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Objective: To increase the understanding of social adjustment and autism spectrum disorder symptoms in adolescents born very preterm by studying the role of emotion recognition and cognitive control processes in the relation between very preterm birth and social adjustment., Study Design: A Dutch cohort of 61 very preterm and 61 full-term adolescents aged 13 years participated. Social adjustment was rated by parents, teachers, and adolescents and autism spectrum disorder symptoms by parents. Emotion recognition was assessed with a computerized task including pictures of child faces expressing anger, fear, sadness, and happiness with varying intensity. Cognitive control was assessed using a visuospatial span, antisaccade, and sustained attention to response task. Performance measures derived from these tasks served as indicators of a latent cognitive control construct, which was tested using confirmatory factor analysis. Mediation analyses were conducted with emotion recognition and cognitive control as mediators of the relation between very preterm birth and social problems., Results: Very preterm adolescents showed more parent- and teacher-rated social problems and increased autism spectrum disorder symptomatology than controls. No difference in self-reported social problems was observed. Moreover, very preterm adolescents showed deficits in emotion recognition and cognitive control compared with full-term adolescents. The relation between very preterm birth and parent-rated social problems was significantly mediated by cognitive control but not by emotion recognition. Very preterm birth was associated with a 0.67-SD increase in parent-rated social problems through its negative effect on cognitive control., Conclusions: The present findings provide strong evidence for a central role of impaired cognitive control in the social problems of adolescents born very preterm., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Fetal brain maturation is disrupted by preterm birth. Inflammation during the neonatal period may further harm neurodevelopmental outcomes. The present study aimed to determine the effect of short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides/pectin-derived acidic oligosaccharides (scGOS/lcFOS/pAOS) on neurodevelopmental outcomes measured by Bayley Scales of Infant and Toddler Development in preterm infants at 24 months., Methods: In this randomized controlled trial, scGOS/lcFOS/pAOS or placebo was supplemented between days 3 and 30 of life. Serum samples at day 1, 7, and 14 were analyzed for cytokine levels. Stool samples at day 1, 7, 14, and 30 were measured for bacterial count and bifidobacteria percentage. At 24 months corrected age infants were followed up by a blinded pediatric psychologist for the Bayley Scales of Infant and Toddler Development II or III., Results: Seventy-seven of one hundred one (76%) eligible infants participated in the follow-up study. Neurodevelopmental outcomes were not different in the scGOS/lcFOS/pAOS and placebo group. Infections during the neonatal period, lower percentages of bifidobacteria at day 7 (F = 3.8, P = 0.05) and day 14 (F = 5.0, P = 0.02) and higher levels of Interleukine (IL)-1β (F = 4.0, P = 0.04) and IL-8 (F = 8.0, P = 0.01) at day 7 are associated with lower mental developmental index. Lower psychomotor outcomes are associated with IL-2 (F = 4.0, P = 0.05), IL-4 (F = 6.0, P = 0.02) at birth, and interferon gamma at day 7 (F = 4.4, P = 0.04)., Conclusions: scGOS/lcFOS/pAOS showed no significant improvement of neurodevelopmental outcomes at 24 months in preterm infants. Infections, lower bifidobacteria counts, and higher serum cytokine levels during the neonatal period were associated with lower neurodevelopmental outcomes at 24 months of age indicating the relevance of microbiome and immune responses in neurodevelopmental processes.

Infections are common in preterm infants and cause differences in cytokine levels. Aim of this study was to measure cytokine levels in preterm infants during the first year of life and to determine the effect of feeding a specific non-digestible carbohydrate mixture (scGOS/lcFOS/pAOS). Furthermore, other perinatal factors in relation to these cytokine levels were analysed. In a randomized controlled trial, preterm infants (GA <32weeks and/or birth weight <1500 g) received a scGOS/lcFOS/pAOS mixture or a placebo (maltodextrin) between days 3 and 30 of life. Cytokine levels (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IFN-γ, and TNF-α) were analysed at 5 time points during the study: before start of the study, at day 7, at day 14 and at 5 and 12 months after the start of the intervention. In total, 55 preterm infants in the scGOS/lcFOS/pAOS group and 58 in the placebo group were included. During the neonatal period cytokine levels increased, followed by a decrease at 5 months and 12 months. Enteral supplementation of the non-digestible oligosaccharides decreased cytokine levels at day 7 but not at day 14, indicating a temporarily anti-inflammatory effect. In the neonatal period, serious infection before sampling increased all cytokine levels. In conclusion, enteral supplementation of this specific non-digestible oligosaccharide mixture decreased cytokine levels in preterm infants at day 7 of life, although this effect disappeared thereafter., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Importance: Perinatal infections are commonly present in preterm and very low-birth-weight (VLWB) infants and might contribute to adverse neurodevelopmental outcome., Objective: To summarize studies evaluating the effect of perinatal infections on neurodevelopmental outcome in very preterm/VLBW infants., Evidence Review: On December 12, 2011, we searched Medline, PsycINFO, Embase, and Web of Knowledge for studies on infections and neurodevelopmental outcome. All titles and abstracts were assessed for eligibility by 2 independent reviewers. We also screened the reference lists of identified articles to search for additional eligible studies. Preselected criteria justified inclusion in this meta-analysis: (1) the study included infants born very preterm (≤32 weeks) and/or with VLBW (≤1500 g); (2) the study compared infants with and without perinatal infection; (3) there was follow-up using the Bayley Scales of Infant Development 2nd edition; and (4) results were published in an English-language peer-reviewed journal. The quality of each included study was assessed using the Newcastle-Ottawa Scale., Findings: This meta-analysis includes 18 studies encompassing data on 13.755 very preterm/VLBW infants. Very preterm/VLBW infants with perinatal infections had poorer mental (d = -0.25; P < .001) and motor (d = -0.37; P < .001) development compared with very preterm/VLBW infants without infections. Mental development was most impaired by necrotizing enterocolitis (d = -0.40; P < .001) and meningitis (d = -0.37; P < .001). Motor development was most impaired by necrotizing enterocolitis (d = -0.66; P < .001). Chorioamnionitis did not affect mental (d = -0.05; P = .37) or motor (d = 0.19; P = .08) development., Conclusions and Relevance: Postnatal infections have detrimental effects on mental and motor development in very preterm/VLBW infants.

Background & Aims: Efforts are directed at reaching the optimal composition of pediatric amino acids (AA) infusions. The goal was to demonstrate the safety and efficacy of a newly developed parenteral AA solution containing alanyl-glutamine (GLN-AA) compared to Standard-AA., Methods: This is a randomized (2:1), double-blind, multicentre clinical pilot trial. Infants after surgical interventions were allocated to receive GLN-AA or Standard-AA over a minimum of 5 days to maximum of 10 days. AA profiles in blood samples obtained at baseline, day 7, and end of treatment were compared to normal ranges. Data regarding safety, and efficacy were also collected., Results: Infants were comparable for (safety population) gestational age at birth (36 vs 38 weeks), birth weight (2460 vs 2955 g), and day of life during start intervention (1 vs 2 days). Plasma AA profiles in infants treated with GLN-AA (n = 13) were closer the normal ranges than those in infants treated with Standard-AA (n = 6). There were no clinical or statistical differences in adverse events, safety and efficacy parameters between both groups., Conclusion: This first-in-man study shows that GLN-AA is safe in infants after surgical interventions, and is well tolerated. Compared to reference values, GLN-AA better reflects the amino acid requirements of the infant., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Unlabelled: Short-term supplementation of non-human neutral and acidic oligosaccharides during the first postnatal weeks may enhance the maturation of the immune response in preterm infants and may lead to less allergic and infectious diseases during the first year of life. In a randomized controlled trial, 113 preterm infants (gestational age <32 weeks and/or birth weight <1500 g) were allocated to receive enteral neutral and acidic oligosaccharide supplementation or placebo between days 3 and 30 of life. The median age at follow-up was not different in both groups: 12 months corrected age (interquartile range [IQR], 11-15) in the prebiotic mixture group and 12 months corrected age in the placebo group (IQR, 10-19), respectively. In addition, baseline patient, maternal, and environmental characteristics were not different between the prebiotic mixture (n = 48) and placebo (n = 46) group. Incidence of allergic and infectious diseases was assessed by validated questionnaires. In total, 94/98 (96 %) of the eligible, surviving infants participated in this follow-up study. The incidence of atopic dermatitis (odds ratio [OR], 0.80; 95 % confidence interval [CI], 0.24-2.67), bronchial hyper-reactivity (OR, 1.04; 95 % CI, 0.38-2.87) and infections of the upper respiratory (OR, 0.95; 95 % CI, 0.37-2.44), lower respiratory (OR, 1.03; 95 % CI, 0.37-2.88), and gastrointestinal (OR, 1.77; 95 % CI, 0.55-5.73) tract was not different between the groups. Adjustment for potential confounding factors did not change the results of the primary analysis., Conclusion: Short-term enteral supplementation of non-human neutral and acidic oligosaccharides during the neonatal period in preterm infants does not decrease the incidence of allergic and infectious diseases during the first year of life.

Objectives: To clarify the severity, specificity, and neurocognitive underpinnings of attention problems in very preterm children., Study Design: A sample of 66 preterm (<32 weeks gestation), mean (SD) age 7.5 (0.4) years, and 66 age-matched term controls participated. Symptoms of inattention were assessed using parent and teacher-rated questionnaires, and neurocognitive measures included speed and consistency in speed of information processing, lapses of attention (tau), alerting, orienting, and executive attention, as well as verbal and visuospatial working memory. Group differences were investigated using ANOVA, and Sobel tests were used to clarify the mediating role of neurocognitive impairments on attention problems., Results: There was a large decrease in visuospatial working memory abilities (P < .001, d = .87), and medium increases in tau (P = .002, d = 0.55) as well as parent and teacher ratings of inattention (range d = 0.40-0.56) in very preterm children compared with term peers. Tau and visuospatial working memory were significant predictors of parent (R(2) = .161, P < .001 and R(2) = .071, P = .001; respectively) and teacher (R(2) = .152, P < .001 and R(2) = .064, P = .002; respectively) ratings of inattention, and completely explained the effects of very preterm birth on attention problems., Conclusions: Increased lapses of attention and poorer visuospatial working memory fully account for the attention problems in very premature children at school-age., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Serious infectious morbidity is high in preterm infants. Enteral supplementation of prebiotics may reduce the incidence of serious infections, especially infections related to the gastrointestinal tract., Objective: The objective was to determine the effect of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides ((SC)GOS/(LC)FOS) and acidic oligosaccharides (AOS) on serious infectious morbidity in preterm infants., Design: In a randomized controlled trial, preterm infants (gestational age <32 wk and/or birth weight <1500 g) received enteral supplementation of 80% (SC)GOS/(LC)FOS and 20% AOS (1.5 g . kg(-1) . d(-1)) or placebo (maltodextrin) between days 3 and 30 of life. Serious infectious morbidity was defined as a culture positive for sepsis, meningitis, pyelonephritis, or pneumonia. The analysis was performed by intention-to-treat and per-protocol, defined as > or =50% supplementation dose during the study period., Results: In total, 113 preterm infants were included. Baseline and nutritional characteristics were not different between groups. In the intention-to-treat analysis, the incidence of > or =1 serious infection, > or =1 serious endogenous infection, or > or =2 serious infectious episodes was not significantly different in the (SC)GOS/(LC)FOS/AOS-supplemented and placebo groups. In the per-protocol analysis, there was a trend toward a lower incidence of > or =1 serious endogenous infection and > or =2 serious infectious episodes in the (SC)GOS/(LC)FOS/AOS-supplemented group than in the placebo group (P = 0.09 and P = 0.07, respectively)., Conclusions: Enteral supplementation of (SC)GOS/(LC)FOS/AOS does not significantly reduce the risk of serious infectious morbidity in preterm infants. However, there was a trend toward a lower incidence of serious infectious morbidity, especially for infections with endogenous bacteria. This finding suggests a possible beneficial effect that should be evaluated in a larger study. This trial was registered at isrctn.org as ISRCTN16211826.

Shoulder dislocation in a preterm infant is very rare. We report a case of a preterm infant, with gestational age of 25 2/7 weeks and birth weight of 910 g, with anterior shoulder dislocation after breech delivery. The infant was successfully treated with closed reduction. In general, long-term outcome of shoulder dislocation in these infants is good. However, prompt recognition and treatment of the dislocated shoulder are essential to maintain normal shoulder girdle function and to prevent functional disability.

In contrast with clinical studies in term infants or older children, it is very difficult to investigate possible immunoregulatory effects of a novel infant formula composition in preterm infants. This is mainly because of the multicausal origin of infections in this high-risk population that is usually admitted to the neonatal intensive care unit. Possible effects of nutrition composition on onset and incidence of nosocomial infections in these very small infants have to be compared with infections that may have originated in utero. The development of the gastrointestinal tract may be inhibited after severe intrauterine growth retardation, leading to functional impairment of the gut shortly after birth. This may be related to the onset of necrotizing enterocolitis of the newborn. However, this disease in very small preterm infants is possibly also related to the initiation of oral feeding and/or the amount of feeding. Specific infection risks of neonatal intensive care as a result of invasive techniques such as artificial ventilation or total parenteral nutrition using indwelling umbilical and/or Silastic lines and so-called "all-in-one" mixtures may influence the incidence of infections. Widespread use of intravenous antibiotics in the neonatal intensive care unit may create an even larger infection risk. Investigation of possible immunomodulatory effects of factors such as prebiotics and probiotics added to the nutrition of preterm infants should always be considered along with other nutritional factors known to influence the immature immune system.

Several studies have described reduced plasma concentrations of arginine, the substrate for nitric oxide synthase (NOS) in infants with necrotizing enterocolitis (NEC). No information on the plasma concentrations of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) in patients with NEC is currently available. We investigated whether plasma concentrations of arginine, ADMA, and their ratio differ between premature infants with and without NEC, and between survivors and non-survivors within the NEC group. In a prospective case-control study, arginine and ADMA concentrations were measured in ten premature infants with NEC (median gestational age 193 d, birth weight 968 g), and ten matched control infants (median gestational age 201 d, birth weight 1102 g), who were admitted to the Neonatal Intensive Care Unit. In the premature infants with NEC, median arginine and ADMA concentrations (micromol/l), and the arginine:ADMA ratio were lower compared to the infants without NEC: 21.4 v. 55.9, P= 0.001; 0.59 v. 0.85, P=0.009 and 36.6 v. 72.3, P=0.023 respectively. In the NEC group, median arginine (micromol/l) and the arginine:ADMA ratio were lower in non-surviving infants than in surviving infants: 14.7 v. 33.8, P=0.01 and 32.0 v. 47.5, P=0.038 respectively. In premature infants with NEC not only the NOS substrate arginine, but also the endogenous NOS inhibitor ADMA and the arginine:ADMA ratio were lower than in infants without NEC. In addition, low arginine and arginine:ADMA were associated with mortality in infants with NEC. Overall, these data suggest that a diminished nitric oxide production may be involved in the pathophysiology of NEC, but this needs further investigation.

Objective: To study the effect of minimal enteral feeding (MEF) on intestinal permeability and feeding tolerance in preterm infants with intrauterine growth retardation (gestational age < 37 weeks, birth weight for gestational age p < 10). Furthermore, to determine whether fetal blood flow pulsatility or intestinal permeability predict feeding tolerance in these infants., Design: Randomised controlled trial., Methods: Within 48 hours of birth, infants were randomised to MEF or no enteral feeding (NEF) for five days in addition to parenteral feeding. Intestinal permeability was measured by the sugar absorption test before (SAT1) and after (SAT2) the study. The sugar absorption test measured the urinary lactulose/mannitol (LM) ratio after oral ingestion of a solution (375 mosm) containing mannitol and lactulose. Charts of all infants were assessed for measures of feeding tolerance. Fetal blood flow pulsatility index (U/C ratio) was measured within the seven days before birth., Results: Of the 56 infants enrolled, 42 completed the study: 20 received MEF and 22 NEF. The decrease in LM ratio (LM ratio 1 - LM ratio 2) was not significantly different between the two groups (0.25 v 0.11; p = 0.14). Feeding tolerance, growth, and incidence of necrotising enterocolitis were not significantly different between the two groups. Neither the U/C nor the LM ratio 1 predicted feeding tolerance., Conclusions: The results suggest that MEF of preterm infants with intrauterine growth retardation has no effect on the decrease in intestinal permeability after birth. Neither fetal blood flow pulsatility nor intestinal permeability predicts feeding tolerance.

A 2-month-old, prematurely-born boy suffered from vomiting and failure to thrive due to the combination of a large hiatal hernia and malrotation of the intestine.

Influenza B infection typically has low mortality. A 1,020-g neonate had a septic clinical picture and pneumonia. Influenza B virus was isolated from nasopharyngeal and tracheal aspirates. The infant died.