A modified Bilirubin-induced neurologic dysfunction (BIND-M) algorithm is useful in evaluating severity of jaundice in a resource-limited setting

Worldwide, neonatal jaundice (NNJ) is one of the most common conditions requiring in-patient treatment in the early postnatal period [1-3]. Successful early detection and postnatal treatment procedures before and after hospital discharge have made the potentially lethal neurotoxic effects of severe neonatal jaundice a rare occurrence in the industrialized world [4,5]. For instance, it is unusual to treat neonatal jaundice beyond phototherapy except in a few extreme cases when exchange blood transfusion (EBT) may be required to quickly reduce the circulating unconjugated bilirubin concentrations and prevent the movement of free bilirubin into the brain tissues.

In resource-limited settings however, neonatal jaundice continues to be a major cause of neonatal mortality as well as morbidity, characterized by acute bilirubin encephalopathy (ABE), and later, kernicterus in the form of auditory neuropathy and chorioathetoid cerebral palsy, and mortality [6]. In Nigeria where the burden of neonatal jaundice is exceptionally high, many infants are born at home or church clinics, and may die before ever seeing a physician or other health care workers [7,8]. Neonatal jaundice is often not easily appreciated by mothers and caregivers in the home setting until it becomes severe enough to deeply discolor the sclera and the skin, at which point neurological damage may have already occurred. Additionally, a considerable number of infants arrive at the hospital or health care facility only after irreversible bilirubin encephalopathy has occurred [8]. In a recently published survey, only 51.5% of community health workers in southwest Nigeria gave a correct definition of neonatal jaundice, and only 45.5% correctly identified danger signs [9]. Even trained medical professionals may miss the clinical signs and features of ABE, especially in the early stages, so that appropriate intervention for infants with reversible brain injury may be delayed [10,11]. Thus there is a need for a tool that clinicians can use to recognize the danger signs of ABE early enough when appropriate intervention is most likely to lead to limiting or reversing adverse neurodevelopmental outcomes.

In resource-limited settings where the diagnosis of ABE is commonly made without magnetic resonance imaging (MRI) or auditory brainstem response (ABR) confirmation, experienced pediatricians are adept at recognizing this constellation of signs. However, attempts to quantify the prevalence of ABE and its severity across communities and among physicians with different levels of expertise were historically limited by the lack of a uniform diagnostic algorithm. In 1999, the bilirubin-induced neurologic dysfunction (BIND) scoring algorithm was developed, assigning 1, 2 or 3 points to indicate mild, moderate, or severe abnormalities in an infant’s mental status, muscle tone, or cry (Additional file 1) [12]. Higher scores indicate worsening signs of acute neurotoxicity associated with excessive hyperbilirubinemia, providing a common descriptive framework for clinicians and researchers to estimate the severity of neonatal jaundice. The simplicity of the BIND scoring system, similar to the Apgar score, makes it an attractive tool for clinical diagnosis of ABE in resource limited locations that lack ready access to MRI) and ABR testing [13]. However, the practicality and acceptance of this scoring algorithm in such settings has not been reported. This study was therefore designed to evaluate the reliability and reproducibility of a modified BIND (BIND-M) scoring system within the scope of the routine newborn examination in Nigeria when used by both trainees and consultant pediatricians. Additionally, BIND-M scores were analyzed for utility in a subset of infants with recorded clinical signs and symptoms of varying degrees of jaundice.

Our results have shown that the physical diagnosis of ABE can be facilitated by a modified BIND-M score. The score showed excellent agreement between residents and consultants (weighted Kappa = 0.7969), and appeared to be accurate in predicting infants with ABE (sensitivity = 90.7%; positive predictive value = 88.9%). Thus, BIND-M may be an important yet simple tool to provide a uniform measure of the degree of ABE in clinically jaundiced infants in resource limited settings. Infants with BIND-M scoring less than 3 were extremely unlikely to be diagnosed with clinical ABE (specificity = 97.7%; negative predictive value = 98.2%). Although, a score of 5 had a higher positive predictive value of 91.7%, it is associated with an unacceptable level of false negatives (80% increase) with an 8% reduction in sensitivity. While we predicted that a score of 1-4 would be indicative of mild ABE and 5-6 would represent moderate ABE, a threshold as low as 3 is definitely more applicable in this population, possibly as a result of the multiple risk factors and a high prevalence of severe NNJ. It is noteworthy that inter-rater agreement for the upward gaze paralysis sub-score (simple Kappa = 0.5802) was lower than that for the altered mental status (weighted Kappa = 0.7692), altered muscle tone (weighted Kappa = 0.8430), and altered cry (weighted Kappa = 0.81399) sub-scores.

Exchange blood transfusion for severe NNJ entails a significant risk for morbidity. This procedure was quite common in the present study, where 24% of the infants at four major teaching hospitals in Nigeria had EBT. Even in the most experienced hands, this procedure is not without significant risk from the procedure itself as well as the risks for infections and non-infectious complications [14,15]. If effectively used in combination with other modalities including intensive phototherapy, BIND-M is capable of reducing the high rate of needless EBT in newborns without ABE as well as enhancing identification of newborns with mild to moderate ABE, considered to be reversible with appropriate and early interventions.

Glucose-6-phosphate dehydrogenase deficiency is known to be a significant risk factor for severe neonatal jaundice and is common in Nigeria. Testing for G6PD deficiency is not routinely available in health institutions and was only performed in a small subset of infants in the present study. Exposure to mentholated products is known to be a significant risk factor for severe jaundice and ABE in infants with G6PD deficiency [16,17], and yet was commonly used with the neonates in our study: 1 in 6 infants overall, and 4 in 10 infants with ABE. It is therefore imperative to continue public enlightenment campaigns, at least in Nigeria, to educate the populace, and pregnant women in particular, as to the danger of using these products in the newborn period [17].

Surprisingly, neither ABO incompatibility nor Rh disease was significantly different between the two groups of infants with and without ABE, suggesting that other factors such as dehydration, sepsis and harmful cultural practices may play a more significant role in determining the course and severity of newborn jaundice in this area. Concurrent sepsis has been alleged to be a significant risk factor for ABE among Nigerian neonates [18]. Sepsis usually coexists with exposure to exogenous agents that predispose the G6PD deficient infants to severe NNJ and ABE.

The primary limitation in the present study is the lack of ABR or MRI to validate the BIND-M score. However, since neither ABR nor MRI is the standard of care in these settings, physicians are quite familiar with the clinical diagnosis of ABE. A subsequent study to validate the BIND-M score with ABR is now ongoing in a children’s hospital in Lagos, Nigeria. Another significant limitation is the lack of the full medical history for these infants. However, since this was not the focus of this study it will be desirable for a future study.

The present study has shown that the use of the BIND-M score among consultant pediatricians and their resident doctors in Nigeria is reliable for identifying infants with the clinical diagnosis of ABE with acceptable sensitivity and specificity. Validation and further modification of this scoring system could provide a much needed tool for use in population studies in Nigeria and elsewhere to estimate the actual magnitude of ABE-related morbidity and mortality. Such data would support the work of child health advocates to devise solutions to reduce or eliminate this preventable morbidity which has long-term, tragic consequences for the infants, their families and their communities.