Patterns of acute bilirubin encephalopathy in Nigeria: a multicenter pre-intervention study.

BACKGROUND: Acute bilirubin encephalopathy (ABE) is an important cause of neonatal morbidity in Nigeria, accounting for 5-14% of neonatal deaths. Most newborns with severe ABE have irreversible damage before receiving treatment emphasizing the need for timely pre-admission monitoring and referral. There is limited evidence that educational interventions targeting mothers and health care providers will reduce delayed care. OBJECTIVE: To provide baseline data on the incidence of ABE and associated pre-admission risk factors in five centers of Nigeria in order to evaluate the effect of subsequent educational interventions on outcome. STUDY DESIGN: The incidence of ABE among newborns treated for hyperbilirubinemia was documented prospectively. Bivariate analysis and multivariate logistic regression were used to evaluate risk factors for acute bilirubin encephalopathy and reasons for regional differences in its occurrence. RESULTS: Of 1040 infants, 159 treated for hyperbilirubinemia (15.3%) had mild to severe bilirubin encephalopathy (including 35 deaths), but the incidence ranged from 7 to 22% between centers. Logistic regression identified four common predictors: total serum bilirubin (odds ratio 1.007 per mg/dl rise), out-of-hospital births (OR 2.6), non-alloimmune hemolytic anemia (OR 2.8), and delayed care seeking (OR 4.3). CONCLUSION: The high occurrence of bilirubin encephalopathy in Nigeria is due in large part to a delay in seeking care. A planned intervention strategy will target conditions leading to severe hyperbilirubinemia and delay.

A neurologic dysfunction scoring protocol for jaundiced neonates requiring exchange transfusion.

AIM: To evaluate the performance of a neurologic assessment protocol among jaundiced infants requiring exchange transfusion (ET). METHODS: We identified infants in a referral children's hospital who received ET and those who met the American Academy of Pediatrics (AAP) criteria for ET based on total serum bilirubin (TSB) levels. The performance of a bilirubin-induced neurologic dysfunction (BIND-M) scoring protocol for acute bilirubin encephalopathy (ABE) in detecting infants treated with ET in both groups was investigated by logistic regression analysis and c-statistic. RESULTS: A total of 438 late-preterm and term infants were enrolled, out of which 141 (32.2%) received ET, and 155 (35.4%) met AAP criteria for ET. Infants with BIND-M scores of 3-6 (intermediate ABE) or 7-12 (advanced ABE) were significantly associated with ET in both groups, but not scores of 1-2 (mild ABE), with or without adjustment for confounding neurotoxicity risk factors. However, the discriminatory ability of BIND-M regression models was modestly satisfactory (c-statistic range: 0.693-0.791). CONCLUSIONS: Our findings suggest that BIND-M is a potentially useful decision-making tool for ET and support current recommendation for immediate ET for infants with intermediate-to-advanced stages of ABE regardless of the TSB levels.

Maternal detection of neonatal jaundice during birth hospitalization using a novel two-color icterometer.

BACKGROUND: Mothers are frequently the first to observe the onset of jaundice in their newborn infants before the decision to seek treatment. However, simple-to-use tools that could facilitate early detection of jaundice and assist mothers to seek professional care, especially after hospital discharge, are rare. This study therefore, set out to evaluate the performance of a -two-color icterometer (Bilistrip™) as a possible screening tool for detecting significant jaundice by mothers or care-givers in the first week of life. METHODS: Prior to discharge, mothers in a maternity hospital were trained to use the Bilistrip™ on the blanched skin of their baby's nose to ascertain absence (Light Yellow) or presence (Dark Yellow) of significant jaundice. Their babies had transcutaneous bilirubin (TcB) measurements independently, along with total serum bilirubin (TSB) if indicated. The reliability of Bilistrip™ as a screening test for significant jaundice was determined at different TcB and TSB thresholds. The predictive performance of Bilistrip™ was also evaluated with multivariable logistic regression. RESULTS: Some 2492 mother-infant pairs were enrolled over 15 months, of which 347 (13.9%) chose Dark Yellow. The mean TcB for Dark Yellow (10mg/dL) was significantly higher (p<0.001) than for Light Yellow (6.1mg/dL). Bilistrip™ showed increasing sensitivity (47.0% - 92.6%) and negative predictive value (NPV) (91.4% - 99.9%) for selected TcB thresholds (≥10mg/dL, ≥12mg/dL, ≥15mg/dL, and ≥17mg/dL). Among neonates with TSB measurements (n = 124), Bilistrip™ was associated also with increasing sensitivity (86.8% - 100%) and NPV (62.5% - 100%). The sensitivity and NPV for detecting neonates requiring phototherapy were 95.8% respectively. Only one of the 24 neonates who required phototherapy was missed by the Bilistrip™. CONCLUSIONS: Bilistrip™ is a potential decision-making tool for empowering mothers to detect neonates with clinically significant jaundice that may require close monitoring or treatment, and neonates not requiring treatment for jaundice in the first week of life.

Severe neonatal hyperbilirubinaemia is frequently associated with long hospitalisation for emergency care in Nigeria.

AIM: This study investigated the frequency and predictors of a long hospital stay (LHS) for severe neonatal hyperbilirubinaemia in Nigeria. METHODS: Length of stay (LOS) for severe hyperbilirubinaemia was examined among neonates consecutively admitted to the emergency department of a children's hospital in Lagos from January 2013 to December 2014. The median LOS was used as the cut-off for LHS. Multivariate logistic regression determined the independent predictors of LHS based on demographic and clinical factors significantly associated with the log-transformed LOS in the bivariate analyses. RESULTS: We enrolled 622 hyperbilirubinaemic infants with a median age of four days (interquartile range 2-6 days) and 276 (44.4%) had LHS based on the median LOS of five days. Regardless of their birth place, infants were significantly more likely to have LHS if they were admitted in the first two days of life (p = 0.008) - especially with birth asphyxia - or had acute bilirubin encephalopathy (p = 0.001) and required one (p = 0.020) or repeat (p = 0.022) exchange transfusions. Infants who required repeat exchange transfusions had the highest odds for LHS (odds ratio 4.98, 95% confidence interval 1.26-19.76). CONCLUSION: Severe hyperbilirubinaemia was frequently associated with long hospitalisation in Nigeria, especially if neonates had birth asphyxia or required exchange transfusions.

Transcutaneous bilirubin nomograms in African neonates.

BACKGROUND: The use of transcutaneous bilirubin (TcB) as a screening tool, based on relevant population-specific nomogram, or proxy for total serum bilirubin (TSB) levels in assessing the risk of subsequent hyperbilirubinemia is supported by several clinical guidelines on the management of neonatal hyperbilirubinemia. However, while TcB has been found to significantly over-estimate TSB in neonates of African-American ancestry, with variations across TcB devices, no nomogram has been specifically reported for this racial group. This study therefore set out to develop TcB nomograms for healthy late pre-term and term black African neonates derived from two widely used bilirubinometers. METHODS: A retrospective analysis of 12,377 TcB measurements obtained from 6,373 neonates in the first postnatal week, over a period of 48 months using Bilichek and JM-103 bilirubinometers. TcB percentiles were computed from hour-specific TcB values and nomograms developed for each of the screening devices. Predictive ability of the 75th and 95th percentiles to detect significant hyperbilirubinemia was evaluated between 24-96 hours of age. The 95th percentile curve was compared with those from other populations. RESULTS: The velocity of TcB rise at 75th and 95th percentiles was generally higher with JM-103 than Bilichek. Both percentiles also peaked at higher TcB levels with JM-103. The 95th percentile for both instruments showed a downward trend as from approximately 114 hours. Both instruments had high negative predictive values across the selected time-epochs and lower discriminatory ability than reported in non-black populations. CONCLUSIONS: The predictive utility of TcB as a potential screening tool varies across devices in black African neonates with or without risk of significant hyperbilirubinemia, and lower than levels reported in non-black populations. Equipment-specific nomograms should be considered for TcB monitoring in this racial population where TSB is not routinely available.

Use of Transcutaneous Bilirubin to Determine the Need for Phototherapy in Resource-Limited Settings.

BACKGROUND: Routine and timely determination of total serum bilirubin (TSB) remains a challenge in many resource-limited countries with substantial burden of severe neonatal hyperbilirubinemia. Limited evidence exists on the potential usefulness of transcutaneous bilirubin (TcB) to identify infants who may require phototherapy based on possible treatment criteria in such settings. OBJECTIVE: To compare the number of infants requiring phototherapy across different TSB criteria and determine the predictive performance of TcB under each criterion. METHODS: Infants with paired TcB and TSB measurements in a maternity hospital in Lagos, Nigeria, were assessed for phototherapy based on TSB criteria by the American Academy of Pediatrics (AAP), National Institute for Health and Clinical Excellence (NICE) UK, and World Health Organization (WHO), and an absolute threshold of ≥12 mg/dL. The predictive performance of TcB across treatment criteria was evaluated with receiver operating curve analysis. RESULTS: A total of 1,011 infants with a mean TcB of 10.54 ± 3.19 (range: 2.7-19.9) mg/dL and TSB of 9.63 ± 2.61 (range: 0.3-19.5) mg/dL were assessed. Some 60 (5.9%) infants required phototherapy by 1 or more TSB criteria, with TSB ≥12 mg/dL identifying 55 (91.7%) and AAP 27 (45%) of these infants. All infants identified by the NICE and WHO criteria were equally detected by the AAP criterion. TcB showed negative predictive values of 99.0-99.9%, and positive predictive values of 7.7-15.5% across all criteria. CONCLUSIONS: The number of infants requiring phototherapy varies significantly across treatment criteria. TcB may be useful in identifying infants who do not require phototherapy, but may also identify a high proportion of false positives that is burdensome in resource-limited settings.

Differences Between Transcutaneous and Serum Bilirubin Measurements in Black African Neonates.

BACKGROUND AND OBJECTIVE: Transcutaneous bilirubin (TcB) correlates positively with total serum bilirubin (TSB) across different racial populations. However, little is known about the pattern of divergence between TcB and TSB at individual patient-level and the relationship with TcB measuring techniques among African neonates. This study, therefore, investigates TcB-TSB discrepancies and the contribution of 2 models of transcutaneous bilirubinometers to the observed divergence in a black African population. METHODS: Medical records were retrieved for late preterm and term infants with 1 to 3 pairs of TcB and TSB measurements between December 2011 to June 2015 in Nigeria. Divergence between TcB and TSB values for each infant was determined and the associated factors explored with generalized estimating equations for logistic regression. Contributions of BiliChek and JM-103 transcutaneous bilirubinometers to the divergence were further explored through linear regression and Bland-Altman analysis. RESULTS: Overall, 2107 TcB/TSB measurements from 1553 infants were analyzed. TSB was overestimated by ≥2 mg/dL in 64.5%, ≥3 mg/dL in 42.7%, and ≥4 mg/dL in 25.7% of all measurements. In contrast, TSB was underestimated by ≥2 mg/dL in 1.1%, ≥3 mg/dL in 0.5%, and ≥4 mg/dL in 0.3% of all recordings. Postnatal age, feeding mode, and type of TcB instrument were predictive of TSB overestimation. The JM-103 was associated with greater imprecision than BiliChek at all TSB levels. CONCLUSIONS: BiliChek and JM-103 bilirubinometers significantly overestimate TSB in black African neonates and may result in unnecessary or excessive treatments. Additional development of appropriate bilirubin determination devices for this racial group, especially in resource-limited settings, is warranted.

Irradiance Decay in Fluorescent and Light-emitting Diode-based Phototherapy Devices: A Pilot Study.

We set out to determine the rate of decline of irradiance for fluorescent tube (FT) and light-emitting diode (LED) phototherapy devices in resource-limited settings where routine irradiance monitoring is uncommon. Irradiance levels (µW/cm(2)/nm) were measured weekly using BiliBlanket(®) II Meter on three FT-based and two LED-based phototherapy devices over a 19 week period. The two LED devices showed stable irradiance levels and did not require any lamp changes. The three FT-based devices showed rapid decline in irradiance, and all required three complete lamp exchanges approximately every 5-6 weeks. FT-based devices are associated with more rapid decline in irradiance to sub-therapeutic levels and require more frequent lamp changes than LED devices. Clinicians should be alert to the maintenance requirements of the phototherapy devices available in their settings to ensure efficacy of treatment.

Heliotherapy for Neonatal Hyperbilirubinemia in Southwest, Nigeria: A Baseline Pre-Intervention Study.

BACKGROUND: A novel filtered-sunlight phototherapy (FSPT) device has been demonstrated to be safe and efficacious for treating infants with neonatal jaundice in resource-constrained tropical settings. We set out to provide baseline data for evaluating the clinical impact of this device in a referral pediatric hospital. METHODS: We reviewed the medical records of infants admitted for neonatal hyperbilirubinemia in an inner-city Children's Hospital in Lagos, between January 2012 and December 2014 to determine the pattern, treatment and outcomes during the pre-intervention period. Factors associated with adverse outcomes were identified through multivariable logistic regression. RESULTS: Of the 5,229 neonatal admissions over the period, a total of 1,153 (22.1%) were admitted for neonatal hyperbilirubinemia. Complete records for 1,118 infants were available for analysis. The incidence of acute bilirubin encephalopathy (ABE) and exchange transfusion (ET) were 17.0% (95% CI: 14.9%-19.3%) and 31.5% (95% CI: 28.8%-34.3%) respectively. A total of 61 (5.5%, 95% CI: 4.3%-6.9%) of the jaundiced infants died. Weight on admission, peak total serum bilirubin (TSB), sepsis and exposure to hemolytic products were predictive of ABE, while age on admission, peak TSB, ABO incompatibility and ABE were predictive of ET. Rhesus incompatibility, asphyxia, exposure to hemolytic substances and ABE were associated with elevated mortality risk, while ET was a protective factor. Lack of routine irradiance monitoring and steady energy supply were frequent challenges for conventional blue-light phototherapy. CONCLUSIONS: Severe hyperbilirubinemia is associated with high rates of ABE and ET in this setting, and remains a significant contributor to neonatal admissions and mortality. To be impactful, FSPT, complemented with improved diagnostic facilities, should effectively curtail jaundice-related adverse outcomes in this and comparable settings.

Predictors of Repeat Exchange Transfusion for Severe Neonatal Hyperbilirubinemia.

OBJECTIVES: To identify the predictors of repeat exchange transfusion among infants with severe hyperbilirubinemia. DESIGN: Retrospective cross-sectional study. SETTING: A referral children's hospital in inner-city Lagos, Nigeria. PATIENTS: Infants who received exchange transfusion for severe hyperbilirubinemia from January 2012 to December 2014. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The predictors of repeat exchange transfusion were identified among all infants who had at least one exchange transfusion using multivariable logistic regression. A total of 352 infants with mean peak total serum bilirubin of 26.32 ± 7.96 mg/dL received exchange transfusion; of these, 49 (13.9%) with mean peak total serum bilirubin of 32.85 ± 10.54 mg/dL had repeat exchange transfusion. More than two thirds of infants who received exchange transfusion and repeat exchange transfusion were male, and at least one third had ABO incompatibility. No infant had more than two exchange transfusions. The mean age of admission was approximately 5 days (range, 1-14 d). Peak total serum bilirubin greater than or equal to 30 mg/dL (odds ratio, 2.88; 95% CI, 1.46-5.70) and acute bilirubin encephalopathy (odds ratio, 2.37; 95% CI, 1.18-4.77) were predictive of repeat exchange transfusion. CONCLUSIONS: Acute bilirubin encephalopathy and excessive total serum bilirubin levels at least 30 mg/dL are predictive of repeat exchange transfusion. A risk assessment framework that combines total serum bilirubin levels, acute bilirubin encephalopathy status, and risk factors of neurotoxicity should be considered for the timely detection and monitoring of infants at risk of repeat exchange transfusion.

Revisiting the Criteria for Exchange Transfusion for Severe Neonatal Hyperbilirubinemia in Resource-Limited Settings.

BACKGROUND: Exchange transfusion (ET) for severe neonatal hyperbilirubinemia (SNH) is frequently undertaken in low- and middle-income countries (LMIC), in sharp contrast to the prevailing practice in high-income countries. However, the criteria for initiating this procedure in settings with limited resources for treating infants with SNH have not been systematically explored. OBJECTIVE: To identify key considerations for initiating ET in resource-poor countries to curtail its unnecessary use for the prevention of kernicterus. METHODS: A review of the existing guidelines and literature on the management of neonatal hyperbilirubinemia worldwide was conducted to identify criteria and underlying factors for initiating ET. RESULTS: There is a dearth of evidence from randomized clinical trials to support clear criteria for indicated ET worldwide. Because risk assessment for kernicterus based solely on the levels of total serum bilirubin (TSB) has often proved inadequate, a combination of plasma/serum bilirubin estimation and clinical evaluation for acute bilirubin encephalopathy (ABE) has been recommended for predicting the risk of kernicterus. However, there is a lack of consistency regarding the TSB levels for which ET should be initiated in relation to the clinical signs/symptoms of ABE and hemolytic disorders. CONCLUSIONS: A decision-making framework that combines TSB thresholds and evidence of neurotoxicity is needed for evaluating the risk of kernicterus and prioritising infants for ET in LMICs to curtail unnecessary interventions.

A Randomized Trial of Phototherapy with Filtered Sunlight in African Neonates.

BACKGROUND: Sequelae of severe neonatal hyperbilirubinemia constitute a substantial disease burden in areas where effective conventional phototherapy is unavailable. We previously found that the use of filtered sunlight for the purpose of phototherapy is a safe and efficacious method for reducing total bilirubin. However, its relative safety and efficacy as compared with conventional phototherapy are unknown. METHODS: We conducted a randomized, controlled noninferiority trial in which filtered sunlight was compared with conventional phototherapy for the treatment of hyperbilirubinemia in term and late-preterm neonates in a large, urban Nigerian maternity hospital. The primary end point was efficacy, which was defined as a rate of increase in total serum bilirubin of less than 0.2 mg per deciliter per hour for infants up to 72 hours of age or a decrease in total serum bilirubin for infants older than 72 hours of age who received at least 5 hours of phototherapy; we prespecified a noninferiority margin of 10% for the difference in efficacy rates between groups. The need for an exchange transfusion was a secondary end point. We also assessed safety, which was defined as the absence of the need to withdraw therapy because of hyperthermia, hypothermia, dehydration, or sunburn. RESULTS: We enrolled 447 infants and randomly assigned 224 to filtered sunlight and 223 to conventional phototherapy. Filtered sunlight was efficacious on 93% of treatment days that could be evaluated, as compared with 90% for conventional phototherapy, and had a higher mean level of irradiance (40 vs. 17 µW per square centimeter per nanometer, P<0.001). Temperatures higher than 38.0°C occurred in 5% of the infants receiving filtered sunlight and in 1% of those receiving conventional phototherapy (P<0.001), but no infant met the criteria for withdrawal from the study for reasons of safety or required an exchange transfusion. CONCLUSIONS: Filtered sunlight was noninferior to conventional phototherapy for the treatment of neonatal hyperbilirubinemia and did not result in any study withdrawals for reasons of safety. (Funded by the Thrasher Research Fund, Salt Lake City, and the National Center for Advancing Translational Sciences of the National Institutes of Health; Clinical Trials.gov number, NCT01434810.).

How are children with HIV faring in Nigeria?--a 7 year retrospective study of children enrolled in HIV care.

BACKGROUND: To review the pediatric care and treatment program at Massey Street Children Hospital, in Lagos, Nigeria a retrospective analysis of medical records focusing on health services, survival and retention in care. METHODS: The analysis covered a cohort of children initiated on antiretroviral therapy (ART) from 2005 to 2011. In this population, pediatric HIV care was defined as initiating ART between ages 0 and 14 years. Treatment initiation and follow-up were according to the Nigerian national guidelines for pediatric ART, which are based on World Health Organization guidelines adapted to our local context. The primary endpoint was mortality measured as cumulative survival. Other outcomes of interest included "loss to follow-up", "transferred out", and "stopped treatment". RESULTS: Mean (SD) age at ART initiation was 51 (39) months in female children and 52 (42) months in male children. After seven years of ART care, 64% of the 660 study children were retained in care and on treatment, 16% were lost to follow-up, 10% were dead, and 9% had discontinued HIV care at this facility for other reasons. World Health Organization disease stage, CD4 count, age, and year of ART initiation were highly predictive of mortality, while anemia at baseline was not statistically significantly associated. CONCLUSIONS: Overall study results suggest a viable pediatric HIV program exists at the study facility. Retention rates were lowest for the earliest cohort of infected children, which implies long-term challenges. Mother-to-child transmission programs need to be dynamic to stem the scourge of pediatric HIV in Nigeria.

Maternal satisfaction with a novel filtered-sunlight phototherapy for newborn jaundice in Southwest Nigeria.

BACKGROUND: In many resource-limited settings, the availability of effective phototherapy for jaundiced infants is frequently hampered by lack of, or inadequate resources to acquire and maintain conventional electric-powered phototherapy devices. This study set out to ascertain maternal experience and satisfaction with a novel treatment of infants with significant hyperbilirubinemia using filtered sunlight phototherapy (FSPT) in a tropical setting with irregular access to effective conventional phototherapy. METHODS: A cross-sectional satisfaction survey was conducted among mothers of jaundiced infants treated with FSPT in an inner-city maternity hospital in Lagos, Nigeria from November 2013 to March 2014. Mothers' experience during treatment was elicited with a pretested questionnaire consisting of closed and open-ended items. Satisfaction was rated on a five-point Likert scale. Correlates of overall maternal satisfaction were explored with descriptive and inferential non-parametric statistics. RESULTS: A total of 191 mothers were surveyed, 77 (40%) of whom had no prior knowledge of neonatal jaundice. Maternal satisfaction was highest for quality of nursing care received (mean: 4.72 ± 0.55, median: 5[IQR: 5-5]) and lowest for physical state of the test environment (mean: 3.85 ± 0.74, median: 4[IQR: 3-4]). The overall rating (mean: 4.17 ± 0.58, median: 4[IQR: 4-5]) and the observed effect of FSPT on the babies (mean: 4.34 ± 0.58, 4[IQR: 4-5]) were quite satisfactory. FSPT experience was significantly correlated with the adequacy of information received (p < 0.0005), test environment (p = 0.002) and the observed effect of FSPT on the child (p < 0.0005). Almost all mothers (98.4%) indicated willingness to use FSPT in future or recommend it to others, although some (30 or 15.7%) disliked the idea of exposing newborns to sunlight. CONCLUSIONS: Mothers of jaundiced newborns in this population are likely to be satisfied with FSPT where it is inevitable as an alternative to conventional electric-powered phototherapy. Adequate information, good test environment and friendly nursing care must be ensured for satisfactory maternal experience.

Addressing the burden of neonatal hyperbilirubinaemia in countries with significant glucose-6-phosphate dehydrogenase deficiency.

UNLABELLED: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an established worldwide risk factor for severe hyperbilirubinaemia. This literature review examined the pattern and management of severe hyperbilirubinaemia in low- and middle-income countries (LMICs) where G6PD deficiency was 10% or more and found that it was frequently associated with neonatal mortality and, or, neurodevelopmental disorders. CONCLUSION: Low- and middle-income countries need to pay urgent attention to G6PD deficiency to curtail the preventable burden of jaundice-related morbidity, mortality and disability.