Maternal and child biomonitoring strategies and levels of exposure in western Canada during the past seventeen years: The Alberta Biomonitoring Program: 2005-2021.

The Alberta Biomonitoring Program (ABP) was created in 2005 with the initial goal of establishing baseline levels of exposure to environmental chemicals in specific populations in the province of Alberta, Canada, and was later expanded to include multiple phases. The first two phases focused on evaluating exposure in pregnant women (Phase One, 2005) and children (Phase Two, 2004-2006) by analyzing residual serum specimens. Phase Three (2013-2016) employed active recruitment techniques to evaluate environmental exposures using a revised list of chemicals in paired serum pools from pregnant women and umbilical cord blood. These three phases of the program monitored a total of 226 chemicals in 285 pooled serum samples representing 31,529 individuals. Phase Four (2017-2020) of the ABP has taken a more targeted approach, focusing on the impact of the federal legalization of cannabis on the exposure of pregnant women in Alberta to cannabis, as well as tobacco and alcohol using residual prenatal screening serum specimens. Chemicals monitored in the first three phases include herbicides, neutral pesticides, metals, metalloids, and micronutrients, methylmercury, organochlorine pesticides, organophosphate pesticides, parabens, phthalate metabolites, perfluoroalkyl substances (PFAS), phenols, phytoestrogens, polybrominated compounds, polychlorinated biphenyls (PCBs), dioxins and furans, polycyclic aromatic hydrocarbons (PAHs), and tobacco biomarkers. Phase Four monitored six biomarkers of tobacco, alcohol, and cannabis. All serum samples were pooled. Mean concentrations and 95% confidence intervals (CIs) were calculated for the chemicals detected in ≥25% of the sample pools. cross the first three phases, the data from the ABP has provided baseline exposure levels for the chemicals in pregnant women, children, and newborns across the province. Comparison within and among the phases has highlighted differences in exposure levels with age, geography, seasonality, sample type, and time. The strategies employed throughout the program phases have been demonstrated to provide effective models for population biomonitoring.

The clinical effect of glucose meter selection upon the detection of neonatal hypoglycemia.

Neonatal hypoglycemia is a common, transitional metabolic state that may lead to poor neurodevelopmental outcomes if unrecognized or managed inadequately. Given its frequency of presentation and immense clinical significance, a myriad of clinical practice guidelines have been published outlining appropriate screening, diagnosis, and treatment principles-many endorsing the use of glucose point-of-care testing (POCT). Unfortunately, the well-intended 'march' toward POCT, with bedside glucose meters as screening devices in the NICU, has resulted in unintended consequences with critical implications: a lack of international traceability to the 'gold' standard glucose method by POCT devices, under-recognition of POCT limitations, and a reliance upon a technology primarily driven to detect hyperglycemia in the adult population as opposed to neonatal hypoglycemia. As providers continue to advocate for improved POCT, there must be robust communication between providers and the clinical laboratory in the selection, standardization, and interpretation of glucose POCT to ensure optimal neonatal glucose detection.

N-Acetylcysteine Interference with a Glucose Dehydrogenase Linked Glucose Meter.

BACKGROUND: Our objective was to determine the effect of therapeutic concentrations of N-acetylcysteine, following intravenous infusion, on the measurement of blood glucose using a Roche Diagnostics glucose dehydrogenase-linked glucose meter compared to hospital laboratory methods. METHODS: N-acetylcysteine was added to aliquots of blood, with glucose promptly measured by the glucose meter, blood gas analyzer (glucose oxidase comparative method) and following centrifugation, plasma glucose measured with a hexokinase spectrophotometric comparative method. Glucose results were evaluated with linear regression and Bland Altman plots. RESULTS: In the presence of NAC, at concentrations greater than 5 mg/dL (0.31 mmol/L), positively biased glucose meter results were compared to the clinical laboratory results. Multivariate linear regression revealed that NAC-mediated meter results are influenced by NAC and glucose concentrations. CONCLUSIONS: The addition of therapeutic concentrations of NAC to blood produces statistically significant positive biases when measured with the glucose dehydrogenase linked glucose meter device.

The effect of the Covid-19 shutdown on glycemic testing and control.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused a halt to in-person ambulatory care. We evaluated how the reduction in access to care affected HbA1c testing and patient HbA1c levels. METHODS: HbA1c data from 11 institutions were extracted to compare testing volume and the percentage of abnormal results between a pre-pandemic period (January-June 2019, period 1) and a portion of the COVID-19 pandemic period (Jan-June 2020, period 2). HbA1c results greater than 6.4% were categorized as abnormal. RESULTS: HbA1C testing volumes decreased in March, April and May by 23, 61 and 40% relative to the corresponding months in 2019. The percentage of abnormal results increased in April, May and June (25, 23, 9%). On average, we found that the frequency of abnormal results increased by 0.31% for every 1% decrease in testing volume (p < 0.0005). CONCLUSION: HbA1c testing volume for outpatients decreased by up to 70% during the early months of the pandemic. The decrease in testing was associated with an increase in abnormal HbA1c results.

Side-Effects of COVID-19 on Patient Care: An INR Story.

BACKGROUND: Numerous studies have documented reduced access to patient care due to the COVID-19 pandemic, including access to diagnostic or screening tests, prescription medications, and treatment for an ongoing condition. In the context of clinical management for venous thromboembolism, this could result in suboptimal therapy with warfarin. We aimed to determine the impact of the pandemic on utilization of International Normalized Ratio (INR) testing and the percentage of high and low results. METHODS: INR data from 11 institutions were extracted to compare testing volume and the percentage of INR results ≥3.5 and ≤1.5 between a pre-pandemic period (January-June 2019, period 1) and a portion of the COVID-19 pandemic period (January-June 2020, period 2). The analysis was performed for inpatient and outpatient cohorts. RESULTS: Testing volumes showed relatively little change in January and February, followed by a significant decrease in March, April, and May, and then returned to baseline in June. Outpatient testing showed a larger percentage decrease in testing volume compared to inpatient testing. At 10 of the 11 study sites, we observed an increase in the percentage of abnormal high INR results as test volumes decreased, primarily among outpatients. CONCLUSION: The COVID-19 pandemic impacted INR testing among outpatients which may be attributable to several factors. Increased supratherapeutic INR results during the pandemic period when there was reduced laboratory utilization and access to care is concerning because of the risk of adverse bleeding events in this group of patients. This could be mitigated in the future by offering drive-through testing and/or widespread implementation of home INR monitoring.

COVID-19 Pandemic Planning: Simulation Models to Predict Biochemistry Test Capacity for Patient Surges.

BACKGROUND: Patient surges beyond hospital capacity during the initial phase of the COVID-19 pandemic emphasized a need for clinical laboratories to prepare test processes to support future patient care. The objective of this study was to determine if current instrumentation in local hospital laboratories can accommodate the anticipated workload from COVID-19 infected patients in hospitals and a proposed field hospital in addition to testing for non-infected patients. METHODS: Simulation models predicted instrument throughput and turn-around-time for chemistry, ion-selective-electrode, and immunoassay tests using vendor-developed software with different workload scenarios. The expanded workload included tests from anticipated COVID patients in 2 local hospitals and a proposed field hospital with a COVID-specific test menu in addition to the pre-pandemic workload. RESULTS: Instrumentation throughput and turn-around time at each site was predicted. With additional COVID-patient beds in each hospital, the maximum throughput was approached with no impact on turnaround time. Addition of the field hospital workload led to significantly increased test turnaround times at each site. CONCLUSIONS: Simulation models depicted the analytic capacity and turn-around times for laboratory tests at each site and identified the laboratory best suited for field hospital laboratory support during the pandemic.

Chemotherapy readiness in pediatric oncology: Assessing an automated method to measure urine specific gravity.

As part of the evaluation for chemotherapy readiness, urine specific gravity is measured to assess the patient's overall hydration status. Depending on the accuracy of the methods used, patients may be adversely affected by having their chemotherapy delayed or prematurely started. To evaluate the diagnostic accuracy of a new automated urine dipstick readout device (Clinitek), we tested 196 consecutive urine samples for urine specific gravity and compared them with the practical gold standard, a urine refractometer. We found a high correlation between both tools among clean urine samples, but a poor correlation among the pathological urine samples.

Providing Inclusive Care for Transgender Patients: Capturing Sex and Gender in the Electronic Medical Record.

BACKGROUND: Providing a positive patient experience for transgender individuals includes making the best care decisions and providing an inclusive care environment in which individuals are welcomed and respected. Over the past decades, introduction of electronic medical record (EMR) systems into healthcare has improved quality of care and patient outcomes through improved communications among care providers and patients and reduced medical errors. Promoting the highest standards of care for the transgender populations requires collecting and documenting detailed information about patient identity, including sex and gender information in both the EMR and laboratory information system (LIS). CONTENT: As EMR systems are beginning to incorporate sex and gender information to accommodate transgender and gender nonconforming patients, it is important for clinical laboratories to understand the importance and complexity of this endeavor. In this review, we highlight the current progress and gaps in EMR/LIS to capture relevant sex and gender information. SUMMARY: Many EMR and LIS systems have the capability to capture sexual orientation and gender identity (SOGI). Fully integrating SOGI into medical records can be challenging, but is very much needed to provide inclusive care for transgender individuals.

Estimated Risk for Insulin Dose Error Among Hospital Patients Due to Glucose Meter Hematocrit Bias in 2020.

CONTEXT.­: Glycemic control requires accurate blood glucose testing. The extent of hematocrit interference is difficult to assess to assure quality patient care. OBJECTIVE.­: To predict the effect of patient hematocrit on the performance of a glucose meter and its corresponding impact on insulin-dosing error. DESIGN.­: Multilevel mixed regression was conducted to assess the extent that patient hematocrit influences Roche Accu-Chek Inform II glucose meters, using the Radiometer ABL 837 as a reference method collected during validation of 35 new meters. Regression coefficients of fixed effects for reference glucose, hematocrit, an interaction term, and random error were applied to 4 months of patient reference method results extracted from the laboratory information system. A hospital inpatient insulin dose algorithm was used to determine the frequency of insulin dose error between reference glucose and meter glucose results. RESULTS.­: Fixed effects regression for method and hematocrit predicted biases to glucose meter results that met the "95% within ±12%" for the US Food and Drug Administration goal, but combinations of fixed and random effects exceeded that target in emergency and hospital inpatient units. Insulin dose errors were predicted from the meter results. Twenty-eight percent of intensive care unit, 20.8% of hospital inpatient, and 17.7% of emergency department results were predicted to trigger a ±1 insulin dose error by fixed and random effects. CONCLUSIONS.­: The current extent of hematocrit interference on glucose meter performance is anticipated to cause insulin error by 1-dose category, which is likely associated with low patient risk.

A Simulation Study to Assess the Effect of Analytic Error on Neonatal Glucose Measurements Using the Canadian Pediatric Society Position Statement Action Thresholds.

BACKGROUND: The Canadian Pediatric Society (CPS) has endorsed an algorithm for the screening and immediate management of babies at risk of neonatal hypoglycemia that provides time-dependent glucose concentration action thresholds. The objective of this study was to evaluate the impact of glucose analytic error (bias and imprecision) on the misclassification of glucose meter results from a neonatal intensive care unit (NICU) using the CPS guidelines. METHODS: A simulation dataset of true glucose values (N = 100 000) was derived by finite mixture model analysis of NICU glucose data (N = 23 749). Bias and imprecision were added to create measured glucose values. The percentages of measured glucose values that were misclassified at CPS action thresholds were determined by Monte Carlo simulation. RESULTS: Measurement biases ranging from -20 to +20 mg/dL combined with coefficients of variation 0% to 20% were evaluated to predict misclassification rates at 32, 36, and 47 mg/dL. The models demonstrated low risk of false normoglycemia-at 5% CV and +10 mg/dL bias: 0.8% to 5% misclassification at the 32 and 47 mg/dL thresholds due to bias. The models demonstrated risk of false hypoglycemia-at 5% CV and -10 mg/dL bias: 3% to 12.5% misclassification at 32 and 47 mg/dL thresholds due to both bias and imprecision. CONCLUSION: Using CPS action thresholds, the simulation model predicted the proportion of neonates at risk of inappropriate clinical action-both of omission or "failure to treat" and commission or "overtreatment" in response to NICU glucose meter results at specific bias and imprecision values.

Evaluation of Precision and Bias Specifications Required to Achieve the 2018 FDA Guidance Criteria for Glucose Meter Performance Using Simulation Models.

BACKGROUND: The objective of this study was to estimate the combinations of total bias and total imprecision required for devices to meet the Food and Drug Administration (FDA) specifications using Monte Carlo simulation rather than collection and analysis of experimental data. METHODS: A model Gaussian distribution of true-glucose values was altered by adding bias and imprecision to create measured-glucose values affected by analytic error. The fraction of measured-glucose values that met the 2018 FDA criteria for blood glucose monitoring system (BGMS) or self-monitoring blood glucose (SMBG) devices was determined as a function of bias and imprecision. RESULTS: The BGMS model determined that a maximum total imprecision of 6% was required with no bias, and with a total bias of +10 mg/dL the total imprecision allowed was reduced to 5% to achieve the 95% FDA performance expectation: 95% of results ≥75 mg/dL within ±12% and 95% of results <75 mg/dL within ±12 mg/dL. The SMBG model determined that a maximum total imprecision of 6% was required at no bias, and with a total bias of +10 mg/dL the total imprecision allowed was reduced to 4% to achieve the 98% FDA expectation: 98% of results ±75 mg/dL within ±15% and 98% of results <75 mg/dL within ±15 mg/dL. CONCLUSIONS: The 2018 FDA guidance criteria require strict conditions for glucose meter clinical trials to achieve <10 mg/dL total bias and total imprecision of <5%. Total imprecision and bias values assessed in models in this study represent the cumulative imprecision and bias errors for the glucose meters, the reference method, and preanalytic processes.

Analytical Concordance of Diverse Point-of-Care and Central Laboratory Troponin I Assays.

BACKGROUND: Cardiac troponin I (cTnI) 99th percentile cutoffs, used in the diagnosis of acute myocardial infarction, are not standardized across cTnI assays. We compared 3 point-of-care (POC) and 1 central laboratory contemporary cTnI assays against the Abbott high-sensitivity (hs) cTnI to evaluate the analytical concordance and the feasibility of using a single cutoff value for all assays. METHODS: Fresh blood samples collected from 102 inpatients in the coronary care unit were measured on central laboratory instruments (Beckman Coulter DxI AccuTnI+3 TnI, Abbott Architect hs-TnI) and cTnI POC analyzers (Alere Triage Troponin I, Radiometer AQT90, Abbott i-STAT). Agreement and correlation between the contemporary cTnI assays and hs-cTnI assay were assessed using regression analysis. Proportional bias was assessed using Bland-Altman plots. Concordance between the contemporary cTnI and hs-cTnI assays was determined by diagnostic contingency tables at specific cutoffs. RESULTS: Most POC cTnI assays had excellent correlation with the Abbott hs-cTnI method (r 2 = 0.955-0.970) except for Alere Triage (r 2 = 0.617), while proportional bias is evident between all cTnI assays. Overall concordance between POC contemporary cTnI assays and hs-cTnI assay was 80% to 90% at their respective 99th percentile cutoffs. The concordance increased to 90% to 95% when a fixed cutoff of 0.03 to 0.05 ng/mL was used across the assays. CONCLUSIONS: This study demonstrates poor analytical concordance between cTnI assays at the 99th percentile and supports the notion of a single clinical decision limit for cTnI and consequently standardization of diagnostic protocols despite the analytical differences among these assays.

An insulin-dose error assessment grid: A new tool to evaluate glucose meter performance.

OBJECTIVE: To develop a tool to assess the clinical accuracy of glucose meter performance using an insulin dosing protocol to assess the frequency and extent of error in insulin dose categories. METHODS: Retrospective comparison of 1815 glucose meter and central laboratory glucose results obtained from 1698 critically ill patients was conducted using the Parkes error grid, Surveillance error grid and an insulin dose error assessment grid with a sliding scale insulin dosing protocol used to manage critically ill patients. RESULTS: Parkes error grid and Surveillance error grid analyses indicated little risk conferred with the glucose meter results. Insulin dose error assessment grid complemented the aforementioned consensus error grids by determining quantifiable metrics, insulin dose category errors. Insulin dose error analysis indicated that 76.8% (1395/1815) would not have any change in insulin dose, 99.2% (1800/1815) within ±1 insulin dose category, 99.9% (1814/1815) within ±2 categories and 100% within ±3 insulin dose categories. CONCLUSIONS: Analysis with an insulin dose error grid provides information about the frequency and extent of insulin dose category errors with a specific insulin dosing protocol and describes potential clinical impact of glucose meter error.

Comparative evaluation of neonatal bilirubin using Radiometer whole blood co-oximetry and plasma bilirubin methods from Roche Diagnostics and Ortho Clinical Diagnostics.

BACKGROUND: Clinically significant variation has been reported within and between plasma and whole blood total bilirubin methods used to identify neonates for whom clinical intervention for hyperbilirubinemia may be required. OBJECTIVE: To evaluate total bilirubin measurements between the Radiometer whole blood co-oximeter and plasma bilirubin methods from Roche Diagnostics and Ortho Clinical Diagnostics using neonatal specimens. METHODS: Total bilirubin levels were analyzed by whole blood co-oximetry (Radiometer® ABL90). Specimens were centrifuged and plasma analyzed for total bilirubin with a diazo method (Roche Cobas® C-601) and a reflectance spectrophotometric BuBc dry film method (Ortho Clinical Diagnostics VITROS® 350). Results were evaluated by regression, Bland-Altman comparisons and t-tests. RESULTS: The patient correlation study yielded the following regression equations in µmol/L: a) Radiometer=1.03 Roche - 3.5µmol/L b) Radiometer=0.98 Ortho - 5.7µmol/L c) Roche=0.97 Ortho - 2.4µmol/L. The mean bias over the range of total bilirubin levels examined was -1.0µmol/L for the Radiometer versus the Roche (p≤0.305); -4.4µmol/L for the Radiometer versus Ortho (p≤0.005) and -4.4µmol/L for the Roche versus Ortho (p≤0.002). CONCLUSIONS: Whole blood total bilirubin measurement using the Radiometer ABL90 blood gas analyzer provides accurate and precise results compared to the Roche plasma diazo method. Compared to the reflectance spectrophotometric method, results are precise and had a small but statistically significant bias of -4.4µmol/L.

Limitations and opportunities of whole blood bilirubin measurements by GEM premier 4000®.

BACKGROUND: Neonatal hyperbilirubinemia has traditionally been screened by either total serum bilirubin or transcutaneous bilirubin. Whole blood bilirubin (TwB) by the GEM Premier 4000® blood gas analyzer (GEM) is a relatively new technology and it provides fast bilirubin results with a small sample volume and can measure co-oximetry and other analytes. Our clinical study was to evaluate the reliability of TwB measured by the GEM and identify analytical and clinical factors that may contribute to possible bias. METHODS: 440 consecutive healthy newborn samples that had plasma bilirubin ordered for neonatal hyperbilirubinemia screening were included. TwB was first measured using the GEM, after which the remainder of the blood was spun and plasma neonatal bilirubin was measured using the VITROS 5600® (VITROS). RESULTS: 62 samples (14%) were excluded from analysis due to failure in obtaining GEM results. Passing-Bablok regression suggested that the GEM results were negatively biased at low concentrations of bilirubin and positively biased at higher concentrations relative to the VITROS results (y = 1.43x-61.13). Bland-Altman plots showed an overall negative bias of the GEM bilirubin with a wide range of differences compared to VITROS. Both hemoglobin concentration and hemolysis affected the accuracy of the GEM results. Clinically, male infants had higher mean bilirubin levels, and infants delivered by caesarean section had lower hemoglobin levels. When comparing the number of results below the 40th percentile and above the 95th percentile cut-offs in the Bhutani nomogram which would trigger discharge or treatment, GEM bilirubin exhibited poor sensitivity and poor specificity in contrast to VITROS bilirubin. CONCLUSIONS: An imperfect correlation was observed between whole blood bilirubin measured on the GEM4000® and plasma bilirubin on the VITROS 5600®. The contributors to the observed differences between the two instruments were specimen hemolysis and the accuracy of hemoglobin measurements, the latter of which affects the calculation of plasma-equivalent bilirubin. Additionally, the lack of standardization of total bilirubin calibration particularly in newborn specimens, may also account for some of the disagreement in results.

Application of a Simulation Model to Estimate Treatment Error and Clinical Risk Derived from Point-of-Care International Normalized Ratio Device Analytic Performance.

BACKGROUND: In 2016, the Food and Drug Administration (FDA) proposed to enhance performance expectations for point-of-care testing (POCT) international normalized ratio (INR) devices relative to International Organization for Standardization (ISO) 17593:2007. The objective of the study was to estimate the frequency of warfarin dosing errors associated with a central laboratory INR method, a POCT INR method, and the proposed FDA performance goals. METHODS: A data set of INR results (n = 51912) from adult patients with INR ≤4 was used to assess the influence of adding assay imprecision and bias on warfarin dose decisions. The frequency of error in warfarin dose and size of error (≥1 or ≥2 dose categories) was compared using published assay specifications for the Instrumentation Laboratory ACL TOP® and the Roche Diagnostics CoaguChek® XS relative to the proposed FDA guidelines. RESULTS: The frequency of warfarin dose misclassification was largely influenced by bias and was not sensitive to assay imprecision. The central laboratory and POCT INR methods met the FDA performance specifications, had equal rates of ≥2 warfarin dose category error, and had statistically different rates of ≥1 warfarin dose category error in large samples (n >250). CONCLUSIONS: Simulation models are useful tools for evaluating POCT INR assay performance criteria required to achieve the proposed FDA guidelines. This simulation depicted how the Roche Diagnostics CoaguChek XS instrument meets the guideline.

Simulation Models of Misclassification Error for Single Thresholds of High-Sensitivity Cardiac Troponin I Due to Assay Bias and Imprecision.

BACKGROUND: Clinical outcome studies for cardiac troponins (cTn) are expensive and difficult to design owing to variation in patients, in the assays, and in the incidence of different types of myocardial infarction (MI). To overcome these difficulties, simulation models were used to estimate the rate of misclassification error for MI and risk prediction resulting from assay bias and imprecision. METHODS: Finite mixture analysis of Abbott high-sensitivity cTnI (hs-cTnI) results at time 0 h in patients presenting early with acute coronary syndrome (ACS) symptoms to the emergency department (ED) [n = 145, Reducing the Time Interval for Identifying New Guideline (RING) study] allowed derivation of a simulation data set (n = 10000). hs-cTnI concentrations were modified by addition of bias or imprecision error. The percentage of all 10000 modified hs-cTnI results that were misclassified for MI at thresholds of 2, 5, 26.2, and 52 ng/L was determined by Monte Carlo simulation. Analyses were replicated with an all-comer emergency department (ED) population (n = 1137) ROMI (Optimum Troponin Cutoffs for ACS in the ED) study. RESULTS: In the RING study, simulation at 26.2-ng/L (99th percentile) and 52-ng/L thresholds were affected by both bias ±2 ng/L and imprecision (10%-20%) and had misclassification rates of 0.4% to 0.6%. Simulations at the 2-ng/L and 5-ng/L thresholds were only affected by bias. Misclassification rates at bias of ±1 ng/L were 10% for the 2-ng/L threshold, and 5% for the 5-ng/L threshold. CONCLUSIONS: Simulation models predicted that hs-cTnI results are seldom misclassified (<1% of patients) when interpretative thresholds are near or exceed the overall 99th percentile. However, simulation models also predicted that low hs-cTnI results, as recommended in guidelines, are prone to misclassification of 5%-10% of patients.

The clinical impact of implementing the Roche® bilirubin total Gen.3 method on neonate phototherapy.

OBJECTIVE: To predict the impact of implementing the Roche® Gen.3 bilirubin total method on the number of bilirubin results that would trigger phototherapy using the phototherapy nomogram published in the Canadian Paediatric Society (CPS) Guidelines for Treatment of Hyperbilirubinemia. DESIGN AND METHODS: BILTS method results (N=563) were obtained on the Roche® C501 analyzer and the corresponding Bilirubin Total Gen.3 assay results were derived by linear regression. Total bilirubin results, gestational age and postnatal age were plotted with the CPS phototherapy nomogram to determine if phototherapy was indicated with both the BILTS and Gen.3 methods. Clinical thresholds for phototherapy using the BILTS and new Gen.3 methods were compared by Pearson's chi square test. RESULTS: 284 bilirubin results obtained from infants 35-37 weeks gestation (n=157 neonates) and 279 results from term infants >38 weeks gestation (n=224 neonates) were interpreted with the CPS phototherapy nomogram as either with or without risk factors. Use of the Gen.3 assay reduced the number of bilirubin results that would meet the high-risk threshold line to initiate phototherapy by 7% (p≤0.05) for 35-37 week gestation infants and would reduce phototherapy by 6% (p≤0.05) for >38 week gestation infants with the medium-risk threshold line compared to when the BILTS method was used. CONCLUSIONS: Replacement of the BILTS method by the Gen.3 bilirubin method is anticipated to be associated with a 7% decrease in the number of neonate results that would meet phototherapy thresholds. It cannot be determined if the BILTS assay was associated with a 7% over-treatment or the Gen.3 assay will be associated with 7% under-treatment. While standardization of bilirubin assays remains elusive, nomograms based on bilirubin methods will remain susceptible to method-biases and patient care decisions will remain subject to this uncertainty.