Hyperbilirubinemia is one of the most common causes of neonatal readmission. Although many disorders can lead to neonatal hyperbilirubinemia, such as infection, G-6-PD deficiency, delayed meconium excretion, insufficient feeding, premature deliveryABO HDN is still the main factor[12–15]. In the neonatal period, about 60% of term infants and 80% of premature babies have a process of jaundice, and 5% -10% of them need phototherapy for treatment. Although hyperbilirubinemia is mostly a benign disease, severe hyperbilirubinemia in some neonates can cause permanent damage of the brain, especially in those with ABO HDN [16–18].In 2013, neonatal jaundice has been taken into the catalog of the main causes of early neonatal death [19], suggesting that timely and effective treatment is in great importance for the good prognosis of neonates with hyperbilirubinemia.
Pearl W. Chang et al [6]. analyzed 7048 neonates with hyperbilirubinemia and found that about 4.6% neonates had rebound hyperbilirubinemia after phototherapy. However, there is a higher incidence of rebound hyperbilirubinemia about 14.5% in premature infants and those neonates with positive direct DAT result. Sachdeva M et al. found that hyperbilirubenemic neonates with specific high-risk factors had a higher rate of rebound hyperbilirubinemia after phototherapy and required close follow-up after discharge [20].Our study found that hyperbilirubinemia due to ABO HDN in 34.4% (100/255) of neonates occurred within 24 hours after birth, and 12.4% of them were readmitted after discharge. Our results were consistent with the previous study. The serum bilirubin level tends to rebound after phototherapy in neonates with hyperbilirubinemia due to ABO HDN. We also found that neonates with higher total serum bilirubin concentration at the beginning of phototherapy, with initial jaundice (especially within 24 hours after birth), or with positive DAT result were more likely to be readmitted for phototherapy, and the differences between the two groups were statistically significant. Therefore, it’s reasonable to perform close follow-up after discharge with high-risk factors as listed above for the neonates due to ABO HDN, in case of left neurological sequelae resulted from severe hyperbilirubinemia.
Barak M et al. suggested those neonates with high-risk factors had a longer hospital stay [21]. Neonatal hyperbilirubinemia caused by ABO hemolysis also resulted in a long hospital stay[1,6]. However, in recent years, breastfeeding, which could be hindered by neonates admission, has been advocated for its irreplaceable advantages. In China, it is much difficult to get breastfeeding for those neonates with ABO HDN who are in hospital for phototherapy. Therefore, it is crucial for these infants during admission period to perform individualized management to reduce the separation time between mother and their babies. Moreover, our study suggested that the initial age for phototherapy and the serum bilirubin at enrollment are independent risk factors for readmission in neonates with ABO HDN. Saeko Tsujimae et al. have found that in early-onset neonatal hyperbilirubinemia, ABO HDN is the main reason, which is consistent with our study [22]. Thus, we speculate that not all neonates with ABO HDN need extended hospitalization, despite of its widespread application. In terms of jaundice management for neonates with ABO HDN, it might be more appropriate to limit the pronged hospitalization strategy to those with early jaundice appearance and high serum bilirubin level, especially the ones received photography within 24 hours after birth, instead of delaying discharge for all the patients in this population. In addition, follow-up after discharge should be strengthened[23]The new strategy is supposed to reduce the possibility of readmission, the frequency of follow-up after discharge, the incidence of cross-infection in outpatient follow-up process and the financial burdens of the families.
With the further improvement of the guidelines, the management for neonatal hyperbilirubinemia is becoming more and more standardized. Based on the AAP guidelines and its native features, Japan has developed its own guideline for full-term infants and preterm infants respectively in jaundice management, and so have Canada, Brazil, and the United Kingdom [4,5,24−26]. To date, we have not established a unified guideline of management and follow-up plan for neonatal hyperbilirubinemia after discharge in China, especially with ABO HDN. Our study is of great significance in providing scientific data for the future guideline, although with some deficiencies like the insufficient sample size.
In conclusion, not all neonates with ABO HDN need prolonged hospitalization. We suggest that it is necessary to extend the length of hospital stay and to implement close follow-up after discharge only for those with early jaundice appearance or high serum bilirubin at enrollment. We suppose this strategy will reduce the separation of mother and infant, the rate of readmission, the frequency of follow-up after discharge, the family's economic burdens and will increase the rate of breastfeeding and improve the combination between mothers and infants.