Optimal Evaluation for DAT-Positive Newborns Remains Elusive

Abstract

Source: Papacostas MF, Robertson DW, McLean MD, et al. Sixth-hour transcutaneous bilirubin and need for phototherapy in DAT positive newborns. Pediatrics. 2022;149(3):e2021054071; doi:10.1542/peds.2021-054071Investigators from Naval Medical Center Portsmouth (NMCP), Portsmouth, VA, and the University of Pittsburgh School of Medicine, Pittsburgh, PA, conducted a retrospective study to assess the utility of a transcutaneous bilirubin (TcB) measurement at 6 hours of age in predicting the need for phototherapy at ≤24 hours of age in newborns with ABO incompatibility. Data on neonates born at NMCP between May 2013 and March 2017 who were ≥35 weeks’ gestation were reviewed. Infants were classified as having ABO incompatibility if born to mothers with type O blood and negative antibody screens and themselves had type A or B blood with positive direct antiglobulin tests (DAT).At NMCP, blood is obtained from newborns with ABO incompatibility at 6 hours of age for total serum bilirubin (TSB), hemoglobin, hematocrit, and reticulocyte counts; providers are encouraged to also obtain a TcB measurement. Infants with paired blood test and TcB results were included in study analyses; demographic and clinical data were abstracted from the medical records of these newborns. The primary study outcome was need for phototherapy at ≤24 hours of age, as determined by the attending pediatrician. Demographic and clinical characteristics associated with this outcome in univariate analyses were included in 2 logistic models; 1 with blood test results and no TcB levels, and the other with TcB results and no blood test data. Receiver operator characteristic (ROC) curves were constructed and the area under the curve (AUC) calculated. The positive and negative predictive values (PPV and NPV, respectively) of different TcB cutoff values in predicting the need for phototherapy at ≤24 hours also were determined.Among 10,942 newborns born at ≥35 weeks’ gestation, 5,167 (47.2%) were born to mothers with type O blood, DAT was positive in 829 (7.6%), and 772 (7.1%) infants met criteria for ABO incompatibility. A total of 346 newborns had paired blood test and TcB results, 21% of whom were treated with phototherapy at ≤24 hours of age. In univariate analyses, birth weight, type B blood, TSB level, reticulocyte count, and TcB were significantly associated with the need for phototherapy at ≤24 hours. In the multivariate model that excluded TcB results, only TSB and reticulocyte counts were independently associated with the outcome (odds ratio [OR], 12.6; 95% CI, 6.1, 25.6; and OR, 1.5; 95% CI, 1.0, 2.1, respectively). In the other model, TcB was significantly associated with the need for phototherapy at ≤24 hours of age (OR, 3.1; 95% CI, 2.4, 4.0). The ROC AUCs were similar for the 2 models (0.96 and 0.90, respectively). A TcB value of ≤3.0 mg/dL yielded a NPV of 98%, a value of ≥5.3 mg/dL, and a PPV of 85% for predicting the need for phototherapy at ≤24 hours of age.The authors conclude that a 6-hour TcB level was predictive of the need for phototherapy at ≤24 hours of life in newborns with ABO incompatibility.Dr Von Kohorn has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The most recent (although outdated) AAP clinical practice guidance advises universal pre-discharge assessment of bilirubin level in newborns, with treatment based on risk stratification combining bilirubin level and risk factors.1,2 Isoimmune hemolytic disease is a risk factor both for severe hyperbilirubinemia and neurotoxicity.2 Although recent evidence about the risks of phototherapy has called universal screening into question, close monitoring of infants with risk factors remains a priority.3,4The current investigators demonstrate that 6-hour blood and TcB tests predict the need for phototherapy at or before 24 hours of life. The investigators do not describe the trend in phototherapy use. They suggest using TcB values that correspond to 98% NPV and 85% PPV to guide clinical practice at 6 hours of life. Importantly, the study does not indicate whether 6-hour testing or the proposed TcB values reduce key outcomes such as severe hyperbilirubinemia, bilirubin encephalopathy, hospital readmission, or cost. The authors report that significantly more infants who received TcB measurements were admitted to the NICU compared to those who received only blood tests, but they do not comment on the explanations for this finding that implies possible overtreatment. In a web comment on the original article by Papacostas, Mazar astutely states that phototherapy should be started at currently recommended thresholds, regardless of projected risk.5 The authors’ reply states “it would be beneficial to identify [infants projected to need phototherapy] and start treatment earlier.” Evidence for such benefit is not presented.Six-hour bilirubin testing predicts phototherapy at ≤24 hours of life, with TcB performing nearly as well as TSB plus reticulocyte count. The relationship of 6-hour testing to clinical outcomes remains unknown.