Early infancy growth, body composition and type of feeding in late and moderate preterms.

BACKGROUND: Late and moderate preterm (LMPT) infants are at risk for adverse later life outcomes. We determined the association between feeding method at enrolment and growth and body composition of LMPT infants until 3 months corrected age (3mCA). METHODS: Infants born between 32+0 and 36+6 weeks of gestation (n = 107) were enrolled up to 4 weeks corrected age and stratified according to feeding at enrolment. We performed anthropometric measurements at enrolment, term equivalent age (TEA) and 3mCA, including skinfold measurements and body composition using dual X-ray absorptiometry (DEXA). RESULTS: Feeding method at enrolment was associated with fat mass (FM) (breast 554.9 g, mixed 716.8 g, formula 637.7 g, p = 0.048), lean body mass (LM) (2512 g, 2853 g, 2722 g, respectively, p = 0.009) and lean mass index (LMI) (10.6 kg/m2, 11.6 kg/m2,11.2 kg/m2 respectively, p = 0.008) at TEA, but not 3mCA. Breastfed infants demonstrated greater increase in LM (breast 1707 g, mixed 1536 g, formula 1384 g, p = 0.03) and LMI (1.23 kg/m2, 0.10 kg/m2, 0.52 kg/m2, respectively, p = 0.022) between TEA and 3mCA. CONCLUSIONS: Breastfed LMPT infants have lower FM and greater LM increase and LMI increase up to 3mCA compared to formula or mixed-fed infants. These findings stress the importance of supporting breastfeeding in this population. IMPACT: Infants born late and moderate preterm age who are exclusively breastfed soon after birth gain more lean mass up to 3 months corrected age compared to mixed- or formula-fed infants. Breastfed infants have lower lean and fat mass at term equivalent age compared to mixed- and formula-fed infants. This is the first study exploring this population's growth and body composition in detail at 3 months corrected age. Our results underline the importance of supporting mothers to initiate and continue breastfeeding at least until 3 months corrected age.

The influence of nutrition on white matter development in preterm infants: a scoping review.

White matter (WM) injury is the most common type of brain injury in preterm infants and is associated with impaired neurodevelopmental outcome (NDO). Currently, there are no treatments for WM injury, but optimal nutrition during early preterm life may support WM development. The main aim of this scoping review was to assess the influence of early postnatal nutrition on WM development in preterm infants. Searches were performed in PubMed, EMBASE, and COCHRANE on September 2022. Inclusion criteria were assessment of preterm infants, nutritional intake before 1 month corrected age, and WM outcome. Methods were congruent with the PRISMA-ScR checklist. Thirty-two articles were included. Negative associations were found between longer parenteral feeding duration and WM development, although likely confounded by illness. Positive associations between macronutrient, energy, and human milk intake and WM development were common, especially when fed enterally. Results on fatty acid and glutamine supplementation remained inconclusive. Significant associations were most often detected at the microstructural level using diffusion magnetic resonance imaging. Optimizing postnatal nutrition can positively influence WM development and subsequent NDO in preterm infants, but more controlled intervention studies using quantitative neuroimaging are needed. IMPACT: White matter brain injury is common in preterm infants and associated with impaired neurodevelopmental outcome. Optimizing postnatal nutrition can positively influence white matter development and subsequent neurodevelopmental outcome in preterm infants. More studies are needed, using quantitative neuroimaging techniques and interventional designs controlling for confounders, to define optimal nutritional intakes in preterm infants.

Neonatal Antibiotics and Food Allergy Are Associated With FGIDs at 4-6 Years of Age.

OBJECTIVES: Antibiotics may contribute to the development of functional gastrointestinal disorders (FGIDs). This study aimed to determine whether antibiotics during the first week of life, infantile colic in the first year of life, gut-associated immune markers at 1 year of age, and allergies at 4-6 years of age in term-born children were associated with a higher prevalence of FGIDs at 4-6 years of age. METHODS: A prospective observational cohort of 436 term-born infants was followed up at the age of 4-6 years; 151 received broad-spectrum antibiotics (AB+), and 285 healthy controls (AB-). Validated Questionnaire On Pediatric Gastrointestinal Symptoms-Rome III and International Study of Asthma and Allergy in Childhood questionnaires were sent to parents of 418 available children. The independent t-test, chi-squared test or non-parametric test and logistic multivariate regression analyses were used. RESULTS: In total, 340 of 418 (81%) questionnaires were completed. Only the presence of functional abdominal pain was significantly higher in AB+ than AB- (4% vs 0.4%, respectively, P  = 0.045). Children with food allergy fulfilled significantly more often the criteria for irritable bowel syndrome (IBS) and abdominal migraine (26% vs 9%, P  = 0.002 and 7% vs 1%, P  = 0.043, respectively) compared to non-allergic children. No differences in FGIDs existed at the age of 4-6 years between children with and without a history of infantile colic. There were significant differences in gut-associated immune markers between children with and without FGIDs. CONCLUSION: Antibiotics during the first week of life resulted in a higher risk for functional abdominal pain at 4-6 years. Furthermore, food allergy was associated with IBS and abdominal migraine at 4-6years.

Serum docosahexaenoic acid levels are associated with brain volumes in extremely preterm born infants.

BACKGROUND: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for fetal brain growth and development. Our aim was to evaluate the association between serum DHA and AA levels and brain volumes in extremely preterm infants. METHODS: Infants born at <28 weeks gestational age in 2013-2015, a cohort derived from a randomized controlled trial comparing two types of parenteral lipid emulsions, were included (n = 90). Serum DHA and AA levels were measured at postnatal days 1, 7, 14, and 28, and the area under the curve was calculated. Magnetic resonance (MR) imaging was performed at term-equivalent age (n = 66), and volumes of six brain regions were automatically generated. RESULTS: After MR image quality assessment and area under the curve calculation, 48 infants were included (gestational age mean [SD] 25.5 [1.4] weeks). DHA levels were positively associated with total brain (B = 7.966, p = 0.012), cortical gray matter (B = 3.653, p = 0.036), deep gray matter (B = 0.439, p = 0.014), cerebellar (B = 0.932, p = 0.003), and white matter volume (B = 3.373, p = 0.022). AA levels showed no association with brain volumes. CONCLUSIONS: Serum DHA levels during the first 28 postnatal days were positively associated with volumes of several brain structures in extremely preterm infants at term-equivalent age. IMPACT: Higher serum levels of DHA in the first 28 postnatal days are positively associated with brain volumes at term-equivalent age in extremely preterm born infants. Especially the most immature infants suffer from low DHA levels in the first 28 postnatal days, with little increase over time. Future research is needed to explore whether postnatal fatty acid supplementation can improve brain development and may serve as a nutritional preventive and therapeutic treatment option in extremely preterm infants.

Mouse fetal intestinal organoids: new model to study epithelial maturation from suckling to weaning.

During the suckling-to-weaning transition, the intestinal epithelium matures, allowing digestion of solid food. Transplantation experiments with rodent fetal epithelium into subcutaneous tissue of adult animals suggest that this transition is intrinsically programmed and occurs in the absence of dietary or hormonal signals. Here, we show that organoids derived from mouse primary fetal intestinal epithelial cells express markers of late fetal and neonatal development. In a stable culture medium, these fetal epithelium-derived organoids lose all markers of neonatal epithelium and start expressing hallmarks of adult epithelium in a time frame that mirrors epithelial maturation in vivoIn vitro postnatal development of the fetal-derived organoids accelerates by dexamethasone, a drug used to accelerate intestinal maturation in vivo Together, our data show that organoids derived from fetal epithelium undergo suckling-to-weaning transition, that the speed of maturation can be modulated, and that fetal organoids can be used to model the molecular mechanisms of postnatal epithelial maturation.

NutriBrain: protocol for a randomised, double-blind, controlled trial to evaluate the effects of a nutritional product on brain integrity in preterm infants.

BACKGROUND: The gut microbiota and the brain are connected through different mechanisms. Bacterial colonisation of the gut plays a substantial role in normal brain development, providing opportunities for nutritional neuroprotective interventions that target the gut microbiome. Preterm infants are at risk for brain injury, especially white matter injury, mediated by inflammation and infection. Probiotics, prebiotics and L-glutamine are nutritional components that have individually already demonstrated beneficial effects in preterm infants, mostly by reducing infections or modulating the inflammatory response. The NutriBrain study aims to evaluate the benefits of a combination of probiotics, prebiotics and L-glutamine on white matter microstructure integrity (i.e., development of white matter tracts) at term equivalent age in very and extremely preterm born infants. METHODS: This study is a double-blind, randomised, controlled, parallel-group, single-center study. Eighty-eight infants born between 24 + 0 and < 30 + 0 weeks gestational age and less than 72 h old will be randomised after parental informed consent to receive either active study product or placebo. Active study product consists of a combination of Bifidobacterium breve M-16V, short-chain galacto-oligosaccharides, long-chain fructo-oligosaccharides and L-glutamine and will be given enterally in addition to regular infant feeding from 48 to 72 h after birth until 36 weeks postmenstrual age. The primary study outcome of white matter microstructure integrity will be measured as fractional anisotropy, assessed using magnetic resonance diffusion tensor imaging at term equivalent age and analysed using Tract-Based Spatial Statistics. Secondary outcomes are white matter injury, brain tissue volumes and cortical morphology, serious neonatal infections, serum inflammatory markers and neurodevelopmental outcome. DISCUSSION: This study will be the first to evaluate the effect of a combination of probiotics, prebiotics and L-glutamine on brain development in preterm infants. It may give new insights in the development and function of the gut microbiota and immune system in relation to brain development and provide a new, safe treatment possibility to improve brain development in the care for preterm infants. TRIAL REGISTRATION: ISRCTN, ISRCTN96620855 . Date assigned: 10/10/2017.

Voluntary and Involuntary Control of Attention in Adolescents Born Very Preterm: A Study of Eye Movements.

Very preterm birth is associated with attention deficits that interfere with academic performance. A better understanding of attention processes is necessary to support very preterm born children. This study examined voluntary and involuntary attentional control in very preterm born adolescents by measuring saccadic eye movements. Additionally, these control processes were related to symptoms of inattention, intelligence, and academic performance. Participants included 47 very preterm and 61 full-term born 13-years-old adolescents. Oculomotor control was assessed using the antisaccade and oculomotor capture paradigm. Very preterm born adolescents showed deficits in antisaccade but not in oculomotor capture performance, indicating impairments in voluntary but not involuntary attentional control. These impairments mediated the relation between very preterm birth and inattention, intelligence, and academic performance.

Dietary Intake of Sodium during Infancy and the Cardiovascular Consequences Later in Life: A Scoping Review.

BACKGROUND: High sodium intake is a leading cause of cardiovascular diseases in adults. Further, there is evidence that events in early life are predictors for health outcomes in later life. However, little is known about the impact of early sodium intake on (cardiovascular) health outcomes in later life. SUMMARY: We performed a scoping review of 25 articles, including 11 review studies, 8 randomized controlled trials, 5 prospective cohort studies, and 1 retrospective cohort study, all describing the relationship between the amount of sodium intake during the first 6 months after birth and the health effects and/or risk to cardiovascular disease later in life. We divided the results into 2 different groups: human and animal studies. Key Messages: The results show that high sodium intake in the first 6 months after birth may lead to negative health effects such as higher blood pressure, due to factors like salty taste preference and alterations of the renal system. The findings of this study suggest that the amount of sodium in the diet of an infant in the first 6 months after birth may have an impact on cardiovascular health outcomes in later life.

Social Adjustment in Adolescents Born Very Preterm: Evidence for a Cognitive Basis of Social Problems.

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.

Synbiotics Combined with Glutamine Stimulate Brain Development and the Immune System in Preterm Pigs.

Background: Preterm infants are born with an immature gut, brain, and immune system, predisposing them to short- and long-term complications. Objective: We hypothesized that a milk diet supplemented with pre- and probiotics (i.e. synbiotics) and glutamine would improve gut, brain, and immune maturation in preterm neonates, using preterm pigs as a model. Methods: Preterm pigs (Landrace x Yorkshire x Duroc, n = 40, delivered by c-section at 90% of gestation) were reared individually until day 23 after birth under highly standardized conditions. Piglets in the intervention group (PPG, n = 20) were fed increasing volumes of bovine milk supplemented with prebiotics (short-chain galacto- and long chain fructo-oligosaccharides 9:1, 4-12 g/L), probiotics (Bifidobacterium breve M16-V, 3 × 109 CFU/d) and l-glutamine [0.15-0.30 g/(kg · d)], and compared with pigs fed bovine milk with added placebo compounds as control (CON, n = 20). Clinical, gastrointestinal, immunological, cognitive, and neurological endpoints were measured. Results: The PPG pigs showed more diarrhea but weight gain, body composition, and gut parameters were similar between the groups. Cognitive performance, assessed in a T-maze, was significantly higher in PPG pigs (P < 0.01), whereas motor function and exploratory interest were similar between the groups. Using ex vivo diffusion imaging, the orientation dispersion index in brain cortical gray matter was 50% higher (P = 0.04), and fractional anisotropy value was 7% lower (P = 0.05) in PPG pigs compared with CON pigs, consistent with increased dendritic branching in PPG. In associative fibers, radial diffusivity was lower and fractional anisotropy was higher in PPG pigs compared with CON pigs (all P < 0.05), while measures in the internal capsule showed a tendency towards reduced radial diffusivity and mean diffusivity (both P = 0.09). On day 23 pigs in the PPG group showed higher blood leukocyte numbers (+43%), neutrophil counts (+100%), and phagocytic rates (+24%), relative to CON, all P < 0.05. Conclusion: Preterm pigs supplemented with Bifidobacterium breve, galacto- and fructo-oligosaccharides, and l-glutamine showed enhanced neuronal and immunological development. The findings indicate the potential for targeted nutritional interventions after preterm birth, to support development of important systems such as immunity and brain.

Antibiotic Treatment in the First Week of Life Impacts the Growth Trajectory in the First Year of Life in Term Infants.

OBJECTIVE: Antibiotic treatment in early life appears to increase the risk for childhood overweight and obesity. So far, the association between antibiotics administrated specifically during the first week of life and growth has not been studied. Therefore, we studied the association between growth and antibiotics, given in the first week of life and antibiotic courses later in the first year of life. METHOD: A prospective observational birth cohort of 436 term infants with 151 receiving broad-spectrum antibiotics for suspected neonatal infection (AB+), and 285 healthy controls (AB-) was followed during their first year. Weight, height, and additional antibiotic courses were collected monthly. A generalized-additive-mixed-effects model was used to fit the growth data. Growth curve estimation was controlled for differences in sex, gestational age, delivery mode, exclusive breast-feeding, tobacco exposure, presence of siblings, and additional antibiotic courses. RESULTS: Weight-for-age and length-for-age increase was lower in AB+ compared with AB- (P < 0.0001), resulting in a lower weight and length increase 6.26 kg (standard error [SE] 0.07 kg) and 25.4 cm (SE 0.27 cm) versus 6.47 kg (SE 0.06 kg) and 26.4 cm (SE 0.21 cm) (P < 0.05 and P < 0.005, respectively) in the first year of life. Approximately 30% of the children in both groups received additional antibiotic course(s) in their first year, whereafter additional weight gain of 76 g per course was observed (P = 0.0285). CONCLUSIONS: Decreased growth was observed after antibiotics in the first week of life, whereas increased growth was observed after later antibiotic course(s) in term born infants in the first year of life. Therefore, timing of antibiotics may determine the association with growth.

Metaproteomics reveals functional differences in intestinal microbiota development of preterm infants.

OBJECTIVE: Development of the gastrointestinal tract and immune system can be modulated by the gut microbiota. Establishment of the intestinal microbiota, in its turn, is affected by host and environmental factors. As such, development of the gut microbiota is greatly impacted in preterm infants, who have an immature gut and are exposed to factors like hospitalization, caesarean section, antibiotics, and respiratory support. DESIGN: We analyzed fecal microbiota composition and activity of ten preterm infants (gestational age 25-30 weeks; birthweight 630-1750 g) during the first six postnatal weeks through metaproteomics (LC-MS/MS) and 16S-rRNA gene sequencing. RESULTS: A gestational-age-dependent microbial signature is observed, enabling microbiota-based differentiation between extremely preterm (25-27 weeks gestation) and very preterm (30 weeks gestation) infants. In very preterm infants, the intestinal microbiota developed toward a Bifidobacterium-dominated community and was associated with high abundance of proteins involved in carbohydrate and energy metabolism. Extremely preterm infants remained predominantly colonized by facultative anaerobes and were associated with proteins involved in membrane transport and translation. Delayed colonization by obligate anaerobes could be associated with antibiotic treatment and respiratory support. CONCLUSION: We speculate that gestational age and its associated intensity of care (e.g. antibiotics and respiratory support) affects intestinal microbiota composition and activity in preterm infants. As the gut microbiota plays a major role in development of the neonate, gestational age and its associated factors could set the stage for early and later life health complications via interference with microbiota development.

Wheezing and infantile colic are associated with neonatal antibiotic treatment.

BACKGROUND: Cohort studies have suggested that early-life antibiotic treatment is associated with increased risk of atopy. We determined whether antibiotic treatment already in the first week of life increases the risk of atopic and non-atopic disorders. METHODS: The INCA study is a prospective observational birth cohort study of 436 term infants, with follow-up of 1 year; 151 neonates received broad-spectrum antibiotics for suspected neonatal infection (AB+), vs a healthy untreated control group (N = 285; AB-). In the first year, parents recorded daily (non-) allergic symptoms. At 1 year, doctors' diagnoses were registered and a blood sample was taken (n = 205). RESULTS: Incidence of wheezing in the first year was higher in AB+ than AB- (41.0% vs 30.5%, P = .026; aOR 1.56 [95%CI 0.99-2.46, P = .06]). Infantile colics were more prevalent in AB+ compared to AB- (21.9% and 14.4% P = .048), and antibiotic treatment was an independent risk factor for infantile colics (aOR 1.66 (95%CI 1.00-2.77) P = .05). Allergic sensitization (Phadiatop >0.70kUA/L) showed a trend toward a higher risk in AB+ (aOR 3.26 (95%CI 0.95-11.13) P = .06). Incidence of eczema, infections, and GP visits in the first year were similar in AB+ and AB-. CONCLUSION: Antibiotic treatment in the first week of life is associated with an increased risk of wheezing and infantile colics. This study may provide a rationale for early cessation of antibiotics in neonates without proven or probable infection.

A randomised trial of enteral glutamine supplementation for very preterm children showed no beneficial or adverse long-term neurodevelopmental outcomes.

AIM: This study evaluated the long-term effects of enteral glutamine supplementation on neurodevelopmental outcomes of a Dutch cohort of very preterm children at 13 years of age. METHODS: The cohort was enrolled in a randomised placebo-controlled trial between 2001 and 2003 in which infants received glutamine- or alanine-supplemented enteral nutrition during the first month of life. Participants were invited for follow-up at a mean age of 13.30 years. Motor, neurocognitive, academic and behavioural outcomes were assessed in 61 children. RESULTS: No differences were found between the groups regarding motor, intellectual, academic and behavioural functioning. Forward span visuospatial working memory performance was better in the controls (crude/adjusted model: d = 0.67/0.64, p = 0.02/0.02), but no difference was found for backward span. After the data were adjusted for confounders, the groups differed regarding parent-rated attention (crude/adjusted model: d = 0.47/0.73, p = 0.07/0.003), but both groups scored within the normal range. CONCLUSION: This was the first study on the long-term effects of enteral glutamine supplementation on the neurodevelopmental outcomes of very preterm children. Our study provided no evidence that enteral glutamine supplementation had any beneficial or adverse effects on the children's motor, neurocognitive, academic and behavioural outcomes at 13 years of age.

Health-care professionals' approach in feeding term small-for-gestational age infants and its potential implications to later growth outcomes.

AIM: To understand feeding practices, nutrition management and postnatal growth monitoring of term small-for-gestational age (tSGA) infants in Southeast Asia. METHODS: Anonymous questionnaires to assess practices on feeding, nutrition management and post-natal growth monitoring of tSGA infants were distributed among health-care professionals (HCPs) participating in regional/local perinatology symposia in Malaysia, Thailand and Singapore. RESULTS: Three hundred seventy-seven respondents from Malaysia (37%), Thailand (27%), Singapore (18%) and other Asian countries (19%) participated in the survey. Respondents were neonatologists (35%), paediatricians (25%) and other HCPs (40%) including nurses and midwives. Exclusive human milk feeding was reported the most preferred feeding option for tSGA infants, followed by fortified human milk feeding (60% and 20%, respectively). This was consistent among the different countries. The perceived nutrient requirements of tSGA infants varied between countries. Most respondents from Malaysia and Singapore reported requirements to be similar to preterm infants, while the majority from Thailand reported that it was less than those of preterm infants. The World Health Organization Growth Chart of 2006 and Fenton Growth Charts of 2013 were the most frequently used charts for growth monitoring in the hospital and after discharge. CONCLUSIONS: Nutrition management and perceived nutrient requirements for tSGA infants among practising HCPs in Southeast Asia showed considerable variation. The impetus to form standardised and evidence based feeding regimens is important as adequate nutritional management and growth monitoring particularly in this population of infants will have long term impact on population health.

Human Milk Processing: A Systematic Review of Innovative Techniques to Ensure the Safety and Quality of Donor Milk.

Pasteurization, performed at 62.5°C for 30 minutes (holder pasteurization), is currently recommended in all international human milk banks guidelines, but it affects some human milk bioactive and nutritive components. The present systematic review is aimed at critically reviewing evidence on the suitability of human milk processing techniques other than holder pasteurization, both thermal and nonthermal, to ensure microbiological safety, and on the effects of these techniques on biologically active donor milk components. A systematic review of English and non-English articles using Medline, PubMed, Embase, SCOPUS, and CAB Abstracts, with no restriction in publication date was performed. Search terms included: human, breast, donor, or banked milk, breastmilk, breast fed, breastfed, breastfeed; HTST, Flash, High Pressure, UV, ultrasonic or nonthermal; process, pasteuris, pasteuriz. Only primary research articles published in peer-reviewed journals were included, providing or not a comparison with holder pasteurized human milk, provided that the pasteurization technique was clearly described, and not intended for domestic use. Additional studies were identified by searching bibliographies of relevant articles. Twenty-six studies were identified as being relevant. Two examined both High Pressure Processing and High-Temperature-Short-Time pasteurization; 10 only examined High Pressure Processing; 10 only examined High-Temperature-Short-Time; 2 articles examined ultraviolet irradiation; 2 articles examined (thermo-)ultrasonic processing. The results indicate that data about safety for microbiological control are still scarce for most of the novel technologies, and that consensus on processing conditions is necessary for nonthermal technologies, before any conclusions on the qualitative and nutritional advantages of these techniques can be drawn.

Neurodevelopment of Preterm Infants at 24 Months After Neonatal Supplementation of a Prebiotic Mix: A Randomized Trial.

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)-1ß (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.

Impact of nutrition on brain development and its neuroprotective implications following preterm birth.

The impact of nutrition on brain development in preterm infants has been increasingly appreciated. Early postnatal growth and nutrient intake have been demonstrated to influence brain growth and maturation with subsequent effects on neurodevelopment that persist into childhood and adolescence. Nutrition could also potentially protect against injury. Inflammation and perinatal infection play a crucial role in the pathogenesis of white matter injury, the most common pattern of brain injury in preterm infants. Therefore, nutritional components with immunomodulatory and/or anti-inflammatory effects may serve as neuroprotective agents. Moreover, growing evidence supports the existence of a microbiome-gut-brain axis. The microbiome is thought to interact with the brain through immunological, endocrine, and neural pathways. Consequently, nutritional components that may influence gut microbiota may also exert beneficial effects on the developing brain. Based on these properties, probiotics, prebiotic oligosaccharides, and certain amino acids are potential candidates for neuroprotection. In addition, the amino acid glutamine has been associated with a decrease in infectious morbidity in preterm infants. In conclusion, early postnatal nutrition is of major importance for brain growth and maturation. Additionally, certain nutritional components might play a neuroprotective role against white matter injury, through modulation of inflammation and infection, and may influence the microbiome-gut-brain axis.