A Pilot Study to Evaluate the Effects of Topically Applied Cosmetic Creams on Epidermal Responses.

Application of exogenous products, such as creams, to the skin can result in subclinical changes in selected epidermal functions such as transepidermal water loss (TEWL), hydration, redness, and pH; these changes may lead to or contribute to irritation. Changes in skin surface inflammatory factors may provide further insight into this potential for irritation. The objective of this study was to evaluate the changes in epidermal properties and inflammatory mediators after 4 days of topical application of 2 different polymers formulated in cosmetic creams. Ten healthy volunteers (mean age ± SD: 20.0 ± 2.4 years) completed the study. TEWL, color, and pH were not significantly different after repeated application of these polymers. Hydration was significantly lower at sites treated with polymer A after 5 days. Significant increases in IL-1α, IL-1RA, and IL-1ß were observed after cream application at sites treated with polymer A. This is the first study to apply noninvasive measurements to quantify subclinical changes in epidermal properties and inflammatory mediator expression before and after the application of a cosmetic product, which will allow for a more enhanced safety profile to be achieved.

Corrigendum: Dynamic Changes in DNA Methylation Occur during the First Year of Life in Preterm Infants.

[This corrects the article on p. 158 in vol. 7, PMID: 28018293.].

Dynamic Changes in DNA Methylation Occur during the First Year of Life in Preterm Infants.

BACKGROUND: Preterm birth associates with a substantially increased risk of later cardiovascular disease and neurodevelopmental disorders. Understanding underlying mechanisms will facilitate the development of screening and intervention strategies to reduce disease risk. Changes in DNA methylation have been proposed as one mechanism linking the early environment with later disease risk. We tested the hypothesis that preterm birth associates with altered DNA methylation in genes encoding insulin-like growth factor 2 (IGF2) and FK506-binding protein 5 (FKBP5), which appear particularly vulnerable to early life adversity. METHODS: Fifty preterm infants were seen and assessed at birth, term equivalent age, 3 months and 1-year corrected ages; 40 term infants were seen at birth, 3 months and 1 year. Saliva was collected for DNA extraction at birth, term, and 1 year. Pyrosequencing of bisulfite-converted DNA was performed to measure DNA methylation at specific CpG sites within the IGF2 and FKBP5 loci. RESULTS: Weight and head circumference was reduced in preterm infants at all time points. Preterm infants had a higher percentage body fat at term-corrected age, but this difference was not persistent. DNA methylation at the differentially methylated region (DMR) of IGF2 (IGF2DMR2) and FKBP5 was lower in preterm infants at birth- and term-corrected age compared to term infants at birth. IGF2DMR2 and FKBP5 methylation was related to birthweight SD score in preterm infants. Among preterm infants, social deprivation was an independent contributor toward reducing DNA methylation at IGF2DMR2 at birth- and term-corrected age and maternal smoking was associated with reduced DNA methylation at FKBP5 at birth. There were no persistent differences in DNA methylation at 1 year of age. CONCLUSION: Changes in DNA methylation were identified at key regions of IGF2/H19 and FKBP5 in preterm infants in early life. Potential contributing factors include maternal smoking and social deprivation. However, these changes did not persist at 1 year of age and further longitudinal studies are required to determine any associations between altered DNA methylation in the perinatal period of individuals born preterm and their long-term health.

Dynamics of DNA methylation at IGF2 in preterm and term infants during the first year of life: an observational study.

BACKGROUND: Preterm infants are at increased risk of cardiometabolic disease in later life. Extrauterine growth restriction, catch-up growth, altered adiposity, and abnormal hypothalamic-pituitary-adrenal axis activity could be predisposing factors. Altered DNA methylation (5-methylcytosine, 5mC) might be one underlying mechanism. We hypothesised that preterm infants have altered 5mC at the linked differentially methylated region 2 (DMR2) of IGF2 and the H19 imprinting control region (H19 ICR) compared with term infants over the first year of life. METHODS: We recruited 46 preterm (range 25 weeks + 2 days' gestation to 31 + 5, mean 28 + 6) and 40 term infants (38 + 3 to 42 + 2 weeks' gestation, mean 40 + 2). Anthropometric variables including body composition were measured at term age and 3 months corrected age with air displacement plethysmography and at 1-year-corrected age with skin-fold thickness. Salivary cortisol was measured at 3 months corrected age after the physical examination. Percentage methylation (%5mC) was analysed with pyrosequencing on buccal DNA. Statistical analysis used Student's t test and multivariate linear regression. FINDINGS: Preterm infants demonstrated growth deficit early in postnatal life but had greater percentage body fat at term age (ß=5·73, p<0·001), but not at 3 months (ß=-0·28, p=0·82). Compared with term infants, preterm infants had a blunted cortisol response to physical examination (mean difference 0·38 µg/dL, p=0·024). At birth, preterm infants had a significant decrease in %5mC at DMR2 compared with term infants at birth (ß=-11·48, p<0·001) and compared with preterm infants at term-corrected age (t=3·13, p=0·01). By term-corrected age, preterm infants had decreased %5mC at both DMR2 (ß=-2·84, p=0·013) and the H19 ICR (ß=-2·31, p=0·048) compared with term infants at birth, although this difference disappeared at 1 year. Social deprivation was independently associated with decreased %5mC at DMR2 at birth (ß=-1·73, p=0·006) and term-corrected age (ß=-0·86, p=0·016) but not at 1 year (ß=-0·89, p=0·07). INTERPRETATION: Our results show that decreased %5mC accompanies the early growth deficit in preterm infants. The marked reduction in %5mC at IGF2 DMR2 in preterm infants at birth compared with term-age supports existing evidence that imprinting at secondary regions is established after fertilisation, whereas imprinting is established during gametogenesis at primary regions (H19 ICR). Both regions might be susceptible to early life stressors such as preterm birth and social deprivation. FUNDING: Chief Scientist Office of the Scottish Government.

Placental 5-methylcytosine and 5-hydroxymethylcytosine patterns associate with size at birth.

Altered placental function as a consequence of aberrant imprinted gene expression may be one mechanism mediating the association between low birth weight and increased cardiometabolic disease risk. Imprinted gene expression is regulated by epigenetic mechanisms, particularly DNA methylation (5mC) at differentially methylated regions (DMRs). While 5-hydroxymethylcytosine (5hmC) is also present at DMRs, many techniques do not distinguish between 5mC and 5hmC. Using human placental samples, we show that the expression of the imprinted gene CDKN1C associates with birth weight. Using specific techniques to map 5mC and 5hmC at DMRs controlling the expression of CDKN1C and the imprinted gene IGF2, we show that 5mC enrichment at KvDMR and DMR0, and 5hmC enrichment within the H19 gene body, associate positively with birth weight. Importantly, the presence of 5hmC at imprinted DMRs may complicate the interpretation of DNA methylation studies in placenta; future studies should consider using techniques that distinguish between, and permit quantification of, both modifications.

Human milk for preterm infants: why, what, when and how?

A mother's expressed breast milk (MEBM) is overall the best feed for her preterm baby during the neonatal period, and is associated with improved short-term and long-term outcomes. Neonatal services should commit the resources needed to optimise its use. The place of banked donor expressed breast milk (DEBM) is less clear, but it probably has a role in reducing the risk of necrotising enterocolitis and sepsis in preterm infants at particularly high risk. There is considerable variation in the composition of human milk and nutrient fortification is often needed to achieve intrauterine growth rates. Human milk can transmit potentially harmful micro-organisms, and pasteurisation, which denatures some of the bioactive factors, is the only known way of preventing this. This is carried out for DEBM but not MEBM in the UK. Future research on human milk should focus on (a) critical exposure periods, (b) understanding better its bioactive properties, (c) the role of DEBM and (d) nutritional quality assurance.

How should we manage pain in ventilated neonates?

Newborn babies, even if extremely preterm, show responses to pain. The major stress responses seen with surgical pain are associated with serious adverse medical outcomes. There is an ethical imperative to consider pain relief in babies, despite the fact that they cannot verbalise their experience. Ventilator support, and accompanying treatments are described as distressing in adults, and are associated with an endocrine stress response in babies. Opiates have been shown to reduce physiological instability in sick newborn babies. Despite this, they have not been shown to reduce morbidity when given by infusion in ventilated infants, and in view of their serious side effects probably should not be used routinely in this way. It is logical and may be appropriate to give opiates peri-operatively and in babies likely to have severe pain (either from an underlying disease process such as necrotising enterocolitis, or during certain procedures). It is now accepted practice to use a potent analgesic/sedative for elective intubation and as cover for the treatment of retinopathy of prematurity. Topical anaesthetic creams reduce the pain response when used in anticipation of phlebotomy or vascular cannulation. Intra-oral sucrose is effective cover for procedures associated with mild to moderate distress, but its role in preterm infants is uncertain. Nursing interventions to reduce environmental stress, although commonly used, have not consistently been shown to be of benefit.