ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy.

Diseases of ectopic calcification of the vascular wall range from lethal orphan diseases such as generalized arterial calcification of infancy (GACI), to common diseases such as hardening of the arteries associated with aging and calciphylaxis of chronic kidney disease (CKD). GACI is a lethal orphan disease in which infants calcify the internal elastic lamina of their medium and large arteries and expire of cardiac failure as neonates, while calciphylaxis of CKD is a ubiquitous vascular calcification in patients with renal failure. Both disorders are characterized by vascular Mönckeburg's sclerosis accompanied by decreased concentrations of plasma inorganic pyrophosphate (PPi). Here we demonstrate that subcutaneous administration of an ENPP1-Fc fusion protein prevents the mortality, vascular calcifications and sequela of disease in animal models of GACI, and is accompanied by a complete clinical and biomarker response. Our findings have implications for the treatment of rare and common diseases of ectopic vascular calcification.

Distinguishing primary from secondary Δ(4) -3-oxosteroid 5ß-reductase (SRD5B1, AKR1D1) deficiency by urinary steroid analysis.

OBJECTIVE: Deficiency of Δ(4) -3-oxosteroid 5ß-reductase (5ß-reductase), a bile acid synthesis disorder, presents findings of neonatal cholestasis and hyper-3-oxo-Δ(4) bile aciduria. The 5ß-reductase enzyme participates in not only bile acid synthesis but also hepatic steroid metabolism. Deficiency of 5ß-reductase includes 2 types: primary deficiency, with an SRD5B1 gene mutation; and secondary deficiency, lacking a mutation. Secondary deficiency is caused by fulminant liver failure from various aetiologies including neonatal hemochromatosis (NH). Distinguishing primary from secondary deficiency based on γ-glutamyltransferase (GGT), serum total bile acids (TBA), and urinary bile acid analysis using gas chromatography-mass spectroscopy (GC-MS) is very difficult. SRD5B1 gene analysis is the only reliable method. We examined urinary steroid analysis as a way to distinguish primary from secondary 5ß-reductase deficiency. DESIGN, PATIENTS AND MEASUREMENTS: We examined 12 patients with cholestatic jaundice, normal or slightly elevated GGT, and hyper-3-oxo-Δ(4) bile aciduria using urinary steroid analysis by GC-MS of both cortisol and cortisone compounds, such as 5ß-tetrahydrocortisol (5ß-THF) and 5ß-tetrahydrocortisone (5ß-THE). Patients previously were diagnosed with primary 5ß-reductase deficiency (n = 3), deficiency secondary to NH (n = 3) and deficiency secondary to other liver disorders (n = 6). RESULTS: Urinary steroid analysis in 3 primary deficiency and 3 NH patients showed low 5ß-THE and elevated 5α/5ß-THE ratios, making distinction difficult without also considering the clinical course and abdominal magnetic resonance imaging (MRI) findings, such as a very low signal intensity in liver and/or pancreas, especially in T2 -weighted images. In the six patients with other secondary deficiencies, urinary 5ß-THF and 5α/5ß-THF differed from those in primary deficiency (P < 0·05). CONCLUSIONS: Urinary steroid analysis can distinguish primary and NH-related deficiencies from other secondary deficiencies.

Tandem mass spectrometry assays of palmitoyl protein thioesterase 1 and tripeptidyl peptidase activity in dried blood spots for the detection of neuronal ceroid lipofuscinoses in newborns.

We report new substrates for quantitative enzyme activity measurements of human palmitoyl protein thioesterase (PPT1) and tripeptidyl peptidase (TPP1) in dried blood spots from newborns using tandem mass spectrometry. Deficiencies in these enzyme activities due to inborn errors of metabolism cause neuronal ceroid lipofuscinoses. The assays use synthetic compounds that were designed to mimic the natural substrates. Incubation produces nanomole quantities of enzymatic products per a blood spot that are quantified by tandem mass spectrometry using synthetic internal standards and selected reaction monitoring. The assays utilize a minimum steps for sample workup and can be run in a duplex format for the detection of neuronal ceroid lipofuscinoses or potentially multiplexed with other mass spectrometry-based assays for newborn screening of lysosomal storage disorders.

Creatine kinase as an indicator for hysterectomy in postpartum endomyometritis due to group A streptococci: a hypothesis illustrated by a case report.

BACKGROUND: Puerperal group A streptococcus (GAS) infection, once the leading cause of postpartum sepsis, has been increasing again since the 1980s. Streptococcal toxic shock syndrome (STSS) is a serious complication characterized by rapidly spreading GAS infection, shock, and multiple organ failure. Immediate recognition and implementation of therapy is crucial for survival. Making informed decisions regarding surgical debridement, namely hysterectomy, based on clinical indicators is difficult for practitioners. OBJECTIVES: This article discusses the potential role of creatine kinase in the decision-making process for treatment of STSS, particularly with regard to hysterectomy. MATERIAL AND METHODS: A case report is presented. The literature was searched using the key words 'group A streptococcus', 'postpartum hysterectomy', 'creatine kinase', 'endomyometritis', and 'streptococcal toxic shock syndrome' in PubMed and the UptoDate database. Relevant articles published between 1991 and 2011 were evaluated. CONCLUSION: Decisions regarding hysterectomy in STSS management are difficult. A rise in CK levels in the serum may indicate involvement of the myometrium and may be an important parameter in the difficult decision of hysterectomy when treating STSS.

Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation.

Lipoic acid is an essential prosthetic group of four mitochondrial enzymes involved in the oxidative decarboxylation of pyruvate, α-ketoglutarate, and branched chain amino acids and in the glycine cleavage. Lipoic acid is synthesized stepwise within mitochondria through a process that includes lipoic acid synthetase. We identified the homozygous mutation c.746G>A (p.Arg249His) in LIAS in an individual with neonatal-onset epilepsy, muscular hypotonia, lactic acidosis, and elevated glycine concentration in plasma and urine. Investigation of the mitochondrial energy metabolism showed reduced oxidation of pyruvate and decreased pyruvate dehydrogenase complex activity. A pronounced reduction of the prosthetic group lipoamide was found in lipoylated proteins.

Biochemical measurement of neonatal hypoxia.

Neonatal hypoxia ischemia is characterized by inadequate blood perfusion of a tissue or a systemic lack of oxygen. This condition is thought to cause/exacerbate well documented neonatal disorders including neurological impairment. Decreased adenosine triphosphate production occurs due to a lack of oxidative phosphorylation. To compensate for this energy deprived state molecules containing high energy phosphate bonds are degraded. This leads to increased levels of adenosine which is subsequently degraded to inosine, hypoxanthine, xanthine, and finally to uric acid. The final two steps in this degradation process are performed by xanthine oxidoreductase. This enzyme exists in the form of xanthine dehydrogenase under normoxic conditions but is converted to xanthine oxidase (XO) under hypoxia-reperfusion circumstances. Unlike xanthine dehydrogenase, XO generates hydrogen peroxide as a byproduct of purine degradation. This hydrogen peroxide in combination with other reactive oxygen species (ROS) produced during hypoxia, oxidizes uric acid to form allantoin and reacts with lipid membranes to generate malondialdehyde (MDA). Most mammals, humans exempted, possess the enzyme uricase, which converts uric acid to allantoin. In humans, however, allantoin can only be formed by ROS-mediated oxidation of uric acid. Because of this, allantoin is considered to be a marker of oxidative stress in humans, but not in the mammals that have uricase. We describe methods employing high pressure liquid chromatography (HPLC) and gas chromatography mass spectrometry (GCMS) to measure biochemical markers of neonatal hypoxia ischemia. Human blood is used for most tests. Animal blood may also be used while recognizing the potential for uricase-generated allantoin. Purine metabolites were linked to hypoxia as early as 1963 and the reliability of hypoxanthine, xanthine, and uric acid as biochemical indicators of neonatal hypoxia was validated by several investigators. The HPLC method used for the quantification of purine compounds is fast, reliable, and reproducible. The GC/MS method used for the quantification of allantoin, a relatively new marker of oxidative stress, was adapted from Gruber et al. This method avoids certain artifacts and requires low volumes of sample. Methods used for synthesis of MMDA were described elsewhere. GC/MS based quantification of MDA was adapted from Paroni et al. and Cighetti et al. Xanthine oxidase activity was measured by HPLC by quantifying the conversion of pterin to isoxanthopterin. This approach proved to be sufficiently sensitive and reproducible.

[Urine cholinesterase activity in full-term neonatal infants with ischemic nephropathy].

To determine urine cholinesterase activity in full-term neonatal infants with varying ischemic nephropathy in an intensive care unit, the investigators studied this enzyme on days 1 and 5-7 of life, by using a kinetic photometric test optimized according to the Deutsche Gesellschaft fur Klinische Chemie (German Society for Clinical Chemistry) recommendations. In the early neonatal period, the newborns with grade III ischemic nephropathy were found to have a high urine cholinesterase activity. The determination of urine cholinesterase activity just on the first day of life may be used for the early diagnosis of grade III ischemic nephropathy in the newborns until the clinical manifestations of this pathology develop.

Molecular genetic and bile acid profiles in two Japanese patients with 3beta-hydroxy-DELTA5-C27-steroid dehydrogenase/isomerase deficiency.

We report definitive diagnosis and effective chenodeoxycholic acid (CDCA) treatment of two Japanese children with 3[beta]-hydroxy-[DELTA]5-C27-steroid dehydrogenase/isomerase deficiency. Findings of cholestasis with normal serum [gamma]-glutamyltransferase activity and total bile acid concentration indicated the need for definitive bile acid analysis. Large amounts of 3[beta]-hydroxy-[DELTA]5 bile acids were detected by gas chromatography-mass spectrometry. HSD3B7 gene analysis using peripheral lymphocyte genomic DNA from the patients and their parents identified four novel mutations of the HSD3B7 gene in the patients. One had a homozygous mutation, 314delA; the other had compound heterozygous mutations: V132F, T149I, and 973_974insCCTGC. Interestingly, the second patient's mother had V132F and T149I mutations in one allele. Excessive 3[beta]-hydroxy-[DELTA]5-bile acids such as 3[beta],7[alpha]-dihydroxy- and 3[beta],7[alpha],12[alpha]-trihydroxy-5-cholenoic acids were detected in the first patient's urine; the second patient's urine contained large amounts of 3[beta]-hydroxy-5-cholenoic acid. Liver dysfunction in both patients decreased with ursodeoxycholic acid treatment, but unusual bile acids were still detected. Normalization of the patients' liver function and improvement of bile acid profiles occurred with CDCA treatment. Thus, we found mutations in the HSD3B7 gene accounting for autosomal recessive neonatal cholestasis caused by 3[beta]-hydroxy-[DELTA]5-C27-steroid dehydrogenase/isomerase deficiency. Early neonatal diagnosis permits initiation of CDCA treatment at this critical time, before the late cholestatic stage.

Functional deficiencies of sulfite oxidase: Differential diagnoses in neonates presenting with intractable seizures and cystic encephalomalacia.

Sulfite oxidase is a mitochondrial enzyme encoded by the SUOX gene and essential for the detoxification of sulfite which results mainly from the catabolism of sulfur-containing amino acids. Decreased activity of this enzyme can either be due to mutations in the SUOX gene or secondary to defects in the synthesis of its cofactor, the molybdenum cofactor. Defects in the synthesis of the molybdenum cofactor are caused by mutations in one of the genes MOCS1, MOCS2, MOCS3 and GEPH and result in combined deficiencies of the enzymes sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Although present in many ethnic groups, isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are rare inborn errors of metabolism, which makes awareness of key clinical and laboratory features of affected individuals crucial for early diagnosis. We report clinical, radiologic, biochemical and genetic data on a Brazilian and on a Turkish child with sulfite oxidase deficiency due to the isolated defect and impaired synthesis of the molybdenum cofactor, respectively. Both patients presented with early onset seizures and neurological deterioration. They showed no sulfite oxidase activity in fibroblasts and were homozygous for the mutations c.1136A>G in the SUOX gene and c.667insCGA in the MOCS1 gene, respectively. Widely available routine laboratory tests such as assessment of total homocysteine and uric acid are indicated in children with a clinical presentation resembling that of hypoxic ischemic encephalopathy and may help in obtaining a tentative diagnosis locally, which requires confirmation by specialized laboratories.

A fatal neonatal presentation of medium-chain acyl coenzyme a dehydrogenase deficiency.

Medium-chain acyl coenzyme A dehydrogenase (MCAD) deficiency is the most common of the inborn errors of mitochondrial fatty acid beta-oxidation. A male infant was born at 39 weeks of gestation following an uneventful pregnancy. He was discharged at age 28 h after a normal first-day check, but was subsequently re-admitted and died aged 44 h. Post-mortem blood and bile spot carnitine analysis revealed a profile consistent with MCAD deficiency. MCAD genotyping revealed 985 A to G (K329E) homozygosity. This is the first confirmed case of neonatal death due to MCAD deficiency in the UK.

A mutation (R826W) in nucleotide-binding domain 1 of ABCC8 reduces ATPase activity and causes transient neonatal diabetes.

Activating mutations in the pore-forming Kir6.2 (KCNJ11) and regulatory sulphonylurea receptor SUR1 (ABCC8) subunits of the K(ATP) channel are a common cause of transient neonatal diabetes mellitus (TNDM). We identified a new TNDM mutation (R826W) in the first nucleotide-binding domain (NBD1) of SUR1. The mutation was found in a region that heterodimerizes with NBD2 to form catalytic site 2. Functional analysis showed that this mutation decreases MgATP hydrolysis by purified maltose-binding protein MBP-NBD1 fusion proteins. Inhibition of ATP hydrolysis by MgADP or BeF was not changed. The results indicate that the ATPase cycle lingers in the post-hydrolytic MgADP.P(i)-bound state, which is associated with channel activation. The extent of MgADP-dependent activation of K(ATP) channel activity was unaffected by the R826W mutation, but the time course of deactivation was slowed. Channel inhibition by MgATP was reduced, leading to an increase in resting whole-cell currents. In pancreatic beta cells, this would lead to less insulin secretion and thereby diabetes.

Chorioamnionitis and increased neonatal lung lavage fluid matrix metalloproteinase-9 levels: implications for antenatal origins of chronic lung disease.

OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) degrades type IV collagen, the major constituent of lung basement membrane. We studied the effects of chorioamnionitis and antenatal corticosteroids on bronchoalveolar lavage (BAL) fluid levels of MMP-9, and its inhibitor, TIMP-1 in preterm infants. STUDY DESIGN: A prospective study was performed on serial BAL samples from 79 ventilated preterm infants at less than 33 weeks' gestation, 18 of whom were from pregnancies complicated by chorioamnionitis. MMP-9 levels were measured by gelatin zymography and TIMP-1 by enzyme-linked immunosorbent assay, and the median value for each infant was calculated. The presence and severity of chorioamnionitis were defined histologically. RESULTS: BAL fluid MMP-9 levels were higher in preterm infants in the chorioamnionitis group (86 [29-518] vs 13 [3-43] ng/mL, P =.001), and levels increased stepwise with the increasing severity of chorioamnionitis. Antenatal corticosteroids had no effect on median MMP-9 levels. Infants in the chorioamnionitis group were more likely to have chronic lung disease (CLD) develop (55% vs 28%, P <.05). TIMP-1 levels were no different between groups. CONCLUSION: Chorioamnionitis is associated with increased lung type IV collagenase levels in the ventilated preterm infant. Antenatal lung inflammation with up-regulation of MMP-9 may be important in the pathogenesis of CLD.

A new case of pyruvate dehydrogenase deficiency due to a novel mutation in the PDX1 gene.

We report a case of neonatal congenital lactic acidosis associated with pyruvate dehydrogenase E3-binding protein deficiency in a newborn girl. She had a severe encephalopathy, and magnetic resonance imaging of the brain showed large subependymal cysts and no basal ganglia lesions. She died 35 days after birth. We detected a novel homozygous deletion (620delC) in the PDX1 gene, which encodes for the E3BP subunit of the pyruvate dehydrogenase complex.

[Neutrophil elastase level in cord blood and diagnosis of infection in mature and premature neonates]. / Elastaza neutrofilowa krwi pepowinowej w diagnostyce zakazen noworodków urodzonych o czasie i urodzonych przedwczesnie.

We determined the concentration of umbilical cord blood neutrophil elastase (EN) in 143 neonates. The infants were divided into four groups: A - Term non-infected, B - Term infected, C - Preterm non-infected, D - Preterm infected. In the study a low concentration of cord blood elastase in premature children was found. It was significantly lower in preterm non-infected (p<0.001) and infected (p<0.05) neonates than in non-infected term children. In full-term infected neonates mean concentration of elastase was markedly (p<0.001) higher as compared to term healthy ones. 87% values of cord blood elastase measured in full-term infected neonates and 6% in preterm ones exceed the upper limit reference interval (209.3 ug/L) while 97% measurements in preterm neonates (all with and without clinical signs of infection) were within the reference range. We conclude that significant differences in elastase level in the cord blood depend on age of gestation at delivery. These age-dependent differences of elastase concentration can be taken into consideration and examination of cord blood elastase concentration may provide a valuable indicator in early diagnosis of sepsis in neonates. In full-term neonates cord blood neutrophil elastase is a good marker of infection.

Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal alpha-N-acetyl-neuraminidase (sialidase) gene.

We report a Turkish family with parental consanguinity and at risk for sialidosis type II, an inherited autosomal recessive disorder caused by lysosomal alpha-N-acetyl-neuraminidase (sialidase, NEU1) deficiency. The proband was a premature male infant that presented with hydrops, hepatomegaly, respiratory distress syndrome, and anemia and that died of respiratory insufficiency 2 months after birth despite intensive care. An abnormally increased [14C]methylamine incorporation and an isolated deficiency of lysosomal alpha-N-acetyl-neuraminidase were found in cultured skin fibroblasts. A previous pregnancy of the mother terminated in a spontaneous abortion in the 13th week of gestation. A successive pregnancy showed hydrops fetalis, and an enzymatic assay of cultured amniotic fluid cells indicated a deficiency of alpha-N-acetyl-neuraminidase. Following pregnancy termination at 20 weeks gestation, light microscopy of fetal tissues revealed classic vacuolation not only in liver, bone marrow, brain, and kidney, but also in endocrine organs such as the thyroid gland, adrenal gland, hypophysis, and testes, and in the thymus. DNA analysis of the family showed that both the proband and the third sibling had a novel homozygous nonsense point mutation at nucleotide 87 in exon 1 of the alpha-N-acetyl-neuraminidase (neu1) gene causing a substitution of tryptophan at codon 29 by a termination codon (W29X). DNA sequencing of polymerase chain reaction products identified the parents as heterozygous carriers. To detect neu1 mRNA expression, a real-time reverse transcription/polymerase chain reaction was performed, and similar rates of neu1 mRNA expression were found in the fibroblasts of the fetus, the 2nd sibling, and in controls. The very early termination codon with complete loss of neuraminidase activity is probably the molecular basis of the unusually severe vacuolation pattern in this form of congenital sialidosis.

Hepatic carnitine palmitoyl transferase 1 (CPT1 A) deficiency in North American Hutterites (Canadian and American): evidence for a founder effect and results of a pilot study on a DNA-based newborn screening program.

We describe six patients with hepatic carnitine palmitoyl transferase (CPT1 A) deficiency who are members of a large extended Hutterite kindred living in widely scattered communities in the United States and Canadian Prairies. Two patients have significant neurological impairment due to severe recurrent hypoglycemic crises. The remaining four patients with earlier detection and treatment have near normal outcomes. The Canadian and American Hutterite families share two common ancestors who married in 1812, about 60 years before the Hutterites arrived in North America and prior to their subdivision into the three groups (Schmiedeleut, Dariusleut, and the Lehrerleut). These patients share a common haplotype on chromosome 11q13 and are all homozygous for a common CPT1 A G710E mutation, suggesting a founder effect. The clustering of such a rare disorder of fatty acid oxidation prompted us to initiate a pilot DNA-based neonatal screening program to determine the carrier frequency of this mutation in Hutterite newborns with the participation and support of the community. To date our carrier frequency is 1/16, close to the predicted frequency based on diagnosed patients and number of births. We believe our newborn screening program for CPT1 A deficiency in the Hutterite community will serve as a prototype model for delivery of targeted genetic services to other similar unique genetic isolates.

Elevated protein carbonyls and lipid peroxidation products correlating with myeloperoxidase in tracheal aspirates from premature infants.

The purpose of this study is to determine whether the oxidative injury markers, protein carbonyls and malondialdehyde (MDA), are elevated in tracheal aspirates from very low birth weight (< 1500 g) infants; to determine whether levels correlate with myeloperoxidase as a marker of neutrophil inflammation; and to assess whether high levels are associated with poor respiratory outcome. Tracheal aspirates (144 samples) were collected from 86 infants < 1500 g at times of routine suctioning. Aspirates (82 samples) from 54 infants > or = 1500 g who required intubation for a variety of diagnoses were analyzed for comparison. Analyses were performed for protein carbonyls by ELISA, total malondialdehyde by HPLC, and myeloperoxidase activity. Respiratory outcome was assessed as oxygen requirement at 28-d or 36-wk postmenstrual age, and as the number of days of oxygen requirement. Protein carbonyls were significantly higher in infants < 1500 g than larger infants, and were highest close to birth. MDA concentrations were also higher in the earlier samples. There was a strong positive correlation between protein carbonyls and myeloperoxidase, suggesting a link between protein oxidation and neutrophil activation. A similar but weaker correlation was seen for MDA. Carbonyls in samples taken after steroid administration were less than for controls with a similar age distribution. We did not see significant associations between oxidant marker levels and development of chronic lung disease. Our findings of higher amounts of protein and lipid oxidation products in tracheal aspirates with high myeloperoxidase activity, taken together with other studies showing a link between neutrophil accumulation and chronic lung disease, suggest a possible contribution by neutrophil-derived reactive oxygen species to the injury.

Dopamine transporter and nitric oxide synthase in hypoxic-ischemic brain.

Changes in dopamine transporter and neuronal nitric oxide synthase (nNOS) were investigated by immunohistochemistry in 18 cases of hypoxic-ischemic basal ganglia necrosis. Neuropil dopamine transporter immunostaining in the striatum was increased in seven cases, with relatively mild basal ganglia necrosis, and decreased in four cases, with marked basal ganglia necrosis, compared with age-matched control subjects. Correspondingly, some striatal neurons had increased immunoreactivity to dopamine transporter in the cases of increased immunostaining in the neuropil. nNOS-positive neurons did not obviously change in cases of basal ganglia necrosis within 2 days after birth and then decreased or were not detectable in cases of basal ganglia necrosis at more than 3 days after birth. The results suggest that the synthesis of dopamine transporter is up-regulated in relatively mild basal ganglia necrosis to compensate for the uptake of increased dopamine, that this compensative ability is lost in marked basal ganglia necrosis, and that nNOS-containing neurons in the striatum are relatively resistant to hypoxic ischemia. We speculate that glutamate excitotoxicity mediated by glutamate receptors 1, 2/3, and 4 and excessive dopaminergic excitatory activity may play important roles in hypoxic-ischemic basal ganglia necrosis and that nNOS does not contribute to that condition.

[Diagnostic value of granulocyte elastase determination in cord blood of newborn infants at risk for maternofetal infection]. / Valeur diagnostique du dosage de l'élastase granulocytaire au sang du cordon ombilical chez des nouveau-nés en situation de risque d'infection maternofoetale.

BACKGROUND: Polymorphonuclear elastase is an early and sensitive indicator of neonatal infection when performed at the beginning of clinical symptoms. PATIENTS AND METHODS: To investigate the diagnostic value of elastase measurement in cord blood immediately after birth, 211 neonates (103 boys vs 108 girls, 154 vaginal delivery vs 57 cesarean section). Mean gestational age 38.9 weeks (range: 30-42), mean birth weight 3,260 g (range: 1,430-4,920 g). After clinical, bacterial and biological screening, the infants were classified in three groups. Group A (n = 118): none infectious risk factor neither clinical signs of infection; group B (n = 79): one or more risk factors but no evidence of infection; group C (n = 14): proved or probable infection. Polymorphonuclear elastase was measured in cord blood of all infants using an heterogeneous enzyme-linked-immunosorbent assay. RESULTS: We observed higher elastase values in group C (176 +/- 67 micrograms/L) than in group A (91 +/- 64 micrograms/L) and B (67 +/- 61 micrograms/L) (mean +/- SD, P = 0.0001). With a cutoff value fixed at 80 micrograms/L, the sensitivity of this test applicated to neonates presenting materno-fetal infectious risk factor(s) was 85% (12/14), specificity 74% (59/79), positive predictive value 37%, and negative predictive value 96%. CONCLUSION: Because two of the 14 infected infants (15%) were not detected by elastase dosage in cord blood, this test cannot be used as an early indicator of materno-fetal infection.