Starter formula enriched in prebiotics and probiotics ensures normal growth of infants and promotes gut health: a randomized clinical trial.

This corrects the article DOI: 10.1038/pr.2016.270.

Starter formula enriched in prebiotics and probiotics ensures normal growth of infants and promotes gut health: a randomized clinical trial.

BACKGROUND: Prebiotics and probiotics exert beneficial effects by modulating gut microbiota and immune system. This study evaluates efficacy and safety of an infant formula containing bovine milk-derived oligosaccharides and Bifidobacterium animalis ssp lactis (B. lactis) (CNCM I-3446) on incidence of diarrhea and febrile infections during the first year of life (primary outcome). METHODS: Full-term infants receiving Test or Control (without bovine milk-derived oligosaccharide and B. lactis) formulae were enrolled in a multicenter, randomized, controlled, and double-blind trial with a reference breastfeeding group. . RESULTS: 413 infants were assigned between Test (n = 206) and Control (n = 207) formula. There was no significant difference for diarrhea and febrile infections incidence between groups at 6 (odds ratio (95% confidence interval) = 0.56 (0.26-1.15), P = 0.096) and 12 mo (odds ratio = 0.66 (0.38-1.14), P = 0.119). Test formula was well tolerated, anthropometrics parameters were not significantly different between groups and aligned with WHO growth standards up to 12 mo. Data from test group showed that gut microbiota pattern, fecal IgA and stool pH were brought to be closer to those of breastfed infants. CONCLUSION: An infant formula enriched with bovine milk-derived oligosaccharide and B. lactis supports normal infant growth, is well tolerated and improves intestinal health markers. No differences in diarrhea and febrile infection incidence were found in the population studied.

Eating problems in very low birthweight children are highest during the first year and independent risk factors include duration of invasive ventilation.

AIM: This study aimed to investigate the incidence and time course of eating problems in children born with a very low birthweight (VLBW) and to identify the perinatal risk factors. METHODS: We used a standard eating questionnaire to study 178 VLBW children, born between 1999 and 2005 at a median of 28.6 weeks' gestation and median birthweight of 1058 g, for the first 6 years of life. The control group comprised 74 children born full term. RESULTS: Just under a quarter of the VLBW children (24.7%) had eating problems before the age of one, and by the age of two, the cumulative incidence had increased to 28.6%. The 69 children born between 1999 and 2001 had eating problems up to the age of six, but 76.5% were resolved by the age of four. Independent risk factors were gestational age at birth, and duration of invasive ventilation and eating problems were associated with significantly poor growth. CONCLUSION: The incidence of eating problems in VLBW children was highest during the first year of life. Gestational age and the duration of invasive ventilation were independent risk factors, and eating problems contributed to continued growth failure. Eating problems require early recognition and intervention.

Comparison of two neonatal pain assessment tools (Children and Infant's Postoperative Pain Scale and the Neonatal Facial Coding System-Revised) and their relations to clinicians' intuitive pain estimates.

BACKGROUND: Many neonatal observational pain assessment tools are available. Their application in clinical settings, however, has been limited. A further difficulty for decision makers may be to choose among the variety of available tools the appropriate one(s) for their patients. Aims of the present study were (1) to compare two commonly cited neonatal pain assessment tools, the Neonatal Facial Coding System-Revised (NFCS-R) and the Children and Infant's Postoperative Pain Scale (CHIPPS), with regard to their psychometric qualities and (2) to explore intuitive clinicians' ratings by relating them to the tools' items. METHODS: Three coders applied both pain assessment tools to videos of 44 neonates who were videotaped while undergoing a painful and a stressful procedure. Clinicians rated the pain neonates experienced on a numerical rating scale. Analyses of variances and regression analyses were used to investigate whether tools could discriminate between the procedures and whether tools' items were predictors of intuitive clinicians' ratings. RESULTS: Interrater reliability, internal consistency and relative convergent validity were high for both assessment tools. Both tools discriminated between painful and stressful situations equally well. Roughly one third of variance in clinicians' intuitive ratings could be explained by items of each tool, however, no single item was found to be a significant predictor. CONCLUSIONS: Both pain assessment tools performed equally well regarding psychometric comparisons. Therefore, clinical utility needs to be considered when having to choose. Possibilities of improvement for both tools were identified. Cues clinicians base their intuitive pain judgements need to be further investigated. SIGNIFICANCE: Psychometric comparisons of neonatal assessment tools provide useful information that can help health care professionals to choose among tools and researchers to improve them. Both tools compared here performed psychometrically equally well. Their clinical utility, however, can be improved, for example by providing a manual (CHIPPS) and training opportunities.

Pain-specific Reactions or Indicators of a General Stress Response?: Investigating the Discriminant Validity of 5 Well-established Neonatal Pain Assessment Tools.

OBJECTIVES: There are many neonatal pain assessment tools available. However, systematic psychometric comparisons between tools are lacking, particularly those comparing tools regarding their ability to differentiate between pain and stressful procedures. The aim of the present study was to compare 5 widely used neonatal pain assessment tools: Neonatal Facial Coding System-Revised, Premature Infant Pain Profile-Revised, Neonatal Pain, Agitation and Sedation Scale, Neonatal Infant Pain Scale, and Bernese Pain Scale Neonates. MATERIALS AND METHODS: Two coders applied all pain assessment tools to videos of 42 neonates who were videotaped during a pain and a stressful procedure. RESULTS: Interrater reliability and relative convergent validity were high and internal consistency good to excellent for all 5 assessment tools. All tools discriminated between painful and stressful events. Tools differed regarding their overall effect sizes as well as their items' effect sizes. Behavioral items tended to have larger effect sizes than physiological ones. Yet, effect sizes of items from one behavioral category differed greatly, which may be due to different operationalization of coding schemes. DISCUSSION: Given that the tools investigated in the present study appear to be fairly comparable psychometrically. Aspects of their clinical utility are discussed and ways of improvement identified.

Influence of PCO2 Control on Clinical and Neurodevelopmental Outcomes of Extremely Low Birth Weight Infants.

BACKGROUND: Levels or fluctuations in the partial pressure of CO2 (PCO2) may affect outcomes for extremely low birth weight infants. OBJECTIVES: In an exploratory analysis of a randomized trial, we hypothesized that the PCO2 values achieved could be related to significant outcomes. METHODS: On each treatment day, infants were divided into 4 groups: relative hypocapnia, normocapnia, hypercapnia, or fluctuating PCO2. Ultimate assignment to a group for the purpose of this analysis was made according to the group in which an infant spent the most days. Statistical analyses were performed with analysis of variance (ANOVA), the Kruskal-Wallis test, the χ2 test, and the Fisher exact test as well as by multiple logistic regression. RESULTS: Of the 359 infants, 57 were classified as hypocapnic, 230 as normocapnic, 70 as hypercapnic, and 2 as fluctuating PCO2. Hypercapnic infants had a higher average product of mean airway pressure and fraction of inspired oxygen (MAP × FiO2). For this group, mortality was higher, as was the likelihood of having moderate/severe bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and poorer neurodevelopment. Multiple logistic regression analyses showed an increased risk for BPD or death associated with birth weight (p < 0.001) and MAP × FiO2 (p < 0.01). The incidence of adverse neurodevelopment was associated with birth weight (p < 0.001) and intraventricular hemorrhage (IVH; p < 0.01). CONCLUSIONS: Birth weight and respiratory morbidity, as measured by MAP × FiO2, were the most predictive of death or BPD and NEC, whereas poor neurodevelopmental outcome was associated with low birth weight and IVH. Univariate models also identified PCO2. Thus, hypercapnia seems to reflect greater disease severity, a likely contributor to differences in outcomes.

Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO2 targets: the PHELBI follow-up study.

BACKGROUND: Tolerating higher partial pressures of carbon dioxide (PCO2) in mechanically ventilated extremely low birthweight infants to reduce ventilator-induced lung injury may have long-term neurodevelopmental side effects. This study analyses the results of neurodevelopmental follow-up of infants enrolled in a randomised multicentre trial. METHODS: Infants (n=359) between 400 and 1000 g birth weight and 23 0/7-28 6/7 weeks gestational age who required endotracheal intubation and mechanical ventilation within 24 hours of birth were randomly assigned to high PCO2 or to a control group with mildly elevated PCO2 targets. Neurodevelopmental follow-up examinations were available for 85% of enrolled infants using the Bayley Scales of Infant Development II, the Gross Motor Function Classification System (GMFCS) and the Child Development Inventory (CDI). RESULTS: There were no differences in body weight, length and head circumference between the two PCO2 target groups. Median Mental Developmental Index (MDI) values were 82 (60-96, high target) and 84 (58-96, p=0.79). Psychomotor Developmental Index (PDI) values were 84 (57-100) and 84 (65-96, p=0.73), respectively. Moreover, there was no difference in the number of infants with MDI or PDI <70 or <85 and the number of infants with a combined outcome of death or MDI<70 and death or PDI<70. No differences were found between results for GMFCS and CDI. The risk factors for MDI<70 or PDI<70 were intracranial haemorrhage, bronchopulmonary dysplasia, periventricular leukomalacia, necrotising enterocolitis and hydrocortisone treatment. CONCLUSIONS: A higher PCO2 target did not influence neurodevelopmental outcomes in mechanically ventilated extremely preterm infants. Adjusting PCO2 targets to optimise short-term outcomes is a safe option. TRIAL REGISTRATION NUMBER: ISRCTN56143743.

Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial.

BACKGROUND: Tolerating higher partial pressure of carbon dioxide (pCO2) in mechanically ventilated, extremely low birthweight infants might reduce ventilator-induced lung injury and bronchopulmonary dysplasia. We aimed to test the hypothesis that higher target ranges for pCO2 decrease the rate of bronchopulmonary dysplasia or death. METHODS: In this randomised multicentre trial, we recruited infants from 16 tertiary care perinatal centres in Germany with birthweight between 400 g and 1000 g and gestational age 23-28 weeks plus 6 days, who needed endotracheal intubation and mechanical ventilation within 24 h of birth. Infants were randomly assigned to either a high target or control group. The high target group aimed at pCO2 values of 55-65 mm Hg on postnatal days 1-3, 60-70 mm Hg on days 4-6, and 65-75 mm Hg on days 7-14, and the control target at pCO2 40-50 mmHg on days 1-3, 45-55 mm Hg on days 4-6, and 50-60 mm Hg on days 7-14. The primary outcome was death or moderate to severe bronchopulmonary dysplasia, defined as need for mechanical pressure support or supplemental oxygen at 36 weeks postmenstrual age. Cranial ultrasonograms were assessed centrally by a masked paediatric radiologist. This trial is registered with the ISRCTN registry, number ISRCTN56143743. RESULTS: Between March 1, 2008, and July 31, 2012, we recruited 362 patients of whom three dropped out, leaving 179 patients in the high target and 180 in the control group. The trial was stopped after an interim analysis (n=359). The rate of bronchopulmonary dysplasia or death in the high target group (65/179 [36%]) did not differ significantly from the control group (54/180 [30%]; p=0·18). Mortality was 25 (14%) in the high target group and 19 (11%; p=0·32) in the control group, grade 3-4 intraventricular haemorrhage was 26 (15%) and 21 (12%; p=0·30), and the rate of severe retinopathy recorded was 20 (11%) and 26 (14%; p=0·36). INTERPRETATION: Targeting a higher pCO2 did not decrease the rate of bronchopulmonary dysplasia or death in ventilated preterm infants. The rates of mortality, intraventricular haemorrhage, and retinopathy did not differ between groups. These results suggest that higher pCO2 targets than in the slightly hypercapnic control group do not confer increased benefits such as lung protection. FUNDING: Deutsche Forschungsgemeinschaft.

Lung volume reduction surgery in preterm infants with bronchopulmonary dysplasia. A case report.

KEY CLINICAL MESSAGE: A preterm infant at the age of 9 months with severe bronchopulmonary dysplasia (BPD) and large lobar emphysema, compromising ventilation into adjacent lobes with respiratory failure under maximal conservative treatment and pulmonary arterial hypertension recovered initially well after bilateral lung volume reduction surgery, but progressed 2 years later into respiratory failure. The initial imaging with Magnetic-Resonance-Imaging (MRI)-Angiography and decision-making was difficult and interdisciplinary treatment was essential.