Potential roles and clinical utility of prebiotics in newborns, infants, and children: proceedings from a global prebiotic summit meeting, New York City, June 27-28, 2008

Initial bacterial colonization, including colonization with health-positive bacteria, such as bifidobacteria and lactobacilli, is necessary for the normal development of intestinal innate and adaptive immune defenses. The predominance of beneficial bacteria in the gut microflora of breast-fed infants is thought to be, at least in part, supported by the metabolism of the complex mixture of oligosaccharides present in human breast milk, and a more adult-type intestinal microbiota is found in formula-fed infants. Inadequate gut colonization, dysbiosis, may lead to an increased risk of infectious, allergic, and autoimmune disorders later in life. The addition of appropriate amounts of selected prebiotics to infant formulas can enhance the growth of bifidobacteria or lactobacilli in the colonic microbiota and, thereby, might produce beneficial effects. Among the substrates considered as prebiotics are the oligosaccharides inulin, fructo-oligosaccharides, galacto-oligosaccharides, and lactulose. There are some reports that such prebiotics have beneficial effects on various markers of health. For example, primary prevention trials in infants have provided promising data on prevention of infections and atopic dermatitis. Additional well-designed prospective clinical trials and mechanistic studies are needed to advance knowledge further in this promising field. (J Pediatr 2009;155:S61-70).

Newborn behavior and risk of postnatal depression in the mother

The aim of this study was to assess which behavioral characteristics of the newborn infant are associated with an increased risk of postnatal depression (PND) in the mother. A total of 497 mothers from a prospective cohort study were recruited during the last trimester of pregnancy. Infants were evaluated at 3 days with the Brazelton Neonatal Behavioral Scale. Maternal PND was assessed at 6 weeks postpartum with the Edinburgh Postnatal Depression Scale. Behavioral characteristics of the infant predicted the occurrence of PND, independent of other risk factors for PND: The lower the infants' orientation performance, the higher the risk that the mother would present with PND 6 weeks after delivery. As orientation capacities play a key role in the interactional skills developed between mothers and their infants, an infant who is difficult to engage in interaction may contribute to the risk of PND.

Influence of birth weight on gene regulators of lipid metabolism and utilization in subcutaneous adipose tissue and skeletal muscle of neonatal pigs.

Epidemiological studies suggest that low-birth weight infants show poor neonatal growth and increased susceptibility to metabolic syndrome, in particular, obesity and diabetes. Adipose tissue development is regulated by many genes, including members of the peroxisome proliferator-activated receptor (PPAR) and the fatty acid-binding protein (FABP) families. The aim of this study was to determine the influence of birth weight on key adipose and skeletal muscle tissue regulating genes. Piglets from 11 litters were ranked according to birth weight and 3 from each litter assigned to small, normal, or large-birth weight groups. Tissue samples were collected on day 7 or 14. Plasma metabolite concentrations and the expression of PPARG2, PPARA, FABP3, and FABP4 genes were determined in subcutaneous adipose tissue and skeletal muscle. Adipocyte number and area were determined histologically. Expression of FABP3 and 4 was significantly reduced in small and large, compared with normal, piglets in adipose tissue on day 7 and in skeletal muscle on day 14. On day 7, PPARA and PPARG2 were significantly reduced in adipose tissue from small and large piglets. Adipose tissue from small piglets contained more adipocytes than normal or large piglets. Birth weight had no effect on adipose tissue and skeletal muscle lipid content. Low-birth weight is associated with tissue-specific and time-dependent effects on lipid-regulating genes as well as morphological changes in adipose tissue. It remains to be seen whether these developmental changes alter an individual's susceptibility to metabolic syndrome.

Effect of facilitation of local maternal-and-newborn stakeholder groups on neonatal mortality : cluster-randomized controlled trial

BACKGROUND: Facilitation of local women's groups may reportedly reduce neonatal mortality. It is not known whether facilitation of groups composed of local health care staff and politicians can improve perinatal outcomes. We hypothesised that facilitation of local stakeholder groups would reduce neonatal mortality (primary outcome) and improve maternal, delivery, and newborn care indicators (secondary outcomes) in Quang Ninh province, Vietnam. METHODS AND FINDINGS: In a cluster-randomized design 44 communes were allocated to intervention and 46 to control. Laywomen facilitated monthly meetings during 3 years in groups composed of health care staff and key persons in the communes. A problem-solving approach was employed. Births and neonatal deaths were monitored, and interviews were performed in households of neonatal deaths and of randomly selected surviving infants. A latent period before effect is expected in this type of intervention, but this timeframe was not pre-specified. Neonatal mortality rate (NMR) from July 2008 to June 2011 was 16.5/1,000 (195 deaths per 11,818 live births) in the intervention communes and 18.4/1,000 (194 per 10,559 live births) in control communes (adjusted odds ratio [OR] 0.96 [95% CI 0.73-1.25]). There was a significant downward time trend of NMR in intervention communes (p = 0.003) but not in control communes (p = 0.184). No significant difference in NMR was observed during the first two years (July 2008 to June 2010) while the third year (July 2010 to June 2011) had significantly lower NMR in intervention arm: adjusted OR 0.51 (95% CI 0.30-0.89). Women in intervention communes more frequently attended antenatal care (adjusted OR 2.27 [95% CI 1.07-4.8]). CONCLUSIONS: A randomized facilitation intervention with local stakeholder groups composed of primary care staff and local politicians working for three years with a perinatal problem-solving approach resulted in increased attendance to antenatal care and reduced neonatal mortality after a latent period. TRIAL REGISTRATION: Current Controlled Trials ISRCTN44599712. Please see later in the article for the Editors' Summary.

Perinatal factors associated with early deaths of preterm infants born in Brazilian Network on Neonatal Research centers

Objective: To evaluate perinatal factors associated with early neonatal death in preterm infants with birth weights (BW) of 400-1,500 g.Methods: A multicenter prospective cohort study of all infants with BW of 400-1,500 g and 23-33 weeks of gestational age (GA), without malformations, who were born alive at eight public university tertiary hospitals in Brazil between June of 2004 and May of 2005. Infants who died within their first 6 days of life were compared with those who did not regarding maternal and neonatal characteristics and morbidity during the first 72 hours of life. Variables associated with the early deaths were identified by stepwise logistic regression.Results: A total of 579 live births met the inclusion criteria. Early deaths occurred in 92 (16%) cases, varying between centers from 5 to 31%, and these differences persisted after controlling for newborn illness severity and mortality risk score (SNAPPE-II). According to the multivariate analysis, the following factors were associated with early intrahospital neonatal deaths: gestational age of 23-27 weeks (odds ratio - OR = 5.0; 95%CI 2.7-9.4), absence of maternal hypertension (OR = 1.9; 95%CI 1.0-3.7), 5th minute Apgar 0-6 (OR = 2.8; 95%CI 1.4-5.4), presence of respiratory distress syndrome (OR = 3.1; 95%CI 1.4-6.6), and network center of birth.Conclusion: Important perinatal factors that are associated with early neonatal deaths in very low birth weight preterm infants can be modified by interventions such as improving fetal vitality at birth and reducing the incidence and severity of respiratory distress syndrome. The heterogeneity of early neonatal rates across the different centers studied indicates that best clinical practices should be identified and disseminated throughout the country.

Muscle protein metabolism in neonatal alloxan-administered rats: effects of continuous and intermittent swimming training

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alkaline ribonuclease activity in maternal serum and in serum of newborns from birth up to thirty days of age. A study made with full-term appropriate-, full-term small- and preterm appropriate-for-gestational-age infants

We have studied the alkaline ribonuclease (RNase) activity in maternal serum and serum of full-term small- (T-SGA), full-term appropriate- (T-AGA) and preterm appropriate-for-gestational age (PT-AGA) newborns. A significantly lower level of RNase was observed in T-AGA and T-SGA newborns on the 30th day of age and in PT-AGA newborns on the 15th and 30th days of age, as compared to other T-AGA, T-SGA and PT-AGA groups of infants at birth. RNase activity was significantly higher in cord blood than in the maternal blood in all categories studied. Moreover, in preterm newborns, RNase activity in cord blood was significantly higher in those presenting a lower gestational age. We did not observe any significant difference in RNase levels in the cord blood of newborns from the 3 categories studied. The same results were observed concerning maternal blood. We, therefore, conclude that RNase activity in cord blood or in maternal blood is not a very statisfactory indicator of fetal malnutrition.

Gut intraepithelial lymphocyte counts in neonates, infants and children

Intraepithelial lymphocyte (IEL) counts were histologically assessed in the jejunum, ileum and appendix of 39 neonates (0-28 days), 32 infants (1-9 months) and 13 children (1-9 years). Small intestinal mucosa samples were obtained from 73 autopsies, and from 8 surgical and 3 aspirative biopsies. IEL counts of specimens from the jejunum, ileum and appendix gave similar results in the same patient. The number of IEL counts was significantly lower in neonates for all three segments. The difference between infants and children was more marked in the jejunum than in the ileum, although this was not significant. In the appendix, there was no difference between the different age groups. Our results indicate that postnatal expansion of IEL occurs homogeneously along the gut after the neonatal period.

Systemic and local teething disturbances: Prevalence in a clinic for infants

The aim of this study was to present data as reported by parents on primary tooth eruption and the occurrence of local and systemic manifestations in children ages 0 to 3 years seen at the baby clinic of the Araçatuba Dental School, UNESP, São Paulo, Brazil. Data from 1,813 records were analyzed, yielding 1,165 records suitable for review. Some type of local and/or systemic manifestation during primary tooth eruption was reported for 95% (1,129) children studied. The predominant manifestation was gingival irritation (85%), while the least frequent symptom (26%) was a runny nose.

Secretion of middle ear in infants - Occurrence, recurrence and related factors

Objective: The present study aimed at evaluating the occurrence and recurrence of middle ear effusion and possible associated factors in the first two years of life of 190 newborns and infants, participants in the interdisciplinary prevention, detection, and intervention program at the Clínica de Educação para Saúde of Universidade do Sagrado Coração, Methods: Newborns and infants were monthly submitted to anamneses, otoscopy, behavioral hearing assessment using sound instruments and pure tones (pediatric audiometry) and tympanometry. Results: The results revealed that 68.4% of infants presented one or more episodes of middle ear effusion during their two first years, with more recurrence among males. Peak occurrence was between four and 12 months of age and, the earlier the first episode, the higher the probability of recurrence. Greatest incidence was during May and August. It was found that, of the variables investigated, the period of exclusive breastfeeding actuated as a protector factor. With respect of risk factors, it was observed that passive smoking, gastro-esophageal reflux and respiratory allergy were related with the recurrences of effusion. Conclusion: Findings revealed the importance of periodic auditory follow-up for infants during their first two years of life, considered to be the critical period of auditory system maturation, during which sensory deprivation can be responsible for damage to the development of speech, language and other auditory abilities. Copyright © 2005 by Sociedade Brasileira de Pediatria.

Melatonin effects on macrophage in diabetic rats and the maternal hyperglycemic implications for newborn rats

The modulatory effects of melatonin (MLT) on maternal and fetal macrophages in diabetic rats and the repercussion of maternal hyperglycemia on fetus-placenta parameters were studied. This was achieved by determining maternal and fetal blood glucose, weight and superoxide release by macrophages. Placental weight, protein, DNA and RNA concentration were also verified. Superoxide levels in macrophages isolated from pregnant healthy rats were higher than those obtained from diabetic animals. Melatonin increased significantly in the macrophages of control animals (18.7 ± 2.8 with MLT compared to 14.2 ± 1.6 without MLT) but decreased with melatonin stimulation in diabetic rats (8.8 ± 1.4 with MLT compared to 12.9 ± 2.1 without MLT). Melatonin significantly decreased superoxide levels in newborns of diabetic mothers (7.3 ± 3.4) compared to those of healthy (14.6 ± 3.5) mothers. Blood glucose levels were significantly higher (p<0.05) in newborn rats of diabetic mothers (108.3 ± 7.8) compared to blood glucose levels in newborn control rats (81.2 ± 10.7). Body weight was significantly higher (p <0.05) in the offspring of rats with alloxan-induced diabetes. No statistical difference (p> 0.05) was observed in the placenta weight, total protein concentration and DNA of rats. The RNA concentration was significantly lower (p <0.05) in the placentas of rats with alloxan-induced diabetes (156.1 ± 71.8), when compared to the concentration of RNA in the placentas of control rats (239.5 ± 77.3). In conclusion, maternal hyperglycemia modified the fetus-placental parameters and melatonin modulated the macrophages activation in maternal and fetal diabetic rats.

Preeclampsia: Effect on the fetus and newborn

Preeclampsia (PE) is the most common medical complication in pregnancy and a major cause of maternal and fetal morbidity and mortality. This disease is a great challenge for obstetricians because there are no effective interventions to treat or prevent it, and antenatal care involves a difficult balance between the risks for women to continue pregnancy and the risks for the baby's early birth. Fetal complications in PE are directly related to gestational age and the severity of maternal disease and include increased rates of preterm delivery, intrauterine growth restriction, placental abruption, and perinatal death. The major complications for the newborn are related to prematurity, although the data on the morbidity and outcome for preterm infants of women who have PE are conflicting, and few studies address this issue. The pathogenesis of PE involves abnormal placentation associated with immune and vascular events that result in endothelial dysfunction and clinical manifestations of PE. This disease has been associated with imbalance in angiogenic factors and oxidative stress. Nevertheless, only a limited number of studies have been carried out on fetuses and newborns that suggest that infants born from women who have PE are exposed to increased oxidative stress. Because oxidative stress and free radicals may play roles in several neonatal diseases, a direct effect of maternal disease on neonatal outcome is expected, and further research on such neonates, in the short- and long-term, is urgently needed. © 2011 by the American Academy of Pediatrics.

Early light reduction for preventing retinopathy of prematurity in very low birth weight infants

BackgroundRetinopathy of prematurity (ROP) is a complex condition of the developing retinal blood vessels and is one of the leading causes of preventable childhood blindness. Several risk factors for ROP have been studied over the past 50 years. Among them, general immaturity (low birth weight and low gestational age) and prolonged oxygen therapy have been consistently related to disease onset. However, it is understood that the progression of the disease is multifactorial and may be associated with others risk factors, such as multiple gestation, apnoea, intracranial haemorrhage, anaemia, sepsis, prolonged mechanical ventilation, multiple transfusions and light exposure. Furthermore, the precise role of these individual factors in the development of the disease has not yet been well established.ObjectivesTo determine whether the reduction of early environmental light exposure reduces the incidence of retinopathy of prematurity (ROP) or poor ROP outcomes among very low birth weight infants.Search methodsWe searched the following databases: the Cochrane Neonatal Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, CINAHL, HealthSTAR, Science Citation Index Database, CANCERLIT, the Oxford Database of Perinatal Trials and www.clinicaltrials.gov. We also searched previous reviews including cross-references, abstracts, conference and symposia proceedings, and contacted expert informants. This search was updated in October 2012.Selection criteriaRandomised or quasi-randomised controlled trials that reduced light exposure to premature infants within the first seven days following birth were considered for this review. We also considered cluster-randomised controlled trials.Data collection and analysisData on clinical outcomes including any acute ROP and poor ROP outcome were extracted by both review authors independently and consensus reached. We conducted data analysis according to the standards of the Cochrane Neonatal Review Group.Main resultsData from four randomised trials with a total of 897 participants failed to show any reduction in acute ROP or poor ROP outcome with the reduction of ambient light to premature infants' retinas. The overall methodological quality of the included studies was about evenly split between those in which the classification was unclear and those in which the studies were categorised as low risk of bias. There was no report on the secondary outcomes considered in this review: quality of life measures; and time of exposure to oxygen.Authors' conclusionsThe evidence shows that bright light is not the cause of retinopathy of prematurity and that the reduction of exposure of the retinas of premature infants to light has no effect on the incidence of the disease.

Late-Onset Sepsis in very Low Birth Weight Infants: A Brazilian Neonatal Research Network Study

Background: Late-onset sepsis (LOS) is an important cause of morbidity and mortality in very low birth weight (VLBW) infants.Aim: To determine the incidence, risk factors and etiology of LOS.Methods: LOS was investigated in a multicenter prospective cohort of infants at eight public university neonatal intensive care units (NICUs). Inclusion criteria included inborn, 23-33 weeks of gestational age, 400-1499 g birth weight, who survived >3 days.Results: Of 1507 infants, 357 (24%) had proven LOS and 345 (23%) had clinical LOS. Infants with LOS were more likely to die. The majority of infections (76%) were caused by Gram-positive organisms. Independent risk factors for proven LOS were use of central venous catheter and mechanical ventilation, age at the first feeding and number of days on parenteral nutrition and on mechanical ventilation.Conclusion: LOS incidence and mortality are high in Brazilian VLBW infants. Most risk factors are associated with routine practices at NICU.

Practices related to late-onset sepsis in very low-birth weight preterm infants

Objective: To understand the practices related to late-onset sepsis (LOS) in the centers of the Brazilian Neonatal Research Network, and to propose strategies to reduce the incidence of LOS.Methods: This was a cross-sectional descriptive multicenter study approved by the Ethics Committee. Three questionnaires regarding hand hygiene, vascular catheters, and diagnosis/treatment of LOS were sent to the coordinator of each center. The center with the lowest incidence of LOS was compared with the others.Results: All 16 centers answered the questionnaires. Regarding hand hygiene, 87% use chlorhexidine or 70% alcohol; alcohol gel is used in 100%; 80% use bedside dispensers (50% had one dispenser for every two beds); practical training occurs in 100% and theoretical training in 70% of the centers, and 37% train once a year. Catheters: 94% have a protocol, and 75% have a line insertion team. Diagnosis/treatment: complete blood count and blood culture are used in 100%, PCR in 87%, hematological scores in 75%; oxacillin and aminoglycosides is the empirical therapy in 50% of centers. Characteristics of the center with lowest incidence of LOS: stricter hand hygiene; catheter insertion and maintenance groups; use of blood culture, PCR, and hematological score for diagnosis; empirical therapy with oxacillin and aminoglycoside.Conclusion: The knowledge of the practices of each center allowed for the identification of aspects to be improved as a strategy to reduce LOS, including: alcohol gel use, hand hygiene training, implementation of catheter teams, and wise use of antibiotic therapy. (C) 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.