BackgroundCurrent 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 findingsA 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.ConclusionsA 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.

BackgroundNew 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 findingsIn 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).ConclusionsThe 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.

Background A low birth weight is an independent risk factor for adverse infant outcomes and a predictor of chronic disease in adulthood. In these situations, differentiating between prematurity and small for gestational age (SGA) or simultaneous conditions is essential to ensuring adequate care. Such diagnoses, however, depend on reliable pregnancy dating, which can be challenging in developing countries. A new medical optoelectronic device was developed to estimate gestational age (GA) at birth based on newborn skin reflection. Objective This study will aim to evaluate the device’s ability to detect prematurity or SGA, or both conditions simultaneously as well as predict short-term pulmonary complications in a cohort of low-birth-weight newborns. Methods This study protocol was designed for a multicenter cohort including referral hospitals in Brazil and Mozambique. Newborns weighing 500-2500 g will be eligible for inclusion with the best GA available, considering the limited resources of low-income countries. Comparator-GA is based on reliable last menstrual period dating or ultrasound assessment before 24 weeks’ gestation. Estimated GA at birth (Test-GA) will be calculated by applying a novel optoelectronic device to the newborn’s skin over the sole. The average difference between Test-GA and Comparator-GA will be analyzed, as will the percentage of newborns who are correctly diagnosed as preterm or SGA. In addition, in a nested case–control study, the accuracy of skin reflection in the prediction of prematurity-related respiratory problems will be evaluated. The estimated required sample size is 298 newborns. Results Teams of health professionals were trained, and standard operating procedures were developed following the good practice guidelines for the clinical investigation of medical devices for human participants. The first recruitment started in March 2019 in Brazil. Data collection is planned to end in December 2020, and the results should be available in March 2021. Conclusions The results of this clinical study have the potential to validate a new device to easily assess postnatal GA, supporting SGA identification when pregnancy dating is unreliable or unknown. Trial Registration ReBec: RBR-33rnjf; http://www.ensaiosclinicos.gov.br/rg/RBR-33rnjf/ International Registered Report Identifier (IRRID) DERR1-10.2196/16477

Background Early access to antenatal care and high-cost technologies for pregnancy dating challenge early neonatal risk assessment at birth in resource-constrained settings. To overcome the absence or inaccuracy of postnatal gestational age (GA), we developed a new medical device to assess GA based on the photobiological properties of newborns’ skin and predictive models. Objective This study aims to validate a device that uses the photobiological model of skin maturity adjusted to the clinical data to detect GA and establish its accuracy in discriminating preterm newborns. Methods A multicenter, single-blinded, and single-arm intention-to-diagnosis clinical trial evaluated the accuracy of a novel device for the detection of GA and preterm newborns. The first-trimester ultrasound, a second comparator ultrasound, and data regarding the last menstrual period (LMP) from antenatal reports were used as references for GA at birth. The new test for validation was performed using a portable multiband reflectance photometer device that assessed the skin maturity of newborns and used machine learning models to predict GA, adjusted for birth weight and antenatal corticosteroid therapy exposure. Results The study group comprised 702 pregnant women who gave birth to 781 newborns, of which 366 (46.9%) were preterm newborns. As the primary outcome, the GA as predicted by the new test was in line with the reference GA that was calculated by using the intraclass correlation coefficient (0.969, 95% CI 0.964-0.973). The paired difference between predicted and reference GAs was −1.34 days, with Bland-Altman limits of −21.2 to 18.4 days. As a secondary outcome, the new test achieved 66.6% (95% CI 62.9%-70.1%) agreement with the reference GA within an error of 1 week. This agreement was similar to that of comparator-LMP-GAs (64.1%, 95% CI 60.7%-67.5%). The discrimination between preterm and term newborns via the device had a similar area under the receiver operating characteristic curve (0.970, 95% CI 0.959-0.981) compared with that for comparator-LMP-GAs (0.957, 95% CI 0.941-0.974). In newborns with absent or unreliable LMPs (n=451), the intent-to-discriminate analysis showed correct preterm versus term classifications with the new test, which achieved an accuracy of 89.6% (95% CI 86.4%-92.2%), while the accuracy for comparator-LMP-GA was 69.6% (95% CI 65.3%-73.7%). Conclusions The assessment of newborn’s skin maturity (adjusted by learning models) promises accurate pregnancy dating at birth, even without the antenatal ultrasound reference. Thus, the novel device could add value to the set of clinical parameters that direct the delivery of neonatal care in birth scenarios where GA is unknown or unreliable. International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2018-027442

IntroductionRecognising prematurity is critical in order to attend to immediate needs in childbirth settings, guiding the extent of medical care provided for newborns. A new medical device has been developed to carry out the preemie-test, an innovative approach to estimate gestational age (GA), based on the photobiological properties of the newborn’s skin. First, this study will validate the preemie-test for GA estimation at birth and its accuracy to detect prematurity. Second, the study intends to associate the infant’s skin reflectance with lung maturity, as well as evaluate safety, precision and usability of a new medical device to offer a suitable product for health professionals during childbirth and in neonatal care settings.Methods and analysisResearch protocol for diagnosis, single­group, single­blinding and single­arm multicenter clinical trial with a reference standard. Alive newborns, with 24 weeks or more of pregnancy age, will be enrolled during the first 24 hours of life. Sample size is 787 subjects. The primary outcome is the difference between the GA calculated by the photobiological neonatal skin assessment methodology and the GA calculated by the comparator antenatal ultrasound or reliable last menstrual period (LMP). Immediate complications caused by pulmonary immaturity during the first 72 hours of life will be associated with skin reflectance in a nested case–control study.Ethics and disseminationEach local independent ethics review board approved the trial protocol. The authors intend to share the minimal anonymised dataset necessary to replicate study findings.Trial registration numberRBR-3f5bm5.