. CONCLUSIONS: Early life feeding of an innovative IMF with large, milk phospholipid-coated lipid droplets enriched with dairy lipids results in a BMI trajectory closer to breastfed infants and a lower blood pressure at school age. This trial was registered at the Dutch Trial Register as NTR3683 and NTR5538.
Subject(s)
Infant Formula , Phospholipids , Female , Humans , Infant , Blood Pressure , Body Mass Index , Follow-Up Studies , Lipid Droplets/metabolism , Milk, Human/metabolism , Phospholipids/metabolism , Child, PreschoolABSTRACT
The Cow's Milk-related Symptom Score (CoMiSSTM) was created as an awareness tool for cow's milk allergy. The aim of the present study was to analyze the inter-rater variability between a pediatrician, parents, and day to day variability. A Health Care Professional (HCP) and parent filled in the CoMiSS independently and blinded for each other to evaluate inter-rater variability. In order to validate day-to-day variability, a parent filled in the CoMiSS during 3 consecutive days and was compared to the CoMiSS scored by the HCP. The absolute agreement between parent and HCP was 75%, and 92.6% and 100% with a tolerance of 0, 1, and 2 points, respectively, resulting in excellent agreement with an intraclass correlation coefficient (ICC) 0.981 (95% Confidence Interval 0.974-0.986, p < 0.001). Day-to-day variability during 3 consecutive days resulted in an absolute agreement of 30%, increasing to 80% and 88.6% when 2 and 3 points, respectively, were accepted. The ICC was excellent for the parental prospective scores (0.93, 95% CI 0.90-0.96; p < 0.001). Day-to-day variability indicates that CoMiSS has a moderate inter-rater reliability. A very low variability was observed when scored prospectively over three days. Data suggest that the CoMiSS can reliably be scored by parents without additional training.
Subject(s)
Health Personnel , Milk Hypersensitivity/diagnosis , Parents , Research Design , Female , Humans , Infant , Male , Milk Hypersensitivity/physiopathology , Reproducibility of Results , Time FactorsABSTRACT
BACKGROUND: Lipid droplets in human milk have a mode diameter of â¼4 µm and are surrounded by a native phospholipid-rich membrane. Current infant milk formulas (IMFs) contain small lipid droplets (mode diameter â¼0.5 µm) primarily coated by proteins. A concept IMF was developed mimicking more closely the structure and composition of human milk lipid droplets. OBJECTIVES: This randomized, controlled, double-blind equivalence trial evaluates the safety and tolerance of a concept IMF with large, milk phospholipid-coated lipid droplets (mode diameter 3-5 µm) containing vegetable and dairy lipids in healthy, term infants. METHODS: Fully formula-fed infants were enrolled up to 35 d of age and randomly assigned to 1 of 2 formulas until 17 wk of age: 1) Control IMF with small lipid droplets containing vegetable oils (n = 108); or 2) Concept IMF with large, milk phospholipid-coated lipid droplets comprised of 48% dairy lipids (n = 115). A group of 88 breastfed infants served as reference. Primary outcome was daily weight gain during intervention. Additionally, number and type of adverse events, growth, and tolerance parameters were monitored. RESULTS: Equivalence of daily weight gain was demonstrated (Concept compared with Control IMF: -1.37 g/d; 90% CI: -2.71, -0.02; equivalence margin ± 3 g/d). No relevant group differences were observed in growth, tolerance and number, severity, or relatedness of adverse events. We did observe a higher prevalence of watery stools in the Concept than in the Control IMF group between 5 and 12 wk of age (P < 0.001), closer to the stool characteristics observed in the breastfed group. CONCLUSIONS: An infant formula with large, milk phospholipid-coated lipid droplets containing dairy lipids is safe, well tolerated, and supports an adequate growth in healthy infants. This trial was registered in the Dutch Trial Register (www.trialregister.nl) as NTR3683.
Subject(s)
Child Development , Infant Formula/chemistry , Lipid Droplets/metabolism , Phospholipids/metabolism , Plant Oils/metabolism , Animals , Double-Blind Method , Female , Humans , Infant , Infant Nutritional Physiological Phenomena , Infant, Newborn , Lipid Droplets/chemistry , Male , Milk, Human/chemistry , Phospholipids/chemistry , Plant Oils/chemistry , Vegetables/chemistry , Weight GainABSTRACT
Those suffering from a severe to profound sensorineural hearing loss can obtain substantial benefit from a cochlear implant prosthesis. An electrode array implanted in the inner ear stimulates auditory nerve fibers by direct injection of electrical current. A major limitation of today's technology is the imprecise control of intracochlear current flow, particularly the relatively wide spread of neural excitation. A better understanding of the intracochlear electrical fields is, therefore, required. This paper analyzes the structure of intracochlear potential measurements in relation to both the subject's anatomy and to the properties of the electrode array. An electrically equivalent network is proposed, composed of small lumped circuits for the interface impedance and for the cochlear tissues. The numerical methods required to estimate the model parameters from high-quality electrical potential recordings are developed. Finally, some models are presented for subjects wearing a Clarion CII device with a HiFocus electrode and discussed in terms of model reliability.
Subject(s)
Cochlea/physiology , Cochlear Implants , Cochlear Microphonic Potentials/physiology , Equipment Failure Analysis/methods , Models, Biological , Computer Simulation , Electric Impedance , HumansABSTRACT
HYPOTHESIS: Electrical properties of the implanted scala tympani could be accurately modeled by means of a simple resistive ladder network model. The subject-specific model parameters can be obtained from electrical field imaging (EFI) recordings. It is a powerful tool for analysis of the cochlear current spread. BACKGROUND: In EFI mode, the telemetry systems of contemporary cochlear implants can measure the intracochlear potential distribution. At present, the clinical use of EFI is typically limited to checking the implant's proper functioning. METHODS: Accurate EFI measurements and estimation algorithms have been developed to fit a small, yet physically relevant electrical model of the conductivity of the intracochlear structures. RESULTS: The model can attain up to 95% agreement with in vivo EFI data. A first discovery is that in a majority of the tested subjects, a substantial fraction of the monopolar current leaves the scala along the facial nerve canal. The role of the facial nerve canal has been confirmed by a temporal bone study and a high-resolution computed tomography (HRCT) scan in two of the implanted subjects. CONCLUSIONS: The clinical use of EFI is not limited to checking the implant's status. For the Clarion II implant, a purely resistive model is able to match in vivo EFI recordings. The model indicates that the facial nerve canal is an important conduction path to the reference electrode. EFI can provide clinically relevant information, especially in problematic cases of cochlear malformations, postoperative fibrosis/ossification, implanted otosclerotic cochleae, postoperative facial nerve stimulation, increased stimulation thresholds, and so on.
Subject(s)
Cochlear Implantation/instrumentation , Cochlear Implants , Facial Nerve/physiology , Scala Tympani/physiology , Algorithms , Cochlear Implants/standards , Electric Conductivity , Electric Impedance , Electrodes, Implanted , Humans , Models, Biological , Prosthesis Design , Scala Tympani/innervation , Temporal Bone/physiology , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE: Typically, symmetrical charge-balanced biphasic current pulses are used in cochlear implants to ensure biological safety. Theoretically, monophasic pulses are more effective, but potentially noxious, stimuli. In this study we charge-balanced such monophasic pulses during selected non-stimulated intervals, effectively leading to triphasic pulses with a 4:1 amplitude ratio between the cathodic and anodic phases. Apart from ensuring safety, this is also expected to reduce power consumption and channel interaction. MATERIAL AND METHODS: Seven experienced Clarion CII cochlear implant users with a multichannel (12-16 channels) monopolar continuous interleaved sampling (CIS) strategy participated in the study. Three different CIS strategies were fitted using the Clarion Research Interface (CRI-2). The reference was an implementation of each subject's own CIS program. The two strategies tested used triphasic pulses on the same channels, one with half-wave rectification (TP-HWR) and one without rectification (TP-NoR) at the input. Directly after fitting (i.e. without any training), speech perception (phoneme score on consonant-vowel-consonant words) was measured in silence (sound-only) and in speech-shaped background noise with signal:noise ratios (SNRs) of +5 and 0 dB. RESULTS: Speech perception with the reference via the CRI-2 was equal to that of the free-field condition with the subjects' own speech processor. With the TP-NoR strategy, speech perception improved significantly (from 89% to 93%) in silence and in the 0-dB SNR condition (from 43% to 49%). With a SNR of +5 dB, performance was stable at approximately 66%. With the TP-HWR strategy, performance increased significantly in the 0- and +5-dB SNR conditions, to 55% and 74%, respectively. Power consumption was reduced in both strategies, to 30% and 36% for TP-HWR and TP-NoR, respectively. CONCLUSION: The new triphasic strategies are most promising, with respect to both their improved speech perception and reduced power requirements. The optimal parameters will have to be identified following long-term use.
Subject(s)
Cochlear Implantation , Cochlear Implants , Speech Perception , Adult , Deafness/rehabilitation , Electric Stimulation/methods , Humans , Middle AgedSubject(s)
Pediatric Obesity/therapy , Physical Therapy Modalities/organization & administration , Practice Guidelines as Topic , Primary Health Care/organization & administration , Behavior Therapy/organization & administration , Belgium , Child , Diet, Reducing/statistics & numerical data , Exercise , Female , Humans , Male , Pediatric Obesity/prevention & controlABSTRACT
OBJECTIVE: To evaluate the impact of probiotics and prebiotics on the health of children. SOURCES: MEDLINE and LILACS were searched for relevant English and French-language articles. SUMMARY OF THE FINDINGS: Human milk is rich in prebiotic oligosaccharides and may contain some probiotics. No data suggest that addition of probiotics to infant formula may be harmful, but evidence of its efficacy is insufficient for its recommendation. Since data suggest that addition of specific prebiotic oligosaccharides may reduce infections and atopy in healthy infants, their addition to infant formula seems reasonable. Long-term health benefits of pro- and prebiotics on the developing immune system remain to be proven. Selected probiotics reduce the duration of infectious diarrhea by 1 day, but evidence in prevention is lacking, except in antibiotic-associated diarrhea. Some specific probiotics prevent necrotizing enterocolitis, and other microorganisms may be beneficial in Helicobacter pylori gastritis and in infantile colic. Evidence is insufficient to recommend probiotics in prevention and treatment of atopic dermatitis. The use of probiotics in constipation, irritable bowel syndrome, inflammatory bowel disease, and extra-intestinal infections requires more studies. CONCLUSIONS: Duration of administration, microbial dosage, and species used need further validation for both pro- and prebiotics. Unjustified health claims are a major threat for the pro- and prebiotic concept.
Subject(s)
Diarrhea, Infantile/prevention & control , Gastroenteritis/prevention & control , Oligosaccharides , Prebiotics , Probiotics/therapeutic use , Child , Diarrhea, Infantile/therapy , Humans , Infant , Infant Formula/chemistry , Milk, Human/chemistry , Oligosaccharides/therapeutic use , Prebiotics/adverse effects , Prebiotics/classification , Probiotics/classificationSubject(s)
Diabetes Mellitus, Type 2/rehabilitation , Exercise Therapy , Accidental Falls , Belgium , Body Composition , Contraindications , Diabetes Mellitus, Type 2/drug therapy , Humans , Hypoglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Muscle Strength , Physical Endurance , Physical Fitness , Risk Assessment , Societies, Medical , Spirometry , Waist CircumferenceABSTRACT
OBJETIVO: Avaliar o impacto do uso de probióticos e prebióticos na saúde das crianças. FONTES DOS DADOS: Foram pesquisados os bancos de dados MEDLINE e LILACS, selecionando-se artigos relevantes em inglês e francês. SÍNTESE DOS DADOS: O leite humano é rico em oligossacarídeos prebióticos e pode conter probióticos. Não existem dados sugerindo que a adição de probióticos a fórmulas para lactentes possa ser prejudicial, mas as evidências de sua eficácia são insuficientes para que seja recomendada. Visto que dados sugerem que a adição de oligossacarídeos prebióticos específicos pode reduzir infecções e atopia em lactentes saudáveis, sua adição parece razoável. Os benefícios a longo prazo dos pro e prebióticos para o sistema imunológico em desenvolvimento ainda precisam ser comprovados. Probióticos selecionados reduzem a duração da diarreia infecciosa em 1 dia, mas faltam evidências quanto à prevenção, exceto na diarreia associada a antibióticos. Alguns probióticos específicos previnem a enterocolite necrosante, e outros micro-organismos podem ser benéficos nos casos de gastrite por Helicobacter pylori e de cólica do lactente. Não há evidências suficientes para recomendar o uso de probióticos na prevenção e no tratamento da dermatite atópica. A utilização de probióticos nos casos de constipação, síndrome do intestino irritável, doença inflamatória intestinal e infecções extraintestinais requer mais estudos. CONCLUSÕES: A duração da administração, a dosagem microbiana e as espécies utilizadas necessitam de maior validação, tanto para probióticos quanto para prebióticos. Alegações de saúde injustificadas são uma grande ameaça ao conceito de pro e prebióticos.
OBJECTIVE: To evaluate the impact of probiotics and prebiotics on the health of children. SOURCES: MEDLINE and LILACS were searched for relevant English and French-language articles. SUMMARY OF THE FINDINGS: Human milk is rich in prebiotic oligosaccharides and may contain some probiotics. No data suggest that addition of probiotics to infant formula may be harmful, but evidence of its efficacy is insufficient for its recommendation. Since data suggest that addition of specific prebiotic oligosaccharides may reduce infections and atopy in healthy infants, their addition to infant formula seems reasonable. Long-term health benefits of pro- and prebiotics on the developing immune system remain to be proven. Selected probiotics reduce the duration of infectious diarrhea by 1 day, but evidence in prevention is lacking, except in antibiotic-associated diarrhea. Some specific probiotics prevent necrotizing enterocolitis, and other microorganisms may be beneficial in Helicobacter pylori gastritis and in infantile colic. Evidence is insufficient to recommend probiotics in prevention and treatment of atopic dermatitis. The use of probiotics in constipation, irritable bowel syndrome, inflammatory bowel disease, and extra-intestinal infections requires more studies. CONCLUSIONS: Duration of administration, microbial dosage, and species used need further validation for both pro- and prebiotics. Unjustified health claims are a major threat for the pro- and prebiotic concept.