Virtually all guidelines recommend measuring total bilirubin (TB) levels within the first 24 h after birth. Countries exhibit significant differences in the scope, timing, and methods of neonatal hyperbilirubinemia screening, which can be broadly categorized into two approaches:

Phototherapy is universally recognized as the first-line treatment for neonatal hyperbilirubinemia. High-intensity blue-light phototherapy—most commonly delivered using light-emitting diode (LED) devices—is recommended for most cases of moderate [typically TSB 15–20 mg/dL (257–342 µmol/L)] to severe hyperbilirubinemia [TSB >20 mg/dL (>342 µmol/L)], whereas exchange transfusion is generally reserved for extreme, rapidly progressive, or phototherapy-refractory cases (4, 7, 28–30). However, initiation thresholds, phototherapy intensity, and monitoring frequency vary across regions, reflecting differences in evidence interpretation, resource availability, and clinical care pathways.

Most clinical guidelines advocate more intensive monitoring and treatment for specific high-risk neonates. Common risk factors include prematurity (gestational age <35 weeks), G6PD deficiency, maternal–infant ABO or Rh incompatibility, prolonged breast milk jaundice, and perinatal asphyxia, infections, and metabolic disorders.

China's 2025 guideline emphasizes routine G6PD screening and recommends assessing bilirubin trends (TSB or TcB, with TSB preferred to accurately quantify the rate of rise and to help exclude hemolysis) in high-risk infants within the first 12 h after birth. Japan has established dedicated management pathways for preterm infants (<35 weeks gestation), adopting lower TSB treatment thresholds. Canada employs a multilayered risk-stratification model that integrates TSB levels, gestational age, postnatal age (in hours), and additional risk factors. In regions with high G6PD prevalence (e.g., India), guidelines underscore the importance of screening and caution against trigger medications. The WHO provides a “rapid assessment checklist” tailored for resource-limited settings to minimize reliance on complex procedures.

With the trend toward early discharge (most infants are discharged within 48 h after birth), post-discharge bilirubin reassessment has become a focal point in many national guidelines. The AAP, China, the United Kingdom, and Canada recommend bilirubin re-evaluation (TcB or TSB) within 48–72 h after discharge. Japan, New Zealand, and Germany advocate establishing community- or primary care–based follow-up systems. The WHO emphasizes that all infants discharged before 48 h should receive follow-up within three days.

Most guidelines advise providing caregivers with written, comprehensible materials on jaundice recognition, emergency contact information, and care instructions. China's 2025 guideline promotes home-based bilirubin monitoring devices and telemedicine platforms (e.g., mobile applications). Canada and New Zealand have developed integrated mother–infant follow-up systems to reduce missed cases. In Australia, New Zealand, and the United Kingdom, home phototherapy is increasingly used. China's 2025 guideline provides specific recommendations for primary care referral, home-based care, and follow-up assessment.

Health-system organization and resource distribution directly influence the feasibility and implementation fidelity of guideline recommendations (33–35). High-income countries—such as the United States, Canada, the United Kingdom, China, and Japan—generally adopt universal screening strategies, supported by comprehensive maternal and child health networks, ample access to TcB and TSB testing resources, and standardized discharge assessment systems. By contrast, LMICs (e.g., India, Malaysia, Italy) often face challenges such as uneven healthcare resource coverage and a lack of phototherapy equipment in rural areas, leading to recommendations that focus on screening high-risk infants or relying only on visual assessments.

Access to phototherapy technology also varies (36). High-income settings widely use high-intensity LED phototherapy, and some have implemented home-phototherapy programs. In resource-limited settings, care may still rely on conventional fluorescent-lamp units, which provide lower irradiance and limited monitoring capacity. In these settings, exchange transfusion is often constrained by limited equipment, workforce shortages, and blood-supply constraints, leading to practical indications that differ from those in high-income countries (37).

Cultural beliefs significantly influence parental understanding of hyperbilirubinemia severity, adherence to medical advice, and acceptance of community interventions (38). In regions such as India, Southeast Asia, and parts of Africa, traditional views—such as the belief that sun exposure benefits jaundiced infants or that yellow skin signifies health—are deeply ingrained, often leading to delayed medical intervention. In contrast, countries like Japan and Germany exhibit a healthcare provider-led approach, where parents are more reliant on professional guidance, resulting in higher screening compliance.

Approaches to breastfeeding policy and clinical management also vary. Some countries (e.g., France and Italy) have historically underemphasized breast milk jaundice and, in some cases, have misconstrued it as an indication for weaning. However, recent guidance from the AAP, China's 2025 guideline, and the United Kingdom's NICE emphasizes continuation of breastfeeding with appropriate monitoring. Family caregiving roles also vary. Countries such as New Zealand and Canada integrate family involvement into hyperbilirubinemia management by providing home-monitoring tools and remote guidance. By contrast, in more clinician-centered settings (e.g., China and Japan), families rely largely on clinician directives, and home phototherapy or hyperbilirubinemia monitoring devices are not yet widely implemented.

National technological capacity substantially influences the choice of screening devices and treatment modalities, as well as the complexity and degree of personalization of guideline recommendations. In high-income settings such as the United States, the United Kingdom, and Japan, TcB devices are commonly used for initial screening. By contrast, WHO guidance and some national guidelines (e.g., India) rely primarily on TSB measurement, largely because of the high procurement and maintenance costs of noninvasive devices. In China, TcB devices are widely deployed in tertiary hospitals; however, TSB remains the primary approach in county-level and lower-tier facilities.

Regarding risk assessment tools, the Bhutani nomogram is widely utilized in countries like the United States and Canada. However, its applicability in East and Southeast Asia remains debated because of differences in population ethnicity and gestational-age distribution. China's 2025 guideline has developed locally derived dynamic curves based on national datasets. Looking ahead, some settings are exploring artificial intelligence (AI)–based risk-prediction models, which may transform risk assessment (39–41).

The integration of telemedicine also varies across settings. China's 2025 guideline proposes using mobile applications and remote platforms to support post-discharge follow-up. Japan and New Zealand have initiated pilot programs for home-based bilirubin monitoring and remote phototherapy oversight, suggesting that technological innovations may gradually narrow urban–rural gaps. By contrast, many settings in Africa and South/Central Asia currently lack the infrastructure required to implement such digital interventions at scale.

Guideline-development methodology—ranging from expert consensus to systematic evidence-based frameworks—shapes both the scientific robustness of recommendations and the factors that precipitate revisions. In high-income settings, updates are frequently triggered by emerging evidence on bilirubin neurotoxicity, recalibration of treatment thresholds, advances in bilirubin measurement and phototherapy, and evolving care-delivery patterns (e.g., earlier postnatal discharge). Notably, the 2022 AAP revision explicitly acknowledges that a major challenge was redefining phototherapy and exchange transfusion thresholds, underscoring evidence-driven reassessment of intervention cutoffs (4). In the United Kingdom, NICE “exceptional surveillance” determined that CG98 requires updating, with a specific focus on TSB thresholds for initiating phototherapy and exchange transfusion—reflecting both new evidence and the need to maintain clinically safe decision thresholds at the health-system level (5). In middle-income settings (e.g., China), revision models often combine evidence synthesis with large-scale national datasets and operational considerations to support implementation across multi-tiered systems. Notably, in several African countries, the absence of unified national guidelines has been reported; hospitals may adopt external CPGs (e.g., AAP or NICE) inconsistently, potentially amplifying inter-facility variability and limiting the generalizability of single-country comparisons. By contrast, WHO-oriented guidance and some national guidelines in resource-limited settings prioritize feasibility, scalability, and minimum effective intervention packages to maximize coverage.

Whether guideline revisions translate into improved outcomes is context-dependent, and direct causal attribution remains challenging because revisions often coincide with broader system reforms and variable implementation fidelity. Nonetheless, multiple high-quality studies report outcome signals temporally associated with guideline-aligned strategies—particularly universal predischarge bilirubin screening coupled with risk-based follow-up. A large health-system study reported that universal bilirubin screening was associated with a lower incidence of severe hyperbilirubinemia, although phototherapy utilization increased (42). Population-level trend analyses further suggest that universal predischarge screening has reduced the incidence of extreme hyperbilirubinemia and the risk of kernicterus over time (43). Complementing these observational data, a randomized trial demonstrated that predischarge TcB screening reduced severe hyperbilirubinemia (risk ratio, 0.27) and jaundice-related readmissions. A subsequent systematic review and meta-analysis synthesized randomized and nonrandomized evidence evaluating universal TcB/TSB screening at discharge across multiple outcomes, including severe hyperbilirubinemia and bilirubin-induced neurologic dysfunction (44). Collectively, these findings suggest that improvements are most consistently observed when guideline updates are coupled with implementation infrastructure—screening coverage, timely access to effective phototherapy, structured post-discharge follow-up, and caregiver education—rather than textual revision alone.

The guideline clearly states that all newborns should undergo bilirubin testing within 12–24 h after birth and recommends that at least two assessments be completed before discharge or within 72 h. This strategy, similar to the universal screening models endorsed by the AAP (United States) and NICE (United Kingdom), reflects a trend toward comprehensive universal screening supplemented by enhanced surveillance for high-risk infants. Given China's vast geography and pronounced urban–rural disparities, the guideline emphasizes tiered deployment of screening tools across levels of care—for example, encouraging broad TcB use in urban hospitals while allowing primary facilities to use TSB testing complemented by visual assessment for initial screening. This capability-oriented approach enhances the guideline's practicality within China and provides a transferable structural template for other settings with heterogeneous resources.

The guideline applies a three-dimensional stratification by gestational age, postnatal age (in hours), and risk factors to guide initiation of phototherapy and exchange transfusion, and provides detailed threshold tables. For instance, preterm infants with gestational age <35 weeks have lower treatment thresholds than term infants, with earlier monitoring and intervention recommended. This logic is consistent with using the Bhutani nomogram as recommended in the AAP guideline and the hour- and risk-zone grouping in NICE. However, a notable addition in the Chinese guideline is the development of indigenous “dynamic bilirubin curves” based on domestic data, thus avoiding the adaptation issues of directly applying the Bhutani nomogram to Chinese populations. Additionally, the guideline recommends high-intensity LED phototherapy, encourages local governments to support equipment procurement, and stipulates that the need for exchange transfusion should be evaluated within 12 h of an inadequate phototherapy response, thereby reducing treatment delays—an approach that may be particularly valuable in low-resource settings.

The guideline elevates G6PD deficiency management to a national recommendation, emphasizing routine G6PD screening in high-prevalence regions (such as South and Southwest China) and avoidance of known hemolysis-inducing drugs. The guideline also includes dedicated sections on Rh or ABO hemolysis, infections (e.g., sepsis), and metabolic disorders. This approach goes beyond the brief mention of high-risk infants in many other national guidelines and provides more explicit pathways than WHO guidance—particularly by integrating local epidemiology with public health system responses—highlighting the potential of a guideline–screening–policy triad.

To address early discharge and variable primary-care follow-up capacity, the guideline proposes a strategy of post-discharge evaluation within 48–72 h, promotion of remote bilirubin monitoring, and standardized family education. Specifically, it encourages recording bilirubin data via mobile apps or WeChat mini-programs; recommends that tertiary hospitals provide wearable TcB devices or home-phototherapy guidance for discharged infants; and includes illustrated training to help families identify warning signs such as lethargy, poor feeding, or high-pitched crying. This system is among the most advanced globally, with few countries (notably New Zealand and some regions of the United Kingdom) having achieved such deep integration of digital follow-up tools with guideline text.

China's 2025 neonatal hyperbilirubinemia management guideline, rooted in international evidence-based principles and enriched by local practice, resource adaptation, and technological innovation, offers a high-standard yet scalable model with strong primary-care orientation. Its detailed recommendations on high-risk management, remote intervention, and family support not only strengthen China's systemic response but also provide actionable lessons for global efforts to harmonize neonatal hyperbilirubinemia management.

The Bhutani nomogram, widely used for risk assessment, is largely derived from U.S. cohorts and may not accurately capture bilirubin trajectories in East Asian, South Asian, or African populations. Countries like China and Japan have developed localized hour-specific bilirubin nomograms based on their own population data (48). However, many countries have yet to establish locally validated standard curves (49, 50). A globally applicable, multiethnic Bhutani nomogram remains unavailable, underscoring the need for large-scale, multi-center validation across diverse ethnic groups.

In some settings—particularly parts of South Asia and Africa—parents may perceive jaundice as normal or even healthy, reducing engagement in early detection (52). Traditional practices, such as sun exposure or herbal remedies, remain prevalent in some communities and can diminish acceptance of evidence-based care. Although parental education is emphasized in most guidelines, the absence of visual aids, translations into local languages, and involvement of community health workers reduces its effectiveness.

Innovations such as affordable LED phototherapy devices, solar-powered phototherapy cribs, and portable TcB instruments are increasingly available (41, 47, 53, 54). International collaborations can reduce procurement costs, enable regional bulk purchasing, and help LMICs expand access to essential devices. China's experience suggests that provincial funding, tiered incentives, and remote maintenance mechanisms can enhance equipment availability and maintenance capacity in primary-care settings.

Global standardization of neonatal hyperbilirubinemia management requires moving beyond harmonizing guideline text to establishing a comprehensive governance framework centered on equitable access to screening, standardized treatment, family engagement, and sustained follow-up.

Beyond policy harmonization, specific research and technological gaps must be addressed to operationalize these guidelines.