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PubMed1998

Idiopathic neonatal hepatitis presenting as neonatal hepatic siderosis and steatosis.

Idiopathic neonatal hepatitis (INH) is a heterogeneous disease of undetermined cause. We report a retrospective histologic reevaluation of INH. Sixty patients with INH were reviewed along with 32 biliary atresia (BA) patients. Histologic findings, iron and fat deposits, giant cell transformation, portal fibrosis, and bile duct proliferation were semiquantitatively graded from 0 to 4+. Significant histologic findings were defined as > or =2+. Frequencies of patients with significant histologic findings in the INH group were compared with those of the BA group. Among the patients with significant histologic findings, those in the INH group had significantly less iron deposits (P < 0.01), portal fibrosis (P < 0.01), and bile duct proliferation (P < 0.01) than those of the BA group. A combination of significant hepatic macrovesicular steatosis and siderosis was observed in 10 INH patients but not in any BA patient (10/60 vs 0/32, P < 0.05). Without extensive treatment, the 10 INH patients all recovered, and hepatic abnormalities normalized by the age of 12 months. In conclusion, the present study showed that the recognition of hepatic siderosis is helpful to distinguish BA from INH and that in a subset of INH patients hepatic macrovesicular steatosis and siderosis occurs.

Biliary Atresia↗
PubMed1991

A controlled trial of synthetic surfactant in infants weighing 1250 g or more with respiratory distress syndrome. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group.

BACKGROUND: Surfactant-replacement therapy is now recognized as a life-saving and safe intervention in small premature infants, but there is little evidence concerning its risks and benefits in larger premature infants. METHODS: We conducted a placebo-controlled, blinded trial in 1237 infants with respiratory distress who were enrolled at 23 hospitals in the United States and 13 hospitals in Canada. At entry all the infants weighed at least 1250 g, were receiving mechanical ventilation, and had a ratio of arterial to alveolar oxygen tension below 0.22. The initial dose of either the synthetic surfactant (Exosurf, 5 ml per kilogram of body weight) or air (the placebo) was administered less than 24 hours after birth, with a second dose given 12 hours later. A total of 614 infants were assigned to receive surfactant, and 623 to receive placebo. RESULTS: Fewer infants in the surfactant group than in the placebo group died before 28 days of age or survived at 28 days with bronchopulmonary dysplasia (7 percent vs. 12 percent, P = 0.002). In the first 28 days of life, there were fewer deaths due to respiratory distress syndrome in the surfactant group (1 percent vs. 3 percent, P = 0.043), lower overall neonatal mortality (4 percent vs. 7 percent, P = 0.04), and a lower incidence of bronchopulmonary dysplasia (3 percent vs. 6 percent, P = 0.008). There was also a significantly lower incidence of pulmonary air leaks, intraventricular hemorrhage, patent ductus arteriosus, seizures, hypotension, and pulmonary hypertension in the surfactant group. The infants treated with surfactant were weaned from oxygen and mechanical ventilation significantly sooner than those given placebo, and they less often required high-frequency ventilation or extracorporeal membrane oxygenation. The primary side effect observed more frequently among the infants who received surfactant treatment was pulmonary hemorrhage (six infants vs. one infant, P = 0.055). CONCLUSIONS: In infants weighing at least 1250 g at birth who have respiratory distress syndrome, treatment with two doses of synthetic surfactant improves survival and reduces perinatal morbidity.

Birth Weight↗
PubMed2004

Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features.

Inwardly rectifying potassium channels (Kir channels) control cell membrane K(+) fluxes and electrical signaling in diverse cell types. Heterozygous mutations in the human Kir6.2 gene (KCNJ11), the pore-forming subunit of the ATP-sensitive (K(ATP)) channel, cause permanent neonatal diabetes mellitus (PNDM). For some mutations, PNDM is accompanied by marked developmental delay, muscle weakness, and epilepsy (severe disease). To determine the molecular basis of these different phenotypes, we expressed wild-type or mutant (R201C, Q52R, or V59G) Kir6.2/sulfonylurea receptor 1 channels in Xenopus oocytes. All mutations increased resting whole-cell K(ATP) currents by reducing channel inhibition by ATP, but, in the simulated heterozygous state, mutations causing PNDM alone (R201C) produced smaller K(ATP) currents and less change in ATP sensitivity than mutations associated with severe disease (Q52R and V59G). This finding suggests that increased K(ATP) currents hyperpolarize pancreatic beta cells and impair insulin secretion, whereas larger K(ATP) currents are required to influence extrapancreatic cell function. We found that mutations causing PNDM alone impair ATP sensitivity directly (at the binding site), whereas those associated with severe disease act indirectly by biasing the channel conformation toward the open state. The effect of the mutation on ATP sensitivity in the heterozygous state reflects the different contributions of a single subunit in the Kir6.2 tetramer to ATP inhibition and to the energy of the open state. Our results also show that mutations in the slide helix of Kir6.2 (V59G) influence the channel kinetics, providing evidence that this domain is involved in Kir channel gating, and suggest that the efficacy of sulfonylurea therapy in PNDM may vary with genotype.

ATP-Binding Cassette Transporters↗
PubMed1980

Ventilatory management of neonates undergoing surgery. A review of the first 3 years' experience in a neonatal surgical intensive care unit.

The results of the ventilatory management of babies, obtained in the first 3 years of a neonatal surgical intensive care unit, are assessed. Overall mortality figures and detailed examination of the cause of death in individual diagnostic groups support a selective approach to intermittent positive pressure ventilation (IPPV) based mainly on clinical criteria. The adoption of a policy of prophylactic IPPV after operation would achieve virtually no improvement in mortality.

Abdomen↗
PubMed2004

Neonatal tetanus incidence in China, 1996-2001, and risk factors for neonatal tetanus, Guangxi Province, China.

BACKGROUND: In China during 1995-1996 widespread tetanus toxoid (TT) mass vaccination of women of childbearing age in high-risk areas was conducted and neonatal tetanus (NT) surveillance was initiated as part of NT elimination efforts. Despite a subsequent decrease in the estimated rate of NT, the NT disease burden remains high in poorer areas of China. METHODS: To describe the recent epidemiology of NT in China and estimate its risk, we analysed national surveillance data in China 1996-2001 and conducted a case-control study in one high-risk county (Bobai): 60 hospitalized cases were sex- and calendar-birth year matched to 60 controls from the same or neighbouring villages. RESULTS: Reported national annual NT incidence decreased from 0.21/1000 live births (LB) in 1997 to 0.16/1000 LB in 2001. Case mothers were more likely to be aged >30 years (odds ratio [OR] = 6; 95% CI: 2.2, 20.2), unschooled (OR = 3.2; 95% CI: 1.1, 11.6), and with an annual income of <1000 yuan ($125 USD) (OR = 6.0; 95% CI: 1.9, 25.6). Only 28% of control mothers and 12% of case mothers reported any TT vaccination. In multivariate analysis, relative to hospital delivery, cases had a 64-fold increased odds of home delivery by a family member or neighbour (95% CI: 8.4, 982.2), and a 13-fold increased odds of home delivery by a traditional birth attendant (95% CI: 1.6, 322.6). CONCLUSIONS: Improved access to clean deliveries in high-risk areas is critically needed in China. Nonetheless, targeted TT vaccination appears to have helped reduce NT incidence in China.

China↗
PubMed2001

A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. II. Perioperative breathing patterns in neonates and infants with pyloric stenosis.

UNLABELLED: Although former preterm birth infants are at risk for postoperative apnea after surgery, it is unclear whether the same is true of full-term birth infants. We evaluated the incidence of apnea in 60 full-term neonates and infants undergoing pyloromyotomy both before and after anesthesia. All subjects were randomized to a remifentanil- or halothane-based anesthetic. Apnea was defined by the presence of prolonged apnea (>15 s) or frequent brief apnea, as observed on the pneumocardiogram. Apnea occurred before surgery in 27% of subjects and after surgery in 16% of subjects, with no significant difference between subjects randomized to remifentanil or halothane anesthesia. This apnea was primarily central in origin, occurred throughout the recording epochs, and was associated with severe desaturation in some instances. Of the subjects with normal preoperative pneumocardiograms, new onset postoperative apnea occurred in 3 (23%) of 13 subjects who received halothane-based anesthetics versus 0 (0%) of 22 subjects who received remifentanil-based anesthetics (P = 0.04). Thus, postoperative apnea can follow anesthesia in otherwise healthy full-term infants after pyloromyotomy and is occasionally severe with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic. IMPLICATIONS: Abnormal breathing patterns can follow anesthesia in infants after surgical repair of pyloric stenosis. Occasionally, these patterns can be associated with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic.

Anesthetics, Inhalation↗
PubMed1998

Antiretroviral therapies in pregnancy: maternal, fetal and neonatal effects. Swiss HIV Cohort Study, the Swiss Collaborative HIV and Pregnancy Study, and the Swiss Neonatal HIV Study.

BACKGROUND: Therapies containing two reverse transcriptase inhibitors (RTI) with or without protease inhibitors are used with increasing frequency in pregnant HIV-infected women. OBJECTIVE: To assess the safety of antiretroviral therapy in pregnant women and their newborns. METHODS: All clinical events and laboratory abnormalities in pregnant women on RTI with or without protease inhibitors and in their newborns were collected through an observational study. RESULTS: A total of 37 HIV-infected pregnant women have given birth to 30 children (by 30 April 1998). All received RTI, which were combined with protease inhibitors in 16 cases. Twelve women became pregnant while on treatment. Drugs used were as follows: zidovudine (n = 33), lamivudine (n = 33), stavudine (n = 4), indinavir (n = 9), ritonavir (n = 4), nelfinavir (n = 2) and saquinavir (n = 2). Adverse events during pregnancy were anaemia (n = 15), elevation of transaminases (n = 4), nausea/vomiting (n = 4), glucose intolerance (n = 2), nephrolithiasis (n = 2), diarrhoea (n = 2), hypertension (n = 1), insulin-requiring diabetes (n = 1). Adverse events in neonates were prematurity (n = 10), anaemia (n = 8), cutaneous angioma (n = 2), cryptorchidism (n = 2), transient hepatitis (n = 1). Non-life-threatening intracerebral haemorrhage occurred in a premature baby (33 weeks gestation) exposed during fetal life to zidovudine-lamivudine-indinavir, and in a term baby exposed to stavudine-lamivudine-indinavir. Extrahepatic biliary atresia occurred in one newborn exposed to zidovudine-lamivudine-indinavir. Maternal viral load was below 400 copies/ml in 18 out of 30 patients who delivered. One case of mother-to-child HIV transmission was identified. CONCLUSIONS: In HIV-infected pregnant women treated with two RTI with or without protease inhibitors, one or more adverse events occurred in 29 out of 37 women and in 14 out of 30 babies. In newborns, frequent prematurity, one case of biliary malformation and one intracerebral haemorrhage in a term baby are of concern. These observations do not preclude combination therapies during pregnancy but emphasize the necessity to maintain updated registers on their safety.

Anti-HIV Agents↗
PubMed1981

An unusual cause of neonatal respiratory distress. RDS in a neonate with a neuro-enteric cyst.

A 2.5 kg male infant developed respiratory distress in the neonatal period. A diagnosis of idiopathic hyaline membrane disease was made and he was treated accordingly. At 24 hours of age he required intubation, and the immediate and dramatic improvement in his condition suggested that the original diagnosis was incorrect. Closer examination of the chest X-ray revealed an intrathoracic cyst and abnormal vertebrae. The cyst was removed surgically, and histological examination showed it to be a neuro-endodermal cyst.

Humans↗
PubMed1982

The importance of neonatal asphyxia and caesarean section as risk factors for neonatal respiratory disorders in an unselected population.

The risk of neonatal respiratory disorders was calculated in an unselected, total population together with the relative contributions of some factors found associated with an increased risk. Postnatal asphyxia, expressed as a low one minute Apgar score, and low gestational age were substantially, independent risk factors. Caesarean section added, though less markedly, to the risk of the above disorders.

Apgar Score↗
PubMed2000

Enhancement of neonatal innate defense: effects of adding an N-terminal recombinant fragment of bactericidal/permeability-increasing protein on growth and tumor necrosis factor-inducing activity of gram-negative bacteria tested in neonatal cord blood ex vivo.

Innate defense against microbial infection requires the action of neutrophils, which have cytoplasmic granules replete with antibiotic proteins and peptides. Bactericidal/permeability-increasing protein (BPI) is found in the primary granules of adult neutrophils, has a high affinity for lipopolysaccharides (or "endotoxins"), and exerts selective cytotoxic, antiendotoxic, and opsonic activity against gram-negative bacteria. We have previously reported that neutrophils derived from newborn cord blood are deficient in BPI (O. Levy et al., Pediatrics 104:1327-1333, 1999). The relative deficiency in BPI of newborns raised the possibility that supplementing the levels of BPI in plasma might enhance newborn antibacterial defense. Here we determined the effects of addition of recombinant 21-kDa N-terminal BPI fragment (rBPI(21)) on the growth and tumor necrosis factor (TNF)-inducing activity of representative gram-negative clinical isolates. Bacteria were tested in citrated newborn cord blood or adult peripheral blood. Bacterial viability was assessed by plating assay, and TNF-alpha release was measured by enzyme-linked immunosorbent assay. Whereas adult blood limited the growth of all isolates except Klebsiella pneumoniae, cord blood also allowed logarithmic growth of Escherichia coli K1/r and Citrobacter koseri. Bacteria varied in their susceptibility to rBPI(21)'s bactericidal action: E. coli K1/r was relatively susceptible (50% inhibitory concentration [IC(50)], approximately 10 nM), C. koseri was intermediate (IC(50), approximately 1,000 nM), Klebsiella pneumoniae was resistant (IC(50), approximately 10,000 nM), and Enterobacter cloacae and Serratia marcescens were highly resistant (IC(50), >10,000 nM). All isolates were potent inducers of TNF-alpha activity in both adult and newborn cord blood. In contrast to its variable antibacterial activity, rBPI(21) consistently inhibited the TNF-inducing activity of all strains tested (IC(50), 1 to 1,000 nM). The antibacterial effects of rBPI(21) were additive with those of a combination of conventional antibiotics typically used to treat bacteremic newborns (ampicillin and gentamicin). Whereas ampicillin and gentamicin demonstrated little inhibition of bacterially induced TNF release, addition of rBPI(21) either alone or together with ampicillin and gentamicin profoundly inhibited release of this cytokine. Thus, supplementing newborn cord blood with rBPI(21) potently inhibited the TNF-inducing activity of a variety of gram-negative bacterial clinical pathogens and, in some cases, enhanced bactericidal activity. These results suggest that administration of rBPI(21) may be of clinical benefit to neonates suffering from gram-negative bacterial infection and/or endotoxemia.

Adult↗
PubMed1989

Maternal determinants of neonatal immune response to ovalbumin: effect of breast feeding on development of anti-ovalbumin antibody in the neonate.

Inbred Brown-Norway female rats were immunized intraperitoneally with ovalbumin (OVA) or sham-immunized 14 days before and 10 days after mating. In subsequent studies with OVA, babies fed by immunized mothers, regardless of whether they were born from immunized or sham-immunized mothers, showed suppression of IgG, IgM and IgE anti-OVA responses. In additional studies, these babies developed OX-8-positive but W3/25-negative phenotypic suppressor T-cells specific for anti-OVA antibody production. However, these regulatory cells did not react with OVA itself when tested for in vitro proliferative response to OVA. Subsequent immunization of the neonates with OVA appeared to abrogate suppression of IgG and IgM antibody responses. However, maternally induced suppression of IgE persisted and was not influenced by subsequent immunization.

Animals↗
PubMedDate not supplied

Fetal and neonatal hematologic parameters in red cell alloimmunization: predicting the need for late neonatal transfusions.

The purpose of this study was to determine whether the need for late neonatal transfusion can be predicted in fetuses who received intrauterine transfusions. The records of 36 patients who underwent intrauterine transfusion were reviewed. Newborns who required late transfusions had a lower reticulocyte count at their last intrauterine transfusion, a longer duration between their lowest fetal reticulocyte count and delivery, and a higher umbilical cord blood hemoglobin and percent adult red cells on Kleihauer-Betke stain at delivery. The need for late transfusions appears to be related to the extent and duration of fetal bone marrow suppression.

Bilirubin↗
PubMed1977

Neonatal lung defense mechanisms: a study of the alveolar macrophage system in neonatal rabbits.

Abnormal function of the alveolar macrophage system may explain the enhanced susceptibility to pulmonary infection in human neonates. This hypothesis was investigated by infecting 1- to 14-day-old rabbits with aerosols of Staphylococcus aureus and then measuring in situ rates of bacterial ingestion, inactivation, and destruction in the lapine lung. The inhaled staphylococci were killed within the lungs of 1-day-old rabbits at a significantly slower rate than that for 7- and 14-day-old rabbits (P less than 0.05). Much of this decrease was due to diminished rates of bacterial ingestion by alveolar macrophages of younger animals. Staphylococci were also killed and destroyed less rapidly within these macrophages, but these differences could not be tested for significance.

Animals↗
PubMed1981

Fetal and neonatal responses to maternal canine starvation: circulating fuels and neonatal glucose production.

Pregnant dogs were starved for 72 hr while controls were fasted overnight. Maternal starvation significantly reduced fetal birth weight (269 +/- 7.2 versus 294 +/- 4.4 g). Total caloric deprivation had no effect on maternal or fetal blood glucose concentration at the time of delivery; however, fasting neonatal blood glucose levels were depressed during the first 9 hr of life. Starvation produced a large elevation of maternal free fatty acids (1.68 +/- 0.39 versus 0.74 +/- 0.2 mM) and ketone bodies (2.99 +/- 0.70 versus 1.04 +/- 0.48). Although fetal free fatty acids increased minimally (0.39 +/- 0.03 versus 0.22 +/- 0.07), ketone body levels were markedly elevated (2.53 +/- 0.35 versus 1.01 +/- 0.32). After birth, plasma-free fatty acid and beta-hydroxybutyrate levels were lower in pups of starved mothers at 3 hr, and acetoacetate was lower at 6 and 9 hr. Other alternate fuels such as amino acids demonstrated lower levels of glutamine in pups of starved mothers throughout the day (except 3 hr), whereas alanine levels declined significantly only at 24 hr (114.9 +/- 15 versus 187.6 +/- 26 microM. Glucose production was significantly depressed in pups of starved mothers at 3 (13.7 +/- 1.4 versus 22.7 +/- 3) and 9 hr (17.5 +/- 2.2 versus 26.0 +/- 2.8 mumoles/kg/min), whereas glucose clearance rates were elevated at 3, 6 and 9 hr of age. Lactate carbon incorporation into glucose increased throughout the day but was not significantly affected by prior maternal starvation.

Amino Acids↗
PubMed1993

Effect of interleukin-11 with and without granulocyte colony-stimulating factor on in vivo neonatal rat hematopoiesis: induction of neonatal thrombocytosis by interleukin-11 and synergistic enhancement of neutrophilia by interleukin-11 + granulocyte colony-stimulating factor.

IL-11, a new hematopoietic cytokine isolated from primate stromal cells (PU-34), has been shown to act synergistically with IL-3 to induce proliferation of early hematopoietic stem cells and induce in vitro CFU-MEG proliferation. We hypothesize that recombinant human (rh)IL-11 alone or in combination with granulocyte colony-stimulating factor (G-CSF) might modulate newborn in vivo granulopoiesis and thrombopoiesis. Newborn Sprague-Dawley rats were given 14 d of intraperitoneal rhIL-11 (0-250 micrograms/kg x 14 d), rhIL-11 (250 micrograms/kg) + rhG-CSF (5 micrograms/kg simultaneously x 14 d), rhIL-11 x 7 d followed by G-CSF x 7 d, G-CSF x 14 d, PBS/human serum albumin x 7 d followed by G-CSF x 7 d, or PBS/human serum albumin x 14 d. rhIL-11 alone had no effect on the circulating hematocrit or absolute neutrophil count. There was, however, a significant increase in the circulating platelet count after rhIL-11 (100 and 250 micrograms/kg) versus PBS/human serum albumin (d 13: 1241 +/- 54, 1262 +/- 58 versus 939 +/- 38 k/mm3; p = 0.01). Sequential and simultaneous IL-11 + G-CSF caused a significant increase in the marrow neutrophil reserve and the circulating absolute neutrophil count above that observed when G-CSF alone was administered. IL-11 +/- G-CSF, however, failed to reduce the 96-h mortality rate during experimental group B streptococcal sepsis. These data suggest that IL-11 alone results in a significant elevation in the blood platelet concentration and, in combination with G-CSF, induces an increase in in vivo neonatal rat myelopoiesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Studies on steroids in fetuses and neonates: identification of 16-dehydropregnenolone in the circulation of pre-term neonates.

Unconjugated steroids were extracted with dichloromethane from the serum of pre-term neonates. Conjugated steroid fraction in the residue was separated and purified by high performance liquid chromatography. The purified steroid fraction was subjected to enzyme (arylsulfatase from Helix pomatia) or acid hydrolysis. Liberated steroid was analyzed by gas chromatography-mass spectrometry (GC/MS) and gas chromatography-Fourier transformation infrared spectroscopy (GC/FT-IR). All of the results obtained from GC/MS and GC/FT-IR analysis were identical with those of authentic 16-dehydropregnenolone (3 beta-hydroxy-5,16-pregnadien-20-one, 16-DHP). This is the first report to demonstrate the presence of 16-DHP in human blood.

Arylsulfatases↗
PubMed2000

International Guidelines for Neonatal Resuscitation: An excerpt from the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science. Contributors and Reviewers for the Neonatal Resuscitation Guidelines.

The International Guidelines 2000 Conference on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiac Care (ECC) formulated new evidenced-based recommendations for neonatal resuscitation. These guidelines comprehensively update the last recommendations, published in 1992 after the Fifth National Conference on CPR and ECC. As a result of the evidence evaluation process, significant changes occurred in the recommended management routines for: * Meconium-stained amniotic fluid: If the newly born infant has absent or depressed respirations, heart rate <100 beats per minute (bpm), or poor muscle tone, direct tracheal suctioning should be performed to remove meconium from the airway. * Preventing heat loss: Hyperthermia should be avoided. * Oxygenation and ventilation: 100% oxygen is recommended for assisted ventilation; however, if supplemental oxygen is unavailable, positive-pressure ventilation should be initiated with room air. The laryngeal mask airway may serve as an effective alternative for establishing an airway if bag-mask ventilation is ineffective or attempts at intubation have failed. Exhaled CO(2) detection can be useful in the secondary confirmation of endotracheal intubation. * Chest compressions: Compressions should be administered if the heart rate is absent or remains <60 bpm despite adequate assisted ventilation for 30 seconds. The 2-thumb, encircling-hands method of chest compression is preferred, with a depth of compression one third the anterior-posterior diameter of the chest and sufficient to generate a palpable pulse. * Medications, volume expansion, and vascular access: Epinephrine in a dose of 0.01-0.03 mg/kg (0.1-0.3 mL/kg of 1:10,000 solution) should be administered if the heart rate remains <60 bpm after a minimum of 30 seconds of adequate ventilation and chest compressions. Emergency volume expansion may be accomplished with an isotonic crystalloid solution or O-negative red blood cells; albumin-containing solutions are no longer the fluid of choice for initial volume expansion. Intraosseous access can serve as an alternative route for medications/volume expansion if umbilical or other direct venous access is not readily available. * Noninitiation and discontinuation of resuscitation: There are circumstances (relating to gestational age, birth weight, known underlying condition, lack of response to interventions) in which noninitiation or discontinuation of resuscitation in the delivery room may be appropriate.

Blood Volume↗