Reference: Pediatrics. 2021 May;147(5)
Neonatal hyperbilirubinemia is the most common cause of hospital readmission in infants in the US, driven in large part by hypervigilance to prevent the extremely rare but permanent sequela, kernicterus. But this comes at a cost, including a number needed to harm of 4 for breastfeeding cessation at one month for infants treated for neonatal hyperbilirubinemia, vulnerable child syndrome, and the psychosocial and financial costs of retesting and readmission. Risk factors for severe hyperbilirubinemia (such as exclusive breastfeeding) are often conflated with neurotoxicity risk factors (such as temperature instability) that have the potential to make the brain more vulnerable to the effects of circulating bilirubin. Similar confusion occurs when “high-risk” bilirubin levels based on the Bhutani nomogram are mistakenly thought to imply that infants would be assigned to the “high-risk” group on the AAP phototherapy curve, leading to phototherapy before the appropriate threshold is met.
In an effort to allay some of this confusion and better predict the need for phototherapy after discharge, investigators analyzed data from 148,162 infants born at ≥ 35 weeks gestation. Total serum bilirubin (TSB) levels collected from birth to one month for each infant were obtained, as well as inpatient feeding (exclusive breastfeeding, formula feeding, or mixed), rate of rise (ROR), and results of direct antiglobulin testing (DAT) when available. In total, 1.8% of infants exceeded the phototherapy threshold postdischarge and 1.2% were readmitted for phototherapy. Notably, the final cohort did not include 3,050 babies that were excluded from this study because they were readmitted for phototherapy despite having subthreshold TSB(!!).
At the time of discharge, the phototherapy threshold was determined for all infants based on the appropriately assigned AAP neurotoxicity risk group (with gestational age < 38 weeks and positive DAT results as the only risk factors for this non-ICU cohort). ΔTSB was then calculated by subtracting the TSB at the time of discharge from the TSB level at which the phototherapy threshold was met. A ΔTSB-Plus score was similarly derived from the ΔTSB plus ROR, inpatient feeding, gestational age, and timing of TSB after birth. The outcome evaluated was subsequent TSB above the AAP phototherapy threshold assessed at 24 hours, 48 hours, and up to 30 days after discharge. Both the ΔTSB and ΔTSB-Plus demonstrated better sensitivity and specificity compared with the Bhutani model at all levels, with better discrimination (based on area under the curve [AUC]) for intermediate-range values. Overall AUC was 0.95 for ΔTSB-Plus, 0.93 for ΔTSB, and 0.88 for Bhutani.
Here’s the bottom line: the ΔTSB, calculated by subtracting discharge TSB from the AAP phototherapy threshold, seems to do a better job than the Bhutani model at predicting the risk of a future TSB crossing the phototherapy threshold, assuming appropriate assignment of neurotoxicity risk group. The ΔTSB is simpler than both the Bhutani nomogram and the ΔTSB-Plus (which provides only a marginal discrimination benefit), and allows for the integration of clinical judgment with evidence when determining if or when a follow up bilirubin is needed rather than just following general instructions to “repeat bili in 48 hours”. The ΔTSB could additionally reduce confusion regarding the multiple meanings of “risk” in the context of neonatal hyperbilirubinemia and the related potential for costly overtesting and overtreatment. Validating this model using transcutaneous bilirubin levels would be an important next step.
For more information, see the topic Neonatal hyperbilirubinemia in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School, Carina Brown, MD, Assistant Professor at Cone Health Family Medicine Residency, and Dan Randall, MD, Deputy Editor for Internal Medicine at DynaMed.