Decreased Acetic Acid in the Stool of Preterm Infants Is Associated with an Increased Risk of Bronchopulmonary Dysplasia

Background: Short-chain fatty acids (SCFAs), microbial metabolites, have been minimally studied in neonatal pathophysiology but have been associated with disease outcomes in adults. The objective of this manuscript was to determine if SCFA levels in maternal breastmilk (BM) and stool from preterm neonates impacted the risk of neonatal morbidities. Methods: SCFA levels were quantified by liquid chromatography with tandem mass spectrometry on maternal BM and neonatal stool for preterm infants < 28 weeks’ gestation (N = 72) on postnatal days 14 and 28. SCFA levels in BM and stool of infants with and without bronchopulmonary disease (BPD) and retinopathy of prematurity (ROP) were compared. Logistic regression was applied to determine the association between stool acetic acid levels and disease. Results: Acetic, propionic, isobutyric, 2-methylbutyric, and isovaleric acid levels increased in BM and neonatal stool between days 14 and 28. Logistic regression demonstrated an inverse relationship between the quartile of fecal acetic acid level and the odds of BPD but not ROP on days 14 and 28. For each quartile increase in fecal acetic acid, the odds ratio (95% CI) of BPD was 0.41 (0.18, 0.83) for day 14 and 0.28 (0.09, 0.64) for day 28. Conclusions: Low acetic acid levels in the stool of preterm infants are associated with increased odds of BPD. These findings support a relationship between intestinal and pulmonary health in preterm infants

Early Nutrition and Weight Gain in Preterm Newborns and the Risk of Retinopathy of Prematurity

Objective: To identify nutritional and weight gain limitations associated with retinopathy of prematurity (ROP) severity among very preterm newborns. Patients and Methods 1180 infants <28 weeks GA at birth with ROP examination results were grouped and analyzed by quartile of weekly total calorie, carbohydrate, protein, and lipid intake, as well as growth velocity between postnatal days 7 and 28 (adjusted for GA and birth weight Z-score). ROP was categorized by development of no, mild (<prethreshold), type 2, or type 1 ROP, as well as markers of ROP severity including stage 3 ROP, zone 1 disease, and plus disease. Associations between nutritional intake and ROP severity were compared. Results: Greater risk for Type 1 ROP (risk/95% confidence intervals) was found for infants with lowest quartile receipt of lipids (2.1/1.1, 3.8), total calories (2.2/1.4, 3.6), and carbohydrates (1.7/1.1, 2.9). Development of zone 1 ROP was associated with lipid or total calorie intake in the lowest quartile, and development of stage 3 ROP was associated with lowest quartile of total calorie intake. Growth velocity in the lowest quartile was associated with increased risk of any ROP, including type 1 ROP. Conclusion: The risk of developing severe ROP in extremely premature infants might be reduced by improving nutritional support, specifically targeting lipids and total calories, and perhaps by improving weight gain

Short Course in the Microbiome

Over the past decade, it has become evident that the microbiome is an important environmental factor that affects many physiological processes, such as cell proliferation and differentiation, behaviour, immune function and metabolism. More importantly, it may contribute to a wide variety of diseases, including cancer, inflammatory diseases, metabolic diseases and responses to pathogens. We expect that international, integrative and interdisciplinary translational research teams, along with the emergence of FDA-approved platforms, will set the framework for microbiome-based therapeutics and diagnostics. We recognize that the microbiome ecosystem offers new promise for personalized/precision medicine and targeted treatment for a variety of diseases. The short course was held as a four-session webinar series in April 2015, taught by pioneers and experts in the microbiome ecosystem, covering a broad range of topics from the healthy microbiome to the effects of an altered microbiome from neonates to adults and the long term effects as it is related to disease, from asthma to cancer. We have learned to appreciate how beneficial our microbes are in breaking down our food, fighting off infections and nurturing our immune system, and this information provides us with ideas as to how we can manipulate our microbiome to prevent certain diseases. However, given the variety of applications, there are scientific challenges, though there are very promising areas in reference to the clinical benefits of understanding more about our microbiome, whether in our gut or on our skin: the outlook is bright. A summary of the short course is presented as a meeting dispatch

Association of maternal body composition and diet on breast milk hormones and neonatal growth during the first month of lactation

Introduction: Preterm birth is associated with altered growth patterns and an increased risk of cardiometabolic diseases, with breast milk (BM) being a counteracting factor. Preterm infants also show alterations in adipokines and gut hormones influencing appetite and metabolism. Since these hormones are present in BM, it is possible that their levels may equilibrate deficiencies improving infant growth. We aimed to assess 1) the BM levels of ghrelin, resistin, leptin, insulin, peptide YY, and the gastrointestinal peptide in women with preterm and term labor; 2) the relationship between BM hormones and neonatal growth; and 3) the influence of maternal body composition and diet on these BM hormones. Methods: BM from 48 women (30 term and 18 preterm labor) was collected at days 7, 14, and 28 of lactation. Maternal body composition was evaluated by bioimpedance, and neonate anthropometric parameters were collected from medical records. The maternal dietary pattern was assessed by a 72-h dietary recall at days 7 and 28 of lactation. BM hormones were analyzed by the U-Plex Ultra-sensitive method. Data were analyzed using linear regression models. BM from women with preterm labor had lower ghrelin levels, with the other hormones being significantly higher compared to women with term delivery. Results: In premature infants, growth was positively associated with BM ghrelin, while, in term infants, it was positively associated with insulin and negatively with peptide YY. In the first week of lactation, women with preterm labor had higher body fat compared to women with term labor. In this group, ghrelin levels were positively associated with maternal body fat and with fiber and protein intake. In women with term labor, no associations between anthropometric parameters and BM hormones were found, and fiber intake was negatively associated with peptide YY. Discussion: Preterm labor is a factor influencing the levels of BM adipokines and gut hormones, with BM ghrelin being a relevant hormone for premature infant growth. Since ghrelin is lower in BM from women with preterm labor and the levels are associated with maternal fat storage and some dietary components, our data support the importance to monitor diet and body composition in women who gave birth prematurely to improve the BM hormonal statusThis research was funded by Promotion of Knowledge Transfer program (PTC-2020) from Universidad Autónoma de Madrid in collaboration with Alter Farmacia, SA, Spanish Ministry of Science, and Innovation (RTI2018-097504-B-I00

Fecal Elastase in Preterm Infants to Predict Growth Outcomes

OBJECTIVES: Preterm infants are born functionally pancreatic insufficient with decreased pancreatic production of lipase and proteases. Developmental pancreatic insufficiency (PI) may contribute to reduced nutrient absorption and growth failure. We sought to determine longitudinal fecal elastase (ELA1) levels in a cohort of preterm infants and whether levels are associated with growth outcomes. METHODS: Prospective observational study of 30 infants 24-34 weeks gestational age and birth weight ≤1250 g fed the exclusive human milk diet, consisting of human milk with human milk-based fortifier. ELA1 was quantified by ELISA during the first 2 weeks of life [Early; 7.5 ± 1.8 days of life (DOL)] and after attainment of full, fortified feedings (Late; 63.6 ± 24.1 DOL). RESULTS: Early ELA1 levels were 192.2 ± 96.4 µg/g, and Late ELA1 levels were 268.0 ± 80.3 µg/g, 39.4% higher (P = 0.01). Infants with early PI (ELA1 \u3c 200 µg/g) were more likely male and of lower gestational age, weight, length, and head circumference at birth. These variables, but not PI status, independently predicted somatic growth. CONCLUSIONS: Fecal ELA1 in preterm infants fed exclusive human milk diet increases with postnatal age. Although pancreatic function in preterm infants may serve as a biological contributor to early postnatal growth failure, additional studies using fecal ELA1 as a predictive biomarker for growth failure are needed in larger cohorts

Non-invasive analysis of intestinal development in preterm and term infants using RNA-Sequencing

The state and development of the intestinal epithelium is vital for infant health, and increased understanding in this area has been limited by an inability to directly assess epithelial cell biology in the healthy newborn intestine. To that end, we have developed a novel, noninvasive, molecular approach that utilizes next generation RNA sequencing on stool samples containing intact epithelial cells for the purpose of quantifying intestinal gene expression. We then applied this technique to compare host gene expression in healthy term and extremely preterm infants. Bioinformatic analyses demonstrate repeatable detection of human mRNA expression, and network analysis shows immune cell function and inflammation pathways to be up-regulated in preterm infants. This study provides incontrovertible evidence that whole-genome sequencing of stool-derived RNA can be used to examine the neonatal host epithelial transcriptome in infants, which opens up opportunities for sequential monitoring of gut gene expression in response to dietary or therapeutic interventions

Association of maternal body composition and diet on breast milk hormones and neonatal growth during the first month of lactation

Preterm birth is associated with altered growth patterns and an increased risk of cardiometabolic diseases, with breast milk (BM) being a counteracting factor. Preterm infants also show alterations in adipokines and gut hormones influencing appetite and metabolism. Since these hormones are present in BM, it is possible that their levels may equilibrate deficiencies improving infant growth. We aimed to assess 1) the BM levels of ghrelin, resistin, leptin, insulin, peptide YY, and the gastrointestinal peptide in women with preterm and term labor; 2) the relationship between BM hormones and neonatal growth; and 3) the influence of maternal body composition and diet on these BM hormone

Fatty Acid Concentrations in Preterm Infants Fed the Exclusive Human Milk Diet: A Prospective Cohort Study

OBJECTIVE: Quantify blood fatty acids and growth outcomes in preterm infants fed the exclusive human milk diet. METHODS: A prospective cohort study of 30 infants 24-34 weeks gestation and ≤1250 g fed the exclusive human milk diet. Blood fatty acids were quantified at two time points. Comparisons were made using two-sample t-tests and Wilcoxon rank sum. RESULTS: Donor human milk-fed (n = 12) compared to mother\u27s own milk-fed infants (n = 18) from birth to after 28 days of life, had an increased interval change of linoleic to docosahexaenoic acid ratio (5.5 vs. -1.1 mole percent ratio, p = 0.034). Docosahexaenoic and eicosapentaenoic acid interval changes were similar between groups. The arachidonic acid change was similar between groups (-2.3 vs. -0.9 mole percent, p = 0.37), however, both experienced a negative change across time. At 36 weeks postmenstrual age, growth velocities were similar for groups. CONCLUSION: An exclusive human milk diet maintains birth docosahexaenoic and eicosapentaenoic acid concentrations. However, the postnatal deficit in arachidonic acid was not prevented

Maternal and neonatal factors modulating breast milk cytokines in the first month of lactation

Breast milk (BM) cytokines support and modulate infant immunity, being particularly relevant in premature neonates with adverse outcomes (NAO). This study aimed to examine, in a cohort of Spanish breastfeeding women, changes in BM cytokines in the first month of lactation, their modulation by neonatal factors (sex, gestational age, and NAO), maternal factors (obstetric complications, C-section, and diet), and their relationship with oxidative status. Sixty-three mother-neonate dyads were studied at days 7 and 28 of lactation. Dietary habits were assessed by a 72-h dietary recall, and the maternal dietary inflammatory index (mDII) was calculated. BM cytokines (IL-10, IL-13, IL-8, MCP-1, and TNFα) were assessed by ultra-sensitive chemiluminescence. Total antioxidant capacity was assessed by the ABTS method and lipid peroxidation by the MDA+HNE kit. From days 7 to 28 of lactation, the levels of IL-10 and TNFα remained stable, while IL-13 increased (β = 0.85 ± 0.12, p < 0.001) and IL-8 and MCP-1 levels decreased (β = −0.64 ± 0.27, p = 0.019; β = −0.98 ± 0.22, p < 0.001; respectively). Antioxidant capacity and lipid peroxidation also decrease during lactation. Neonatal sex did not influence any of the cytokines, but BM from mothers with male infants had a higher antioxidant capacity. Gestational age was associated with male sex and NAO, being inversely correlated with the BM proinflammatory cytokines IL-8, MCP-1, and TNFα. From days 7 to 28 of lactation, BM from women with NAO infants increased MCP-1 levels and had a larger drop in antioxidant capacity, with the opposite trend in lipid peroxidation. MCP-1 was also significantly higher in women undergoing C-section; this cytokine declined in women who decreased mDII during lactation, while IL-10 increased. Linear mixed regression models evidenced that the most important factors modulating BM cytokines were lactation period and gestational age. In conclusion, during the first month of lactation, BM cytokines shift towards an anti-inflammatory profile, influenced mainly by prematurity. BM MCP-1 is associated with maternal and neonatal inflammatory processe