Implementing Higher Phototherapy Thresholds for Jaundice in Healthy Infants 35 Plus Weeks Free

Our retrospective, observational (quality improvement [QI]) study was set in the well-baby nursery of a large safety net hospital in a public health system that includes 3 hospitals and 10 outpatient clinics. The QI project was implemented in the main hospital that has an AAP level IV NICU with an annual delivery volume of approximately 3000 live births. The study population included newborns admitted to the well-baby nursery from July 2018 to December 2020. Our pediatric hospitalist group (n = 9 staff physicians and ∼8 contracted physicians) provides clinical coverage of the well-baby nursery, the pediatric ward, and the NICU (during nonbusiness hours). During baseline data collection (pregroup, July 2018 to December 2018), our nursery followed the 2004 AAP guidelines for neonatal hyperbilirubinemia. Before discharge, all infants had transcutaneous bilirubin (TCB) determined with a BiliChek (Philips Healthcare, Monroeville PA); if bilirubin was in “high” or “high intermediate” risk zones of the Bhutani nomogram,¹¹  total serum bilirubin (TSB) was tested. Phototherapy was initiated per 2004 AAP phototherapy guidelines. Readmission for phototherapy was also based on 2004 AAP guidelines.

The NCNC guidelines were disseminated between January 2019 and March 2019. During this period, we instituted an educational curriculum for inpatient and outpatient providers, consisting of grand rounds and other targeted lectures, emails, and 1-page handouts that were posted in shared workspaces. Our nursing champions also educated all well-baby nurses about the new guidelines. We created a smart phrase in our electronic medical records system (Epic) for nurses to document TCB results. During this implementation phase, we also provided direct feedback to providers who initiated phototherapy under the old rather than new guidelines.

We implemented NCNC guidelines in April 2019. During the post NCNC implementation data collection period (postgroup, April 2019 to December 2020), we continued to obtain TCB on all infants before discharge. We obtained TSB if the TCB level was within 3 mg/dL of the threshold for phototherapy. Phototherapy was initiated per NCNC guidelines in well-baby nursery.

Our outcome measures were newborns requiring TSB measurements and newborns receiving phototherapy. Our balancing measures were readmission for phototherapy, critical hyperbilirubinemia including TSB >25 mg/dL, TSB within 2 mg/dL of the exchange transfusion threshold, and exchange transfusion. TSB within 2 mg/dL of the threshold for exchange was chosen since more intensive management is generally recommended at this threshold. We used exchange thresholds according to the 2004 AAP and the NCNC guidelines for the pregroup and postgroup, respectively. In addition to phototherapy, some infants with positive direct antigen test (DAT) received intravenous immunoglobulin (IVIG) treatment. Criteria for IVIG administration at our institution includes evidence of isoimmune hemolytic disease and bilirubin rising rapidly despite intensive phototherapy. Our process measures included adherence to the protocol: if the threshold for phototherapy was met before initiating phototherapy and if phototherapy was initiated for all infants who met the phototherapy thresholds. The reasons for not initiating phototherapy despite meeting the threshold were documented for all relevant patients.

We used Statistical Process Control (SPC) for the outcome measures displayed on a p chart. We used established rules for differentiating special versus common cause variation; special cause variation was defined as 8 consecutive points in a row above or below the mean line or any point beyond the control limits. We compared the difference in the balancing and process measures between the pre and post groups using χ square tests (proportional data) and t tests (continuous data), as appropriate. χ-square tests were conducted using an online calculator (https://www.socscistatistics.com/tests/chisquare/default2.aspx). t tests were conducted using Excel (Excel for Microsoft 365, v.2210, Microsoft, Redmond WA). The SPC charts were created using QI macros 2019 Excel add on software (KnowWare International, Denver, CO).

Our institutional review board determined this project to be a quality improvement study and therefore, it is exempt from institutional review board approval.

Our population included 6173 infants admitted to the well-baby nursery during the study period (pregroup n = 1472, postgroup n = 4701). After introducing the NCNC guidelines, there was a significant shift in the proportion of infants who received phototherapy from a baseline of 6.4% to 4% (Fig 1). Most of this decrease happened during the birth hospitalization (3.9% pre vs 1.8% post, Fig 2). We also observed a significant shift in the proportion of infants requiring TSB, from a baseline of 70% in the pregroup to 26% in the postgroup (Fig 3).

There were no significant increases in our balancing measures (Table 1). There was a similar rate of readmission for phototherapy and infants with bilirubin within 2 mg/dL of the exchange transfusion thresholds, or those who received exchange transfusion, between the pre and postgroups. For bilirubin >25 mg/dL, there were 0 such babies in our pre group, and 7 babies in our post group; this difference was not statistically significant. For our process measures, there was no difference in the rate of guideline adherence for infants who received phototherapy (ie, rate of subthreshold phototherapy). While using the 2004 AAP guideline, recommended phototherapy was not administered 0.9% of the time, whereas all neonates over the NCNC thresholds received phototherapy (P < .01).

The demographics and clinical characteristics of the 13 infants with critical levels of TSB (bilirubin levels >25 mg/dL or within 2 mg/dL of the exchange transfusion thresholds) are shown in Table 2. One infant in the pregroup was readmitted to the hospital for TSB just above the 2004 AAP exchange transfusion threshold. The hyperbilirubinemia resolved quickly after phototherapy. This infant was diagnosed with auditory neuropathy spectrum disorder, which was improved at age 2. One infant in the postgroup had TSB >30 mg/dL and required an exchange transfusion. This infant was born at 35 6/7 weeks’ gestation and was discharged at 48 hours of life. TCB before discharge was 7.4 at 24 hours of life (treatment threshold = 11 mg/dL by NCNC guidelines, 9.9 mg/dL by 2004 AAP guidelines). The infant had a delay in presenting for follow up testing; by the time of return to care at day of life 9, the infant had clinical features consistent with acute encephalopathy and the TSB was 39.9 mg/dL. Neurodevelopmental evaluation (Bayley III) confirmed that the hazardous hyperbilirubinemia resulted in chronic bilirubin encephalopathy in this infant. Genetic testing was negative for causes of hyperbilirubinemia, including glucose-6-phosphate dehydrogenase deficiency and Crigglar Najjar.

Four of the remaining 11 infants were positive for DAT. Their hyperbilirubinemia resolved after phototherapy and, for 2 infants, IVIG. The other 7 infants were readmitted for phototherapy on days of life 3 to 6 and had prompt resolution of the hyperbilirubinemia after 1 to 2 days of phototherapy. None of these 11 infants had clinical presentations of acute encephalopathy. Ten of these 11 infants had follow-ups in our health system and no neurodevelopmental concerns were identified by pediatricians during routine checkups or by parents using the Ages and Stages Questionnaire (ASQ, 7 infants).

Regarding compliance with our protocol, for infants receiving phototherapy, a similar proportion in pre and postgroups were below the thresholds (18% vs 15%, P = .71). We also examined infants who had TSB over the phototherapy thresholds but did not receive phototherapy. There were 9 such infants in the pregroup and none in the post (P < .01). All 9 infants had TSB within 1.1 mg/dL of the AAP phototherapy threshold. In 3 of these infants, the provider used the NCNC guidelines rather than AAP (before NCNC was implemented). In 3 other infants, providers noted the infant to be in the “high risk” category but did not notice that the infant was also over the threshold for phototherapy. Two infants had incorrect calculations of the threshold for phototherapy. One infant was noted to be exactly at the threshold; a recheck found this infant below threshold and no phototherapy was performed. All 9 infants’ follow-up bilirubin levels were below the phototherapy thresholds.

Our QI project shows that implementation of the NCNC neonatal hyperbilirubinemia guidelines that use higher phototherapy thresholds is feasible and reduces TSB testing and phototherapy treatment of hyperbilirubinemia. Higher phototherapy treatment thresholds resulted in significantly fewer infants receiving phototherapy; we estimate that 2.4 in 100 infants avoided phototherapy. There was an increase in infants experiencing bilirubin over 25 mg/dL, however there was no increase in infants with bilirubin within 2 mg/dL of the exchange transfusion threshold.

We did not note an increase in readmissions for phototherapy. This finding indicates that the reduction in phototherapy in the birth hospitalization does not represent a shift in phototherapy from early to later in the neonatal period, but instead represents an actual decrease in total infants exposed to phototherapy.

In our study, we had a total of 13 infants with critical hyperbilirubinemia. During the study period, the number of cases with TSB close to or over the exchange transfusion thresholds remained low (0.3% to 0.1%). The 1 infant who presented over the exchange threshold had a 3-day delay in follow up testing from what had been recommended. It is probable that had the follow up been completed 48 hours earlier as planned that the exchange threshold would not have been exceeded. This case emphasizes the importance of close outpatient follow-up in the 48 to 72 hours after discharge, especially in late preterm infants, regardless of the thresholds used for phototherapy.^6,20–22 

We did experience a trend toward an increase in the number of infants with TSB between 25 and 30 mg/dL after implementing NCNC guidelines (0% to 0.2%). Although bilirubin >25 mg/dL has been used to define “extreme” or “hazardous” hyperbilirubinemia (California Perinatal Quality Care Collaborative toolkit),²³  evidence from multiple studies has suggested that bilirubin values between 25 and 30 mg/dL do not result in adverse neurologic outcomes if these at-risk infants are identified and treated in a timely fashion.^{3–6,14–16,24}  Most detailed was the study by Newman et al¹⁶  where infants with bilirubin in the range of 25 mg/dL to 29 mg/dL (who received treatment) had neurologic outcomes on formal developmental assessments that were equivalent to control infants. In total, we had 13 infants with critical hyperbilirubinemia. Except for the 2 infants with evidence of bilirubin encephalopathy (1 with auditory neuropathy and 1 with kernicterus), the other 10 infants showed normal development on pediatric checkups and ASQ, with 1 additional infant lost to follow-up immediately after discharge. The new AAP guidelines provide recommendations for escalation of care when the serum bilirubin is within 2 mg/dL of the exchange threshold. As the transition is made to tolerating higher thresholds for phototherapy, it will be important to identify and provide prompt treatment of infants presenting with bilirubin levels at or above this escalation of care threshold, including those with bilirubin values over 25 mg/dL.

We had a high rate of compliance with the phototherapy guidelines, before and after the transition. Nine infants in the pregroup did not receive phototherapy despite bilirubin above the threshold; about half of these babies had inaccurate assessment of the need for phototherapy (either inaccurate calculation of the threshold or lack of recognition that a “high risk zone” baby also qualified for phototherapy). After implementation education, all infants in the postgroup who met the treatment thresholds received phototherapy. In both groups some babies received phototherapy when the bilirubin was below phototherapy threshold. During the pregroup, deviation from guidelines occurred for several infants because of an inaccurate calculation of the phototherapy threshold, usually because of inaccurate classification of the neurotoxicity risk category; eg, a baby born at 35 weeks with no additional risk factors was classified as “high risk” for neurotoxicity. By contrast, when phototherapy was administered below threshold in the postgroup, providers always accurately noted the recommended threshold and that the baby was below that threshold. Subthreshold phototherapy was documented by providers to be caused by either difficulty assuring follow-up, a fast rate of rise, or TSB level quite close to the threshold when the infant was near discharge from the well-baby nursery. These cases represented adherence to the guideline, which encourages clinical judgement when bilirubin is within 1 mg/dL of threshold as it was for these infants. By contrast, infants in the pregroup received guideline non adherent treatment (both subthreshold phototherapy and missed phototherapy) because of inaccurate assessment of the phototherapy threshold. Both the NCNC and 2022 AAP guidelines have made “neurotoxicity risk factors” the only variable in interpreting results from clinical decision-making tools; this facilitates accurate assessment of phototherapy threshold.

The adoption of the NCNC guidelines went well at our institution. Both before and after the change, we had high compliance with the guidelines; our already standardized care made the transition easier. Our success with the transition to the new guidelines is likely attributable to a few factors. We have a limited set of physicians responsible for decisions about phototherapy; our pediatric hospitalist group covers the well-baby nursery, the pediatric ward, and the NICU (during nonbusiness hours). We had a comprehensive education process for all inpatient and outpatient pediatric providers and well-baby nursing staff. Our health care system is a well-integrated system, with most of our infants following up within our system and if needed, readmitted to our hospital. Those who do not remain with our primary care are followed by affiliated private pediatricians who refer infants to our hospital system for TSB testing and readmission. Our inpatient and outpatient providers have a close working relationship, which strengthens our ability to work together on projects such as this that bridge those 2 areas.

Our study has a few limitations. It was conducted in a single center with a relatively small sample size. During our pre cohort, our decision rule for obtaining a TSB was to obtain a TSB if TCB was at the 75th percentile (high or high intermediate risk zone on Bhutani nomogram). Others have used more restrictive decision rules, such as obtaining TSB when TCB is within 3 mg/dL of the threshold for phototherapy or is at 70% of the threshold for phototherapy.²⁵  We did not record TCB values as part of our data collection; we cannot determine what our rate of TSB would have been under alternate TSB strategies. Institutions using more restrictive decision rules would have a lower baseline rate of TSB testing and therefore would have less of a decrease after adoption of these new guidelines.

Our study was conducted before the 2022 AAP guidelines publication. The 2022 AAP guidelines are closer to the NCNC¹²  guidelines than to the 2004 AAP guidelines.¹³  The 2022 AAP guidelines and NCNC guidelines are similar in many regards. In particular, both the 2022 AAP guidelines and the NCNC guidelines differentiate gestational age week by week, rather than in categories as in the 2004 AAP guidelines. For infants with more risk for neurotoxicity (eg, infants at 35 weeks gestational age and infants with hemolytic disease) both the NCNC and the AAP 2022 guidelines are similar or identical to the AAP 2004 guidelines. The 2022 guidelines and the NCNC guidelines then provide gradually higher thresholds for each increasing week of gestational age. In most cases, the 2022 AAP phototherapy thresholds are similar to or higher than the NCNC thresholds; thus, adoption of the former can be expected to have an even greater reduction in phototherapy than described in our study. Our experience using NCNC guidelines will help to evaluate the benefits and safety of transition to the newer 2022 AAP thresholds for phototherapy.

Implementation of NCNC guidelines is feasible and reduces testing and phototherapy treatment of hyperbilirubinemia without increasing critical hyperbilirubinemia or readmissions. Regardless of the thresholds for phototherapy, close outpatient follow-up, in particular for preterm infants and those with neurotoxic risk factors, are important to prevent severe adverse effects of hyperbilirubinemia.

We thank Jamie Zeitzer, PhD for his help in preparing this manuscript; and the Department of Pediatrics at Santa Clara Valley Medical Center for their continuing commitment to safely doing less.