For the most part, in the developed world, neonatal jaundice occurs without significant morbidity and/or mortality due to early diagnosis and treatment.1 However, most literature from low-middle-income countries (LMICs) suggests that it accounts for significant morbidity and mortality in contrast to that in the United States and developed world (Table 13-1).2–18 For example, based on limited population-based data available worldwide, severe neonatal jaundice is about 100-fold greater in Nigeria than in the developed world. In one of the few population-based studies from the developed world, Ebbesen et al.17 from Denmark reported that 24/100,000 neonates met exchange blood transfusion (exchange transfusion [ET]) criteria, while 9/100,000 developed acute bilirubin encephalopathy (ABE), in comparison to results from the only population-based study in Nigeria, in which Olusanya et al. reported 1860/100,000 infants had an EBT.19 Based on the limited data available, ABE is at least as common as tetanus as a cause of neonatal deaths in Nigeria, Kenya, and Pakistan,11,13,20–23 and likely in most LMICs often ranking as one of the top five causes of neonatal death.8,11,13,24

The available literature indicates that, in LMICs, a significant proportion of survivors of severe neonatal hyperbilirubinemia have signs of chronic bilirubin encephalopathy or kernicterus1 (e.g., cerebral palsy, deafness, and language processing disorders (Table 13-2).25–34 Children with disabilities are a tremendous burden on families in LMICs, where resources are already stretched thin; such children are often left with few or no options for improved quality of life35,36 and experience greater maltreatment than do those without disabilities. Notably, children with communication problems have a greater preponderance of first incidents of maltreatment by their mothers/caretakers from birth to 5 years than any other group of disabled children.37–40 Such adverse childhood experiences are associated with significant short- and long-term medical, mental, psychosocial, and economic problems.41–45 Overall, children suffering from the effects of neonatal hyperbilirubinemia readily fit into UNICEF’s category of “excluded and invisible”46 children. Unfortunately, current global efforts are doing little to highlight the burden of neonatal hyperbilirubinemia; these children are excluded from the global burden of disease measurement.47

Efforts to reduce or eliminate the sequelae of severe neonatal hyperbilirubinemia are hampered by a lack of adequate tools to objectively quantify the problem’s magnitude.48 One glaring gap is the paucity of population-based studies in the developing world; only two of the five countries represented in the literature are from the LMICs.14,19,49–51 According to Lawn et al., population-based data on severe acute neonatal morbidities including jaundice are limited and only two cohort hospital-based follow-up studies on neonatal encephalopathy exist.48,52 Studies by the World Health Organization (WHO) and others have been limited by the lack of an appropriate survey instrument to accurately determine the percentage of infants with ABE in the community.53 WHO published A Standard Verbal Autopsy Method for Investigating Causes of Death in Infants and Children54 to provide a tool for health care workers to arrive at a reasonable cause of death in countries where systems for recording deaths are not well developed or where most deaths occur outside of medical facilities. This tool employs a structured interview with the next of kin (or significant other) to conduct mortality investigations. Specific questions for ABE and kernicterus are absent from this questionnaire, except to ask about whether the infant “was yellow,” and about postneonatal deaths, which excluded neonatal jaundice as a preexisting condition, and posed only general questions about tone and eye movements. Large-scale efforts to prevent ABE are crucial, but are unlikely to happen until the actual burden of disease from severe hyperbilirubinemia is appreciated including appropriate population-based studies.

Available data suggest that the detection and treatment of severe neonatal hyperbilirubinemia is not rated high on the list of priorities in LMICs. However, recently the multinational Global Prevention of Kernicterus Network has been formed with the express purpose of both bringing the problem to the world’s attention and developing affordable, sustainable solutions.

Efforts to both define the magnitude of the problem and treat the problem effectively are also limited by lack of a screening tool. Neither visual assessment for jaundice nor any kind of quantitative measure of bilirubin is available in most locations in many LMICs. Recognition of jaundice and appropriate referral to and treatment at the community level is often lacking with delayed referral hampering timely recommended treatment.10,55

As the first step, mothers, traditional birth attendants, community health workers, as well as more advanced health care providers should be taught to visually assess jaundice after birth and at least for the following week. Recognizing its limitation, the modified Kramer scale56 (Figure 13-1) can still be used to improve visual assessment. Community health workers have been taught to perform jaundice evaluations in some locations including Pakistan14,57 and Bangladesh.58 If possible, every infant should be reevaluated on days 2–4 of life. One logical solution in many locations may be to set up the BCG (tuberculosis vaccine) clinic appointment during this time interval. In addition to assessing feeding problems, cord care, and general issues with the newborn, the infant should be assessed visually for jaundice. If there is jaundice present, the infant should be reevaluated the following day and at least daily if jaundice appears to be progressing. In many locals trained traditional birth attendants and other trained community health workers will be essential in this process as transport and other obstacles will make it impossible for these babies to be brought to higher-level health care facilities for screening. If any infant is noted to be jaundiced in the first day of life or have jaundice involving the hands and feet at any point, the infant should be referred urgently for further evaluation in a center capable of performing TSB measurements and phototherapy at a minimum.

Measuring TSB levels is a challenge facing many health care facilities in LMICs. Many facilities have no way of measuring TSB, and those that do often lack resources such as reagents, blood collection tubes, centrifuges, and a consistent supply of electricity to run the machines. In addition, many machines require large volumes of blood from infants from whom the sample is difficult to obtain, discouraging frequent rechecks even when clinically indicated. Finally, the cost of supplies and limited trained lab personnel also preclude appropriate bilirubin rechecks in many facilities. Each of these obstacles needs to be addressed in health care facilities and every effort should be made to provide TSB levels at admission and as needed around the clock. In the event that there is a delay in obtaining TSB levels in an infant deemed to have significant jaundice, phototherapy should be initiated and a TSB level measured as soon as possible. If this is not possible, the serum should be separated from the cells and the sample stored in the dark.

In many parts of the world, glucose-6-phosphate dehydrogenase (G6PD) deficiency is an important cause of severe neonatal hyperbilirubinemia. Efforts to provide low-cost, easy-to-perform G6PD testing are urgently needed to help identify at-risk infants. Health care providers and parents should be told to avoid products commonly used in normal newborn care such as mentholated rub, mentholated dusting powder, naphthalene balls, and other agents (e.g., certain foods such as fava beans) that might trigger hemolysis in a G6PD-deficient infant (Table 13-3).59–61 Harmful practices such as applying mentholated rub on the fontanel should be avoided; instead, alternatives such as petroleum jelly in cultures should be suggested.

Routine blood typing of pregnant women and, when indicated, the use of Rho(D) immune globulin are standard practices in the developed world but, in many settings, especially in rural areas, blood typing is not available. Rh immune globulin is usually unavailable and, when available, is often cost prohibitive. Although the incidence of Rh hemolytic disease is substantially lower in many LMICs compared with the United States and Europe before the use of Rh immune globulin, tens of thousands of mothers in India, Pakistan, and Kenya are nevertheless sensitized to the D antigen.62 Routine blood typing should be done for all women of childbearing age either during or before pregnancy. One practical approach to blood typing could involve the routine screening of young women in secondary schools together with tetanus immunization. Blood typing could also be done on all students on school entry and become part of their personal health records. Mothers at risk for ABO or Rh incompatibility should be counseled to observe their infants for jaundice and seek treatment early. It is important to plan ahead to have Rh immune globulin available and affordable, perhaps through international subsidies to those women who need it.