Antonio Balata

Favism in a female newborn infant whose mother ingested fava beans before delivery

We describe a case of favism in a female newborn infant with glucose-6-phosphate dehydrogenase (G6PD) deficiency whose mother had ingested fava beans 5 days before delivery. At birth there were clinical and hematologic signs of hemolytic anemia, hemoglobinuria, and no blood group immunization. Study of the G6PD activity and 2-deoxy-glucose-6-phosphate utilization rate revealed that the infant and the mother were heterozygous for G6PD deficiency.

Perimortem cesarean delivery 30 minutes after a laboring patient jumped from a fourth-floor window: Baby survives and is normal at age 4 years

We describe the first case of a perimortem cesarean section on a patient who committed suicide during labor by jumping from the fourth-floor window of the labor ward. The cesarean section was performed 30 minutes after the death of the woman, and a child of 3037 g was born with an Apgar score of 0 at 1 minute. Today, 4 years later, the baby is well and has no apparent neurological problems.

Routine second trimester ultrasound screening for prenatal detection of fetal malformations in Sassari University Hospital, Italy: 23 years of experience in 42,256 pregnancies.

OBJECTIVE To establish, for a determined period of time, the effectiveness of a program of ultrasound screening in detecting fetal malformations in prenatal time. To assess the sensitivity, the specificity, the positive and the negative predictive value of the ultrasound screening. To examine the trend of such indexes of diagnostic accuracy in a long time period. STUDY DESIGN The patients admitted to the study had effected at least one ultrasound examination within the second trimester of pregnancy (< or =23 gestational weeks). The examined pregnant women were 42,256 and the period of reference ranged from January 1981 to December 2004. All patients delivered in Gynecologic and Obstetric Clinic of Sassari University, Sassari, Italy. RESULTS In the considered period were reported 1050/42,256 (2.48%) cases of fetal malformations, of which 974 single and 76 multiple malformations. The cases of malformations diagnosed in prenatal period were 578/1050 (55.05%), of which 65/578 (11.24%) multiple anomalies. The overall sensitivity was 55.05% (95% confidence interval: 52-58%), with a variability from the 32.95% (cardiovascular system) to 81.05% (central nervous system) in relationship to the typology of the examined apparatus. The overall specificity was 99.88% (95% confidence interval: 98-99.9%), the predictive positive value 91.89% (95% confidence interval: 89-93%) and the negative predictive value 98.87% (95% confidence interval: 95-99%). CONCLUSION The sensitivity of the ultrasound screening undoubtedly appeared to be satisfactory. We believe that, for the examination of some apparatuses, as for the cardiovascular apparatus, with the extension of the standard examination (four-chamber view) to further plans of scanning, sensitivity could subsequently be improved.

Increased bilirubin production, ceruloplasmin concentrations and hyperbilirubinaemia in full-term newborn infants

Ceruloplasmin possesses antioxidant activity in vitro, but such a property has not been substantiated in vivo so far. However, it has been suggested that the lack of factors protective against oxidative haemolysis might have a role in neonatal hyperbilirubinaemia. Ceruloplasmin and alphafetoprotein concentrations were measured in cord blood in 78 unselected full-term singleton newborn infants without G6PD deficiency and haemolytic disease of the newborn; in the same infants, the carboxyhaemoglobin level was assessed on the fourth day of life and taken as an index of bilirubin production. The relationship between these variables and maximum bilirubin level in the first 4 days was studied by multiple regression analysis. High carboxyhaemoglobin levels and low ceruloplasmin concentrations, but not alphafetoprotein resulted, associated with hyperbilirubinaemia (P < 0.001). No relationship was found between carboxyhaemoglobin and ceruloplasmin levels. These results exclude an important role for ceruloplasmin in protecting against possible oxidative haemolysis in full-term newborn infants. Ceruloplasmin levels in cord blood are most probably related to hepatic metabolism and are better predictors of hyperbilirubinaemia than alphafetoprotein concentrations.

98 PLASMA CERULOPLASMIN (CP) LEVELS IN NEWBORN INFANTS WITH SEVER JAUNDICE (J) OF UNKNOWN ETILOGY AND WITH J DUE TO GLUCOSE-6-PHOSPHATE-DEHYDROGENASE (G6PD) DEFICIENCY

The role of liver immaturity in the pathogenesis of severe J in G6PD deficient newborns is debated. Plasma levels of CP, a protein synthesized by the liver, could provide an assessment of hepatic immaturity. CP was measured by nephelometry in cord-blood in 4 Groups of newborns either without J (maximum serum bilirubin <8 mg/dl) or with J (max.bilirubin >15 mg/dl) :Group 1),20 full-term without J; Group 2), 20 full-term with J of unknown etiology;Group 3), 12 G6PD deficient without J;Group 4), 12 G6PD deficient with J. Mean CP levels in Groups 2) and 4) were significantly lower than in 1) and 3) (p<0.05). CP was also measured on day 2-3 in 3 Groups of infants: Group 5), 26 full-term without J;Group 6),36 full-term with J;Group 7), 31 G6PD deficient with J.Mean CP levels in Groups 6) and 7) were significantly lower than in 5), (p<0.05). These results, and our previous observations of an elevated α-Fetoprotein level in cord-blood of newborns with J (*), suggest that liver immaturity plays an important role in the genesis of J in both normal and G6PD deficient newborns. They also suggest the possibility of identifying at birth those infants who are at risk of severe J requiring treatment. (*) Ped.Res.22:225, 1987 and 24:268, 1988.

Elements of pharmacoeconomics.

© E.S.I.F.T. srl Firenze ISSN 1120-009X The increasing awareness of healthcare institutions concerning the limited availability of economic resources concurs with the affirmation of a relatively new discipline known as pharmacoeconomics whose main purpose is to estimate the priorities of resource allocation. As M. Drummond has effectively summed up, pharmacoeconomics should answer this question: “Who should do what to whom, with what health care resources, and with what relation to other health services ?”1 It is necessary to perform a careful evaluation of the distribution of all resources, both from an economic and ethical point of view, because a careless policy of sharing resources could affect the availability of those treatments so essential to all patients within a Healthcare System. On the other hand, scientific progress and the complexity of healthcare protocols have increased the cost of the new therapies, pharmacological and non-pharmacological. With these assumptions, it has been essential to introduce, also in a healthcare context, some evaluation techniques generally used in economic analyses in order to address all choices regarding a proper distribution of the limited resources available and, according to the most objective criteria. The complexity of pharmacoeconomic analyses is increased according to the different points of view from which it is possible to spot the problem. This one has a wide range of features based on different points of view: that of a single patient, of all patients, of the medical prescriber and of the healthcare system, the so-called “third payer” 2. Even if pharmacoeconomic surveys never assume the perspectives of the medical prescriber but those of healthcare institutions (healthcare system, healthcare insurance and organisations that supply healthcare services), the involvement of physicians, on which the effect of the measures raised by the pharmacoeconomic analysis, is unavoidable. It would not be possible to apply these measures without the contribution and the collaboration of the front line operators. The main aim of a pharmacoeconomic analysis is the assessment of the cost of a sanitary action, according to the benefits deriving from it. The therapeutic benefit of a drug can be estimated on the basis of effectiveness, tolerability and duration of influence on the health of patients; this benefit can influence the quality of life of patients and their relatives: as a matter of fact the quality of life is improved if the treatment is effective, and becomes worse if the treatment turn out to be harmful. The modifications influencing the quality of life and therefore the subjective appreciation of the treatment can be expressed in terms of usefulness of the treatment itself. Finally, every treatment reflects an economic value represented by the cost of treatment that includes the cost of drug, of the necessary devices used during its administration and, obviously, the cost of the staff assigned to administer the drug. To the effective cost of the drug can be added several indirect or associated costs: the loss of working days of the patient, or, in patients in pediatric age, those of the relative who assists him/her during the drug administration. In most treatments, however, the therapy, besides creating costs can also generate economic benefits: reducing the duration and severity of the disease, of the long-term outcome, thus affecting the direct costs and those induced by pathology. Nevertheless it is true that, even if an appropriate therapy can produce a temporary and economic benefit, this benefit can be transformed, during the years, in an increase of expenses for the healthcare institutions. A typical example is that of a treatment that can produce a greater use of resources, as a result of the lengthening of patients’ life and, consequently, the incidence of chronic pathologies commonly present in old age. The complexity of the problem imposes on the operators of Healthcare Institutions, on the society and on those who have specific roles in planning sanitary resources, a careful assessment of the economic impact of a therapy in relation to the benefits that it can produce. In any case, the judgement of the economic value of a therapy is almost always relative to a choice of reference that is represented by an alterElements of Pharmacoeconomics

53 ABSENCE OF RELATIONSHIP BETWEEN CERULOPLASMIN CONCENTRATIONS AND CARBOXYHEMOGLOBIN IN NEWBORN INFANTS WITH JAUNDICE OF UNKNOWN ETIOLOGY

The aim of this study was to find out whether an inverse relationship between ceruloplasmin (CPL) levels and bilirubin production rate could support the hypothesis that CPL has antioxidant activity in vivo protecting from possible oxidative hemolysis in the first days of life.Study subjects were 78 unselected at-term singleton newborn infants weighing >2500 g, without G6PD deficiency, blood group immunization, or clinical problems other than jaundice. The variables studied were maximum bilirubin level in the first 4 days of life, CPL and alpha-fetoprotein (AFP) concentration in cord blood, and % carboxyhemoglobin (%COHb) on the fourth day after birth, taken as an estimate of the bilirubin production rate. %COHb was measured by multicomponent analysis with correction for HbF concentration.In a logistic regression analysis CPL levels <7.66 mg/dl and %COHb >1.1% resulted independently associated with bilirubin values >14.9 mg/dl (>256 micromol/L); odds ratios (OR) were 6.17 (95%CI=1.73-22.02) and 4.34 (95%CI=1.16-16.28), respectively. OR for AFP levels >66 mg/L was 3.17, but it was not statistically significant (95%CI=0.87-11.51). No relationship was found between CPL concentrations and %COHb.The results of this study does not support that CPL has an important biological role in protecting from possible oxidative hemolysis in infants born at term. Low CPL levels in cord blood mainly reflect hepatic metabolism and are better predictors of hyperbilirubinemia than high AFP concentrations.