Neonatal Obstructive Jaundice Research Articles

Identifying and validating molecular subtypes of biliary atresia using multiple high-throughput data integration analysis.

Biliary atresia (BA) is the most common form of severe neonatal obstructive jaundice. The etiology and pathogenesis of BA are multifactorial, and different factors may interact to produce heterogeneous pathological features and clinical outcomes. Despite different pathological features, all patients received the same treatment strategy. This study performed integrative clustering analysis based on multiple high-throughput datasets to identify the molecular subtypes of BA and provide a new treatment strategy for personalized treatment of the different subtypes of BA. The RNA sequence dataset GSE122340 in the Gene Expression Omnibus (GEO) database was downloaded; 31 BA and 20 control normal liver tissues were collected at our center for transcriptome sequencing, and clinical and follow-up data of BA patients were available. Molecular subtypes were identified using integrated unsupervised cluster analysis involving gene expression, biliary fibrosis, and immune enrichment scores based on the transcriptome dataset, and the results were validated using independent datasets. Based on the results of the integrated unsupervised clustering analysis, four molecular subtypes were identified: autoimmune, inflammatory, virus infection-related, and oxidative stress. The autoimmune subtype with a moderate prognosis was dominated by autoimmune responses and morphogenesis, such as the Fc-gamma receptor and Wnt signaling pathway. The biological process of the inflammatory subtype was mainly the inflammatory response, with the best prognosis, youngest age at surgery, and lowest liver stiffness. The virus infection-related subtype had the worst prognosis and was enriched for a variety of biological processes such as viral infection, immunity, anatomical morphogenesis, and epithelial mesenchymal transition. The oxidative stress subtype was characterized by the activation of oxidative stress and various metabolic pathways and had a poor prognosis. The above results were verified independently in the validation sets. This study identified four molecular subtypes of BA with distinct prognosis and biological processes. According to the pathological characteristics of the different subtypes, individualized perioperative and preoperative treatment may be a new strategy to improve the prognosis of BA.

Gamma-glutamyl transpeptidase has different efficacy on biliary atresia diagnosis in different hospital patient groups: an application of machine learning approach.

Gamma-glutamyl transpeptidase (GGT) is the most widely used biomarker in the early diagnosis of biliary atresia (BA), but its diagnostic efficacy is questionable in different sub-populations. We aim to identify subgroups that are defined by specific variables with cut-offs and can significantly affect the diagnostic efficacy of GGT for detecting BA. Clinical data from 1273 infants with neonatal obstructive jaundice (NOJ) diagnosed between January 2012 and December 2017 at the Children's Hospital of Fudan University were enrolled, reviewed, and analyzed. Random forest-based Virtual Twins method was used to identify potential subgroups. Hemoglobin (HGB) and fasting gallbladder filling were selected as defining variables. The diagnostic efficacy of GGT was significantly better (AUC = 0.855) for patients with hemoglobin (HGB) ≤ 105g/L and a gallbladder that was not or poorly filled. Diagnostic efficacy was worst in the subgroup defined by HGB > 105g/L (AUC = 0.722). The inclusion of interaction terms between GGT and the subgroups in a logistic regression model significantly improved (p = 0.002) prediction performance. This study provides evidence that the diagnostic efficacy of GGT can differ significantly across different subgroups. Therefore, a GGT diagnostic result should be interpreted cautiously when patients belong to subgroups with low diagnostic efficacy. The development of a prediction model and/or clinical diagnostic pathway for early detection of BA should also account for the heterogeneous diagnostic efficacy of GGT.

Development and Assessment of Screening Nomogram for Biliary Atresia Based on Hepatobiliary Ultrasonographic Features.

Objectives: Biliary atresia (BA) is a rare neonatal liver disease of which the early diagnosis remains a challenge for clinicians. Our center has established a nomogram diagnostic model based on clinical characteristics and liver function characteristics. We aim to develop and validate a nomogram that includes additional ultrasound and finds hepatobiliary abnormality with better BA early screening performance.Methods: In this single-center, retrospective cohort analysis, 1,001 neonatal obstructive jaundice (NOJ) patients between 2012 and 2015 were enrolled. Multivariable analysis was used to identify clinical characteristics, laboratory liver function characteristics, and ultrasonic features that may early screen BA. A nomogram was developed to predict the probability of BA using multiple logistic regression analysis. This nomogram was subsequently validated using another cohort of 501 NOJ patients between 2015 and 2017. Calibration curve analysis and decision curve analyses were performed to evaluate and interpret the nomogram's clinical benefits.Results: Gender, direct bilirubin (DB), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), fasting gallbladder visibility, fasting gallbladder filling, and common bile duct visibility were found to have profound statistical significance between the BA and non-BA groups (P < 0.05). The significant features were used to build the nomogram. The area under the receiver operating characteristic (ROC) curve (AUC) value of the novel nomogram (0.87) was superior to those of the former nomogram (0.83) and GGT alone (0.81) in the prediction of BA. The calibration curve revealed a close resemblance between the predicted and actual BA probabilities. Also, the net benefit from the decision curve analysis (DCA) of the nomogram (0.54) was superior to those of the former nomogram (0.49) and GGT alone (0.45) at 80% of threshold possibility.Conclusions: The nomogram has demonstrated better performance for BA screening by including additional information of the US finding, holding a promising future as a non-invasive method for BA patients.

Gamma-Glutamyl Transpeptidase Has Different Efficacy on Biliary Atresia Diagnosis in Different Hospital Patient Groups - An Application of Machine Learning Approach

Background: Gamma-glutamyl transpeptidase (GGT) is the most widely used biomarker in the early diagnosis of biliary atresia (BA), but its diagnostic efficacy is questionable in different sub-populations. We aim to identify subgroups that are defined by specific variables with cut-offs and can significantly affect the diagnostic efficacy of GGT for detecting BA. Methods: Clinical data from 1273 infants with neonatal obstructive jaundice (NOJ) diagnosed between January 2012 and December 2017 at the Children’s Hospital of Fudan University were collected, reviewed, and analyzed. Random forest-based Virtual Twins method was used to identify potential subgroups . Findings: Hemoglobin (HGB) and fasting gallbladder filling were selected as defining variables. The diagnostic efficacy of GGT was significantly better (AUC=0.855) for patients with hemoglobin (HGB)≤105 g/L and a gallbladder that was not or poorly filled. Diagnostic efficacy was worst in the subgroup defined by HGB>105 g/L (AUC=0.722). The inclusion of interaction terms between GGT and the subgroups in a logistic regression model significantly improved (p=0.002) prediction performance. Interpretation: This study provides evidence that the diagnostic efficacy of GGT can differ significantly across different subgroups. Therefore, a GGT diagnostic result should be interpreted cautiously when patients belong to subgroups with low diagnostic efficacy. The development of a prediction model and/or clinical diagnostic pathway for early detection of BA should also account for the heterogeneous diagnostic efficacy of GGT. Funding Statement: This study received financial support from Shanghai Key Disciplines (no.2017ZZ02022), National Natural Science Foundation of China (no. 81770519, no. 81771633, no. 81873545 and no. 81974059), The Science Foundation of Shanghai (no. 14411969800, no. 16411952200, no. 18411969100 and 19ZR1406600), and Children's National Medical Center (no. EK1125180104, no. EKYY20180204, EK112520180211 and no. EK112520180310). Declaration of Interests: The authors have no conflict of interest to disclose. Ethics Approval Statement: The study was approved by the Ethics Committee of the Children’s Hospital of Fudan University. Written informed consent was obtained from the legal guardians of all patients before the enrollment of the study.

Serum MMP-7 in the Diagnosis of Biliary Atresia.

The overlapping features of biliary atresia (BA) and other neonatal cholestasis with alternative causes (non-BA) have posed challenges for diagnosis. Matrix metalloproteinase-7 (MMP-7) has been reported to be promising in diagnosing BA. We aimed to validate the diagnostic accuracy of MMP-7 for BA in a large population sample. We enrolled 288 patients with neonatal obstructive jaundice from March 2017 to October 2018. Serum MMP-7 levels were measured by using an enzyme-linked immunosorbent assay. Receiver operating characteristic curves were constructed, and decision curve analysis was done. A Pearson correlation coefficient test was conducted to assess the correlation between MMP-7 levels and other characteristics. The median serum MMP-7 levels were 38.89 ng/mL (interquartile range: 22.96-56.46) for the BA group and 4.4 ng/mL (interquartile range: 2.73-6.56) for the non-BA group (P < .001). The area under the receiver operating characteristic curve value was 0.9829 for MMP-7, and the sensitivity, specificity, positive predictive value, and negative predictive value were 95.19%, 93.07%, 97.27%, and 91.43%, respectively, at a cutoff value of 10.37 ng/mL. When MMP-7 was combined with γ glutamyl transferase, the diagnostic accuracy was slightly improved without significance when compared with MMP-7 alone and had an area under the curve of 0.9880 (P = .08). Decision curve analysis also showed potential for MMP-7 to be used for clinical applications. A significant correlation was found with fibrosis stage from liver biopsy (R = 0.47; P < .001). MMP-7 demonstrated good accuracy in diagnosing BA and holds promise for future clinical application. Furthermore, its correlation with liver fibrosis indicated its potential use as a therapeutic target or prognostic biomarker.

Development and Validation of Novel Diagnostic Models for Biliary Atresia in a Large Cohort of Chinese Patients.

Background & aimsThe overlapping features of biliary atresia (BA) and the other forms of neonatal cholestasis (NC) with different causes (non-BA) has posed challenges for the diagnosis of BA. This study aimed at developing new and better diagnostic models for BA.MethodsWe retrospectively analyzed data from 1728 newborn infants with neonatal obstructive jaundice (NOJ). New prediction models, including decision tree (DT), random forest (RF), and multivariate logistic regression-based nomogram for BA were created and externally validated in an independent set of 508 infant patients.ResultsFiver predictors, including gender, weight, direct bilirubin (DB), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (GGT) were significantly different between the BA and non-BA groups (P < .05), from which DT, RF, and nomogram models were developed. The area under the receiver operating characteristic (ROC) curve (AUC) value for the nomogram was 0.898, which was greater than that of a single biomarker in the prediction of BA. Performance comparison of the three diagnostic models showed that the nomogram displayed better discriminative ability (sensitivity, 85.7%; specificity, 80.3%; PPV, 0.969) at the optimal cut-off value compared with DT and RF, which had relatively similar high sensitivity and PPV (0.941 and 0.947, respectively), but low specificity in the modeling group. In sub-analysis of the discriminative capacity between the nomogram and GGT (<300 or ≥ 300), we found that the nomogram was superior to the GGT alone in the preoperative diagnosis of BA.ConclusionsThe nomogram has demonstrated better performance for the prediction of BA, holding promise for future clinical application.

Clinical value of single photon emission computed tomography imaging in differential diagnosis of neonatal obstructive jaundice

Objective To investigate and explore the clinical value of single-photon emission computed tomography(SPECT) imaging in the differential diagnosis of neonatal obstructive jaundice. Methods From January 2012 to April 2017, 130 cases of suspected neonatal obstructive jaundice in the First Hospital of Jiaxing were enrolled in the study.All patients were given SPECT hepatobiliary scintigraphy, were injected 99mTc-EHIDA imaging agent, 99mTc-MIBI imaging agent, diagnosis of hepatobiliary scintigraphy after the acquisition.The result of operative cholangiography was viewed as the gold standard, the diagnostic sensitivity, specificity, accuracy of simple 99mTc-EHIDA SPECT imaging examination, combined with SPECT imaging agent in the diagnosis of neonatal obstructive jaundice were calculated and compared.The coincidence rate of differential diagnosis of different etiologies of neonatal obstructive jaundice was also compared. Results The diagnostic sensitivity, specificity and accuracy of combined with SPECT imaging agent in the diagnosis of neonatal obstructive jaundice were 94.23%, 96.15%, 94.61%, respectively, which of simple 99mTc-EHIDA imaging agent SPECT were 83.65%, 76.92%, 82.31%, respectively, the differences were statistically significant(χ2=5.915, 4.127, 9.646, all P<0.05). The coincidence rates of extrahepatic biliary atresia, hepatitis syndrome of the two kinds of SPECT imaging agents combined examination were 96.05%, 96.43%, respectively, which were significantly higher than those of the 99mTc-EHIDA imaging agent SPECT examination (84.21%, 85.00%)(χ2=5.991, 5.250, all P<0.05). Conclusion SPECT imaging in the diagnosis of neonatal obstructive jaundice has high sensitivity and accuracy, especially in combination with 99mTc-EHIDA imaging agent, 99mTc-MIBI imaging agent can identify and distinguish different causes of jaundice, and provide a reliable basis for clinical treatment. Key words: Jaundice, neonatal; Jaundice, obstructive; Diagnosis; Single-photon emission computed tomography

Value of Gamma-Glutamyl Transpeptidase for Diagnosis of Biliary Atresia by Correlation With Age.

The aim of the study was to analyze the value of gamma-glutamyl transpeptidase (GGT) for distinguishing biliary atresia (BA) from non-BA for patients suspected of having neonatal obstructive jaundice by correlation with age. From January 2003 to March 2014, cholangiography and/or surgical exploration were undertaken in 1469 patients with suspicion of having neonatal obstructive jaundice. A total of 1338 patients were diagnosed with BA intraoperatively. Preoperative medical records were compared between BA and non-BA patients. Preoperative levels of total bilirubin, direct bilirubin, and GGT were significantly higher in the BA group (P < 0.05), whereas the non-BA group had higher alkaline phosphatase levels (P = 0.0003). The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin, GGT, and alkaline phosphatase was 0.584, 0.614, 0.843, and 0.398, respectively. In all age groups (i: 31-60 days; ii: 61-90 days; iii: 91-120 days; iv: ≥121 days), BA groups had higher GGT levels (in IU/L) (i: 725.3 ± 549.9; ii: 927.0 ± 679.8; iii: 1114.3 ± 823.1; iv: 767.5 ± 666.7). The level of GGT in patients with BA younger than 30 days was 834.2 ± 475.3 IU/L. GGT levels had the highest diagnostic value (0.869) in group ii (61-90 days) and the lowest diagnosis value (0.712) in group iv (≥121 days). At a cutoff of >303 IU/L in group ii (61-90 days), GGT had 82.8% sensitivity and 81.6% specificity for the discrimination of BA. GGT levels contribute to the diagnosis of BA before 120 days. Age must be considered if using GGT levels as a diagnostic test for BA.

A Rare Cause of Neonatal Obstructive Jaundice

A Rare Cause of Neonatal Obstructive Jaundice

Extra Hepatic Biliary Atresia associated with Choledochal Cyst: A Challenging Neonatal Obstructive Jaundice

Biliary atresia and choledochal cyst have the similar clinical presentation in infants. Herein, we report a case that presented with prolonged hyperbilirubinemia and abdominal distension and diagnosed as choledochal cyst. At surgery, in addition to a large choledochal cyst, biliary atresia was also encountered.

Cystic Biliary Atresia: A Wolf in Sheep's Clothing

Neonatal obstructive jaundice is frequently explained by biliary atresia (BA) or the presence of a choledochal cyst (CC). Cystic biliary atresia (CBA) has been a proposed as a subtype of BA with projected improved outcomes. We aimed to characterize these lesions further. We conducted an Institutional Review Board-approved review of all patients treated for obstructive jaundice at our tertiary children's hospital over 10 years. Over the decade we evaluated 91 children with obstructive jaundice: 13 CBA, 52 BA, and 26 CC. Patients with isolated CBA and BA were diagnosed significantly earlier than those with CC (15.9, 54, and 281 days, respectively; P = 0.0001). There was a significant delay between diagnosis and surgical intervention for patients with CBA compared with BA: 17 days versus 5.7 days (P = 0.004). There was no difference in rate of transplant between CBA and BA (31 vs. 50%; P = 0.35). The time from surgery until transplant was 13.9 and 18.6 months for CBA and BA, respectively (P = 0.62). Although radiographically similar to CC, CBA behaves similarly to isolated BA. Delay in recognition and surgical treatment may affect outcomes and lead to an increased incidence of liver failure. The presence of a cystic biliary malformation in the setting of neonatal jaundice should be regarded as CBA until proven otherwise.

Extra Hepatic Biliary Atresia Associated with Choledochal Cyst: A Diagnostic Dilemma in Neonatal Obstructive Jaundice

The presentation of extra hepatic biliary-atresia (EHBA) as well as choledochal cyst (CDC) in the neonate may be similar. Since the surgical management and prognosis are entirely different, it is important to differentiate between the two entities. We present a case with co-existing EHBA and CDC which led to a diagnostic dilemma.

Les cholestases néonatales

Neonatal jaundice lasting more than two weeks needs urgent investigations, starting with examination of stool colour and blood tests with total and conjugated serum bilirubin. If neonatal cholestasis (NC) is confirmed, vitamin K should be immediately injected, and the child should be referred to a specialised centre for investigations and treatment. Biliary atresia (BA) is the first cause of NC. Its diagnosis is urgent, since the chance of success of the conservative surgical treatment (Kasai operation or variants) decreases rapidly as the age at surgery increases. Normal ultrasound scans cannot rule out BA. The diagnosis can often be suspected before surgery, and is confirmed by operative findings with or without cholangiogram. In case of failure to restore the biliary drainage, biliary cirrhosis progresses and leads to liver transplantation, generally in the first years of life. The other causes of neonatal obstructive jaundice are stones in the main bile duct, choledocal cyst and spontaneous perforation of bile ducts. Correction of biliary obstruction (by surgery or interventional radiology) is also urgent to prevent progression of liver fibrosis, which is very rapid in the first months of life. The most common medical aetiologies of NC are: Alagille syndrome, 1-antitrypsin deficiency, progressive familial intrahepatic cholestasis and cystic fibrosis. Other medical causes of NC are numerous, including infectious, hormonal, nutritional, metabolic or storage diseases. Some of the conditions may require a specific therapy.

Neonatal Obstructive Jaundice Caused by a Malpositioned Gastrostomy Tube

Sebastian MV, Coley BD(AQ1) irst successfully performed more than 120 years ago by Verneuil [1], gastrostomy tube placement in the pediatric population is now common, performed most often for intestinal atresias, neurologic and swallowing disorders, and other conditions in which nutritional support is needed. As the procedure has become more common in the last 40 years, many types of complications have been documented, including tube obstruction and dislodgement, malpositioning of replaced tubes, stomal leak, and tube migration and prolapse with or without gastric outlet obstruction and intussusception [1–3]. A rare complication is obstructive jaundice caused by migration of balloon catheters into the duodenum [4–7]. We present such a case in a neonate. Case Report A 36-week-old preterm boy with a history of polyhydramnios was diagnosed with upper esophageal atresia with distal tracheoesophageal fistula. Fistula ligation was performed on day-oflife 1, but primary esophageal reanastomosis could not be performed. For enteric feeding, a surgical Stamm gastrostomy was performed and a 12-French self-retaining Malecot tip gastros-

Distortion in TGF beta 1 peptide immunolocalization in biliary atresia: comparison with the normal pattern in the developing human intrahepatic bile duct system.

Biliary atresia is an important cause of neonatal obstructive jaundice in which there is inflammation, sclerosis and eventual obliteration of the bile duct system. Its onset may be antenatal, affecting the normal development of the biliary system. The intrahepatic biliary system is derived from the ductal plate, a sheath of cuboidal epithelium that appears at the hepatocyte-mesenchymal junction around the portal vein branches at 6 weeks gestation. This epithelial structure is moulded into a network of tubular bile ducts by the proliferating mesenchyme. Certain portions of the ductal plate are selected to become definitive bile ducts, while redundant biliary epithelium is deleted. The molecular dynamics controlling the intra-uterine development of the biliary system in humans are not yet clearly understood. Transforming growth factor-beta 1 is a cytokine that stimulates mesenchymal proliferation and inhibits epithelial growth, and has been shown to be important in organogenesis. In the present study, the pattern of TGF beta 1 peptide immunolocalization was investigated with the aid of computerized image analysis, in normal human bile duct development and in biliary atresia. TGF beta 1 peptide was detected within hepatocytes and ductal plate epithelium from 7 weeks gestation; increased TGF beta 1 immunoreactivity was present within the epithelium of developing bile ducts at 13 weeks gestation, and apical polarization of the cytokine was observed from 16 weeks gestation. In biliary atresia, the TGF beta 1 immunoreactivity pattern within the bile duct structures at the porta hepatis and within intrahepatic portal tracts resembled that of the primitive ductal plate, and there was no significant apical polarization. This may indicate a developmental arrest in the normal ductal plate remodelling process in biliary atresia, and suggests an underlying epithelial-mesenchymal interactive disorder.

The developing human biliary system at the porta hepatis level between 11 and 25 weeks of gestation: a way to understanding biliary atresia. Part 2.

In biliary atresia, inflammation and destruction of extrahepatic and intrahepatic bile ducts with eventual fibrous obliteration occurs, causing neonatal obstructive jaundice. The onset of the disorder may start antenatally and progress after birth, and the porta hepatis is a constant site of involvement. To date, little is known about the intrauterine development of the bile ducts at the porta hepatis. The present work gives an account of the developmental pattern of bile ducts at the level of the porta hepatis in the normal human fetus from the 11th to the 25th weeks of gestation. It has been observed that the proximal portion of the hilar bile ducts derives from the intrahepatic biliary ductal plate. This occurs following a predictable remodeling sequence by which, from many ductal plate-derived ductules, those destined to become definitive bile ducts are enveloped in a concentric cuff of mesenchyma. Those which are not are deleted. The distal portions of the right and left main hepatic ducts develop from the extrahepatic bile duct. There was no gestational period in which the extrahepatic bile duct and the intrahepatic biliary system were separated. Furthermore, the developing intrahepatic bile ducts maintain luminal continuity with the common bile duct from the start of organogenesis. Biliary atresia may result from: (i) failure to establish a definitive type of bile duct; (ii) leakage of bile from primitive bile ducts resulting in an interstitial inflammatory reaction in the adjacent mesenchyma; and (iii) continuous proliferation of primitive bile ducts at the level of the porta hepatis beyond the 25th week of gestation, as a failed compensatory mechanism.

675 Effects of Monohydroxy Bile Acids on Bile Acid Transport in Newborn Rabbit Hepatccytes

Neonatal obstructive jaundice, neonatal hepatitis, and congenital biliary atresia are thought to be caused by the toxic effects of bile acids, especially toxic monohydroxy bile acids. These studies were performed to examine the effects of lithocolic acid (LCA) and taurolithocholic acid (TLCA) on cellular toxicity, bile acid uptake and secretion in freshly isolated hepatccytes from newborn and 23 day old rabbits. Cellular bile acid uptake and secretion were quantitated using radiolabelled glycocholic acid. Both control and treated hepatocytes were incubated for one hour in the presence of varying concentrations of monohydroxy bile acids prior to kinetic analysis of bile acid transport. A summary of transport data for hepatocytes from 23 day old rabbits is presented in the table. Hepatocytes from 4 day old rabbit under control conditions showed only negligible secretion of bile acid. The effects of LCA and TLCA on bile acid uptake in hepatocytes from 4 day old rabbits were similar to those observed with hepatccytes from 23 day old rabbit. Electron microscopy revealed that the most striking effects of monohydroxy bile acids were on the bile canaliculi (BC). The EC were greatly dilated with prominent thickening and fewer and irregular microvilli. It is concluded that BC function is selectively sensitive to disruption by monohydroxy bile acids and demonstrates significant post natal maturation.

The investigation of neonatal obstructive jaundice using 123I rose bengal.

With the development of new surgical techniques the outlook for infants with biliary atresia has improved significantly. It has therefore become increasingly important to identify these patients quickly in order to allow prompt surgical intervention. Differentiation of biliary atresia from other causes of jaundice, in particular idiopathic neonatal hepatitis, is often difficult as there is considerable clinical and histological overlap of the two conditions. Demonstration of biliary patency using radiopharmaceuticals is a well established technique. 131I rose bengal and the 99Tcm-labelled iminodiacetic acid derivatives have both been used, but are not completely satisfactory, and controversy still exists as to which is the most suitable agent. Nine infants with prolonged jaundice have been studied using 123I-labelled rose bengal. All infants with biliary atresia and neonatal hepatitis were correctly identified. The results indicate that 123I rose bengal provides a reliable tracer for assessing biliary patency and is the agent of choice in the investigation of neonatal obstructive jaundice.

Infants with a congenital anomaly and the concentration of Mo, As, Mn, Zn and Cu in the mother's milk

Thirty-one samples of mothers' milk were analysed by neutron activation analysis for the concentrations of Mo, As, Mn, Zn, Cu 1.5 to 3 months post-partum. Group I consisted of 6 mothers having infants with neonatal obstructive jaundice and exhibited lower mean values of Cu and Mn at 0.18 μg/g and 11.7 μg/g as compared with 16 control subjects with 0.34 μg/g Cu and 23.0 μg/g Mn; Mo levels were approximately twice as high (12.2 μg/g) as the control values (6.4 μg/g); Zn and As were grossly comparable. Group II consisted of 9 mothers who had delivered infants with either a congenital hydrocephalus ( n = 7) or meningomyelocoele ( n = 2), exhibited a mean Cu level of 0.27 μg/g, Zn 1.7 μg/g, Mn 25.3 μg/g and As 0.45 μg/g. These findings are discussed in the light of the patho-physiology of the congenital anomaly of the infant.

Management of Neonatal Obstructive Jaundice

A plan of management of neonatal obstructive jaundice is proposed for use in units specializing in the treatment of this difficult condition. Reliance is placed in needle liver biopsy used early (and repeatedly if necessary) to judge the rate of development of fibrosis in the liver and to reach a diagnosis. Blind porto-enterostomy is used in biliary atresia when no patent proximal duct is found. Emotional support of parents through this long illness is important. The procedures described should not be attempted by surgeons less experienced with this disease.