Skin thickness as a potential marker of gestational age at birth despite different fetal growth profiles: A feasibility study

Abstract

Background: New methodologies to estimate gestational age (GA) at birth are demanded to face the limited access to obstetric ultrasonography and imprecision of postnatal scores. The study analyzed the correlation between neonatal skin thickness and pregnancy duration. Secondarily, it investigated the influence of fetal growth profiles on tissue layer dimensions.

Methods and findings: In a feasibility study, 222 infants selected at a term-to-preterm ratio of 1:1 were assessed. Reliable information on GA was based on the early ultrasonography-based reference. The thicknesses of the epidermal and dermal skin layers were examined using high-frequency ultrasonography. We scanned the skin over the forearm and foot plantar surface of the newborns. A multivariate regression model was adjusted to determine the correlation of GA with skin layer dimensions. The best model to correlate skin thickness with GA was fitted using the epidermal layer on the forearm site, adjusted to cofactors, as follows: Gestational age (weeks) = -28.0 + 12.8 Ln (Thickness) - 4.4 Incubator staying; R2 = 0.604 (P<0.001). In this model, the constant value for the standard of fetal growth was statistically null. The dermal layer thickness on the forearm and plantar surfaces had a negative moderate linear correlation with GA (R = -0.370, P<0.001 and R = -0.421, P<0.001, respectively). The univariate statistical analyses revealed the influence of underweight and overweight profiles on neonatal skin thickness at birth. Of the 222 infants, 53 (23.9%) had inappropriate fetal growths expected for their GA. Epidermal thickness was not fetal growth standard dependent as follows: 172.2 (19.8) μm for adequate for GA, 171.4 (20.6) μm for SGA, and 177.7 (15.2) μm for LGA (P = 0.525, mean [SD] on the forearm).

Conclusions: The analysis highlights a new opportunity to relate GA at birth to neonatal skin layer thickness. As this parameter was not influenced by the standard of fetal growth, skin maturity can contribute to clinical applications.

Fig 1. High-frequency ultrasonography image of the skin over the forearm with automated epidermal thickness estimation.

(A) Skin ultrasonography image. (B) The red lines and the grid in between indicate the area over which dermal thickness is calculated using the DermaLab^® software. (C) The red color corresponds to the automated epidermal boundary detection by our dedicated software. (D) The white and black limits of the epidermis correspond to the automated mean thickness estimation by our dedicated software.

Fig 2. Magnitudes of the skin layer thicknesses of 222 newborns on the first day of life.

(A) Distribution corresponds to the epidermal skin over the forearm. Values: n = 217; mean (SD), 172.4 (19.6) μm and 95% CI of the mean, 169.8–175.1. (B) Distribution corresponds to the dermal skin over the forearm. Values: n = 217; mean (SD), 974.0 (290.0) μm; 95% CI of the mean, 994.9–1061.8; and median (IQR), 974.0 (290.0) μm. (C) Distribution corresponds to the epidermal skin over the plantar surface. Values: n = 219; mean (SD), 174.6 (17.5) μm; 95% CI of the mean, 172.2–176.9. (D) Distribution corresponds to the dermal skin over the plantar surface. Values: n = 219; mean (SD), 1244.5 (869.0) μm; 95% CI of the mean, 1125.2–1263.9); and median (IQR), 1244.5 (869.0) μm.

Fig 3. Gestational age estimated using the epidermal skin thickness of the forearm in comparison with GA at birth by early obstetric ultrasonography.

Equation: Gestational age (weeks) = −28.0 + 12.8 Ln (Thickness) − 4.4 Incubator stay + 0.015 standard fetal growth; R = 0.777, R² = 0.604, P < 0.001.

Fig 4. Histogram of residual value for the skin thickness vs. gestational age.

Fig 5. Neonatal skin with dermal layer measurements in stillbirths from biopsies over the plantar surface of the foot.

Scale: 200 μm. Skin at (A) 21 weeks of gestation, 406.5 μm; (B) 34 weeks of gestation, 284.6 μm; and (C) 40 weeks of gestation.