Biology of the vernix caseosa: A review.

The vernix caseosa is a complex membranous structure comprising 80% water, 10% protein, and 10% lipids including barrier lipids such as ceramides, free fatty acids, phospholipids and cholesterol, synthesized partly by fetal sebaceous glands during the last trimester of pregnancy in an antero-posterior and dorsoventral manner. Because of its lipid content, vernix is hydrophobic and protects the skin from excessive water exposure during the development of the stratum corneum. The vernix caseosa has various functions during fetal transition from an intrauterine to an extrauterine environment, including lubrication of the birth canal during parturition, barrier function to prevent water loss, temperature regulation, for innate immunity and for intestinal development. This review discusses the evidence supporting the prenatal and postnatal functions of vernix caseosa, along with its structure, composition, and physical and biological characteristics. Understanding the biology of the vernix may facilitate improved care of preterm infants immediately post-partum.

Interactions among pulmonary surfactant, vernix caseosa, and intestinal enterocytes: intra-amniotic administration of fluorescently liposomes to pregnant rabbits.

Although vernix caseosa is known to be a natural biofilm at birth, human pulmonary surfactant commences to remove the vernix from fetal skin into the amniotic fluid at gestational week 34, i.e., well before delivery. To explain this paradox, we first produced two types of fluorescently labeled liposomes displaying morphology similar to that of pulmonary surfactant and vernix caseosa complexes. We then continuously administered these liposomes into the amniotic fluid space of pregnant rabbits. In addition, we produced pulmonary surfactant and vernix caseosa complexes and administered them into the amniotic fluid space of pregnant rabbits. The intra-amniotic infused fluorescently labeled liposomes were absorbed into the fetal intestinal epithelium. However, the liposomes were not transported to the livers of fetal rabbits. We also revealed that continuous administration of micelles derived from pulmonary surfactants and vernix caseosa protected the small intestine of the rabbit fetus from damage due to surgical intervention. Our results indicate that pulmonary surfactant and vernix caseosa complexes in swallowed amniotic fluid might locally influence fetal intestinal enterocytes. Although the present studies are primarily observational and further studies are needed, our findings elucidate the physiological interactions among pulmonary, dermal-epidermal, and gastrointestinal developmental processes.

Epidermal barrier treatments based on vernix caseosa.

BACKGROUND/AIMS: Premature infants lack the vernix caseosa, have an incompetent stratum corneum (SC) barrier and are predisposed to infection. Use of topical agents to improve barrier function has had mixed outcomes. The aim was to determine the effect of vernix versus common barrier creams on the rate and quality of the epidermal barrier repair following controlled wounding. METHODS: Minor wounds were created with (1) laser ablation in the minipig and (2) tape stripping of mother's volar skin as a model for premature skin. Native vernix was applied to the mother's tape-stripped skin. Treatments were no occlusion (NO), vernix and a petrolatum-based cream (PBC) in the pig, and NO, vernix, PBC, an oil-in-water cream (OWC), a semipermeable film (SP) and full occlusion (FO) in adults. RESULTS: Outcomes for both trials were barrier recovery and skin hydration (moisture accumulation rate, MAT), initial hydration, erythema and dryness in adults. Vernix and PBC produced greater barrier repair than NO in the pig. SP produced greater recovery than NO and FO in adults. Vernix yielded greater recovery than FO and was similar to PBC, OWC and NO. Vernix had a directionally higher MAT than OWC and directionally higher initial hydration than NO. CONCLUSIONS: The findings suggest that vernix-based topical creams would be effective for the treatment of epidermal wounds and show promise to augment SC repair and maturation in infants.

Why do humans get acne? A hypothesis.

Acne is a disease unique to humans and is associated with sebaceous glands that are found at high density on the scalp, forehead and face. Despite being a near universal problem in adolescence, the reason why such troublesome sebaceous glands exist at all is not well understood. Some interesting theories have been postulated including roles for skin maintenance, immunological function and perhaps even pheromones, but pre-pubertal skin which has sebaceous glands that are largely inactive, is healthy. Dystocia, obstructed labour, is unique to humans and no other animal has as much trouble giving birth. This is thought to reflect the relatively large human foetal head and proportionally small maternal pelvis. Noting the high density of sebaceous glands on the face, chest and back; these are exactly the same structures that pose the greatest obstruction during childbirth. Sebaceous glands develop after the fourth month of gestation and are large and well-developed at birth. Sebum production is also relatively high at birth. Having extra lubrication at these sites would help make the baby more slippery for birth conferring a selective advantage to successful delivery, as does the presence of the vernix caseosa, a white creamy substance, unique to humans that coats new-born infants. It is proposed that the sebaceous glands that cause acne are present on the face and forehead as they confer a selective advantage by 'lubricating' the widest parts of the new born baby to ease the passage of childbirth. Later in life, sebaceous glands may be inappropriately and pathologically primed, driven by a combination of hormones, diet and lifestyle to create acne.

Development of a murine model to evaluate the effect of vernix caseosa on skin barrier recovery.

The aim of this study was twofold, that is the generation of a reliable model for skin barrier disruption and repair and to evaluate recovery of damaged skin after application of vernix caseosa (VC). VC was selected as its wound healing properties were suggested previously, but never clearly demonstrated. Five different levels of barrier disruption in mice, accomplished by tape-stripping, were evaluated. Disruption models such as moderate, severe #1 and #2 (transepidermal water loss (TEWL) of 31 +/- 2, 59 +/- 4 and 66 +/- 3 g/m(2)/h, respectively) showed complete recovery within 72 h. However, not all corneocytes were removed after tape-stripping. Additionally, models such as severe #3 and #4 (TEWL of 73 +/- 5 and 79 +/- 6 g/m(2)/h, respectively) with a more severe disruption were evaluated. After tape-stripping, all corneocytes were removed and the remaining epidermis was intact. However, model #3 still showed complete recovery within 72 h. With model #4, a crust was formed and almost complete recovery (approximately 90%) was obtained within only 8 days. The effect of VC application on recovery of disrupted skin was evaluated with model #3 and #4. Model #3 showed that application of VC predominantly influenced initial recovery and is therefore merely appropriate to study the effect of formulations in the initial recovery period. Topical application of VC on model #4 considerably increased initial and long-term recovery. Moreover, VC application promoted rapid formation of stratum corneum and prevented epidermal thickening. These observations not only confirm the ability of VC to enhance barrier recovery, but also suggest potential use of this treatment clinically.

Novel mechanism of human fetal growth regulation: a potential role of lanugo, vernix caseosa and a second tactile system of unmyelinated low-threshold C-afferents.

Novel hypothesis of human fetal growth regulation in amniotic fluid environment integrates lanugo, vernix caseosa and a second tactile system of unmyelinated low-threshold C-afferents - all three forming a unique natural instrument powerfully speeding fetal growth during mid-gestation and lowering its tempo at the end of gestation. Repeated oscillations of lanugo hairs encased by vernix caseosa during fetal movements in amniotic fluid activate highly sensitive mechanoreceptors connected to unmyelinated C-afferents, which prime function is to conduct originated impulses from all fetal skin dermatoms via spinal cord and to activate vagal sensory zone, hypothalamus and insular cortex, for concomitant promotion of the anti-stress effect through oxytocin release, and stimulation of fetal growth by the incretin effect of gastrointestinal hormones.

Vernix caseosa in neonatal adaptation.

OBJECTIVES: To characterize vernix caseosa in newborn infants with respect to factors that influence vernix distribution on the skin surface, vernix effects on thermal stability, skin hydration, acid mantle development, and vernix antioxidant properties. STUDY DESIGN: Vernix distribution was determined for 430 infants. Thermal stability was assessed in parallel groups following vernix retention (n=66) and removal (n=64). The effects of vernix retention on skin hydration, pH, erythema, and dryness/scaling were determined. Samples were analyzed for vitamin E before and after UV exposure. RESULTS: Vernix distribution depended upon gestational age, delivery mode, gender, race, and meconium exposure. Retention had no effect on axillary temperatures. Skin hydration was significantly higher for vernix-retained skin. Skin pH and erythema were significantly lower with retention. Vitamin E levels were decreased by ultraviolet radiation. CONCLUSIONS: Vernix is a naturally occurring barrier cream with multiple salubrious effects, which support its retention on the skin surface at birth.

Lipid mediator profile in vernix caseosa reflects skin barrier development.

Vernix caseosa (VC) is a protective layer that covers the skin of most human newborns. This study characterized the VC lipid mediator profile, and examined its relationship to gestational period, gender of the newborn and maternal lifestyle. VC collected at birth from 156 newborns within the ALADDIN birth cohort was analyzed and 3 different groups of lipid mediators (eicosanoids and related oxylipin analogs, endocannabinoids and sphingolipids) were screened using LC-MS/MS. A total of 54 compounds were detected in VC. A number of associations between lipid mediators and the gestational period were observed, including increases in the ceramide to sphingomyelin ratio as well as the endocannabinoids anandamide and 2-arachidonoylglycerol. Gender-specific differences in lipid mediator levels were observed for all 3 lipid classes. In addition, levels of the linoleic acid oxidation products 9(10)-epoxy-12Z-octadecenoic and 12(13)-epoxy-9Z-octadecenoic acid (EpOMEs) as well as 12,13-dihydroxy-9Z-octadecenoic acid (DiHOME) were increased in VC of children from mothers with an anthroposophic lifestyle. Accordingly, VC was found to be rich in multiple classes of bioactive lipid mediators, which evidence lifestyle, gender and gestational week dependencies. Levels of lipid mediators in VC may therefore be useful as early stage non-invasive markers of the development of the skin as a protective barrier.

Transmission of electric and magnetic foetal cardiac signals in a case of ectopia cordis: the dominant role of the vernix. caseosa.

Foetal electrocardiograms (fECGs) and foetal magnetocardiograms (fMCGs) were recorded in the 26th, 29th and 31st weeks of gestation from a foetus with ectopia cordis-a rare condition in which the heart lies outside the chest wall. This provided an opportunity to study foetal cardiograms uninfluenced by the insulating effects of the foetal skin and vernix caseosa. The fECG of the ectopia cordis foetus was striking. Unlike recordings from age-matched normal foetuses, recordings from this subject had very high signal-to-noise ratio and showed no anomalous signal transmission properties. In contrast, fMCGs recorded from the ectopia cordis foetus and normal foetuses were largely similar. Both showed high signal-to-noise ratio and signal transmission properties consistent with volume conduction. The findings corroborate the hypothesis that high foetal skin resistance due primarily to the vernix caseosa is responsible for the low amplitude and anomalous transmission properties of the normal fECG, and demonstrate that the fMCG is relatively insensitive to conductivity inhomogeneities.

Is vernix caseosa a protective material to the newborn? A biochemical approach.

Twenty random samples of vernix caseosa were collected from immediately born neonates, in Jamahiriya Hospital, Benghazi. Biochemical studies of these samples revealed presence of lipids (62.5%), proteins (36%) and carbohydrate (1.5%). Also we could observe inhibition of staph. aureus and klebsiella growth on nutrient agar by this vernix. This observation could be explained either by its higher asparagine content or by its elevated lipid component. In addition tripalmitin was found to be the major lipid constituent, responsible for its hydrophobic property. So we recommend leaving this vernix layer on newborn skin until spontaneous drying.

The effect of volume conductor modeling on the estimation of cardiac vectors in fetal magnetocardiography.

Previous studies based on fetal magnetocardiographic (fMCG) recordings used simplified volume conductor models to estimate the fetal cardiac vector as an unequivocal measure of the cardiac source strength. However, the effect of simplified volume conductor modeling on the accuracy of the fMCG inverse solution remains largely unknown. Aiming to determine the sensitivity of the source estimators to the details of the volume conductor model, we performed simulations using fetal-maternal anatomical information from ultrasound images obtained in 20 pregnant women in various stages of pregnancy. The magnetic field produced by a cardiac source model was computed using the boundary-element method for a piecewise homogeneous volume conductor with three nested compartments (fetal body, amniotic fluid and maternal abdomen) of different electrical conductivities. For late gestation, we also considered the case of a fourth highly insulating layer of vernix caseosa covering the fetus. The errors introduced for simplified volume conductors were assessed by comparing the reconstruction results obtained with realistic versus spherically symmetric models. Our study demonstrates the significant effect of simplified volume conductor modeling, resulting mainly in an underestimation of the cardiac vector magnitude and low goodness-of-fit. These findings are confirmed by the analysis of real fMCG data recorded in mid-gestation.

Mimicking vernix caseosa--preparation and characterization of synthetic biofilms.

The multiple protecting and barrier-supporting properties of the creamy, white biofilm vernix caseosa (VC) before and after birth suggest that a VC biomimetic could be an innovative barrier cream for barrier-deficient skin. The aim of this study was the rational design and preparation of synthetic biofilms mimicking the unique composition and properties of natural VC. Hexagonal, highly hydrated hyperbranched polyglycerol microgel particles (30 microm in diameter) were embedded in a synthetic lanolin-based lipid mixture using a micromixer. In these formulations, the water content of the particles (i.e. 50% and 80%), an additional lipid coating of the particles and different particle/lipid ratios were varied. Characterization with confocal laser scanning microscopy (CLSM) showed a homogeneous distribution of the labeled particles in the lipid matrix. Regarding structural appearance, particle density and distribution, the formulations with a high particle/lipid ratio (5:1) resembled native VC very closely. Comparable results between native VC and the synthetic formulations were obtained concerning water handling properties, thermotropic behavior while lower elasticity and lower viscosity were observed for the synthetic biofilms. The biofilm formulations were stable for at least 1 month at 4 degrees C. In conclusion, our formulations mimic natural VC very closely and are promising candidates for in vivo studies.

Temperature-induced changes in structural and physicochemical properties of vernix caseosa.

The skin of the third trimester fetus and early newborn exhibits a complex, multifunctional, highly hydrated but viscous skin-surface biofilm called vernix caseosa (VC). During birth, VC undergoes a substantial change from an aqueous and warm surrounding into a gaseous and colder environment postnatally. The aim of this study was to investigate the structural and physicochemical changes in VC, which accompany physiologically relevant variations in environment parameters, such as temperature and humidity. A remarkable difference was observed in water release and uptake properties: dehydration and rehydration processes take place two to four times faster at 37 degrees C than at room temperature (RT). The dehydration was irreversible; rehydration was only possible to a final weight of 55% (37 degrees C) and 46% (RT) of the pre-desiccation weight. Differential scanning calorimetry showed two different overlapping phase transitions within physiological temperature range. Investigation of the lipid organization by Fourier transform infrared spectroscopy and small-angle X-ray diffraction revealed a more disordered state of lipids at 37 degrees C than at RT, which might explain the faster dehydration and rehydration process at 37 degrees C as well as the changes in thermotropic rheological behavior. In conclusion, we demonstrated that VC properties adjust to the fundamental change from the intrauterine to the post-natal environment.

Cutaneous bacterial infections in the newborn.

PURPOSE OF REVIEW: This review examines neonatal bacterial skin infections with respect to host immunity, bacterial pathogens, patterns of infection, and new therapeutic approaches. RECENT FINDINGS: Advances have been made in our understanding of innate host defense and the emerging role of cutaneous antimicrobial peptides of the cathelicidin and defensin families. Toll-like receptors are being investigated with respect to their interactions with bacteria and other components of the innate immune defense, such as the antimicrobial peptides. The epidermal barrier remains an active area of research. Studies confirm that maintaining an intact epidermal barrier by minimizing exposure to soap and by not removing vernix caseosa are simple measures to improve skin barrier function. Active barrier-enhancing measures such as the application of topical emollients have shown mixed results in the prevention of nosocomial infection. A meta-analysis of studies performed in developed countries showed a trend of increasing risk for coagulase-negative staphylococcal infection. By contrast, a randomized controlled trial showed that infants treated with sunflower oil are less likely to experience nosocomial infections than are control infants. Infants with bacteremia and no known source of infection should be carefully examined because cutaneous abscesses have been shown to be an important nidus of infection. Methicillin-resistant Staphylococcus aureus is reaching epidemic proportions, making surface cultures an essential part of the evaluation of cutaneous bacterial infection. SUMMARY: New insights have been gained regarding the basic science of neonatal host defense and these advances may produce new ways of approaching the prevention and treatment of bacterial skin infections in the newborn period.

A novel role for vernix caseosa as a skin cleanser.

OBJECTIVES: Skin cleansing is a complex process involving endogenous and exogenous mechanisms. This study examines the role of vernix caseosa in the process of skin cleansing in the perinatal period. METHODS: Vernix was evaluated as an exogenously applied skin cleanser using digitized image analysis which quantified residual carbon particles following a standardized cleansing assay. In addition, the detachment of vernix from human cadaveric skin and Gore-Tex supports was investigated following timed exposures to a variety of commonly used commercial surfactants. Detachment was quantified spectrophotometrically as increased turbidity at 650 nm. RESULTS: Image analysis showed that exogenous application of vernix exhibited a cleansing capability comparable or superior to standard skin cleansers. Dose-dependent increases in solution turbidity (vernix detachment) were seen following exposure of vernix-covered Gore-Tex vehicles to sodium laureth sulfate, sodium lauryl sulfate, and cocamidopropyl betaine solutions. Similar results were seen with cadaveric skin. CONCLUSIONS: These results demonstrate a role for vernix caseosa as a skin cleanser. Previous views of vernix as a soil or skin contaminant at birth need to be reevaluated.

The effect of changes in the conductive medium on the fetal ECG throughout gestation.

The electrical conduction of the ECG from the fetal heart to the maternal abdomen has been modelled by using volume conductor models based on the measured actual geometry. The models have been verified by means of multi-lead recordings of the fetal ECG. The results show that early in pregnancy (less than 28 weeks) the conduction can successfully be described by an electrically homogeneous model. Based on this model, a description of the fetal ECG that is independent of the position of the fetus is derived. In late pregnancies, the conduction is dominated by the isolating effect of the vernix caseosa. As the distribution of the vernix over the fetal body is unknown, the shape of the fetal ECG is disturbed in an unintelligible way. As a consequence, caution has to be applied when using the shape of the fetal ECG for diagnostic means.

Surface free energy characterization of vernix caseosa. Potential role in waterproofing the newborn infant.

BACKGROUND/AIMS: Vernix caseosa is a proteolipid biofilm synthesized by the human fetus, which progressively covers the fetal skin surface during the last trimester of pregnancy. The exact physiological functions of vernix are unclear. Hypothetically, it serves a role in "waterproofing" the fetus during the critical period of epidermal barrier development before birth. Vernix may also play a role in adaptation of the fetal skin surface to the dry, cool extrauterine environment after birth. Given the strategic position of vernix on the fetal skin surface and the rapidly changing environment encountered by the skin at birth, we proposed that investigation of vernix surface characteristics would facilitate understanding its putative physiological roles. METHODS: In this paper, we focused on the determination of the surface free energy (SFE) of vernix caseosa. Different approaches were used to calculate the SFE of vernix from contact angle (theta) measurements between vernix and various liquids (benzyl alcohol, diiodomethane, glycerol, and water). The critical surface tension (CST) of vernix was calculated using Zisman plots. The dispersive and the polar components of vernix SFE were calculated using the Owens-Wendt geometric mean method. Vernix was contrasted with petrolatum, a commonly used skin protectant. RESULTS: CST of fresh vernix was 40.5 dyne/cm while that of petrolatum was 35.8 dyne/cm. Fresh vernix polar SFE was 1.5 dyne/cm while petrolatum had almost no polar SFE component (0.03 dyne/cm). For all liquids (except the nonpolar diiodomethane) there was a significant decrease in contact angle with time. CONCLUSIONS: The CST and the total SFE values suggest that vernix has very low surface energy and is highly unwettable. These findings are significant insofar as the main component in vernix is water, which is highly energetic. Although vernix has a very high water content, the major part of its SFE is hydrophobic (dispersive). The limited interaction between vernix and hydrophilic liquids supports the hypothesis that vernix acts as a natural protectant cream to "waterproof" the fetus in utero while submerged in the amniotic fluid.

Role of Vernix caseosa in the neonate: potential application in the adult population.

Vernix caseosa is a naturally occurring fetal barrier film produced in late pregnancy as a result of sebaceous and epidermal lipids combined with desquamation of maturing fetal corneocytes. Vernix lacks desmosomal interconnections between corneocytes as demonstrated in adult stratum corneum and is, therefore, referred to as a "mobile phase" stratum corneum. Vernix is proposed to have multiple fetal/newborn overlapping biological functions: moisturization, anti-infective, antioxidant, wound healing, and waterproofing. Patients with altered skin integrity due to burn injuries lack the protective qualities necessary for wound healing. Emerging research suggests that Vernix applied to skin cultures may enhance wound healing. Application of the fetal/neonatal skin science findings to the adult burn population offers the potential for a clinically relevant homologous substitute for impaired tissue integrity.