In the last decade, technological advances, combined with an improved appreciation of the ability of saliva to inform caregivers about both oral health and systemic disease, have led to the emergence of salivary diagnostic platforms. However, the majority of these assays have targeted diseases that more commonly affect the adult population, largely neglecting infants and children who arguably could benefit the most from non-invasive assessment tools for health monitoring. Gaining access into development, infection, and disease through comprehensive “omic” analyses of saliva could significantly improve care and enhance health access. In this review, we will highlight novel applications of salivary diagnostics in pediatrics across the “omic” spectrum, including at the genomic, transcriptomic, proteomic, microbiomic, and metabolomic level. The challenges to implementing salivary platforms into care, including the effects of age, diet, and developmental stage on salivary components, will be reviewed. Ultimately, large-scale, multicenter trials must be performed to establish normative biomarker values across the age spectrum to accurately discriminate between health and disease. Only then can salivary diagnostics truly translate into pediatric care.

Objectives To evaluate salivary biomarkers that elucidate the molecular mechanisms by which in utero opioid exposure exerts sex-specific effects on select hypothalamic and reward genes driving hyperphagia, a hallmark symptom of infants suffering from neonatal opioid withdrawal syndrome (NOWS). Study design We prospectively collected saliva from 50 newborns born at ³34 weeks of gestational age with prenatal opioid exposure and 50 sex-and gestational age-matched infants without exposure. Saliva underwent transcriptomic analysis for 4 select genes involved in homeostatic and hedonic feeding regulation (neuropeptide Y2 receptor [NPY2R], proopiomelanocortin [POMC], leptin receptor [LEPR], dopamine type 2 receptor [DRD2]). Normalized gene expression data were stratified based on sex and correlated with feeding volume on day of life 7 and length of stay in infants with NOWS requiring pharmacotherapy. Results Expression of DRD2, a hedonistic/reward regulator, was significantly higher in male newborns compared with female newborns with NOWS (D threshold cycle 10.8 AE 3.8 vs 13.9 AE 3.7, P = .01). In NOWS requiring pharmacotherapy expression of leptin receptor, an appetite suppressor, was higher in male subjects than female subjects (D threshold cycle 8.4 AE 2.5 vs 12.4 AE 5.1, P = .05), DRD2 expression significantly correlated with intake volume on day of life 7 (r = 0.58, P = .02), and expression of NPY2R, an appetite regulator, negatively correlated with length of stay (r = À0.24, P = .05). Conclusions Prenatal opioid exposure exerts sex-dependent effects on hypothalamic feeding regulatory genes with clinical correlations. Neonatal salivary gene expression analyses may predict hyperphagia, severity of withdrawal state, and length of stay in infants with NOWS.