post-menstrual age. At discharge, automated auditory brainstem response (ABR) for both ears was r... more post-menstrual age. At discharge, automated auditory brainstem response (ABR) for both ears was referred. Magnetic resonance imaging at age 2 yrs indicated increased signals in the globus pallidus and signs of periventricular leukomalacia. Her neurologic examination showed signs of kernicterus and hearing impairment.
Articles Translational Investigation nature publishing group Background: Bilirubin binding capaci... more Articles Translational Investigation nature publishing group Background: Bilirubin binding capacity (BBC) defines the dynamic relationship between an infant's level of unbound or "free" bilirubin and his/her ability to "tolerate" increasing bilirubin loads. BBC is not synonymous with albumin (Alb) levels because Alb binding of bilirubin is confounded by a variety of molecular, biologic, and metabolic factors. Methods: We utilized a novel modification of a previously developed hematofluorometric method to directly assay BBC in whole blood from preterm and term neonates and then combined these data with an archived database. Total bilirubin (TB) was also measured, and multiple regression modeling was used to determine whether BBC in combination with TB measurements can assess an infant's risk for developing bilirubininduced neurotoxicity. results: TB and BBC levels ranged from 0.7-22.8 to 6.3-47.5 mg/dl, respectively. Gestational age (GA) correlated with BBC (r = 0.54; P < 0.0002) with a slope of 0.93 mg/dl/wk by logistic regression. Our calculations demonstrate that recently recommended GA-modulated TB thresholds for phototherapy and exchange transfusion correspond to 45 and 67% saturation of our observed regression line, respectively. conclusion: We speculate that the spread of BBC levels around the regression line (±5.8 mg/dl) suggests that individualized BBC assays would provide a robust approach to gauge risk of bilirubin neurotoxicity compared with TB and GA.
Participants: 156 children aged 65-117 months. Methods: After randomization, INDT-ADHD and Connor... more Participants: 156 children aged 65-117 months. Methods: After randomization, INDT-ADHD and Connor's 3 Parent Rating Scale (C3PS) were administered, followed by an expert evaluation by DSM-IV-TR diagnostic criteria. Main outcome measures: Psychometric evaluation of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency. Results: INDT-ADHD had 18 items that quantified symptoms and impairment. Attention deficit hyperactivity disorder was identified in 57, 87 and 116 children by expert evaluation, INDT-ADHD and C3PS, respectively. Psychometric parameters of INDT-ADHD for differentiating attention deficit hyperactivity disorder and normal children were: sensitivity 87.7%, specificity 97.2%, positive predictive value 98.0% and negative predictive value 83.3%, whereas for differentiating from other neuro-developmental disorders were 87.7%, 42.9%, 58.1% and 79.4%, respectively. Internal consistency was 0.91. INDT-ADHD has a 4-factor structure explaining 60.4% of the variance. Convergent validity with Conner's Parents Rating Scale was moderate (r =0.73, P= 0.001). Conclusions: INDT-ADHD is suitable for diagnosing attention deficit hyperactivity disorder in Indian children between the ages of 6 to 9 years.
A utism Spectrum Disorder (ASD) is widely recognized for many decades, yet there are no definitiv... more A utism Spectrum Disorder (ASD) is widely recognized for many decades, yet there are no definitive or universally accepted diagnostic criteria. [1]. Most diagnostic systems and measures consider ASD to be a 3-symptom cluster disorder with varying severity and etiology. This is reflected in the diagnostic systems of Diagnostic and Statistical Manual of Mental Disorders-IV Text Revision (DSM-IV TR) and International Classification of Diseases-10 (ICD-10), as well as the various measures that evolved from them [2,3]. However, the field trials of the draft version of Diagnostic and Statistical Manual of
Translational Investigation nature publishing group Background: The therapeutic phototherapy acti... more Translational Investigation nature publishing group Background: The therapeutic phototherapy action spectrum ranges from 420 to 500 nm. However, a recent report of improved efficacy of fluorescent "turquoise" light (~490 nm) as compared with blue light (~450 nm) underscores the need to define an optimal action spectrum for precision-targeted phototherapy using very narrow wavelength ranges. Methods: We used a current semi-empirical model of the optical properties of skin for robust calculations of the fraction of light absorbed by bilirubin at various wavelengths that could be confounded by hemoglobin (Hb), melanin, and skin thickness. Applying assumptions regarding the wavelength dependence of bilirubin photochemistry, "action spectra" were assembled from the calculated values. results: All the calculated action spectra displayed a peak between 472 and 480 nm (most at 476 nm), which is a significant shift from the well-reported 460 nm absorption peak of bilirubin. Of note, the relative amplitudes of the action spectra showed an inverse relationship with hematocrit (Hct). conclusion: We speculate that a narrow range of light at 476 nm would be 60% more effective than blue (broadband) fluorescent lamps. Because Hb serves as a major competitor of bilirubin for light absorption, the calculations also predict that the efficacy of phototherapy is dependent on the Hct. A high Hct could reduce therapeutic efficiency.
nature publishing group Background: Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) resu... more nature publishing group Background: Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden. Methods: Systematic reviews and meta-analyses were undertaken of national prevalence, mortality, and kernicterus due to Rh disease and EHB. We applied a compartmental model to estimate neonatal survivors and impairment cases for 2010. results: Twenty-four million (18% of 134 million live births ≥32 wk gestational age from 184 countries; uncertainty range: 23-26 million) were at risk for neonatal hyperbilirubinemiarelated adverse outcomes. Of these, 480,700 (0.36%) had either Rh disease (373,300; uncertainty range: 271,800-477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000-131,000), with a 24% risk for death (114,100; uncertainty range: 59,700-172,000), 13% for kernicterus (75,400), and 11% for stillbirths. Three-quarters of mortality occurred in sub-Saharan Africa and South Asia. Kernicterus with Rh disease ranged from 38, 28, 28, and 25/100,000 live births for Eastern Europe/Central Asian, sub-Saharan African, South Asian, and Latin American regions, respectively. More than 83% of survivors with kernicterus had one or more impairments. conclusion: Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries. n eonatal hyperbilirubinemia and jaundice occur in almost all newborns (1-10) and may be benign if its progression to extreme hyperbilirubinemia (EHB; total bilirubin (TB) >428 μmol/l in full-term babies) is recognized, monitored, and prevented or managed in a timely manner. Major risk factors include neonatal hemolysis (such as Rhesus (Rh) disease), glucose-6-phosphate dehydrogenase (G6PD) deficiency, infections, and an array of familial and genetic disorders. In addition to conditions such as preterm birth that make the neonate more susceptible to bilirubin neurotoxicity, suboptimal breast milk intake or dehydration may also contribute to EHB (1-10). At present, once the early stages of hyperbilirubinemic brain damage occur, therapeutic options are limited to the prompt (<8 h) use of exchange transfusion, hence the imperative for preventive approaches. Universal prenatal Rh screening for specific risk of perinatal hemolysis and its prophylaxis with Rh immunoglobulin have been highly effective practices for preventing neonatal morbidities and mortality (11-14). Countries with universal access to perinatal health services have virtually eliminated severe hyperbilirubinemia (icterus gravis neonatorum), which had been so common in the late 19th century (15-28). Now with emerging affordable technologies, the worldwide prevention and management of newborn jaundice can more feasibly reach those at risk even in low-income settings (1,2,29-31). Yet, there remains a paucity of quality population data on the prevalence of hyperbilirubinemia and related outcomes to inform such a strategy for most countries (8). In the absence of direct national or regional reporting, we report systematic estimates for the prevalence, mortality, and neurodevelopmental outcomes of Rh disease and EHB due to other causes, e.g., G6PD deficiency, prematurity, neonatal hemolysis, and idiopathic causes. We based these estimates, as
Kernicterus, thought to be due to severe hyperbilirubinemia, is an uncommon disorder with tragic ... more Kernicterus, thought to be due to severe hyperbilirubinemia, is an uncommon disorder with tragic consequences, especially when it affects healthy term and near-term infants. Early identification, prevention and treatment of severe hyperbilirubinemia should make kernicterus a preventable disease. However, national epidemiologic data are needed to monitor any preventive strategies. Recommendations are provided to obtain prospective data on the prevalence and incidence of severe hyperbilirubinemia and associate mortality and neurologic injury using standardized definitions, explore the clinical characteristics and root causes of kernicterus in children identified in the Kernicterus Pilot Registry, identify and test an indicator for population surveillance, validating systems-based approaches to the management of newborn jaundice, and explore the feasibility of using biologic or genetic markers to identify infants at risk for hyperbilirubinemia. Increased knowledge about the incidence and consequences of severe hyperbilirubinemia is essential to the planning, implementation and assessment of interventions to ensure that infants discharged as healthy from their birth hospitals have a safer transition to home, avoiding morbidity due to hyperbilirubinemia and other disorders. At a recent NIHCD-sponsored conference, key questions were raised about kernicterus and the need for additional strategies for its prevention. These questions and an approach to their answers form the basis of this report.
service for caregivers that will prove invaluable to physicians, midwives, nurses, ancillary memb... more service for caregivers that will prove invaluable to physicians, midwives, nurses, ancillary members of the healthcare team, and, most importantly, the parents of late preterm infants. The methodical approach to the evaluation and management of these neonates, thoroughly supported by up-to-date references, will serve as an ideal road map to improve the outcomes for these infants. I would urge all neonatal providers to carefully read this manual and adopt these carefully considered and clearly outlined strategic approaches to the care of the late preterm infant.
ABSTRAn. The mechanical properties of the newborn piglet gallbladder were evaluated in both the s... more ABSTRAn. The mechanical properties of the newborn piglet gallbladder were evaluated in both the stimulated and unstimulated states. The pressure-volume relationships, compliance, and the estimated active tension of the gallbladder were determined in 10 newborn piglets (2-7 days of age). Agonist stimulation was achieved by administration of histamine (25 pg/kg/h) and cholecystokinin (CCK) (60 ngjkglh). Both histamine and CCK increased the intracholecystic pressure at the 50% resting volume from 12.4 cm H z 0 to 18.9 and 15.5 cm H20, respectively. This resulted in a significant (p c 0.05) increase in the active tension. However, no significant changes were observed in the gallbladder compliance after stimulation. These findings characterize the mechanical properties of the normal neonatal gallbladder. The low magnitude of intracholecystic pressure response to agonist stimulation, when compared to adult data, may explain the occurrence of decreased neonatal choledochal bile flow.
To develop and validate a diagnostic tool for use by primary care physicians for diagnosing neuro... more To develop and validate a diagnostic tool for use by primary care physicians for diagnosing neuro-motor impairment among 2-9 year old children in primary care settings. Modified Delphi technique involving national (n=49) and international (n=6) experts was used for development of INDT-NMI. The tool was then validated through a cross sectional study. Neurology specialty clinics of three tertiary care pediatric centers in New Delhi, India. 454 children aged 2-9 years [mean (SD) age: 60.4 (23.7) mo], selected through systematic random sampling, underwent assessment for identification and classification of neuromotor impairments (NMI). All study subjects were first administered INDT-NMI (candidate test) by a trained physician followed by expert assessment for NMI and other neurodevelopment disorders (NDD) by team of two pediatric neurologists (Gold standard). According to expert evaluation, 171 (37.8%) children had neuromotor impairments. There were four categories of subjects: NMI alone (n=66); NMI+other NDDs (n=105); Other NDDs without NMI (n=225) and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Normal&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; group (n=58). Using expert evaluation as gold standard, overall sensitivity of the INDT-NMI was 75.4% and specificity was 86.8%. INDT-NMI helped graduate physicians to correctly classify 86.6% (112/129) children with NMI into different types (cerebral palsy, neuromotor diseases and other NMI). Graduate physicians assigned 40 children (8.8%) as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;indeterminate&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;, 38 (95%) of whom had either NDD and/or NMI and thus merited referral. Misclassification of NMI occurred in those with mild changes in muscle tone, dystonia, or ataxia and associated NDDs. Graduate primary care physicians with a structured short training can administer the new tool and diagnose NMI in 2-9 year old children with high validity. INDT-NMI requires further evaluation in actual primary care settings.
post-menstrual age. At discharge, automated auditory brainstem response (ABR) for both ears was r... more post-menstrual age. At discharge, automated auditory brainstem response (ABR) for both ears was referred. Magnetic resonance imaging at age 2 yrs indicated increased signals in the globus pallidus and signs of periventricular leukomalacia. Her neurologic examination showed signs of kernicterus and hearing impairment.
Articles Translational Investigation nature publishing group Background: Bilirubin binding capaci... more Articles Translational Investigation nature publishing group Background: Bilirubin binding capacity (BBC) defines the dynamic relationship between an infant's level of unbound or "free" bilirubin and his/her ability to "tolerate" increasing bilirubin loads. BBC is not synonymous with albumin (Alb) levels because Alb binding of bilirubin is confounded by a variety of molecular, biologic, and metabolic factors. Methods: We utilized a novel modification of a previously developed hematofluorometric method to directly assay BBC in whole blood from preterm and term neonates and then combined these data with an archived database. Total bilirubin (TB) was also measured, and multiple regression modeling was used to determine whether BBC in combination with TB measurements can assess an infant's risk for developing bilirubininduced neurotoxicity. results: TB and BBC levels ranged from 0.7-22.8 to 6.3-47.5 mg/dl, respectively. Gestational age (GA) correlated with BBC (r = 0.54; P < 0.0002) with a slope of 0.93 mg/dl/wk by logistic regression. Our calculations demonstrate that recently recommended GA-modulated TB thresholds for phototherapy and exchange transfusion correspond to 45 and 67% saturation of our observed regression line, respectively. conclusion: We speculate that the spread of BBC levels around the regression line (±5.8 mg/dl) suggests that individualized BBC assays would provide a robust approach to gauge risk of bilirubin neurotoxicity compared with TB and GA.
Participants: 156 children aged 65-117 months. Methods: After randomization, INDT-ADHD and Connor... more Participants: 156 children aged 65-117 months. Methods: After randomization, INDT-ADHD and Connor's 3 Parent Rating Scale (C3PS) were administered, followed by an expert evaluation by DSM-IV-TR diagnostic criteria. Main outcome measures: Psychometric evaluation of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency. Results: INDT-ADHD had 18 items that quantified symptoms and impairment. Attention deficit hyperactivity disorder was identified in 57, 87 and 116 children by expert evaluation, INDT-ADHD and C3PS, respectively. Psychometric parameters of INDT-ADHD for differentiating attention deficit hyperactivity disorder and normal children were: sensitivity 87.7%, specificity 97.2%, positive predictive value 98.0% and negative predictive value 83.3%, whereas for differentiating from other neuro-developmental disorders were 87.7%, 42.9%, 58.1% and 79.4%, respectively. Internal consistency was 0.91. INDT-ADHD has a 4-factor structure explaining 60.4% of the variance. Convergent validity with Conner's Parents Rating Scale was moderate (r =0.73, P= 0.001). Conclusions: INDT-ADHD is suitable for diagnosing attention deficit hyperactivity disorder in Indian children between the ages of 6 to 9 years.
A utism Spectrum Disorder (ASD) is widely recognized for many decades, yet there are no definitiv... more A utism Spectrum Disorder (ASD) is widely recognized for many decades, yet there are no definitive or universally accepted diagnostic criteria. [1]. Most diagnostic systems and measures consider ASD to be a 3-symptom cluster disorder with varying severity and etiology. This is reflected in the diagnostic systems of Diagnostic and Statistical Manual of Mental Disorders-IV Text Revision (DSM-IV TR) and International Classification of Diseases-10 (ICD-10), as well as the various measures that evolved from them [2,3]. However, the field trials of the draft version of Diagnostic and Statistical Manual of
Translational Investigation nature publishing group Background: The therapeutic phototherapy acti... more Translational Investigation nature publishing group Background: The therapeutic phototherapy action spectrum ranges from 420 to 500 nm. However, a recent report of improved efficacy of fluorescent "turquoise" light (~490 nm) as compared with blue light (~450 nm) underscores the need to define an optimal action spectrum for precision-targeted phototherapy using very narrow wavelength ranges. Methods: We used a current semi-empirical model of the optical properties of skin for robust calculations of the fraction of light absorbed by bilirubin at various wavelengths that could be confounded by hemoglobin (Hb), melanin, and skin thickness. Applying assumptions regarding the wavelength dependence of bilirubin photochemistry, "action spectra" were assembled from the calculated values. results: All the calculated action spectra displayed a peak between 472 and 480 nm (most at 476 nm), which is a significant shift from the well-reported 460 nm absorption peak of bilirubin. Of note, the relative amplitudes of the action spectra showed an inverse relationship with hematocrit (Hct). conclusion: We speculate that a narrow range of light at 476 nm would be 60% more effective than blue (broadband) fluorescent lamps. Because Hb serves as a major competitor of bilirubin for light absorption, the calculations also predict that the efficacy of phototherapy is dependent on the Hct. A high Hct could reduce therapeutic efficiency.
nature publishing group Background: Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) resu... more nature publishing group Background: Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden. Methods: Systematic reviews and meta-analyses were undertaken of national prevalence, mortality, and kernicterus due to Rh disease and EHB. We applied a compartmental model to estimate neonatal survivors and impairment cases for 2010. results: Twenty-four million (18% of 134 million live births ≥32 wk gestational age from 184 countries; uncertainty range: 23-26 million) were at risk for neonatal hyperbilirubinemiarelated adverse outcomes. Of these, 480,700 (0.36%) had either Rh disease (373,300; uncertainty range: 271,800-477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000-131,000), with a 24% risk for death (114,100; uncertainty range: 59,700-172,000), 13% for kernicterus (75,400), and 11% for stillbirths. Three-quarters of mortality occurred in sub-Saharan Africa and South Asia. Kernicterus with Rh disease ranged from 38, 28, 28, and 25/100,000 live births for Eastern Europe/Central Asian, sub-Saharan African, South Asian, and Latin American regions, respectively. More than 83% of survivors with kernicterus had one or more impairments. conclusion: Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries. n eonatal hyperbilirubinemia and jaundice occur in almost all newborns (1-10) and may be benign if its progression to extreme hyperbilirubinemia (EHB; total bilirubin (TB) >428 μmol/l in full-term babies) is recognized, monitored, and prevented or managed in a timely manner. Major risk factors include neonatal hemolysis (such as Rhesus (Rh) disease), glucose-6-phosphate dehydrogenase (G6PD) deficiency, infections, and an array of familial and genetic disorders. In addition to conditions such as preterm birth that make the neonate more susceptible to bilirubin neurotoxicity, suboptimal breast milk intake or dehydration may also contribute to EHB (1-10). At present, once the early stages of hyperbilirubinemic brain damage occur, therapeutic options are limited to the prompt (<8 h) use of exchange transfusion, hence the imperative for preventive approaches. Universal prenatal Rh screening for specific risk of perinatal hemolysis and its prophylaxis with Rh immunoglobulin have been highly effective practices for preventing neonatal morbidities and mortality (11-14). Countries with universal access to perinatal health services have virtually eliminated severe hyperbilirubinemia (icterus gravis neonatorum), which had been so common in the late 19th century (15-28). Now with emerging affordable technologies, the worldwide prevention and management of newborn jaundice can more feasibly reach those at risk even in low-income settings (1,2,29-31). Yet, there remains a paucity of quality population data on the prevalence of hyperbilirubinemia and related outcomes to inform such a strategy for most countries (8). In the absence of direct national or regional reporting, we report systematic estimates for the prevalence, mortality, and neurodevelopmental outcomes of Rh disease and EHB due to other causes, e.g., G6PD deficiency, prematurity, neonatal hemolysis, and idiopathic causes. We based these estimates, as
Kernicterus, thought to be due to severe hyperbilirubinemia, is an uncommon disorder with tragic ... more Kernicterus, thought to be due to severe hyperbilirubinemia, is an uncommon disorder with tragic consequences, especially when it affects healthy term and near-term infants. Early identification, prevention and treatment of severe hyperbilirubinemia should make kernicterus a preventable disease. However, national epidemiologic data are needed to monitor any preventive strategies. Recommendations are provided to obtain prospective data on the prevalence and incidence of severe hyperbilirubinemia and associate mortality and neurologic injury using standardized definitions, explore the clinical characteristics and root causes of kernicterus in children identified in the Kernicterus Pilot Registry, identify and test an indicator for population surveillance, validating systems-based approaches to the management of newborn jaundice, and explore the feasibility of using biologic or genetic markers to identify infants at risk for hyperbilirubinemia. Increased knowledge about the incidence and consequences of severe hyperbilirubinemia is essential to the planning, implementation and assessment of interventions to ensure that infants discharged as healthy from their birth hospitals have a safer transition to home, avoiding morbidity due to hyperbilirubinemia and other disorders. At a recent NIHCD-sponsored conference, key questions were raised about kernicterus and the need for additional strategies for its prevention. These questions and an approach to their answers form the basis of this report.
service for caregivers that will prove invaluable to physicians, midwives, nurses, ancillary memb... more service for caregivers that will prove invaluable to physicians, midwives, nurses, ancillary members of the healthcare team, and, most importantly, the parents of late preterm infants. The methodical approach to the evaluation and management of these neonates, thoroughly supported by up-to-date references, will serve as an ideal road map to improve the outcomes for these infants. I would urge all neonatal providers to carefully read this manual and adopt these carefully considered and clearly outlined strategic approaches to the care of the late preterm infant.
ABSTRAn. The mechanical properties of the newborn piglet gallbladder were evaluated in both the s... more ABSTRAn. The mechanical properties of the newborn piglet gallbladder were evaluated in both the stimulated and unstimulated states. The pressure-volume relationships, compliance, and the estimated active tension of the gallbladder were determined in 10 newborn piglets (2-7 days of age). Agonist stimulation was achieved by administration of histamine (25 pg/kg/h) and cholecystokinin (CCK) (60 ngjkglh). Both histamine and CCK increased the intracholecystic pressure at the 50% resting volume from 12.4 cm H z 0 to 18.9 and 15.5 cm H20, respectively. This resulted in a significant (p c 0.05) increase in the active tension. However, no significant changes were observed in the gallbladder compliance after stimulation. These findings characterize the mechanical properties of the normal neonatal gallbladder. The low magnitude of intracholecystic pressure response to agonist stimulation, when compared to adult data, may explain the occurrence of decreased neonatal choledochal bile flow.
To develop and validate a diagnostic tool for use by primary care physicians for diagnosing neuro... more To develop and validate a diagnostic tool for use by primary care physicians for diagnosing neuro-motor impairment among 2-9 year old children in primary care settings. Modified Delphi technique involving national (n=49) and international (n=6) experts was used for development of INDT-NMI. The tool was then validated through a cross sectional study. Neurology specialty clinics of three tertiary care pediatric centers in New Delhi, India. 454 children aged 2-9 years [mean (SD) age: 60.4 (23.7) mo], selected through systematic random sampling, underwent assessment for identification and classification of neuromotor impairments (NMI). All study subjects were first administered INDT-NMI (candidate test) by a trained physician followed by expert assessment for NMI and other neurodevelopment disorders (NDD) by team of two pediatric neurologists (Gold standard). According to expert evaluation, 171 (37.8%) children had neuromotor impairments. There were four categories of subjects: NMI alone (n=66); NMI+other NDDs (n=105); Other NDDs without NMI (n=225) and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Normal&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; group (n=58). Using expert evaluation as gold standard, overall sensitivity of the INDT-NMI was 75.4% and specificity was 86.8%. INDT-NMI helped graduate physicians to correctly classify 86.6% (112/129) children with NMI into different types (cerebral palsy, neuromotor diseases and other NMI). Graduate physicians assigned 40 children (8.8%) as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;indeterminate&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;, 38 (95%) of whom had either NDD and/or NMI and thus merited referral. Misclassification of NMI occurred in those with mild changes in muscle tone, dystonia, or ataxia and associated NDDs. Graduate primary care physicians with a structured short training can administer the new tool and diagnose NMI in 2-9 year old children with high validity. INDT-NMI requires further evaluation in actual primary care settings.
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