Kate Coleman

Newborn screening (NBS) bloodspots are primarily used to test for a defined panel of conditions, yet screening expansion has necessitated the implementation of new tests. Integral to test implementation across all clinical laboratories is the need to evaluate the method with clinical samples, and a common secondary use of residual bloodspots, which are samples that remain following conventional screening, is validating new testing methods by establishing “normal” analyte concentrations and setting action decision limits for NBS protocols prior to implementation. Analysis of de-identified residual bloodspots may potentially reveal an infant with a treatable condition, and re-identification and clinical notification of the infant may then be prudent. However, consent to test residual samples for conditions under implementation may not have been obtained. This ethical dilemma risks the inclusion of residual bloodspots in test development being declined by over-arching NBS authorities. Consequently, the Human Genetics Society of Australasia (HGSA) NBS Committee issued a survey to the Australasian NBS laboratories regarding the current practices of the use of residual bloodspots for new test implementation. The questionnaire revealed a consistent requirement for residual NBS bloodspot analysis to determine reference ranges and screening cutoffs for biochemical variants. If using de-identified residual samples as a component of test validation, re-identification of infants with out-of-range results for clinical referral was considered ethically justified for potentially treatable conditions. The survey results will be used to develop a consensus approach in the region that is both ethically and scientifically valid.

Prolactin is a 23 kDa protein synthesised and released by lactotrophs located in the anterior pituitary gland. The main function of prolactin is the development of the mammary glands and the production and maintenance of milk secretion during pregnancy and lactation. Prolactin is present in 3 forms in the circulation monomeric, dimeric and macroprolactin which is one of the causes of variability between assay manufacturers. Although most assays have been standardised using the WHO’s 3rd international standard there is still considerable variability between commercially available assays and as such laboratories need to establish their own reference intervals. Clinicians use reference intervals to distinguish between healthy and diseased individuals. Direct methods to establish reference intervals are expensive and time consuming and are impractical for most routine clinical laboratories. Indirect methods using the laboratories own data are more commonly used but also have drawbacks. Determination of reference intervals for prolactin is particularly difficult due to various physiological causes for variation in prolactin levels including age, sex and menopause. The presence of macroprolactin, its detection and methods for reporting its presence adds to reference interval determination complexity and harmonisation of these methods may improve clinical care.