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Background/Objectives: Adequate folate intake is required in preterm infants for rapid growth and development, but there is little evidence to back recommendations. We aimed to assess folate status in preterm infants at discharge and in early infancy, according to exposure to folate sources, particularly in those exclusively/predominantly breastfed. Methods: A prospective, multicenter, observational cohort study was conducted in the UK, involving 45 preterm infants <33 weeks' gestational age (GA) exclusively/predominantly fed human milk when approaching NICU (Neonatal Intensive Care Unit) discharge. Serum folate levels were measured near NICU discharge (T1) and at 2–3 months corrected age (T2). Folate status was categorized per WHO (World Health Organization) guidelines: deficiency (<6.8 nmol/L), possible deficiency (6.8–13.4 nmol/L), normal (13.5–45.3 nmol/L), and elevated (>45.3 nmol/L). Nutritional information on feed and supplements was collected from hospital notes and maternal interviews. Results: Thirty-two infants (71%) received parenteral nutrition. Twelve infants (32%) remained exclusively breastfed at T2. No infant from the whole cohort had a serum folate concentration <13.5 nmol/L at either time point. A proportion of infants had serum folate concentrations >45.3 nmol/L: 14/45 (31%) at T1, 19/37 (42%) at T2, and 7/37 (16%) at both time points. Elevated concentrations were seen particularly in infants who received folic acid supplements or nutrition containing folic acid, such as parenteral nutrition and breastmilk fortifiers. Conclusions: Folate deficiency was not observed in this cohort; folate concentrations were high and in line with those observed in healthy term infants. Further research is needed to assess the high folate concentrations in premature babies and whether they may have any adverse clinical impact. [ABSTRACT FROM AUTHOR]

Human milk adipokines in term babies seem partially determined by maternal factors and affect infant's development. We aimed to describe bioactive peptide concentration in very preterm human milk and associations to maternal characteristics and postnatal growth. Mothers delivering ≤32 weeks of gestation and their infant/s were recruited. At 4 weeks of lactation, an aliquot of 24‐h‐pooled milk was collected for exclusively breastfeeding dyads. Insulin, leptin, adiponectin, and milk fat globule epidermal growth factor‐8 (MFG‐E8) were measured by enzyme‐linked immunoabsorbent assay in skimmed milk. One hundred mothers (28.8 ± 2.3 weeks at delivery) provided a milk sample. Milk insulin was related to gestational age, pre‐pregnancy body mass index (BMI), and galactagogue treatment (final model: adjusted R2: 0.330, p < 0.0001; adjusted β coefficients: galactagogue treatment: 0.348, p 0.001; pre‐pregnancy BMI: 0.274, p 0.009; gestational age: −0.290, p 0.007). Adiponectin was higher in mothers with gestational diabetes (30.7 ± 6.5 vs. 24.8 ± 8 ng/mL, p 0.044). Leptin was associated with pre‐pregnancy BMI (Spearman's ρ: 0.648, p < 0.0001) and MFG‐E8 to presence of labor and multiple pregnancy (final linear regression model, R2: 0.073, p 0.028, adjusted β coefficients: presence of labor −0.229, p 0.050; twins: −0.192, p 0.099). Milk adiponectin was associated with a greater decrease in length z‐scores from birth to 28 days (Pearson's r: −0.225, p 0.032) and to discharge (Pearson's r: −0.290, p 0.003). Milk MFG‐E8 was lower in milk of mothers whose babies experienced late‐onset sepsis (13.3 ± 5.8 vs. 16.8 ± 6.3 μg/mL, p 0.023). Adipokines levels in preterm human milk are partially related to maternal metabolic status. Milk peptide concentration associates with early neonatal growth trajectories. [ABSTRACT FROM AUTHOR]

Postnatal growth restriction remains one of the most common problems of very preterm infants (VPI). Chorioamnionitis is a frequent cause of prematurity. Both have been related to worse postnatal outcomes. To evaluate the influence of histological chorioamnionitis (CA) on postnatal growth in very premature infants. Retrospective one-to-one matched cohort study assessing growth in infants born at or below 32.0 weeks gestation from mothers for whom histological examination of the placenta was available. Newborns with histological CA were matched and compared with those without it. Postnatal growth was recorded at admission, 14 days of life, 28 days of life and 36 weeks postmenstrual age (PMA). Nutritional support and clinical outcomes were used as covariables. Eighty-eight patients were included: 44 with fetal or/and maternal placental inflammation, and 44 without histological CA (41% with vasculopathy findings and 59% without). Baseline characteristics were similar between the groups. Change in weight z-scores at 14 days of life, 28 days of life, 36 weeks PMA or at discharge were similar in both groups, with a steady fall and no signs of catch-up. No differences were found in enteral and parenteral nutritional intakes between groups. Histological CA did not affect postnatal growth of very preterm infants after matching for birth weight z-scores with non-CA newborns. [ABSTRACT FROM AUTHOR]

DNA methylation (5-methylcytosine, 5 mC) is involved in many cellular processes and is an epigenetic mechanism primarily associated with transcriptional repression. The recent discovery that 5mC can be oxidized to 5-hydromethylcytosine (5hmC) by TET proteins has revealed the "sixth base" of DNA and provides additional complexity to what was originally thought to be a stable repressive mark. However, our knowledge of the genome-wide distribution of 5hmC in different tissues is currently limited. Here, we sought to define loci enriched for 5hmC in the placenta genome by combining oxidative bisulphite (oxBS) treatment with high-density Illumina Infinium HumanMethylation450 methylation arrays and to compare our results with those obtained in brain. Despite identifying over 17,000 high-confidence CpG sites with consistent 5hmC enrichment, the distribution of this modification in placenta is relatively sparse when compared to cerebellum and frontal cortex. Supported by validation using allelic T4 b-glucosyltransferase assays we identify 5hmC at numerous imprinted loci, often overlapping regions associated with parent-oforigin allelic 5mC in both placenta and brain samples. Furthermore, we observe tissue-specific monoallelic enrichment of 5hmC overlapping large clusters of imprinted snoRNAs-miRNAs processed from long noncoding RNAs (lncRNAs) within the DLK1-DIO3 cluster on chromosome 14 and SNRPN-UBE3A domain on chromosome 15. Enrichment is observed solely on the transcribed alleles suggesting 5hmC is positively associated with transcription at these loci. Our study provides an extensive description of the 5hmC/5mC landscape in placenta with our data available at www.humanimprints.net, which represents the most comprehensive resource for exploring the epigenetic profiles associated with human imprinted genes. [ABSTRACT FROM AUTHOR]