Newborn skin reflection: Proof of concept for a new approach for predicting gestational age at birth. A cross-sectional study

Background
Current methods to assess the gestational age during prenatal care or at birth are a global challenge. Disadvantages, such as low accessibility, high costs, and imprecision of clinical tests and ultrasonography measurements, may compromise health decisions at birth, based on the gestational age. Newborns’ organs and tissues can indirectly indicate their physical maturity, and we hypothesized that evolutionary changes in their skin, detected using an optoelectronic device meter, may aid in estimating the gestational age. This study analyzed the feasibility of using newborn skin reflectance to estimate the gestational age at birth noninvasively.
Methods and findings
A cross-sectional study evaluated the skin reflectance of selected infants, preferably premature, at birth. The first-trimester ultrasound was the reference for gestational age. A prototype of a new noninvasive optoelectronic device measured the backscattering of light from the skin, using a light emitting diode at wavelengths of 470 nm, 575 nm, and 630 nm. Univariate and multivariate regression analysis models were employed to predict gestational age, combining skin reflectance with clinical variables for gestational age estimation. The gestational age at birth of 115 newborns from 24.1 to 41.8 weeks of gestation correlated with the light at 630 nm wavelength reflectance 3.3 mm/6.5 mm ratio distant of the sensor, at the forearm and sole (Pearson’s correlation = 0.505, P < 0.001 and 0.710, P < 0.001, respectively). The best-combined variables to predict the gold standard gestational age at birth was the skin reflectance at wavelengths of 630 nm and 470 nm in combination with birth weight, phototherapy, and adjusted to include incubator stay, and sex (R2 = 0.828, P < 0.001). The main limitation of the study is that it was very specific to the premature population we studied and needs to be studied in a broader spectrum of newborns.
Conclusions
A novel automated skin reflectometer device, in combination with clinical variables, was able to predict the gestational age and could be useful when the information is in doubt or is unknown. Multivariable predictive models associated the skin reflectance with easy to obtain clinical parameters, at the birth scenario. External validation needs to be proven in an actual population with the real incidence of premature infants.

背景
目前在产前保健或分娩时评估胎龄（gestational age）的方法是一项全球性难题。临床检验与超声测量（ultrasonography）存在可及性低、成本高昂、精度不足等缺陷，可能会影响基于胎龄做出的分娩期健康决策。新生儿的器官与组织可间接反映其身体成熟度，我们推测：使用光电子检测仪（optoelectronic device）检测到的皮肤发育变化，或可辅助估算胎龄。本研究分析了利用新生儿皮肤反射率无创估算分娩时胎龄的可行性。

方法与结果
本研究通过横断面研究（cross-sectional study）评估了分娩时入选婴儿（优先纳入早产儿）的皮肤反射率。以妊娠早期超声检查（first-trimester ultrasound）作为胎龄判定的参照标准。一款新型无创光电子检测仪原型机采用波长分别为470 nm、575 nm与630 nm的发光二极管（light emitting diode），检测皮肤对光线的背向散射情况。本研究采用单变量与多变量回归分析模型，将皮肤反射率与临床变量相结合以预测胎龄，用于胎龄估算。
本研究纳入115名胎龄介于24.1至41.8周的新生儿，其分娩时胎龄与前臂、足底部位630 nm波长下、传感器距皮肤3.3 mm与6.5 mm处的反射率比值具有相关性（皮尔逊相关系数（Pearson’s correlation）分别为0.505、P < 0.001与0.710、P < 0.001）。用于预测分娩时金标准胎龄（gold standard）的最优联合变量为：630 nm与470 nm波长下的皮肤反射率，结合出生体重、光疗情况，并校正暖箱停留时长与性别因素（决定系数R²=0.828，P < 0.001）。本研究的主要局限性在于：研究对象仅限定于本次纳入的早产儿群体，需在更广泛的新生儿人群中开展进一步验证。

结论
一款新型自动化皮肤反射仪（skin reflectometer）与临床变量相结合，可实现胎龄预测，在胎龄信息存疑或缺失的场景中具有应用价值。多变量预测模型将皮肤反射率与分娩场景下易于获取的临床参数相结合。仍需在包含真实早产儿发病率的实际人群中开展外部验证。