Rational Approach to the Diagnosis of Severe Growth Hormone Deficiency in the Newborn

Context: Severe congenital GH deficiency (GHD) of the newborn is a rare disease, which can cause life-threatening hypoglycemias beginning in the first week of life. Reviews and consensus papers on the diagnosis of GHD repeatedly state the lack of a practical evidence-based approach to the diagnosis of GHD in the newborn. Objective: Here we provide for the first time sound reference values and a diagnostic cutoff for the GH levels in newborns at the age between d 3 and 5. Design, Setting, and Patients: GH was measured in the eluate from 314 filter papers of the newborn screening test performed in our university hospital by using a highly sensitive human GH-ELISA. Reference data are compared with measurements from nine newborns with very high likelihood of having severe GHD, and cutoffs for the diagnostic work-up are defined. Results: In the presence of clinical evidence, the diagnosis of neonatal GHD can be confirmed during the first week of life by a single randomly taken GH level less than 7 mu g/liter with 100% sensitivity and 98% specificity on the basis of our assay method. GH content in newborn screening cards stored for almost 3 yr were not different from the content found in recently used screening cards indicating high immunological stability of GH over time. Therefore, the diagnostic approach can use stored screening cards. In addition, we observed a clear gender dichotomy in respect to GH, with healthy female newborns having significantly higher GH levels than males. Cigarette smoking during pregnancy was associated with higher, transient tachypnea of the newborn with lower GH levels. Conclusions: We provide the first rational approach to the diagnosis of severe GHD in the newborn and evidence for gender dichotomy of the neonatal GH axis. (J Clin Endocrinol Metab 95: 2219-2226, 2010)