a statistical model based on serological parameters for predicting occult HBV infection: implications for organ/ blood donations.

The transmission of hepatitis B virus by donors with occult HBV infection (OBI) is a threat for blood transfusion and organ/tissue transplantation. The risk of carrying HBV DNA is currently not predictable by simple serologic markers, while HBV DNA testing is not universally deployed. This study evaluated an integrated serologic approach for assessing this risk. Anti-HBc positive subjects (461 HIV-negative, 262 HIV-positive) were selected for the study. Serology was analyzed by a commercial CMIA technique. HBV DNA was analyzed by both commercial and home-brew real-time amplification assays. A penalized maximum likelihood logistic approach was used to analyze the data. In HBsAg-negative subjects (HIV-negative), anti-HBc signal/cut off values, the presence of anti-HBc IgM, the absence of anti-HBsAg, and the absence of anti-HCV were correlated to the probability of finding circulating HBV DNA. A model for predicting HBV DNA presence by 4 serological parameters is therefore proposed. The predictive value of the logistic model based on simple serologic markers may represent a reasonable tool for the assessment of HBV transmission risk by transfusion or organ/tissue donation in the context of limited resources and where nucleic acid testing is not performed. In addition, it may be helpful for assessing the risk of reactivation in immunosuppressed OBI patients.

Bilirubin influence on oxidative lung damage and surfactant surface tension properties.

To study the hypothesis that hyperbilirubinemia might reduce in vivo oxidative lung damage while also diminishing lung surfactant surface tension properties during acute lung injury, we performed a randomized study in a rabbit model of acute lung injury. Twenty rabbits were randomized to receive bilirubin or saline intravenously. Acute lung injury was induced by lung lavages with saline. Lung tissue oxidation was evaluated by measuring total hydroperoxide (TH), advanced oxidation protein products (AOPP), and protein carbonyls (PC) in bronchial aspirate (BA) samples. Surface surfactant activity was studied in BA samples using a capillary surfactometer. Bilirubin BA concentration increased in bilirubin-treated rabbits, while it remained undetectable in controls. A similar increase in TH, AOPP, and PC bronchial aspirate concentrations was found in both the study and control groups, while surfactant surface activity was lower in the bilirubin than in the control group. We conclude that during hyperbilirubinemia, bilirubin enters the lung tissue, where it can be detected in BA fluid. Bilirubin is not effective as an antioxidant agent and exerts a detrimental effect on lung surfactant surface tension properties. These findings may have relevance to the management of premature neonates suffering from respiratory distress syndrome and hyperbilirubinemia.

Pathogenic mechanism, prophylaxis, and therapy of symptomatic acidosis induced by acetazolamide.

BACKGROUND: Acetazolamide, a noncompetitive carbonic anhydrase inhibitor, can produce symptomatic acidosis and bone marrow suppression by a mechanism that is still unknown. This presentation occurs in the elderly, patients with renal or liver failure, people with diabetes, and newborns. The objective of this study was to understand the pathogenic mechanism of these adverse effects and to propose a possible prophylaxis and therapy. METHODS: Four human clinical cases were studied, and one animal experiment was performed. Four preterm newborns with posthemorrhagic ventricular dilation developed severe metabolic acidosis after treatment with acetazolamide. The acidosis suddenly disappeared after a packed red blood cell transfusion. Metabolic studies were performed in one patient and in newborn guinea pigs treated with 200 mg/kg acetazolamide. RESULTS: Acetazolamide can produce severe lactic acidosis with an increased lactate-to-pyruvate ratio, ketosis with a low beta-hydroxybutyrate-to-acetoacetate ratio, and a urinary organic acid profile typical of pyruvate carboxylase deficiency. The acquired enzymatic injury resulting from the inhibition of mitochondrial carbonic anhydrase V that provides bicarbonate to pyruvate carboxylase can produce tricarboxylic acid cycle damage. We demonstrate that the dramatic disappearance of metabolic acidosis and normalizing metabolism after blood transfusion were due to the citrate contained in the packed red blood cell bag. This hypothesis was confirmed by animal experimentation. We argue that the metabolic disorder and bone marrow suppression may be related. CONCLUSION: We demonstrate how acetazolamide can lead to symptomatic metabolic acidosis and probably to bone marrow suppression. We suggest citrate as a possible prophylaxis and treatment for these adverse reactions.

Evaluation of bilirubin concentration in hemolysed samples, is it really impossible? The altitude-curve cartography approach to interfered assays.

BACKGROUND: Neonatal jaundice might lead to severe clinical consequences. Measurement of bilirubin in samples is interfered by hemolysis. Over a method-depending cut-off value of measured hemolysis, bilirubin value is not accepted and a new sample is required for evaluation although this is not always possible, especially with newborns and cachectic oncological patients. When usage of different methods, less prone to interferences, is not feasible an alternative recovery method for analytical significance of rejected data might help clinicians to take appropriate decisions. METHODS: We studied the effects of hemolysis over total bilirubin measurement, comparing hemolysis-interfered bilirubin measurement with the non-interfered value. Interference curves were extrapolated over a wide range of bilirubin (0-30 mg/mL) and hemolysis (H Index 0-1100). RESULTS: Interference "altitude" curves were calculated and plotted. A bimodal acceptance table was calculated. Non-interfered bilirubin of given samples was calculated, by linear interpolation between the nearest lower and upper interference curves. CONCLUSIONS: Rejection of interference-sensitive data from hemolysed samples for every method should be based not upon the interferent concentration but upon a more complex algorithm based upon the concentration-dependent bimodal interaction between the interfered analyte and the measured interferent. The altitude-curve cartography approach to interfered assays may help laboratories to build up their own method-dependent algorithm and to improve the trueness of their data by choosing a cut-off value different from the one (-10% interference) proposed by manufacturers. When re-sampling or an alternative method is not available the altitude-curve cartography approach might also represent an alternative recovery method for analytical significance of rejected data.

Diagnosis of gastro-oesophageal reflux in preterm infants: sonography vs. pH-monitoring.

OBJECTIVES: To compare the ultrasound examination with pH-metry in order to evaluate the diagnostic accuracy of sonography for diagnosis of gastro-oesophageal reflux (GOR) in preterm infants. METHODS: A prospective study was conducted on 31 premature infants <34 weeks with clinically diagnosed GOR. First, they underwent 24-hour pH-monitoring; successively, the sonographic assessment was performed within 12 h after pH-monitoring. The two operators who performed the pH-monitoring and sonography respectively, were unaware of each other's results. RESULTS: Twenty-one patients (67.7%) had significant GOR with a reflux index >5 (GOR group). The median (range) reflux index in this group was 9.19% (6.04-20.1). Ten newborns (32.3%) did not have significant GOR with a reflux index <5. Sonography was positive for GOR in 8 patients (25.8%); all 8 infants with sonographic diagnosis of GOR had a reflux index >5. Therefore, sonographic diagnosis did not produce false positives. Sonography was negative in 23 newborns (74.2%); 13 of these were positive to pH-monitoring and may therefore be considered as false negatives. Respect to continuous 24-hour pH-monitoring, sonography showed a specificity of 100% but a very low sensitivity of 38% with a positive prediction value of 100% and a negative prediction value of 43%. CONCLUSIONS: Sonography should not replace 24-hour pH monitoring for detecting GOR in preterm infants. However, sonography has a very high specificity and a positive predictive value of 100%. When clinicians suspect GOR in preterm infants, it could be useful for selection of cases to refer for pH-metry.

Dopamine infusion and anterior pituitary gland function in very low birth weight infants.

BACKGROUND: Previous studies demonstrated that dopamine infusion reduces plasma concentration of thyroxine (T4), thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) in adults, children, and infants. OBJECTIVES: The purpose of this prospective observational study was to evaluate the relationship between dopamine infusion and the dynamics of T4, TSH, PRL, and GH in preterm newborns weighing less than 1,500 g (very low birth weight infants, VLBW) admitted in a neonatal intensive care unit of a university hospital over a one year period. METHODS: A total of 97 preterm newborns were enrolled and divided into two groups: group B included hypotensive infants treated with plasma expanders and dopamine infusion; group A was the control group including newborns who were never treated with dopamine. The newborns were studied dynamically through blood samples taken every day till 10 days. Newborns of group B were studied during dopamine infusion and after its withdrawal. RESULTS: Among the VLBW newborns who were given dopamine, the four pituitary hormones had different dynamics: a reduction of T4, TSH, and PRL levels was noticed since the first day of treatment, and a rebound of their levels was evident since the first day after its interruption. On the contrary, the postprandial GH levels were roughly constant: GH plasma concentrations were in fact a little lower in newborns treated with dopamine, and a slight increase was observed after its withdrawal. However, observed differences were not statistically significant. CONCLUSIONS: The results suggest that dopamine infusion reduces T4, TSH, and PRL plasma levels in preterm VLBW infants and have no effect on postprandial GH rate. This hormonal suppression reverses rapidly after dopamine withdrawal. This observation suggests that the iatrogenic pituitary suppression probably cannot produce long-term injuries.

Brain hemodynamic effects of doxapram in preterm infants.

BACKGROUND: Doxapram is a respiratory stimulant widely used for the treatment of idiopathic apnea of prematurity, although it has been demonstrated that it can induce a transient decrease of cerebral blood flow and that isolated mental delay in infants weighing <1,250 g is associated with the total dosage and duration of doxapram therapy. OBJECTIVES: To evaluate the effects of doxapram on cerebral hemodynamics in preterm infants using cerebral Doppler ultrasonography and near-infrared spectroscopy. METHODS: Preterm infants who required treatment with doxapram for apnea of prematurity unresponsive to caffeine were treated with doxapram at an hourly dose of 0.5 mg x kg(-1).h(-1), followed by 1.5 and 2.5 mg x kg(-1).h(-1). RESULTS: 20 preterm infants were studied. Doxapram induced a significant decrease of oxygenated hemoglobin (O(2)Hb) and cerebral intravascular oxygenation (HbD = O(2)Hb - HHb) and an increase of HHb and CtOx concentrations, while cerebral blood volume and cerebral blood flow velocity did not change. CONCLUSIONS: Doxapram infusion induces the increase of cerebral oxygen consumption and requirement and the contemporary decrease of oxygen delivery probably mediated by a decrease of cerebral blood flow. Caution must be recommended in prescribing this drug for apnea of prematurity.

Umbilical cord care in premature infants: the effect of two different cord-care regimens (salicylic sugar powder vs chlorhexidine) on cord separation time and other outcomes.

OBJECTIVES: To evaluate the effect of 2 cord-care regimens (salicylic sugar powder vs chlorhexidine as a 4% detergent water solution) on cord separation time and other outcomes in preterm infants. METHODS: A prospective, randomized, controlled trial was conducted on 244 preterm newborns with a gestational age of <34 weeks and a birth weight of <2500 g. All preterm newborns were enrolled, regardless of their health condition. We excluded from the study infants whose conditions during the first hours of life required the catheterization of umbilical vessels. We also excluded from the general statistical analysis all newborns who had their programmed cord-care regimen changed because of the presence or the suspicion of omphalitis. On arrival at our neonatal intensive care unit or neonatal special care unit, infants were bathed thoroughly with a soap solution (Saugella, Guieu, Italy), and the umbilical cord (UC) was treated with 1 of the 2 antiseptic products chosen for the study. The stump was then folded and covered with common sterile, dry gauze and kept in place by an elastic net. Until cord detachment and at every diaper change, the cord stump was cleaned with sterile water and treated with the same product initially used for first-time cord care. On the third day of life, we obtained an umbilical swab either from the base of the cord or from the umbilicus if the cord was already sloughed. Six weeks after birth, during hospitalization or during a follow-up visit if already discharged, all infants had a medical examination to check the umbilicus area. Cord separation time, changing of the programmed cord-care regimen, death, omphalitis, sepsis, cord bleeding, nurses' opinion on treatments efficacy, and UC colonization were measured. RESULTS: The cord separation time was significantly lower in infants who were treated with salicylic sugar powder (6 +/- 2 days) than in infants who were treated with chlorhexidine (9 +/- 2 days). The programmed cord-care regimen was changed in a significantly higher number of newborns in the chlorhexidine group (17) than in the salicylic sugar group (3). None of the newborns died, and we found only sporadic cases of sepsis (1 patient in each group) and omphalitis (1 patient in the chlorhexidine group). A significantly higher percentage of nurses were satisfied with the salicylic sugar powder treatment (98%) than with the chlorhexidine treatment (67%), notwithstanding a more frequent occurrence of slight cord scar bleeding in the salicylic sugar group (7.8%) than in the chlorhexidine group (4%). The rate of negative umbilical swabs was significantly higher in infants treated with salicylic sugar powder (73.1%) than with chlorhexidine (53%). CONCLUSIONS: In neonatal intensive care units and neonatal special care units of developed countries, salicylic sugar powder can be used effectively and safely for UC care of preterm infants.

Maternal education and the incidence and duration of breast feeding: a prospective study.

INTRODUCTION: Duration of breast feeding and factors possibly affecting duration were studied in a population of 2174 newborn infants, with gestational age of >37 weeks, who were born in the Department of Obstetrics and Gynaecology at the University of Florence Hospital between November 15, 1997, and November 14, 1998. PATIENTS AND METHODS: Nine hundred mothers agreed to participate in the study. Five questionnaires were completed at the end of the 1st, 3rd, 6th, 9th, and 12th postpartum month. These dealt with infant feeding practices, including breast feeding during the previous week. Breast feeding duration was defined as short (1 month); medium-short (>1 month-<3 months); medium (>3-<6 months); medium-long (>6-<9 months), and long (>9 months). RESULTS: The authors found that 76.3%, 64.7%, 42.3%, 26.4%, and 17% of mothers were still breast feeding at 1, 3, 6, 9, and 12 months after delivery, respectively. The multivariate analysis of the correspondence shows that lack of breast feeding is associated with a birth weight of less than 3000 g, a low level of maternal education, and maternal profession as a housewife or blue collar worker in the commercial sector. A period of breast feeding defined as short or medium-short is associated with mothers who smoke, primiparous mothers, and absence of maternal allergy. The survival curves highlight how the single factor of smoking is an element that leads to a significant difference in the duration of breast feeding. The multiple Cox regression analysis shows a significant negative influence associated with birth weight of less than 3000 g, maternal smoking, and first parity. Above all, among low-birth-weight infants of mothers who smoke, there is a strong correlation with a shorter duration of breast feeding. DISCUSSION: There is still a need for programs that support and encourage breast feeding, focusing particularly on mothers with a low level of education who give birth to a low-weight infant, primiparous mothers, and smokers.

Congenital syphilis: unique clinical presentation in three preterm newborns.

Three preterm newborns affected by congenital syphilis, born to mothers not adequately treated during pregnancy, are described. The clinical picture is characterized by a severe cholestatic hepatopathy and, in the two surviving patients, by an unusually wide ischemic-hemorrhagic lesion of the cerebral parenchyma. This lesion is probably due to a syphilitic endarteritis, and has rarely been described before in preterm infants.

Effects of phototherapy on cerebral haemodynamics in preterm infants: is fibre-optic different from conventional phototherapy?

We hypothesized that conventional phototherapy (CPT) and fibre-optic phototherapy (FPT) could exert different effects on cerebral blood perfusion. Our aim was to assess this hypothesis in a prospective study of the cerebral haemodynamics in preterm infants. Twenty-three infants (gestational age <34 weeks) were randomized for CPT (n=12) and for FPT (n=11). Cerebral Doppler ultrasounds were performed on all infants immediately before phototherapy (time 0), 6-12 hours (time 1) and 24-36 hours (time 2) after the start of phototherapy, and 6-12 hours after discontinuing phototherapy (time 3). CPT and FPT were associated with a significant increase of peak-systolic blood flow velocity and mean blood flow velocity at time 1 and 2, which disappeared at time 3, whereas end-diastolic blood flow velocity and resistance index were unchanged. No difference was shown between the groups. CPT and FPT were found to exert similar effects on cerebral haemodynamics. Both were associated with an increase of cerebral blood flow velocity which ended when phototherapy was stopped.

Dopamine infusion and hypothyroxinaemia in very low birth weight preterm infants.

UNLABELLED: The purpose of this study was to assess the relationship between transient hypothyroxinaemia of prematurity (THOP) in very low birth weight newborns and dopamine administration. A total of 172 newborns was enrolled in a prospective observational study and divided into three groups: group A included newborns who were never treated with dopamine; group B were infants in whom dopamine treatment was discontinued for at least 6 h before the congenital hypothyroidism screening and group C included infants who were given dopamine during the screening. Among those newborns given dopamine, the THOP incidence was higher (11.6% in group A; 53.8% in group B; 89.3% in group C), and the vales of TSH (1.67+/-2.32 microU/ml in group A; 1.29+/-1.74 microU/ml in group B; 0.89+/-1.34 microU/ml in group C) and thyroxine (6.1+/-2.2 microg/dl in group A; 3.9+/-1.9 microg/dl in group B; 2.4+/-1.4 microg/dl in group C) were significantly lower. These differences were further confirmed even after gestational age stratification and mathematical correction for differences in clinical conditions. The effects of dopamine appear to be dose-dependent. CONCLUSION: Even if it cannot be excluded that reduced thyroid stimulating hormone and thyroxine concentrations are caused by non-thyroidal illness, the results suggest that the infusion of dopamine reduces the thyroid stimulating hormone and thyroxine levels in very low birth weight newborns.