|Year : 2016 | Volume
| Issue : 1 | Page : 1-17
The burden and management of neonatal jaundice in Nigeria: A scoping review of the literature
BO Olusanya1, FB Osibanjo1, CA Mabogunje2, TM Slusher3, SA Olowe4
1 Centre for Healthy Start Initiative, 286A Corporation Drive, Dolphin Estate, Ikoyi, Lagos, Nigeria
2 Newborn Unit, Massey Street Children's Hospital, Lagos, Nigeria
3 Department of Pediatrics, Hennepin County Medical Center and University of Minnesota, Minneapolis, MN 55415, USA
4 Department of Pediatrics, Lagos University Teaching Hospital, Idi Araba, Surulere, Lagos, Nigeria
|Date of Acceptance||28-May-2015|
|Date of Web Publication||12-Jan-2016|
B O Olusanya
Centre for Healthy Start Initiative, 286A Corporation Drive, Dolphin Estate, Ikoyi, Lagos
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Neonatal jaundice is a leading cause of hospitalization in the first week of life worldwide. If inappropriately managed, it may result in significant bilirubin-induced mortality and disability. We set out to describe the epidemiology of neonatal hyperbilirubinemia as well as the practices and challenges in the care of infants with significant neonatal hyperbilirubinemia (SNH) in Nigeria, as basis for policy intervention and research priorities. We systematically searched PubMed, Scopus, EMBASE, Cumulative Index to Nursing and Allied Health Literature, WHO Library Database, African Index Medicus, African Journals Online, and local journals for studies published between January 1960 and December 2014. We included studies, without restriction on methodological design that provided evidence on the incidence/prevalence, etiological /risk factors and adverse outcomes of hyperbilirubinemia, care-seeking practices, diagnosis and treatment, as well as follow-up evaluation of infants with SNH in Nigeria. A total of 558 studies were identified from all sources out of which 198 (35.5%) were finally selected. SNH accounted for about one in five neonatal admissions and has been associated consistently with substantial case fatality and neuro-developmental sequelae such as cerebral palsy and auditory impairments, especially among out-born babies. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, prematurity/low birth weight, infection, and ABO incompatibility were most frequently, and Rhesus disease rarely, associated with SNH. Late presentation at appropriate health facilities was common and resulted in high rates of acute bilirubin encephalopathy (ABE), kernicterus and avoidable exchange transfusions. Uniform practice guidelines, including developmental assessment and surveillance of infants with SNH, were rare at all levels of healthcare delivery. In summary, since 1960, SHN persists as a major contributor to neonatal mortality and developmental disabilities in Nigeria. The underpinning maternal, perinatal and neonatal factors as well as systems-based constraints are not insurmountable. Systematic and sustained interventions are warranted to curtail the disproportionate and perennial burden of this condition in this population.
Keywords: Etiology, bilirubin-encephalopathy, care-seeking behavior, developing country, developmental disabilities, kernicterus, newborn care, risk factors
|How to cite this article:|
Olusanya B O, Osibanjo F B, Mabogunje C A, Slusher T M, Olowe S A. The burden and management of neonatal jaundice in Nigeria: A scoping review of the literature. Niger J Clin Pract 2016;19:1-17
|How to cite this URL:|
Olusanya B O, Osibanjo F B, Mabogunje C A, Slusher T M, Olowe S A. The burden and management of neonatal jaundice in Nigeria: A scoping review of the literature. Niger J Clin Pract [serial online] 2016 [cited 2019 Dec 14];19:1-17. Available from: http://www.njcponline.com/text.asp?2016/19/1/1/173703
| Introduction|| |
Hyperbilirubinemia is one of the most common causes of morbidity in newborns worldwide, and the most frequent cause of hospitalization or readmission for special care in the 1st week of life.,, Recent global estimates suggest that every year, roughly 1.1 million babies would develop severe hyperbilirubinemia and the vast majority reside in sub-Saharan Africa and South Asia. Available evidence also shows that severe hyperbilirubinemia, with or without bilirubin encephalopathy, is associated with substantial mortality and long-term morbidities in low- and middle-income countries (LMICs).,,, This is corroborated by several studies spanning more than five decades in Nigeria, where the burden of severe hyperbilirubinemia is underpinned by widespread glucose-6-phosphate dehydrogenase (G6PD) deficiency,,,,,, and possibly exacerbated by polymorphism of the uridine-diphosphate-glucuronosyl transferase 1A1 gene (UGT1A1), and widespread exclusive breastfeeding in the first few days of life. In one nationwide survey of pediatricians in Nigeria, neonatal jaundice was ranked as a priority neonatal morbidity for global health intervention. However, no comprehensive literature review has been conducted in Nigeria to inform policy initiatives and research priorities for improved newborn care.
Scoping reviews are effective in capturing a range of literature to establish available evidence and the overall state of research on the topic of interest. Unlike systematic reviews, they target all types of study designs without focusing on the assessment of quality as defined within a biomedical research convention. We therefore, conducted a scoping review: (i) To assemble available evidence on the burden of neonatal hyperbilirubinemia, (ii) to identify current practices and challenges for the effective management of infants with clinically significant hyperbilirubinemia, and (iii) to identify gaps in the existing literature that should be addressed in future research efforts.
| Methods|| |
We adopted the methodological framework proposed by Arksey and O'Malley for scoping studies. The framework consists of five stages: Defining the research question, identifying the relevant studies, study selection, charting the data and collating, summarizing and reporting the results. The optional sixth stage requiring a consultation exercise to validate findings from the review was not considered necessary for our purpose. Furthermore, a systematic evaluation of the methodological quality of included articles was not conducted as such analysis is not mandatory under this framework.
Defining the research questions
The focus of this study was to address two main questions, namely: (i) “What are the epidemiological findings among infants diagnosed with clinically significant hyperbilirubinemia with or without bilirubin encephalopathy?” and (ii) “what are the practices associated with the management of infants with or at risk of significant hyperbilirubinemia in Nigeria?” In addressing the first question, we examined available evidence on the incidence/prevalence, etiological/risk factors, and adverse outcomes of hyperbilirubinemia in Nigeria. The second research question sought evidence on care-seeking practices, diagnosis and treatment, as well as follow-up evaluation for infants with significant hyperbilirubinemia. For the purpose of this review, neonatal hyperbilirubinemia of any unconjugated bilirubin level (typically from total serum bilirubin [TSB] ≥10 mg/dL or 170 µmol/L) requiring immediate treatment with phototherapy or exchange transfusion was considered as clinically significant neonatal hyperbilirubinemia and abbreviated as “SNH”.
Identifying relevant studies
Electronic databases including PubMed, Scopus, EMBASE and Cumulative Index to Nursing and Allied Health Literature (CINAHL), WHO Library Database, African Index Medicus and African Journals Online were searched to identify relevant articles published between January 1960 (Nigeria Year of Independence) and December 2014 (55 years). The search terms used for major databases such as PubMed, Scopus, EMBASSE, and CINAHL were “neonatal jaundice” or “neonatal hyperbilirubinemia” and Nigeria while search term for other databases was restricted to “jaundice” or “hyperbilirubinemia” for optimum hit of relevant articles. We applied a snowball method to examine the reference lists of retrieved articles as well as other relevant reports to identify additional studies.
Three authors (BOO, FBO and TMS) screened all titles and abstracts of retrieved studies from all the databases and other sources to identify articles relevant to our two primary research questions. We included studies of subpopulations of infants with specific risk profile such as diabetic mothers, preterm/low birth weight, sepsis, or hemolytic conditions including G6PD deficiency, maternal-fetal ABO blood group incompatibility, and rhesus hemolytic disease. Studies exploring the association between neonatal hyperbilirubinemia and adverse neonatal outcomes such as mortality and neurodevelopmental disorders were included. Thereafter, duplicates were systematically removed starting with all eligible articles from PubMed through to the last database. After reviewing full-texts of eligible studies, we excluded papers in which data relevant to our research questions was not provided. Abstracts in conference proceedings without full-texts were excluded. All three authors agreed on this selection procedure. Discrepancies in the final selection were resolved through consensus after joint reassessment.
Data charting and collation
Articles that met our inclusion criteria were listed in the appropriate sub-headings of our two main research questions. Issues related to the main research questions were extracted into a spreadsheet for further descriptive analysis. The selected studies were identified by first author, year of publication and location. Distribution across the six geographical regions in Nigeria: South-West, South-South, South-East, North-West, North-Central, and North-East, was also explored. The most notable findings under each thematic section were agreed among the three authors based on thematic content analysis of the selected references.,
| Results|| |
The initial search yielded 463 studies across databases and 95 from additional sources resulting in a total of 558 records [Figure 1]. After assessment of titles and abstracts, 382 studies were assembled from all sources, out of which full-texts for 223 studies were required after excluding 159 duplicates. A total of 25 studies were further excluded because they did not provide any relevant data for our study objectives resulting in a final selection of 198 studies [Table S1].[w1-w198] The years of publication of the included studies are presented in [Figure 2]. The earliest studies were published in 1960 and the highest number of studies was recorded in 2011. Of the finally selected studies, 37.4% (n = 74) were retrieved from PubMed and 48.0% (n = 95) from sources outside the major databases [Figure 3]. By geographical spread, 51% (n = 101) were conducted in Southwest, 19.2% (n = 38) in South-South, 12.1% (n = 24) in South-East, 8.1% (n = 16) in North-West, 7.6% (n = 15) in North-Central, 1.0% (n = 2) in North-East, and 1% (n = 2) were multi-center. The studies addressing each of the sub-themes of interest are presented in [Table 1].[w1-w198] The key findings from the eligible studies are summarized as follows:
|Figure 2: Year of publication of eligible studies on neonatal jaundice in Nigeria|
Click here to view
|Table 1: Studies on the burden and management of neonatal hyperbilirubinemia in Nigeria (1960-2014) |
Click here to view
Incidence/prevalence of neonatal hyperbilirubinemia
All but one of the studies that provided data on the incidence of SNH was hospital-based. In the only community-based study in inner-city Lagos, 351 (6.7%) of 5262 infants enrolled were reported to be jaundiced based on parental history. From this group, 291 (82.9%) were treated with phototherapy while 98 (27.9%) had exchange transfusion.[w134] Crude incidence of severe hyperbilirubinemia was at least 5.5% (95% confidence interval: 4.9–6.2%).
The incidence of SNH is likely to be grossly under-reported in hospital cohorts without adequate postdischarge surveillance till the 8th day after birth. Only two studies appeared to have met this requirement.[w30, w43] The first study was conducted in 1971 in Ibadan (South-West) over a period of 12 months.[w43] In a cohort of 6502 live births from two hospitals, a total of 1052 (17%) babies were reported with jaundice.[w43] Out of 741 jaundiced infants in one of the two hospitals, 240 (32.4%) had TSB ≥10 mg/dL (170 µmol/L). From this group, 131 (54.6%) had TSB >15 mg/dL (255 µmol/L) and 53 (2.3%) required exchange transfusion. In the second and more recent study in 2011, 140 (21.7%) of the 644 term and near-term (35–36 weeks) infants recruited consecutively over a 6-month period in Ile-Ife (South-West) were found to have SNH (TSB ≥12 mg/dL or 204 µmol/L) and 134 (95.7%) received phototherapy.[w30] No infants developed SNH that required exchange transfusion.
Three studies provided data on the incidence SNH from birth cohorts but without adequate information on surveillance in the 1st week of life. For example, in one study from Enugu (South-East), jaundice (TSB ≥10 mg/dL or 170 µmol/L) was reported in 206 (10%) of 2,140 live births.[w29] Of this group, 80 babies (39%) had TSB >15 mg/dL (255 µmol/L), and 25 (12.1%) required exchange transfusion. Similarly, a study from Zaria (North-West), showed that 30 (2%) of a cohort of 1,478 live births in Zaria developed jaundice (TSB ≥10 mg/dL or 170 µmol/L).[w195] Another study from Port Harcourt, (South-South) reported that 18 (1.6%) of the 1120 live births born within a 6-month period had jaundice (TSB ≥10 mg/dL or 170 µmol/L).[w54]
Overall, barring methodological limitations, these studies suggest that SNH is highly prevalent in Nigeria when compared to the rates per 100,000 live births reported in developed countries which ranges from 7.1 to 45 for SNH and 0.4 to 2.7 for kernicterus., SNH was also less commonly reported and also less severe in babies born and observed in hospitals in the 1st week of life than in those delivered at home, as well as in those discharged from hospital within 48 h of birth.[w44, w65] Investigation of the underlying causes and risk factors of SNH in this population is therefore warranted.
Etiological and risk factors for significant neonatal hyperbilirubinemia
A summary of etiological or risk factors associated with SNH is presented in [Table 2]. The leading causes of SNH from studies that conducted appropriate clinical and laboratory investigations among infants detected with TSB ≥10 mg/dL (170 µmol/L) were G6PD deficiency, ABO incompatibility, sepsis and prematurity/low birth weight, singly or in combination. A quantitative synthesis of the reported rates was hampered by inadequate treatment of cases with multiple etiologies across studies. G6PD deficiency was the leading cause of SNH in the vast majority of the studies. Infection, especially umbilical sepsis resulting from traditional practices regarding cutting and subsequent management of the newborn cord with unsterile materials as well as delivery in the unhygienic environment was common among babies delivered outside hospitals.[w13], [w29], [w54], [w84], [w164], [w167], [w182], [w195] Such infection often triggered hemolysis in both G6PD deficient and normal infants.
|Table 2: Summary of reported etiological/risk factors for SNH in Nigeria* |
Click here to view
Rhesus disease was not confirmed in several studies as a major cause of SNH in this population especially among outpatients.[w12], [w13], [w29], [w33], [w38], [w44], [w54], [w84], [w156], [w182], [w195] This was also noted in the few studies that reported isolated cases, especially among inborn patients.[w5], [w29], [w36], [w43], [w111], [w112], [w147], [w164], [w181] The proportion of idiopathic SNH ranged from 7.8% to 54.5%.[w11], [w12], [w36], [w47], [w111], [w156]
Several studies, predominantly from the South-West, demonstrated exposure to icterogenic agents or oxidant stressors such as insecticides, menthol-based, naphthalene-camphor products, sulfonamides or sulfa-containing drugs and herbal concoctions as important contributors to the incidence, and severity of SNH especially in G6PD-deficient babies.[w30], [w40], [w66], [w71], [w84], [w133], [w150], [w156], [w159], [w165], [w181] One study established the prevalence of UGT1A1, confirming that unconjugated bilirubin levels in infants with G6PD deficiency in combination with (TA)n promoter polymorphism may rise exponentially from hemolysis triggered by exposure to oxidant stressors such as sepsis and menthol-based products.[w89] While one study from Ibadan (South-West) found aflatoxins to be an important contributor to the severity of SNH,[w181] other reports from Zaria (North-West), did not find any such association.[w11, w12]
Few case-control studies have explored risk factors for SNH, with explicit adjustment for confounding variables. For example, in one recent systematic review and meta-analysis, only four studies were adjudged to provide reliable data on possible maternal and neonatal risk factors for SNH in Nigeria.[w5, w115, w134, w181] Factors reported in two or more studies were social class, delivery outside hospital and underweight/excessive weight loss. Factors reported in single studies included religion, occupation, herbal drug use in pregnancy, serum aflatoxin, gender (male), severe anemia, and acidosis. One study from Zaria (North-West) however, found no association between maternal use of herbal medication during pregnancy and SNH.[w13] Factors reported in other descriptive studies without adjustment for confounders, included oxytocin in labor,[w13], [w144] birth trauma including cephalhematoma,[w13, w111, w150, w181] and birth asphyxia.[w84] Two studies suggested that hyponatremia contributed significantly to SNH associated with oxytocin use in labor.[w18], [w144] These findings are comparable to those reported from other developing countries.,
In general, some studies have suggested some plausible but unverified link between SNH and congenital malaria, Nigeria being a prominent malaria endemic country [Table 1]. For example, jaundice, irritability, and poor feeding were reported in one birth cohort in Lagos as the most common symptoms associated with congenital malaria; and that jaundice was significantly associated with malaria parasitemia between day 7 (P = 0.04) and day 14 (P = 0.002).[w95] A few studies also reported SNH as one of the neonatal conditions accounting for self-discharge by mothers of sick infants against medical advice. Although breastfed babies are more likely than bottle-fed babies, to develop jaundice within the 1st week of life, the impact of the ubiquitous exclusive breastfeeding in Nigeria was not documented in any study. In some culture, jaundice is believed to be transferred from the mother to the fetus or caused by shortage of blood in the newborn, fever, mosquito bites, blood spilling into the eyes of the baby at birth, bad water in the baby's body, the mother eating bananas during pregnancy or germs in mother's breast milk.[w46, w55, w109, w167, w173]
[Table 2] provides an overview of putative factors that have not been (sufficiently) investigated based on findings from other LMICs.,
Adverse neonatal and long-term outcomes
Several studies showed that SNH was one of the most common causes of readmissions.[w45, w53, w54, w100, w174] The proportion of total neonatal admissions into children emergency departments or Special Care Baby Units varied from 9.4% in one study from Kano (North-West),[w100] to 64% in Lagos (South-South).[w174] Studies that failed to disaggregate neonatal admissions from overall pediatric admissions were likely to under-report the contribution of SNH to neonatal morbidity in the 1st week of life as demonstrated in some older reports from Benin City., Acute bilirubin encephalopathy (ABE) or kernicterus was more commonly reported among outborn infants presenting late for emergency treatment.[w5, w111, w112, w156, w162]
As shown in [Table 1], several studies as far back as 1972 have reported bilirubin-induced mortality among infants with SNH. These reports demonstrated significant rates of mortality among infants with SNH or a substantial contribution of SNH-related deaths to overall neonatal mortality.[w9, w31, w45, w68, w82, w84, w96, w113, w163, w185] One study that examined the trend in child mortality over a 20 year period in the Children's Emergency Unit of a Teaching Hospital in Lagos reported a significant rise in the contribution of SNH to mortality from 4.0% in 1972,[w174] to 13.1% in 1990.[w96]
While routine developmental evaluation of survivors of SNH including ABE/kernicterus was rarely reported, several studies have implicated SNH as a major contributor to the incidence of cerebral palsy and hearing impairment in infants and young children [Table 1]. Prior to the introduction of newborn hearing screening in Nigeria, available evidence on the association between SNH and hearing impairment relied on parental reports or medical records predominantly in school-aged children., Recent studies among infants enrolled for newborn hearing screening based on otoacoustic emissions and auditory brainstem response audiometry have shown significant risks of hearing impairments including auditory neuropathy spectrum disorders in infants with SNH even after phototherapy and/or exchange transfusion.[w134], [w140], Other less frequently reported adverse long-term outcomes include epilepsy (with or without cerebral palsy),[w24, w83, w117] speech and language disorders,[w182] and mental retardation.[w87]
A national survey among pediatricians in Nigeria to elicit their perspectives on priorities for newborn care showed that neonatal jaundice ranked next to preterm birth/low birth weight and birth asphyxia for disability; and above tetanus by all measures except mortality [Figure 4].[w135] In effect, the exclusion of SNH in the global health campaign for newborn care under the millennium development goals (MDG) project was inappropriate for Nigeria.
|Figure 4: Priority rating of common neonatal conditions by pediatricians in Nigeria [source: Reference w135]|
Click here to view
Care-seeking practices for jaundiced infants
The vast majority of babies in Nigeria are delivered outside hospitals. Based on data from the Nigeria Demographic and Health Survey 2008, 35% of births in Nigeria are delivered in a health facility (20% in public hospitals and 15% in private facilities). Of the 65% delivered outside hospitals, 62% occur at home. South-East has the highest proportion of institutional deliveries (74%), followed by South-West (70%), while North-West has the lowest proportion (8%). Among those delivered in hospitals and with uneventful delivery, hospital stay rarely exceeded 48 h of birth. In one birth cohort of 741 preterm and term babies delivered in a Teaching Hospital in Ibadan, onset of jaundice was reported on the 1st day in 12.8% of the infants, between the 2nd and 4th day in 72.4%, and between the 5th and the 8th day in 14.8%.[w43] In another cohort of 208 preterm babies admitted in the same hospital, jaundice was noticed by the 2nd day of life in 78 (37.5%), on the 3rd day in 74 (35.6%) and on the 4th day in 34 (16.3%). Thus, by the 4th day of life, jaundice had manifested in 186 (89.4%) of the preterm infants.[w158] Thus, the onset of SNH in the vast majority of both inborn and outborn babies occurred outside hospital. It was often difficult to ascertain the time of onset in out-born babies. However, such infants typically presented between the 3rd and 9th day of life.[w5, w29]
A number of studies have reported that many mothers are able to distinguish jaundice by yellowish discoloration of the skin and sclera of the newborn, but have a poor knowledge of the underlying causes and potential consequences.[w46], [w55], [w57], [w108], [w116], [w134] Late presentation in hospitals was therefore a major contributor to the high incidence of avoidable exchange transfusions and adverse outcomes among infants with SNH in Nigeria [Table 1]. The delay in seeking timely and appropriate care was underpinned by several factors including late or failed recognition of the onset of severe jaundice and poor perception of its severity.[w5], [w55], [w109], [w116], [w129], [w162], Before seeking medical attention, mothers commonly resorted to self-medication with antibiotics, vitamins or traditional therapies such as herbal preparations and exposure to direct “early morning” sunlight.[w109, w116, w129] Inappropriate advice from health workers was also not uncommon. For example, it was reported in one study that over 25% of community health workers at primary care centers were likely to prescribe antibiotics, natural (direct sunlight) phototherapy or herbal therapies.[w109] On occasions when mothers chose to seek care outside their homes, they could be constrained by difficulties with accessibility to health facilities and/or finances or identifying an “appropriate” hospital that routinely admits and provides essential care for sick babies.[w53] Some mothers therefore presented first to the nearest primary health centers or private clinics most of which were poorly-equipped to provide special care for sick neonates.
Diagnosis and treatment
Practice guidelines for the prevention, diagnosis and management of infants with SNH do not exist in Nigeria. The guidelines for hyperbilirubinemia in developed countries such as the NICE in UK, or the American Academy of Pediatrics, were rarely cited because their adoption and implementation was constrained by several systems-based and biological factors. Modern tools for real-time objective measurement or monitoring of bilirubin levels (transcutaneous bilirubin [TcB] and plasma/serum bilirubin [TSB]) have been reported in several studies.[w30, w177] The noninvasive TcB measurement has also been demonstrated as a reliable proxy for the more invasive and diagnostic TSB.[w172] However, these tools were not routinely available in most hospitals including tertiary institutions. As a result, it was common practice for hospital personnel to make a clinical judgment based on visual assessment of the cephalocaudal progression or ominous signs of ABE/kernicterus particularly among outborn infants. Similarly, laboratory investigations such blood typing for baby and mother, direct Coombs' test, blood culture, G6PD assay, and full blood count to establish the risk status of infants were not readily available in most hospitals. In some hospitals, facilities for laboratory investigations were located far away from neonatal units, thus, forestalling quick turn-around in obtaining results for prompt clinical decisions.
Phototherapy and exchange transfusion were the mainstay treatments for hospital patients. Case definition for SNH and treatment thresholds for phototherapy and exchange transfusion varied across studies. The minimum TSB threshold for clinically significant jaundice across studies was 10–12 mg/dL for term infants. In general, phototherapy was commenced at approximately TSB ≥12 mg/dL (204 μmol/L) in otherwise healthy normal weight (≥2500 g) babies.[w43, w44, w76, w162, w164] Exchange transfusion was indicated at TSB ≥20 mg/dL (340 µmol/L) in apparently healthy term infants and sometimes at TSB <20 mg/dL (340 µmol/L) in very ill term infants with or without features of kernicterus. Exchange transfusion was indicated in preterm at TSB> 10 mg/dL per kilogram body weight.
Effective first-line treatment with conventional blue-light phototherapy requires light emission spectrum within the bilirubin absorption spectrum of 400–520 nm (peak 450 ± 20 nm); irradiance level ≥30 μW/cm 2/nm, exposed to ~80% of an infant's body surface area, and optimized duration of exposure. However, in one survey, the vast majority (94%) of 63 phototherapy devices tested in twelve referral level hospitals delivered irradiances of ≤10 μW/cm 2/nm and none were ≥30 μW/cm 2/nm.[w155] This finding was corroborated in another report in which 76 “functional” phototherapy devices across 16 hospitals were evaluated.[w37] The functionality of the devices was frequently compromised by erratic power supply and breakdowns due to poor device maintenance. High rates of exchange transfusion were therefore common due to sub-therapeutic phototherapy and lack of intensive phototherapy especially in combination with late presentation of outborn babies with SNH.[w27, w76, w93, w114, w164, w170]
Because of the widespread constraints with conventional phototherapy, a novel, low-cost canopy has been developed in Lagos as a potential alternative for treating infants with SNH in Nigeria and other tropical countries.[w178, w180] It is a noteworthy advancement to the initial “sunshine phototherapy cot” piloted almost three decades ago by a foremost neonatologist in Nigeria. The canopy is covered with special window-tinting films that filter out virtually all ultraviolet (UV)-A, UV-B, and UV-C light, as well as significant levels of infrared radiation (heat) in natural sunlight. The need for this device was further prompted by the common practice of mothers and caregivers to expose their jaundiced babies to direct sunlight, with or without the support of health workers.[w46, w49, w55, w129] The canopy allows mothers to sit comfortably while holding or feeding their babies during treatment. Preliminary data from a randomized clinical trial has established that this phototherapy device is no less efficacious than conventional blue-light phototherapy. Mothers have also expressed satisfaction with the device as an alternative to conventional phototherapy.[w136] However, its use is still experimental and limited to daytime care and periods with favorable climatic conditions.
Other traditional therapies typically for mild-to-moderate SNH included medicinal plants, herbal concoctions, black soap, and water extract of unripe pawpaw.[w70, w80, w116, w167] Traditional treatment for severe SNH (TSB ≥20 mg/dL or 340 µmol/L) including ABE or kernicterus was not documented in any study.
Postdischarge developmental surveillance
Although long-term adverse outcomes such as cerebral palsy, hearing impairments, epilepsy, and intellectual difficulties have been reported in studies [Table 1], developmental screening and evaluation of survivors of ABE or kernicterus was rarely considered as a component of the clinical management for SNH. In the only study identified in this review with evidence of postdischarge surveillance, 4 (5%) of the 79 infants treated for SNH over a 5-year period were followed up.[w47] Two were diagnosed with motor retardation and the remaining two had poor neck control between 6 and 12 months. Hearing evaluation was not reported.
| Discussion|| |
To our best knowledge, this is the first comprehensive review of the burden of SNH in Nigeria or any other LMIC in sub-Saharan Africa. There are six overarching observations to be noted. First, as expected and barring weaknesses in study design and quality of available records, the scoping methodology resulted in a substantially greater number of studies and a wider range of factors than would have been identified in a traditional systematic review.
Second, no remarkable progress has been observed on the epidemiological profile of SNH since the earliest reports 55 years ago.[w35], [w81], [w96], [w98], [w174], [w182],,, SNH is highly prevalent in Nigeria and continues to be associated with substantial case fatality and long-term morbidity., The dearth of population-based epidemiological studies often preferred for global health programming cannot be justifiably construed as an evidence of lack of disease burden in this population. For example, one unpublished nationwide survey conducted in 2012 by Nigerian Society of Neonatal Medicine (NISONM) estimated that SNH accounted for 1 out every 5 neonatal admissions. NISONM data also suggests that SNH accounts for at least 5% of all neonatal mortality in Nigeria.
Third, the most frequently reported etiological factors for SNH are still G6PD deficiency, ABO incompatibility, prematurity, and infection. Despite the significant national G6PD deficiency allele frequency of at least 15.0% and its important contribution to the incidence of SNH in this population in particular,[w197], routine screening for G6PD deficiency as recommended by WHO, is rare in birthing hospitals.
Fourth, contrary to a recent report on the worldwide prevalence of rhesus disease and its contribution to the global burden of SNH based primarily on mathematical modeling, this review has established that this factor is not a significant contributor to the burden of SNH in Nigeria. This observation is consistent with earlier reports that suggested that the predicted frequency of hemolytic disease of newborn due to rhesus immunization is about 1–800 as only 5% of Nigerian women are estimated to be rhesus negative.[w198] It is also postulated that rhesus-negative Nigerians have a low iso-immunization potential, probably due to some genetic predisposition.[w97, w198]
Fifth, the current weaknesses in the care-seeking pathways and clinical framework for the management of infants with or at risk of SNH are not insurmountable to significantly curtail the burden of this condition.,
Finally, the burden of SNH has not been sufficiently documented in some regions which may lead to under-representation of the nationwide burden and challenges of SNH.
The substantial burden of SNH in regions with adequate data can be attributed to three phases of delay in the care of jaundiced infants: The decision to seek appropriate care, reaching an appropriate health facility, and receiving adequate/appropriate care. Strategies to address these delays have been well documented in a recent review. At the very core is the need for a bold public health initiative to educate women of childbearing age routinely on the early signs of the onset of SNH and dangers of late presentation to appropriate health facilities. All birthing hospitals should be equipped to provide effective and timely phototherapy for jaundiced infants. Infants who have been treated for SNH should also be placed under developmental surveillance routinely at least in the first year of life to facilitate early detection of disabilities. As has been demonstrated in developed countries, the burden of SNH and the current excessive rates of exchange transfusion can be substantially curtailed by timely and effective phototherapy even among high-risk infants. The development of a novel, low-cost filtered-sunlight phototherapy device offers the prospect of expanding the coverage of this treatment beyond traditional hospital settings.
The exclusion of SNH in the global agenda for newborn care within the MDG framework in the last 15 years has contributed in no small measure to the lack of globally-backed national programs for this condition. While conditions such as prematurity, birth asphyxia, and infection remain prominent contributors to neonatal mortality in LMICs, they should not distract from the substantial and perennial burden of SNH in many LMICs including Nigeria. This is corroborated by the views of pediatricians in a nationwide survey on the preferred component of essential newborn care in Nigeria.[w135] It is therefore gratifying to observe increasing global interest in addressing the burden of SNH in LMICs. For example, for the 1st time ever, “hemolytic disease in fetus and newborn, and other neonatal jaundice” has been recognized by the WHO's Child Health Epidemiology Reference Group and the Global Burden of Disease Collaborators as a distinct entity under the leading causes of neonatal mortality and long-term morbidity., The lack of a robust and practical framework for the effective management of infants with or at risk of SNH at all levels of health care delivery in LMICs has been addressed by a team of international experts from all world regions in a landmark paper. The tasks and resources required to ensure optimal care of infants with SNH have been outlined comprehensively in the document. This framework can be easily adapted to suit the local practice needs in different settings in Nigeria, especially at the primary care level which is the first level of medical intervention for the vast majority of infants with SNH.
Finally, the number of publications on SNH peaked in 2011. Furthermore, most (82.3%) of the identified studies in this review were conducted in Southern regions. Evidently, there is need to reverse the downward trend since 2011 and build greater research capacity for SNH in the rest of the country to more accurately determine possible differences in the epidemiological and clinical practice profile across the country. It is also important that studies are published in journals indexed by key databases to improve accessibility for potential users.
Typical of scoping reviews, this study has a number of limitations that are worth noting. First, no quality assessment of the included studies was undertaken to determine publication bias or the validity of the diagnostic criteria for the reported etiological factors. Second, despite the liberal inclusion criteria, it was still possible to have excluded other relevant studies not available from the selected databases. Third, no distinction was made in the severity of SNH including acute and chronic bilirubin encephalopathy whereas associated factors may differ for various levels of severity. Notwithstanding, the key findings from this review clearly underscore the scope of the burden of SNH in a poorly-resourced African setting and the urgent need for appropriate intervention. While jaundice cannot be prevented in newborns, its progression to bilirubin-induced neurologic dysfunction and the potential adverse outcomes can be prevented. They also highlight areas for focused education for mothers and care-givers to address erroneous beliefs and customs on SNH as well as capacity-building for further research and advocacy to facilitate improved care for infants with or at risk of SNH in this population and comparable LMICs.
| Conclusion|| |
This scoping review has highlighted the epidemiological profile of SNH and the current challenges for the effective care of the affected infants in Nigeria. No significant progress appeared to have been recorded for more than half a century in all regions of the country, especially during the 15-year MDG era ending 2015. The emerging global interest and recognition for hemolytic disease and neonatal jaundice as an important contributor to neonatal mortality and long-term morbidity especially in LMICs presents a unique opportunity to address the disease burden in Nigeria through appropriate maternal and child health initiatives.
| Acknowledgments|| |
We would like to thank Kathleen Warner and Paul Reid and the staff at Hennepin County Medical Center Library, Minneapolis, MN, USA for their valued assistance in retrieving several older articles used in this review. We also thank the research team at the Centre for Health Start Initiative, Ikoyi, Lagos, Nigeria, for their administrative support and assistance with the data management. The authors also received valuable blinded comments from five external reviewers invited by the journal.
| References|| |
Burke BL, Robbins JM, Bird TM, Hobbs CA, Nesmith C, Tilford JM. Trends in hospitalizations for neonatal jaundice and kernicterus in the United States, 1988-2005. Pediatrics 2009;123:524-32.
National Institute for Health and Clinical Excellence. Neonatal Jaundice. (Clinical Guideline 98); 2010. Available from: http://www.nice.org.uk/CG98
. [Last accessed on 2015 Feb 16].
Young Infants Clinical Signs Study Group. Clinical signs that predict severe illness in children under age 2 months: A multicentre study. Lancet 2008;371:135-42.
Bhutani VK, Zipursky A, Blencowe H, Khanna R, Sgro M, Ebbesen F, et al.
Neonatal hyperbilirubinemia and Rhesus disease of the newborn: Incidence and impairment estimates for 2010 at regional and global levels. Pediatr Res 2013;74 Suppl 1:86-100.
Olusanya BO, Ogunlesi TA, Slusher TM. Why is kernicterus still a major cause of death and disability in low-income and middle-income countries? Arch Dis Child 2014;99:1117-21.
Slusher TM, Olusanya BO. Neonatal jaundice in low- and middle-income countries. In: Stevenson DK, Maisels J, Watchko J, editors. Care of the Jaundiced Neonate. New York: McGraw-Hill; 2012. p. 263-73.
Mwaniki MK, Atieno M, Lawn JE, Newton CR. Long-term neurodevelopmental outcomes after intrauterine and neonatal insults: A systematic review. Lancet 2012;379:445-52.
Maulik PK, Darmstadt GL. Childhood disability in low- and middle-income countries: Overview of screening, prevention, services, legislation, and epidemiology. Pediatrics 2007;120 Suppl 1:S1-55.
Capps FP, Gilles HM, Jolly H, Worlledge SM. Glucose-6-phosphate dehydrogenase deficiency and neonatal jaundice in Nigeria: Their relation to the use of prophylactic vitamin K. Lancet 1963;2:379-83.
Effiong CE, Aimaku VE, Bienzle U, Oyedeji GA, Ikpe DE. Neonatal jaundice in Ibadan. Incidence and etiologic factors in babies born in hospital. J Natl Med Assoc 1975;67:208-13.
Azubuike JC. Neonatal jaundice in Eastern Nigeria. J Trop Pediatr 1985;31:82-4.
Okolo AA, Omene JA. Trends in neonatal mortality in Benin City, Nigeria. Int J Gynaecol Obstet 1985;23:191-5.
Ahmed H, Yukubu AM, Hendrickse RG. Neonatal jaundice in Zaria, Nigeria – A second prospective study. West Afr J Med 1995;14:15-23.
Olusanya BO, Emokpae AA, Zamora TG, Slusher TM. Addressing the burden of neonatal hyperbilirubinaemia in countries with significant glucose-6-phosphate dehydrogenase deficiency. Acta Paediatr 2014;103:1102-9.
Kaplan M, Slusher T, Renbaum P, Essiet DF, Pam S, Levy-Lahad E, et al.
UDP-glucuronosyltransferase 1A1 promoter polymorphism in Nigerian neonates. Pediatr Res 2008;63:109-11.
Chang PF, Lin YC, Liu K, Yeh SJ, Ni YH. Risk of hyperbilirubinemia in breast-fed infants. J Pediatr 2011;159:561-5.
Olusanya BO, Ezeaka CV, Ajayi-Obe EK, Mukhtar-Yola M, Ofovwe GE. Paediatricians' perspectives on global health priorities for newborn care in a developing country: A national survey from Nigeria. BMC Int Health Hum Rights 2012;12:9.
Arksey H, O'Malley L. Scoping studies: Towards a methodological framework. Int J Soc Psychiatry Res Methodol 2005;8:19-32.
Gough D, Thomas J, Oliver S. Clarifying differences between review designs and methods. Syst Rev 2012;1:28.
Joffe H. Thematic analysis. In: Harper D, Thompson AR, editors. Qualitative Research Methods in Mental Health and Psychotherapy: A Guide for Students and Practitioners. Ch. 15. UK: John Wiley and Sons, Ltd.; 2011. p. 209-23.
Vaismoradi M, Turunen H, Bondas T. Content analysis and thematic analysis: Implications for conducting a qualitative descriptive study. Nurs Health Sci 2013;15:398-405.
McGillivray A, Evans N. Severe neonatal jaundice: Is it a rare event in Australia? J Paediatr Child Health 2012;48:801-7.
Gotink MJ, Benders MJ, Lavrijsen SW, Rodrigues Pereira R, Hulzebos CV, Dijk PH. Severe neonatal hyperbilirubinemia in the Netherlands. Neonatology 2013;104:137-42.
Olusanya BO, Osibanjo FB, Slusher TM. Risk factors for severe neonatal hyperbilirubinemia in low and middle-income countries: A systematic review and meta-analysis. PLoS One 2015;10:e0117229.
Olusanya BO, Slusher TM. Infants at risk of significant hyperbilirubinemia in poorly resourced countries: Evidence from a scoping review. World J Pediatr 2015;11:293-9.
Obi JO. Analysis of paediatric medical cases admitted to Children's Clinic Benin City. Niger Med J 1976;6:69-73.
Diakparomre MA, Obi JO. The pattern of paediatrics emergencies in the University of Benin Teaching Hospital. Niger J Paediatr 1980;7:43-5.
Dunmade AD, Segun-Busari S, Olajide TG, Ologe FE. Profound bilateral sensorineural hearing loss in Nigerian children: any shift in etiology? J Deaf Stud Deaf Educ 2007;12:112-8.
Olusanya BO, Okolo AA. Adverse perinatal conditions in hearing-impaired children in a developing country. Paediatr Perinat Epidemiol 2006;20:366-71.
Olusanya BO, Wirz SL, Luxon LM. Factors associated with auditory neuropathy/dys-synchrony in a developing country. Audiol Med 2008;6:120-128.
National Population Commission (NPC) [Nigeria] and ICF Macro. Nigeria Demographic and Health Survey 2008. Abuja, Nigeria: National Population Commission and ICF Macro; 2009.
American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297-316.
Olusanya BO, Ogunlesi TA, Kumar P, Boo NY, Iskander IF, de Almeida MF, et al.
Management of late-preterm and term infants with hyperbilirubinaemia in resource-constrained settings. BMC Pediatr 2015;15:39.
Bhutani VK, Cline BK, Donaldson KM, Vreman HJ. The need to implement effective phototherapy in resource-constrained settings. Semin Perinatol 2011;35:192-7.
Olowe SA. Sunshine phototherapy cot: Utilization of sunlight for phototherapy. Niger J Paediatr 1985;12:69-70.
Slusher TM, Olusanya BO, Vreman HJ, Brearley AM, Vaucher YE, Lund TC, et al
. A randomized trial of filtered sunlight phototherapy in African neonates. N Engl J Med 2015;373:1115-24.
Macgregor M. Paediatrics in Western Nigeria. Arch Dis Child 1958;33:277-91.
Hendrickse RG. Aspects of tropical paediatrics. Trans R Soc Trop Med Hyg 1976;70:268-73.
Hendrickse RG. M for Misery: An account of some major pediatric problems in Nigeria. Clin Pediatr 1966;5:315-21.
GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;385:117-71.
WHO Working Group. Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ 1989;67:601-11.
Ogunlesi TA. Managing neonatal jaundice at the general practice and primary health care level: An overview. Niger J Paediatr 2004;31:33-8.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table S1]
|This article has been cited by|
||The spectrum of bilirubin neurotoxicity in term and near-term babies with hyperbilirubinemia: Does outcome improve with time?
| ||Sarah S. ElTatawy,Esraa A. Elmazzahy,Amira M. El Shennawy,Hanan A. Madani,Hazem Abou Youssef,Iman F. Iskander |
| ||Early Human Development. 2020; 140: 104909 |
|[Pubmed] | [DOI]|
||Use of serum bilirubin/albumin ratio for early prediction of bilirubin induced neurological dysfunction
| ||Dalia Mosallam,Reem N. Said,Marwa A. Abd Elsamad,Nada M. Abdelfatah |
| ||Egyptian Pediatric Association Gazette. 2019; 67(1) |
|[Pubmed] | [DOI]|
||Comparative outcome of overhead and total body phototherapy for treatment of severe neonatal jaundice in Nigeria
| ||Hippolite O. Amadi,Ruqayya A. Abdullahi,Olugbenga A. Mokuolu,Obumneme B. Ezeanosike,Christiana T. Adesina,Isyaku L. Mohammed,Eyinade K. Olateju,Amina L. Abubakar,Mustapha A. Bello,Augusta U. Eneh,Emeka Onwe Ogah,Bessie C. Eziechila,Assumpta U. Chapp-Jumbo,Abdulrasheed Jimoh,Jacob J. Udo |
| ||Paediatrics and International Child Health. 2019; : 1 |
|[Pubmed] | [DOI]|
||Indirect neonatal hyperbilirubinemia in hospitalized neonates on the Thai-Myanmar border: a review of neonatal medical records from 2009 to 2014
| ||L. Thielemans,M. Trip-Hoving,J. Landier,C. Turner,T. J. Prins,E. M. N. Wouda,B. Hanboonkunupakarn,C. Po,C. Beau,M. Mu,T. Hannay,F. Nosten,B. Van Overmeire,R. McGready,V. I. Carrara |
| ||BMC Pediatrics. 2018; 18(1) |
|[Pubmed] | [DOI]|
||Filtered sunlight versus intensive electric powered phototherapy in moderate-to-severe neonatal hyperbilirubinaemia: a randomised controlled non-inferiority trial
| ||Tina M Slusher,Hendrik J Vreman,Ann M Brearley,Yvonne E Vaucher,Ronald J Wong,David K Stevenson,Olumide T Adeleke,Ifelayo P Ojo,Grace Edowhorhu,Troy C Lund,Daniel A Gbadero |
| ||The Lancet Global Health. 2018; 6(10): e1122 |
|[Pubmed] | [DOI]|
||Humanized UGT1 Mice, Regulation of UGT1A1, and the Role of the Intestinal Tract in Neonatal Hyperbilirubinemia and Breast Milk-Induced Jaundice
| ||Shujuan Chen,Robert H. Tukey |
| ||Drug Metabolism and Disposition. 2018; 46(11): 1745 |
|[Pubmed] | [DOI]|
||Factors influencing irradiance of locally fabricated phototherapy devices in Jos, north-central Nigeria
| ||Udochukwu M Diala,Akinyemi OD Ofakunrin,Bose O Toma,David D Shwe,Christopher S Yilgwan,Fidelia Bode-Thomas |
| ||Tropical Doctor. 2018; 48(2): 142 |
|[Pubmed] | [DOI]|
||Newborn screening of glucose-6-phosphate dehydrogenase deficiency in Guangxi, China: determination of optimal cutoff value to identify heterozygous female neonates
| ||Chunyun Fu,Shiyu Luo,Qifei Li,Bobo Xie,Qi Yang,Guoxing Geng,Caijuan Lin,Jiasun Su,Yue Zhang,Jin Wang,Zailong Qin,Jingsi Luo,Shaoke Chen,Xin Fan |
| ||Scientific Reports. 2018; 8(1) |
|[Pubmed] | [DOI]|
||Patterns of acute bilirubin encephalopathy in Nigeria: a multicenter pre-intervention study
| ||Udochukwu M Diala,Richard P Wennberg,Isa Abdulkadir,Zubaida L Farouk,Carlos D. Coda Zabetta,Efe Omoyibo,Abieyuwa Emokpae,Aleksandr Aravkin,Bose Toma,Stephen Oguche,Tina Slusher |
| ||Journal of Perinatology. 2018; |
|[Pubmed] | [DOI]|
||Follow-up of Children with Kernicterus in Kano, Nigeria
| ||Zubaida Ladan Farouk,Abdussalam Muhammed,Safiya Gambo,Maria Mukhtar-Yola,Shehu Umar Abdullahi,Tina M. Slusher |
| ||Journal of Tropical Pediatrics. 2017; |
|[Pubmed] | [DOI]|
||Use of Transcutaneous Bilirubin to Determine the Need for Phototherapy in Resource-Limited Settings
| ||Bolajoko O. Olusanya,Abieyuwa A. Emokpae |
| ||Neonatology. 2017; 111(4): 324 |
|[Pubmed] | [DOI]|
||Clinical presentation and management of dyskinetic cerebral palsy
| ||Elegast Monbaliu,Kate Himmelmann,Jean-Pierre Lin,Els Ortibus,Laura Bonouvriť,Hilde Feys,R Jeroen Vermeulen,Bernard Dan |
| ||The Lancet Neurology. 2017; 16(9): 741 |
|[Pubmed] | [DOI]|
||Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia
| ||Shujuan Chen,Wenqi Lu,Mei-Fei Yueh,Eva Rettenmeier,Miao Liu,Johan Auwerx,Ruth T. Yu,Ronald M. Evans,Kepeng Wang,Michael Karin,Robert H. Tukey |
| ||Proceedings of the National Academy of Sciences. 2017; 114(8): E1432 |
|[Pubmed] | [DOI]|
||Maternal detection of neonatal jaundice during birth hospitalization using a novel two-color icterometer
| ||Bolajoko O. Olusanya,Tina M. Slusher,Donald O. Imosemi,Abieyuwa A. Emokpae,Edgardo Szyld |
| ||PLOS ONE. 2017; 12(8): e0183882 |
|[Pubmed] | [DOI]|
||The authors reply
| ||Bolajoko O. Olusanya,Cecilia A. Mabogunje,Abieyuwa A. Emokpae |
| ||Pediatric Critical Care Medicine. 2016; 17(7): 705 |
|[Pubmed] | [DOI]|
||Insight into the metabolic mechanism of scoparone on biomarkers for inhibiting Yanghuang syndrome
| ||Heng Fang,Aihua Zhang,Jingbo Yu,Liang Wang,Chang Liu,Xiaohang Zhou,Hui Sun,Qi Song,Xijun Wang |
| ||Scientific Reports. 2016; 6: 37519 |
|[Pubmed] | [DOI]|
||Predictors of Repeat Exchange Transfusion for Severe Neonatal Hyperbilirubinemia*
| ||Cecilia A. Mabogunje,Abieyuwa A. Emokpae,Bolajoko O. Olusanya |
| ||Pediatric Critical Care Medicine. 2016; 17(3): 231 |
|[Pubmed] | [DOI]|