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.

The association between exposure to antibiotics in the first week of life and later otitis media: The INCA study.

Otitis media (OM) is one of the most common diagnoses in preschool-age children. Its pathophysiology is poorly understood, but is associated with changes in the nasopharyngeal microbiome, immune system, and presence of allergies. These, in turn, can be affected by early-life antibiotic exposure. Therefore, this study aimed to determine if antibiotic treatment in the first week of life in children born at term was associated with acute otitis media (AOM) and otitis media with effusion (OME) in the first 4-6 years of life. METHODS: A prospective birth cohort of 436 term-born infants was followed up at 4-6 years of age. Parents reported (recurrent) AOM and OME through online questionnaires, sent to parents of 418 eligible children. Doctors' diagnoses of AOM and OME were collected after additional informed consent. Multivariate logistic regression analyses were used to study the association between antibiotic exposure and AOM and OME. RESULTS: Of the 436 infants, 151 infants received antibiotics in the first week of life. In total, 341 (82%) questionnaires were collected. The parental-reported prevalence was 45% (155/341) for AOM. Of these 155 children, 33 children also had OME (10% of the total cohort). Doctor's diagnoses were obtained from 308 (74%) children, of which 30% (91/308) had AOM. Of these 91 children, 12 children also had OME and 8 children had OME without a diagnosis of AOM (6% of the total obtained diagnoses). Antibiotic treatment in the first week of life was not significantly associated with parent-reported nor doctor-diagnosed (recurrent) AOM and OME in the first 4-6 years of life in the regression models. CONCLUSION: Antibiotic treatment in the first week of life was not associated with AOM and OME in the first 4-6 years of life in this prospective cohort of Dutch infants. More insight into the pathophysiology of OM is warranted to determine whether antibiotic-induced microbiome changes play a role in the susceptibility to OM.

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.

Microbial effects of prebiotics, probiotics and synbiotics after Caesarean section or exposure to antibiotics in the first week of life: A systematic review.

BACKGROUND AND AIMS: Disruption of the developing microbiota by Caesarean birth or early exposure to antibiotics may impact long-term health outcomes, which can potentially be prevented by nutritional supplements. This systematic review aimed to summarise the evidence regarding the effects of prebiotics, probiotics and synbiotics on the intestinal microbiota composition of term infants born by Caesarean section or exposed to antibiotics in the first week of life. METHODS: A systematic search was performed from inception to August 2022 in Medline and Embase. Two researchers independently performed title and abstract screening (n = 12,230), full-text screening (n = 46) and critical appraisal. We included randomised controlled trials which included term-born infants who were born following Caesarean section or who were exposed to postpartum antibiotics in the first week of life, pre-, pro- or synbiotics were administered <6 weeks after birth and outcome(s) consisted of microbiota analyses. RESULTS: Twelve randomised controlled trials investigating Caesarean born infants and one randomised controlled trial including infants exposed to antibiotics were included. Group sizes varied from 11 to 230 with 1193 infants in total. Probiotic (n = 7) or synbiotic (n = 3) supplementation significantly increased the abundance of the supplemented bacterial species (of the Bifidobacterium and Lactobacillus genus), and there was a decrease in Enterobacteriaceae, especially <4 weeks of age. At phylum level, Actinobacteria (two studies), Proteobacteria (one study) and Firmicutes (one study) increased after probiotic supplementation. In three studies on prebiotics, two studies reported a significant increase in Bifidobacteria and one study found a significant increase in Enterobacteriaceae. DISCUSSION: Prebiotic, probiotic and synbiotic supplements seem to restore dysbiosis after Caesarean section towards a microbial signature of vaginally born infants by increasing the abundance of beneficial bacteria. However, given the variety in study products and study procedures, it is yet too early to advocate specific products in clinical settings.

Clinical outcomes following pre-, pro- and synbiotic supplementation after caesarean birth or antibiotic exposure in the first week of life in term born infants: A systematic review of the literature.

Background: Caesarean section and early exposure to antibiotics disrupt the developing gastrointestinal microbiome, which is associated with long-term health effects. Objective: The aim of this systematic review was to summarise the impact of prebiotics, probiotics, or synbiotics supplementation on clinical health outcomes of term infants born by caesarean section or exposed to antibiotics in the first week of life. Design: A systematic search was performed in Medline and Embase from inception to August 2021. Title and abstract screening (n = 11,248), full text screening (n = 48), and quality assessment were performed independently by two researchers. Results: Six RCTs studying caesarean born infants were included, group sizes varied between 32-193 with in total 752 children. No studies regarding supplementation after neonatal antibiotic exposure were found. Three studies administered a probiotic, one a prebiotic, one a synbiotic, and one study investigated a prebiotic and synbiotic. Several significant effects were reported at follow-up varying between 10 days and 13 years: a decrease in atopic diseases (n = 2 studies), higher immune response to tetanus and polio vaccinations (n = 2), lower response to influenza vaccination (n = 1), fewer infectious diseases (n = 2), and less infantile colic (n = 1), although results were inconsistent. Conclusions: Supplementation of caesarean-born infants with prebiotics, probiotics, or synbiotics resulted in significant improvements in some health outcomes as well as vaccination responses. Due to the variety of studied products and the paucity of studies, no recommendations can be given yet on the routine application of prebiotics, probiotics, or synbiotics to improve health outcomes after caesarean section or neonatal antibiotic exposure.

Effect of antibiotics in the first week of life on faecal microbiota development.

BACKGROUND: Infants are frequently exposed to antibiotics (AB) in the first week of life for suspected bacterial infections. Little is known about the effect of AB on the developing intestinal microbiota. Therefore, we studied intestinal microbiota development with and without AB exposure in the first week of life in term born infants. METHODS: We analysed the faecal microbiota from birth until 2.5 years of age by 16S rRNA gene amplicon sequencing in a cohort with 56 term born infants, exposed to AB in the first week of life (AB+) (AB for 2-3 days (AB2, n=20), AB for 7 days (AB7, n=36)), compared with 126 healthy controls (AB-). The effects of AB and duration were examined in relation to delivery and feeding mode. RESULTS: AB+ was associated with significantly increased relative abundance of Enterobacteriaceae at 3 weeks and 1 year and a decrease of Bifidobacteriaceae, from 1 week until 3 months of age only in vaginally delivered, but not in C-section born infants. Similar deviations were noted in AB7, but not in AB2. After AB, breastfed infants had lower relative abundance of potentially pathogenic Enterobacteriaceae compared with formula fed infants and recovered 2 weeks faster towards controls. CONCLUSIONS: AB exposure in the first week of life alters faecal microbiota development with deviations in the relative abundance of individual taxa until 1 year of age. These alterations can have long-term health consequences, which emphasises the need for future studies aiming at restoring intestinal microbiota after AB administration.

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.

Effects of High-Pressure Processing, UV-C Irradiation and Thermoultrasonication on Donor Human Milk Safety and Quality.

Holder pasteurization (HoP) is the current recommended treatment for donor human milk. Although this method inactivates microbial contaminants, it also negatively affects various milk components. High-pressure processing (HPP, 400, 500, and 600 MPa), ultraviolet-C irradiation (UV-C, 2,430, 3,645, and 4,863 J/L) and thermoultrasonication (TUS, 1,080 and 1,620 kJ/L) were investigated as alternatives to thermal pasteurization (HoP). We assessed the effects of these methods on microbiological safety, and on concentration and functionality of immunoglobulin A, lactoferrin, lysozyme and bile salt-stimulated lipase, with LC-MS/MS-based proteomics and activity assays. HoP, HPP, TUS, and UV-C at 4863 J/L, achieved >5-log10 microbial reduction. Native protein levels and functionality showed the highest reduction following HoP, while no significant reduction was found after less intense HPP and all UV-C treatments. Immunoglobulin A, lactoferrin, and lysozyme contents were also preserved after low intensity TUS, but bile salt-stimulated lipase activity was significantly reduced. This study demonstrated that HPP and UV-C may be considered as suitable alternatives to HoP, since they were able to ensure sufficient microbial inactivation while at the same time better preserving the bioactive components of donor human milk. In summary, our results provide valuable insights regarding the evaluation and selection of suitable processing methods for donor human milk treatment, which may replace HoP in the future.

Altered Gut Structure and Anti-Bacterial Defense in Adult Mice Treated with Antibiotics during Early Life.

The association between prolonged antibiotic (AB) use in neonates and increased incidence of later life diseases is not yet fully understood. AB treatment in early life alters intestinal epithelial cell composition, functioning, and maturation, which could be the basis for later life health effects. Here, we investigated whether AB-induced changes in the neonatal gut persisted up to adulthood and whether early life AB had additional long-term consequences for gut functioning. Mice received AB orally from postnatal day 10 to 20. Intestinal morphology, permeability, and gene and protein expression at 8 weeks were analyzed. Our data showed that the majority of the early life AB-induced gut effects did not persist into adulthood, yet early life AB did impact later life gut functioning. Specifically, the proximal small intestine (SI) of adult mice treated with AB in early life was characterized by hyperproliferative crypts, increased number of Paneth cells, and alterations in enteroendocrine cell-specific gene expression profiles. The distal SI of adult mice displayed a reduced expression of antibacterial defense markers. Together, our results suggest that early life AB leads to structural and physiological changes in the adult gut, which may contribute to disease development when homeostatic conditions are under challenge.

Testing the effects of processing on donor human Milk: Analytical methods.

Holder pasteurization is the current recommended method for donor human milk treatment. This method effectively eliminates most life-threatening contaminants in donor milk, but it also greatly reduces some of its biological properties. Consequently, there is a growing interest for developing novel processing methods that can ensure both microbial inactivation and a higher retention of the functional components of donor milk. Our aim was to offer a comprehensive overview of the analytical techniques available for the evaluation of such methods. To suggest an efficient workflow for the analysis of processed donor milk, a safety analytical panel as well as a nutritional value and functionality analytical panel are discussed, together with the principles, benefits, and drawbacks of the available techniques. Concluding on the suitability of a novel method requires a multifactorial approach which can be achieved by a combination of analytical targets and by using complementary assays to cross-validate the obtained results.

Prevalence of Zinc Deficiency in Healthy 1-3-Year-Old Children from Three Western European Countries.

Zinc deficiency (ZnD) has adverse health consequences such as stunted growth. Since young children have an increased risk of developing ZnD, it is important to determine its prevalence and associated factors in this population. However, only a few studies have reported on ZnD prevalence in young children from Western high-income countries. This study evaluated ZnD prevalence and associated factors, including dietary Zn intake, in healthy 1-3-year-old children from Western European, high-income countries. ZnD was defined as serum Zn concentration <9.9 µmol/L. A total of 278 children were included with a median age of 1.7 years (Q1-Q3: 1.2-2.3). The median Zn concentration was 11.0 µmol/L (Q1-Q3: 9.0-12.2), and ZnD prevalence was 31.3%. No significant differences were observed in the socio-economic characteristics between children with and without ZnD. Dietary Zn intake was not associated with ZnD. ZnD is common in healthy 1-3-year-old children from Western European countries. However, the use of currently available cut-off values defining ZnD in young children has its limitations since these are largely based on reference values in older children. Moreover, these values were not evaluated in relation to health consequences, warranting further research.

Thermoultrasonication, ultraviolet-C irradiation, and high-pressure processing: Novel techniques to preserve insulin in donor human milk.

BACKGROUND & AIMS: Donor human milk (DHM) is recommended as the first alternative for preterm infants if their mother's own milk is not available or if the quantity is not sufficient. The most commonly used technique to eliminate microbial contaminants in DHM is holder pasteurization (HoP). However, the heating process during HoP partially destroys milk bioactive factors such as insulin. Therefore, innovative techniques have been developed as alternatives to HoP. The objective of this study was to determine the effect of HoP, high-temperature-short-time (HTST), thermoultrasonication (TUS), ultraviolet-C irradiation (UV-C), and high-pressure processing (HPP) on the insulin concentration in DHM. METHODS: Milk samples from 28 non-diabetic mothers were collected. The milk samples were aliquoted and either left untreated or treated with HoP (62.5 °C; 30 min), HTST (72 °C; 15 s), TUS (60 W; 6 min), UV-C (4863 J/L), or HPP (500 MPa; 5 min). RESULTS: The mean insulin concentration in untreated milk was 79 ± 41 pmol/L. The mean insulin retention rate was 67% for HoP, 78% for HTST, 97% for TUS, 94% for UV-C, and 106% for HPP. The mean insulin concentration in milk treated with HoP was significantly lower compared to untreated milk (p = 0.01). CONCLUSION: TUS, UV-C, and HPP preserve insulin in DHM. The insulin concentration in DHM is affected to a larger extent by HoP than by HTST. These results indicate that TUS, UV-C, and HPP may serve as alternatives to HoP.

Nutritional Intake, White Matter Integrity, and Neurodevelopment in Extremely Preterm Born Infants.

BACKGROUND: Determining optimal nutritional regimens in extremely preterm infants remains challenging. This study aimed to evaluate the effect of a new nutritional regimen and individual macronutrient intake on white matter integrity and neurodevelopmental outcome. METHODS: Two retrospective cohorts of extremely preterm infants (gestational age < 28 weeks) were included. Cohort B (n = 79) received a new nutritional regimen, with more rapidly increased, higher protein intake compared to cohort A (n = 99). Individual protein, lipid, and caloric intakes were calculated for the first 28 postnatal days. Diffusion tensor imaging was performed at term-equivalent age, and cognitive and motor development were evaluated at 2 years corrected age (CA) (Bayley-III-NL) and 5.9 years chronological age (WPPSI-III-NL, MABC-2-NL). RESULTS: Compared to cohort A, infants in cohort B had significantly higher protein intake (3.4 g/kg/day vs. 2.7 g/kg/day) and higher fractional anisotropy (FA) in several white matter tracts but lower motor scores at 2 years CA (mean (SD) 103 (12) vs. 109 (12)). Higher protein intake was associated with higher FA and lower motor scores at 2 years CA (B = -6.7, p = 0.001). However, motor scores at 2 years CA were still within the normal range and differences were not sustained at 5.9 years. There were no significant associations with lipid or caloric intake. CONCLUSION: In extremely preterm born infants, postnatal protein intake seems important for white matter development but does not necessarily improve long-term cognitive and motor development.

A Chatbot to Engage Parents of Preterm and Term Infants on Parental Stress, Parental Sleep, and Infant Feeding: Usability and Feasibility Study.

BACKGROUND: Parents commonly experience anxiety, worry, and psychological distress in caring for newborn infants, particularly those born preterm. Web-based therapist services may offer greater accessibility and timely psychological support for parents but are nevertheless labor intensive due to their interactive nature. Chatbots that simulate humanlike conversations show promise for such interactive applications. OBJECTIVE: The aim of this study is to explore the usability and feasibility of chatbot technology for gathering real-life conversation data on stress, sleep, and infant feeding from parents with newborn infants and to investigate differences between the experiences of parents with preterm and term infants. METHODS: Parents aged ≥21 years with infants aged ≤6 months were enrolled from November 2018 to March 2019. Three chatbot scripts (stress, sleep, feeding) were developed to capture conversations with parents via their mobile devices. Parents completed a chatbot usability questionnaire upon study completion. Responses to closed-ended questions and manually coded open-ended responses were summarized descriptively. Open-ended responses were analyzed using the latent Dirichlet allocation method to uncover semantic topics. RESULTS: Of 45 enrolled participants (20 preterm, 25 term), 26 completed the study. Parents rated the chatbot as "easy" to use (mean 4.08, SD 0.74; 1=very difficult, 5=very easy) and were "satisfied" (mean 3.81, SD 0.90; 1=very dissatisfied, 5 very satisfied). Of 45 enrolled parents, those with preterm infants reported emotional stress more frequently than did parents of term infants (33 vs 24 occasions). Parents generally reported satisfactory sleep quality. The preterm group reported feeding problems more frequently than did the term group (8 vs 2 occasions). In stress domain conversations, topics linked to "discomfort" and "tiredness" were more prevalent in preterm group conversations, whereas the topic of "positive feelings" occurred more frequently in the term group conversations. Interestingly, feeding-related topics dominated the content of sleep domain conversations, suggesting that frequent or irregular feeding may affect parents' ability to get adequate sleep or rest. CONCLUSIONS: The chatbot was successfully used to collect real-time conversation data on stress, sleep, and infant feeding from a group of 45 parents. In their chatbot conversations, term group parents frequently expressed positive emotions, whereas preterm group parents frequently expressed physical discomfort and tiredness, as well as emotional stress. Overall, parents who completed the study gave positive feedback on their user experience with the chatbot as a tool to express their thoughts and concerns. TRIAL REGISTRATION: ClinicalTrials.gov NCT03630679; https://clinicaltrials.gov/ct2/show/NCT03630679.

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.

"Donor milk banking: Improving the future". A survey on the operation of the European donor human milk banks.

BACKGROUND: Provision of donor human milk is handled by established human milk banks that implement all required measures to ensure its safety and quality. Detailed human milk banking guidelines on a European level are currently lacking, while the information available on the actual practices followed by the European human milk banks, remains limited. The aim of this study was to collect detailed data on the actual milk banking practices across Europe with particular emphasis on the practices affecting the safety and quality of donor human milk. MATERIALS AND METHODS: A web-based questionnaire was developed by the European Milk Bank Association (EMBA) Survey Group, for distribution to the European human milk banks. The questionnaire included 35 questions covering every step from donor recruitment to provision of donor human milk to each recipient. To assess the variation in practices, all responses were then analyzed for each country individually and for all human milk banks together. RESULTS: A total of 123 human milk banks completed the questionnaire, representing 85% of the European countries that have a milk bank. Both inter- and intra-country variation was documented for most milk banking practices. The highest variability was observed in pasteurization practices, storage and milk screening, both pre- and post-pasteurization. CONCLUSION: We show that there is a wide variability in milk banking practices across Europe, including practices that could further improve the efficacy of donor human milk banking. The findings of this study could serve as a tool for a global discussion on the efficacy and development of additional evidence-based guidelines that could further improve those practices.

Maturation of the preterm gastrointestinal tract can be defined by host and microbial markers for digestion and barrier defense.

Functionality of the gastrointestinal tract is essential for growth and development of newborns. Preterm infants have an immature gastrointestinal tract, which is a major challenge in neonatal care. This study aims to improve the understanding of gastrointestinal functionality and maturation during the early life of preterm infants by means of gastrointestinal enzyme activity assays and metaproteomics. In this single-center, observational study, preterm infants born between 24 and 33 weeks (n = 40) and term infants born between 37 and 42 weeks (n = 3), who were admitted to Isala (Zwolle, the Netherlands), were studied. Enzyme activity analyses identified active proteases in gastric aspirates of preterm infants. Metaproteomics revealed human milk, digestive and immunological proteins in gastric aspirates of preterm infants and feces of preterm and term infants. The fecal proteome of preterm infants was deprived of gastrointestinal barrier-related proteins during the first six postnatal weeks compared to term infants. In preterm infants, bacterial oxidative stress proteins were increased compared to term infants and higher birth weight correlated to higher relative abundance of bifidobacterial proteins in postnatal week 3 to 6. Our findings indicate that gastrointestinal and beneficial microbial proteins involved in gastrointestinal maturity are associated with gestational and postnatal age.

Macrosomia and large for gestational age in Asia: One size does not fit all.

Macrosomia, usually defined as infant birth weight of ≥4000 g, does not consider gestational age, sex, or country/region-specific differences in mean birth weight and maternal body weight. This issue is particularly relevant for Asia, where 60% of the world's population lives, due to variations in maternal size and birth weights across populations. Large for gestational age (LGA), defined as birth weight > 90th centile, is a more sensitive measure as it considers gestational age and sex, though it is dependent on the choice of growth charts. We aimed to review reporting of macrosomia and LGA in Asia. We reviewed the literature on prevalence and risk of macrosomia and LGA in Asia over the last 29 years. Prevalence of macrosomia ranged from 0.5% (India) to 13.9% (China) while prevalence of LGA ranged from 4.3% (Korea) to 22.1% (China), indicating substantial variation in prevalence within and between Asian countries. High pre-pregnancy body mass index, excessive gestational weight gain, and impaired glucose tolerance conferred risk of macrosomia/LGA. Incidence of macrosomia and LGA varies substantially within and between Asian countries, as do the growth charts and definitions. The latter makes it impossible to make comparisons but suggests differences in intrauterine growth between populations. Reporting LGA, using standardized country/regional growth charts, would better capture the incidence of high birth weight and allow for comparison and identification of contributing factors. Better understanding of local drivers of excessive intrauterine growth could enable development of improved strategies for prevention and management of LGA.

Early Life Antibiotics Influence In Vivo and In Vitro Mouse Intestinal Epithelium Maturation and Functioning.

BACKGROUND & AIMS: The use of antibiotics (ABs) is a common practice during the first months of life. ABs can perturb the intestinal microbiota, indirectly influencing the intestinal epithelial cells (IECs), but can also directly affect IECs independent of the microbiota. Previous studies have focused mostly on the impact of AB treatment during adulthood. However, the difference between the adult and neonatal intestine warrants careful investigation of AB effects in early life. METHODS: Neonatal mice were treated with a combination of amoxicillin, vancomycin, and metronidazole from postnatal day 10 to 20. Intestinal permeability and whole-intestine gene and protein expression were analyzed. IECs were sorted by a fluorescence-activated cell sorter and their genome-wide gene expression was analyzed. Mouse fetal intestinal organoids were treated with the same AB combination and their gene and protein expression and metabolic capacity were determined. RESULTS: We found that in vivo treatment of neonatal mice led to decreased intestinal permeability and a reduced number of specialized vacuolated cells, characteristic of the neonatal period and necessary for absorption of milk macromolecules. In addition, the expression of genes typically present in the neonatal intestinal epithelium was lower, whereas the adult gene expression signature was higher. Moreover, we found altered epithelial defense and transepithelial-sensing capacity. In vitro treatment of intestinal fetal organoids with AB showed that part of the consequences observed in vivo is a result of the direct action of the ABs on IECs. Lastly, ABs reduced the metabolic capacity of intestinal fetal organoids. CONCLUSIONS: Our results show that early life AB treatment induces direct and indirect effects on IECs, influencing their maturation and functioning.