Lacticaseibacillus rhamnosus and breastmilk are associated with a decreased risk of atopic dermatitis in very low birth weight premature infants.

In this study, we analyse the influence of nutrition during the early neonatal period on the development and prevention of atopic dermatitis (AD) in children with a history of very low birth weight (VLBW). A retrospective cohort study was performed of VLBW preterm infants to assess the risk of their developing AD during childhood, according to nutrition with breastmilk and/or probiotic supplementation during the neonatal period. The analysis focused on nutritional and early childhood follow-up data for 437 newborns, of whom 184 received probiotics up to 36 weeks postmenstrual age. AD was present in 23.5% of the study sample. Of the children who did not develop AD, 44.9% had received probiotics from birth to 36 weeks of gestational age. Therefore, the administration of probiotics to infants at less than 36 weeks postmenstrual age is associated with a protective effect against the development of AD (odds ratio (OR) 0.57; 95% confidence interval (CI) 0.34-0.93). Moreover, a protective interaction was observed between probiotic administration and breastmilk (OR 0.46; 95% CI 0.25-0.82). The adjusted data in the regression model allow us to observe a statistically significant association with the protective effect of Lacticaseibacillus rhamnosus with the development of AD at school age (OR 0.55; 95% CI 0.30-0.99). Probiotic supplementation in VLBW newborns is associated with a decreased risk of subsequent development of AD. Breastmilk strengthens the protective effect of probiotics against the development of AD.

Effectiveness of two probiotics in preventing necrotising enterocolitis in a cohort of very-low-birth-weight premature new-borns.

According to previous research, the incidence of necrotising enterocolitis (NEC) decreases after supplementation with probiotics. However, few studies have considered the equivalence or otherwise of different strains of probiotics in this respect. Accordingly, this prospective observational study was conducted in a cohort of 245 very-low-birth-weight (VLBW) new-borns to assess the prevalence of NEC after supplementation with the probiotic Inforan® (Berna Biotech, Madrid, Spain) 250 mg capsules containing 109 cfu of Lactobacillus acidophilus (ATCC 4356) and 109 cfu of Bifidobacterium bifidum (ATCC 15696); or with Bivos® (Ferring, Madrid, Spain) containing Lacticaseibacillus (formerly Lactobacillus) rhamnnosus (LGG) (ATCC 53103) (109 cfu); or with no probiotic supplementation. Statistical analysis was performed using multivariant regression for the duration of parenteral nutrition, length of neonatal intensive care unit stay, use of oxygen therapy and presence of chorioamnionitis. Of the VLBW new-borns in the study group, 65 received Infloran, 108 received Bivos and 72 received no probiotic. A significant association was observed between a reduced presence of NEC Stage ≥2 and probiotic supplementation. The odds risk (OR) obtained was 0.174 (95% confidence interval (CI): 0.032-0.936) for Infloran and 0.196 (95%CI: 0.053-0.732) for Bivos. Therefore, both probiotics are associated with a lower prevalence of NEC in VLBW new-borns, with no significant differences.

Effects of Lactobacillus fermentum CECT5716 Lc40 on infant growth and health: a randomised clinical trial in nursing women.

The breast milk microbiota has been described as a source of bacteria for infant gut colonisation. We studied the effect of Lactobacillus fermentum CECT5716 (Lc40) on growth and infection incidence of the infants, when the probiotic is administrated to the mothers. Moreover, whether such effects might depend on the interaction between the mother or infant microbiota and the probiotic administration. A total of 291 mother-infant pairs were studied for 16 weeks in a randomised double-blinded placebo-controlled multicentre trial. The Lc40 group (n=139) received 1 capsule/day containing 3×109 cfu Lc40; the control group (n=152) received 1 placebo (maltodextrin) capsule/day. A positive and significant correlation of the Staphylococcus load between breast milk and infant faeces was only observed in control group. Additionally, the weight z-score of the infants whose mothers had higher values of Lactobacillus in their breast milk were significantly higher for the Lc40 group. We observed a significant lower incidence of conjunctivitis in the infants whose mothers received Lc40. A higher load of Staphylococcus in infant faeces significantly increased the risk of respiratory infections. Such incidence, under an absent or low Staphylococcus load in the faeces, was significantly 36 times higher in the infants in the control group than in the infants in the Lc40 group. However, the protective effect of Lc40 was gradually reduced as the Staphylococcus load of the milk increased. The administration of Lc40 to nursing women might influence infant growth and health but it seems to depend on its interactions with mother or infant microbiota. Registered in the US Library of Medicine (www.clinicaltrials.gov): NCT02203877.

Probiotics to prevent necrotising enterocolitis and nosocomial infection in very low birth weight preterm infants.

The aim of the study was to determine whether routine probiotic supplementation (RPS) with Lactobacillus rhamnosus GG (LGG) or Lactobacillus acidophilus +Lactobacillus bifidum is associated with reduced risk of necrotising enterocolitis (NEC)≥Stage II in preterm neonates born at ≤32 weeks' gestation. We conducted a retrospective cohort study on the effect of probiotic supplementation in very low birth weight infants in our neonatal unit by comparing two periods: before and after supplementation. The incidence of NEC≥Stage II, late-onset sepsis and all-cause mortality was compared for an equal period 'before' (Period I) and 'after' (Period II) RPS with LGG or L. acidophillus+L. bifidum. Multivariate logistic regression analysis was conducted to adjust for relevant confounders. The study population was composed of 261 neonates (Period I v. II: 134 v. 127) with comparable gestation duration and birth weights. In <32 weeks, we observed a significant reduction in NEC≥Stage II (11·3 v. 4·8 %), late-onset sepsis (16 v. 10·5 %) and mortality (19·4 v. 2·3 %). The benefits in neonates aged ≤27 weeks did not reach statistical significance. RPS with LGG or L. acidophillus+L. bifidum is associated with a reduced risk of NEC≥Stage II, late-onset sepsis and mortality in preterm neonates born at ≤32 weeks' gestation.

[Efficacy and safety profile of cranberry in infants and children with recurrent urinary tract infection]. / Eficacia y perfil de seguridad del arándano americano en lactantes y niños con infección urinaria recurrente.

OBJECTIVE: Cranberry prophylaxis of recurrent urinary tract infection in infants has proven effective in the experimental model of the adult. There are few data on its efficacy, safety and recommended dose in the pediatric population. METHODS: A controlled, double-blind Phase III clinical trial was conducted on children older than 1 month of age to evaluate the efficacy and safety of cranberry in recurrent urinary tract infection. The assumption was of the non-inferiority of cranberry versus trimethoprim. Statistical analysis was performed using Kaplan Meier analysis. RESULTS: A total of 85 patients under 1 year of age and 107 over 1 year were recruited. Trimethoprim was prescribed to 75 patients and 117 received cranberry. The cumulative rate of urinary infection associated with cranberry prophylaxis in children under 1 year was 46% (95% CI; 23-70) in children and 17% (95% CI; 0-38) in girls, effectively at doses inferior to trimethoprim. In children over 1 year-old cranberry was not inferior to trimethoprim, with a cumulative rate of urine infection of 26% (95% CI; 12-41). The cranberry was well tolerated and with no new adverse effects. CONCLUSIONS: Our study confirms that cranberry is safe and effective in the prophylaxis of recurrent urinary tract infection in infants and children. With the doses used, their efficiency is not less than that observed for trimethoprim among those over 1 year-old. (Clinical Trials Registry ISRCTN16968287).

Assessment of the stability of proanthocyanidins and other phenolic compounds in cranberry syrup after gamma-irradiation treatment and during storage.

Shelf life of commercial cranberry syrup irradiated with gamma radiation at a rate of 5 kGy and stored for 6 months at 25 °C and 60% relative humidity (RH) and under accelerated stability conditions was investigated. High-performance liquid chromatography coupled to electrospray ionisation quadrupole-time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS) was used to characterise cranberry syrup. Afterwards, these compounds were quantified by HPLC-ESI-QTOF-MS and 4-dimethylaminocinnamaldehyde (DMAC) assay. A significant increase in the content of procyanidin B isomer 1 (from 4.4 to 7.0 µg/ml) and procyanidin A2 (from 83 to 93 µg/ml) was observed after irradiation and compared with the non-irradiated syrup. Procyanidin B isomers and prodelphinidin were stable at 25 °C during the first month of storage, whereas quercetin and some derivatives remained constant for 3 months of storage at this temperature. In short, after gamma-irradiation in dose of 5 kGy, most compounds were highly stable for a month at 25 °C.

Effectiveness of vitamin A in the prevention of complications of prematurity.

BACKGROUND: To assess the effectiveness of vitamin A supplementation in very low birth weight (VLBW) infants to prevent complications of prematurity. METHODS: This was a retrospective cohort study to determine the effectiveness of vitamin A in preventing complications of prematurity in VLBW infants. Vitamin A was delivered intramuscularly at a dose of 5000 IU, three times weekly during the first 28 days of life. RESULTS: Of the 187 eligible VLBW infants, we excluded from the analysis (due to death or transfer to another hospital), 16 infants weighing <1000 g and 17 weighing 1000-1500 g. Sixty VLBW infants received the vitamin supplement. We observed no differences between the groups in the duration of oxygen therapy or in the risk of bronchopulmonary dysplasia. The risk of sepsis was up to three times higher among the infants who were given the vitamin A supplement. CONCLUSION: Given the increased risk of sepsis in patients weighing >1000 g, the risk associated with repeated intramuscular injections of vitamin A and the modest clinical results described, we do not believe the universal administration of vitamin A to VLBW infants to be justified as prophylaxis for bronchopulmonary dysplasia.

Hypertension and Biliary Ductopenia in a Patient with Duplication of Exon 6 of the JAG1 Gene.

We describe a neonatal patient with biliary ductopenia featuring duplication of exon 6 of the JAG1 gene. Facial alterations were observed, consisting of a prominent forehead, sunken eyes, upward slanting palpebral fissures, hypertelorism, flat nasal root and prominent chin. From birth, these were accompanied by the development of haematuria and renal failure and by renal Doppler findings indicative of peripheral renal artery stenosis. JAG1 gene mutations on chromosome 20 have been associated with various anomalies, including biliary cholestasis, vertebral abnormalities, eye disorders, heart defects and facial dysmorphia. This syndrome, first described by Alagille, is an infrequent congenital disorder caused by a dominant autosomal inheritance with variable expressivity. Anatomopathological effects include the destruction and disappearance of hepatic bile ducts (ductopenia). The duplication of exon 6 of JAG1 has not previously been described as an alteration related to the Alagille syndrome with peripheral renal artery stenosis.

Urinary excretion of phenolic acids by infants and children: a randomised double-blind clinical assay.

OBJECTIVES: The present study, which is part of the ISRCTN16968287 clinical assay, is aimed at determining the effects of cranberry syrup or trimethoprim treatment for UTI. METHODS: This Phase III randomised clinical trial was conducted at the San Cecilio Clinical Hospital (Granada, Spain) with a study population of 192 patients, aged between 1 month and 13 years. Criteria for inclusion were a background of recurrent UTI, associated or otherwise with vesico-ureteral reflux of any degree, or renal pelvic dilatation associated with urinary infection. Each child was randomly given 0.2 mL/Kg/day of either cranberry syrup or trimethoprim (8 mg/mL). The primary and secondary objectives, respectively, were to determine the risk of UTI and the levels of phenolic acids in urine associated with each intervention. RESULTS: With respect to UTI, the cranberry treatment was non-inferior to trimethoprim. Increased urinary excretion of ferulic acid was associated with a greater risk of UTI developing in infants aged under 1 year (RR 1.06; CI 95% 1.024-1.1; P = 0.001). CONCLUSIONS: The results obtained show the excretion of ferulic acid is higher in infants aged under 1 year, giving rise to an increased risk of UTI, for both treatment options.

Normalization of the sleep-wake pattern and melatonin and 6-sulphatoxy-melatonin levels after a therapeutic trial with melatonin in children with severe epilepsy.

This study evaluated the sleep-wake pattern, plasma melatonin levels and the urinary excretion of its metabolite, 6-sulphatoxy-melatonin among children with severe epileptic disorders, before and after a therapeutic trial with melatonin. Ten paediatric patients, suffering from severe epileptic disorders, were selected and given a nightly dose of 3 mg of a placebo, for 1 wk; for the next 3 months, the placebo was replaced with a nightly dose of 3 mg of melatonin. At the end of each treatment period, the urinary excretion of 6-sulphatoxy-melatonin (for the intervals 09.00 - 21:00 hr or 21:00-09:00 hr) and plasma levels of melatonin (recorded at 01:00, 05:00, 09:00, 13:00, 17:00 and 21:00 hr) were recorded, over a period of 24 hr; an actigraph record was also kept. Sleep efficiency among patients who received melatonin was significantly higher than among those given the placebo, with fewer night-time awakenings. Periodic plasma melatonin levels were regained and a better control gained of convulsive episodes, in that the number of seizures decreased. We conclude that melatonin is a good regulator of the sleep-wake cycle for paediatric patients suffering from severe epilepsy, moreover, it to a better control of convulsive episodes.

Melatonin and elimination of kynurenines in children with Down's syndrome.

BACKGROUND: Heightened activity of superoxide dimutase is an effect derived from the gene dose in the trisomy of Down's syndrome (DS), and has been related to the increased production of hydrogen peroxide and with greater lipid peroxidation. Many of the degenerative changes observed in patients with DS have been associated with the pathological effects of free radicals, and for this reason it is of interest to determine the levels present in these patients of powerful antioxidant molecules such as melatonin, and of metabolites with important neuroprotector and neurotoxic consequences such as those derived from the kynurenine pathway. PATIENTS AND METHODS: A study was made of 15 children with DS, together with a control group of 15 non-DS children, matched for age and sex, examined at the Hospital Costa del Sol, Marbella, Spain. Serum melatonin and serotonin were analyzed by RIA; urinary tryptophan metabolites (kynurenine pathway) were determined during periods of light and darkness (09.00-21.00 h and 21.00-9.00 h) by thin-layer chromatography. RESULTS: The mean values of serotonin and melatonin were found to be lower in the patients with DS, although the level of nocturnal secretion of melatonin was higher. Urinary excretion of kynurenine was lower in the patients with DS, although greater quantities of kynurenic acid and anthranilic acid were excreted. CONCLUSIONS: Patients with DS present levels of plasma melatonin and urinary kynurenine that are lower than the corresponding levels in the control population, together with higher values of kynurenic acid and anthranilic acid. These circumstances constitute an added risk to these patients of damage by free radicals.

Overweight and obesity as risk factors for the asymptomatic carrier state of Neisseria meningitidis among a paediatric population.

We analysed the asymptomatic carrier state of Neisseria meningitidis in a sample of 339 children. We obtained data for the children's weight and height, in order to calculate the body mass index (BMI). The cutoff points defined by Cole were employed in determining the BMI, and the population was divided into three groups: normal, overweight and obese. Twenty carriers of N. meningitidis were identified. There was found to be a statistically significant trend to increased risk of being a carrier with increased BMI (z=2.03; P=0.04); after adjusting for age using the Mantel-Haenszel weighting method, this relationship was strengthened (z=2.38; P=0.01). Paediatric patients with increased BMI in the range of obesity present a three times greater risk of being carriers of N. meningitidis than non-obese patients, with a trend for this risk to increase with higher BMI.

Effects on the glutathione pool of the insulin-induced hypoglycaemia test.

The growth hormone (GH) stimulation test shows that hypoglycaemia can cause the generation of free radicals, or reactive oxygen species (ROS), together with the migration of amino acids, glutathione and various ions to the interior of fat or muscle cells. The aim of the present study is to evaluate the splitting of plasma glutathione into its two fractions, oxidized (GSSG) and reduced (GSH), after the induction of hypoglycaemia with insulin in the course of the GH stimulation test. We studied 41 short children (47% boys and 53% girls) at the Paediatric Department of the San Cecilio Hospital (Granada, Spain) to evaluate their size and growth. A GH stimulation test using insulin-induced hypoglycaemia was carried out, and GSSG and GSH values in plasma were determined. The glutathione level is associated with the level of glucose reached at 30 min after initiating the test. This provoked an initial reduction in the GSH/GSSG ratio, which fell to a minimum at 30 min after starting the test, although the values rose again at 60 min. The results obtained show that the insulin-induced GH stimulation test produces a decrease in plasma levels of the glutathione pool, that persists at least for 2 hours following the beginning of the test.

Serum melatonin concentration in the child with non-organic failure to thrive: comparison with other types of stress.

Human beings must adapt both to novel, unfavourable conditions and to circumstances of physical or psychological isolation. The initial response to stress depends fundamentally on the activation of the HPA axis. In regaining homeostatic equilibrium, melatonin plays a role due to its synchronising and anti-stress properties. To study the role of melatonin and the pineal gland in the organic and/or behavioural response to acute or chronic stress, 311 children were divided into two large groups: 1) Control Group - 121 healthy children classified, in turn, into 4 control subgroups, one for each pathology being studied; 2) Problem Groups, classified as traumatic stress (n=58), surgical stress (n=38), psychic stress (n=64) and febrile stress (n=30), according to pre-established clinical criteria. These groups were sub-classified according to the degree (low or high) and duration (acute or chronic) of the stress. This study used a case controlled, cross sectional design. Serum melatonin was measured by radioimmunoassay (RIA). In all the situations of acute stress, melatonin increased at a rate directly proportional to the severity and/or duration of the stress-causing stimulus. In contrast, in chronic stress, i.e. the Affective Deprivation Syndrome (or Psychological Dwarfism) with or without non-organic failure to thrive, resulted in the opposite response with a significant reduction of melatonin. In conclusion, in acute stress an increase in the bioavailability of melatonin could contribute to maintaining homeostatic balance. The lack of an appropriate response to acute stress could make some groups of patients (Affective deprivation syndrome with or without growth failure) predisposed to suffer depressive symptoms associated with a wide range of neurological, endocrinological or immunological consequences.

Influence of the antioxidant content of saliva on dental caries in an at-risk community.

OBJECTIVE: This study aims to evaluate the relationship between the total antioxidant capacity of saliva and the presence of dental caries in deciduous and permanent teeth, in a group of Saharan children. METHODS: The dental examination was carried out in accordance with the recommendations of the World Health Organization (WHO). The total antioxidant capacity of the saliva was determined by colorimetry. RESULTS: The total antioxidant capacity (TAC) of the saliva of patients with caries in deciduous teeth was 2.89 1/IC50 greater than among those without. We observed a statistically significant linear regression between the number of deciduous teeth affected by caries and the total antioxidant capacity of the saliva: y = 0.24 + 0.53 x TAC saliva (t = 2.93; p = 0.004) (95% CI of b: 0.018-0.088). CONCLUSIONS: Our results show that the amount of caries in deciduous teeth is in direct proportion to the observed TAC of saliva, and that the presence of caries in deciduous teeth is associated with caries in permanent teeth.

The presence of precursors of benign pre-B lymphoblasts (hematogones) in the bone marrow of a paediatric patient with cytomegalovirus infection.

Hematogones are normal B-lymphoid precursors that multiply in the bone marrow of small children and of adults with ferropenic anaemia, neuroblastoma or idiopathic thrombocytopenic purpura. They are not normally found in peripheral blood, and the immunophenotype is virtually indistinguishable from that of B lymphoblasts. We discuss the case of a 3-month infant with an active cytomegalovirus infection, with hepatitis and pancytopenia associated with 13% hematogones in the bone marrow.

Neuroendocrine and circadian aspects (melatonin and beta-endorphin) of atopic dermatitis in the child.

Atopic dermatitis (AD) is a disease of increasing incidence among paediatric patients. Among the factors involved in its pathogenesis is the alteration of the immune response, and so the objective of this study was to evaluate the involvement of certain neuroendocrine factors with immune properties in the development of the disease. Fifty-five subjects were selected and divided into the following three groups: healthy subjects, those diagnosed with symptomatic AD and those with asymptomatic AD. Plasma levels of melatonin and beta-endorphins were measured by radioimmunoassay, in serum samples obtained at 9 am and 9 pm, with two samples being obtained from each of the patients and controls. In the phases of AD outbreaks, there is a reduction in the serum levels of both melatonin and beta-endorphin. In the case of melatonin, the difference is statistically significant only during the day, although nocturnal levels are greater for both hormones. In AD, a central neuroendocrine dysfunction may be a primary pathogenic event. Our hypothesis is that the physiological nocturnal peak of melatonin due to pineal gland production may mask the decline of melatonin of possibly extrapineal (immunological) origin during episodes of dermatitis outbreaks. Further studies are required, particularly of neurovegetative and hormonal aspects, to better define this process. Such a definition would also be of therapeutic interest.

Melatonin levels during the first week of life and their relation with the antioxidant response in the perinatal period.

AIM: Melatonin is a potent free radical scavenger and an indirect antioxidant. Knowledge about the behavior of melatonin secretion in the early neonatal period, which may relate to its properties at a vital stage during very high antioxidant demands, is limited. PATIENTS AND METHODS: We studied 35 newborns admitted to the Neonatal Unit with respiratory distress syndrome (RDS) and with no signs of sepsis, severe anemia, hemodynamic compromise or malformation. The gestational age of the newborns was 26-40 weeks (mean value 32.5 weeks) and the weight at birth was 870-4,400 g (mean value 1,800 g). They were classified into two groups: 1,500 g birthweight. In all cases, at 09:00 h on their 1st, 3rd and 7th days of life, serum melatonin was measured by RIA. The clinical history was recorded and treatment and follow-up were performed according to established neonatology practice, and the resultant data recorded. Informed consent from the parents or guardians was obtained in accordance with the Declaration of Helsinki. Statistical analysis was carried out using ANOVA-II (factor I: day of sample; factor II: birthweight). RESULTS: There were significant increases in melatonin levels with increasing birthweight (p = 0.017), but no changes by day of sample. Although in both study groups melatonin levels increased during the first few days this was not statistically significant. CONCLUSIONS: In newborns of low birthweight, we report high melatonin concentrations in the morning and during the first week of life. These increase with maturation, and at full-term were similar to nocturnal levels during the acrophase of pineal gland secretion in toddlers and schoolage children, when pineal gland secretion is maximal and takes place reflecting environmental variations. In the early neonatal period these high levels of melatonin seem to derive from extrapineal sources, which mature to provide antioxidant protection in accordance with other elements of the antioxidant network to compensate for the high levels of oxidative stress that are present in the perinatal period.