A regional-based newborn hearing screening program: the Emilia-Romagna model after ten years of legislation.

Background: Hearing loss, occurring in 1-3/1,000 newborns in the well-babies population, is one of the most common congenital diseases, and hearing screening at birth still represents the only means for its early detection. Since 2011 the Emilia Romagna Regional Health Agency has recommended Newborn Hearing Screening for all babies at its birth points and for newborns moving to the region. The aims of this study are to analyze the results of this regional-based Newborn Hearing Screening program and to discuss the impact of the legislative endorsement on the organization. Material and methods: This is an observational retrospective chart study. The recordings of well-babies and babies at Neonatal Intensive Care Units were collected during the period from January 1st 2015 to December 31st 2020. The following data were included: Newborn Hearing Screening coverage, percentage of refer at otoacoustic emissions, prevalence and entity of hearing loss, unilateral/bilateral rate, presence of audiological risk factors. Results: More than 99% of a total of 198,396 newborns underwent the Newborn Hearing Screening test during the period January 1st 2015 to December 31st 2020, with a coverage ranging between 99.6% and 99.9%. Overall, the percentage of confirmed hearing loss cases was about 17-30 % of refer cases, 745 children received a diagnosis of hearing loss (prevalence 3.7/1,000). Considering profound hearing loss cases, these represent 13% of bilateral hearing loss. Conclusion: A regional-based Newborn Hearing Screening program is valuable and cost-effective. In our experience, the centralization of the data system and of the data control is crucial in order to implement its efficiency and effectiveness. Healthcare policies, tracking systems and public awareness are decisive for a successful programme implementation.

Travellers' risk behaviors and health problems: Post-travel follow up in two travel medicine centers in Italy.

OBJECTIVES: We examined the association between travellers' characteristics, compliance with pre-travel recommendations and health problems. METHODS: Volunteer travellers were enrolled and data collected using a questionnaire between 30-60 days after returning home. We analyzed the associations through bivariate and multivariate models. RESULTS: Of the 468 enrolled travelers, 68% consumed raw food and 81% food containing milk and/or eggs. 32% consumed street vendor food and 30% drinks containing ice. 24% used the recommended mechanical prophylaxis measures. 46% got sick during and/or after travel (gastrointestinal symptoms most frequently). Factors predisposing to health problems were female gender, youth/middle age, intermediate travel duration and profession. The American continent and staying in hostels and tents were significantly associated with febrile illness. Street vendor food was significantly associated with skin reactions. CONCLUSIONS: Adherence to behavioral recommendations remains low. Travellers must be informed of health risks during and after travel.

Long-term persistency of hepatitis B immunity: an observational cross-sectional study on medical students and resident doctors.

Hepatitis B virus (HBV) is a main cause of chronic and acute hepatitis. Healthcare workers (HCWs), including medical students and resident doctors, have an occupational risk of HBV infection. The study aimed to evaluate the long-term persistence of protective anti-HBs antibody levels in healthcare students and resident doctors at risk for occupational exposure to HBV at 15 years after primary vaccination course. Further objective was to evaluate the anamnestic response observed in non-seroprotected subjects receiving a booster dose. Data were collected from the clinical documentation filled in during the occupational medical check of medical students and resident doctors undergoing Occupational Health Surveillance by the University of Ferrara. Of the 621 included individuals, 27.7% had an anti-HBs concentration < 10 mIU/mL. Subjects vaccinated during infancy had more frequently a concentration < 10 mIU/mL than those vaccinated during adolescence (42.7% vs 6.9%; p-value < 0.001). Multivariate analysis confirmed the statistical significance of the vaccination age. 94 subjects who had an anti-HBs concentration < 10 mIU/mL received a booster dose. The proportion of subjects who had an anamnestic response was higher in those vaccinated in infancy rather than during adolescence (94.1% vs 77.8% respectively). These findings suggest that the anti-HBs concentration decreases below 10 mIU/mL more frequently in subjects vaccinated during infancy. Immunological memory seems to persist after the decline of the anti-HB titer, as observed in response to a booster dose. In conclusion, vaccinated subjects at increased risk of HBV infection should be monitored and a booster dose administered if anti-HBs titer is below 10 mIU/mL.

Vaccination coverage in healthcare workers: a multicenter cross-sectional study in Italy.

INTRODUCTION: In recent years, a phenomenon known as "vaccine hesitancy" has spread throughout the world, even among health workers, determining a reduction in vaccination coverage (VC).A study aimed at evaluating VC among healthcare workers (HCWs) in 10 Italian cities (L'Aquila, Genoa, Milan, Palermo, Sassari, Catanzaro, Ferrara, Catania, Naples, Messina) was performed. MATERIALS AND METHODS: Annex 3 of the Presidential Decree n. 445 of 28 December 2000 was used to collect information on the vaccination status of HCWs. The mean and standard deviation (SD) were calculated with regard to the quantitative variable (age), while absolute and relative frequencies were obtained for categorical data (sex, professional profile, working sector, vaccination status). The connection between VC and the categorical variables was evaluated by chi-square method (statistical significance at p < 0.05). The statistical analyses were performed by SPSS and Stata software. RESULTS: A total of 3,454 HCWs participated in the project: 1,236 males and 2,218 females.The sample comprised: physicians (26.9%), trainee physicians (16.1%), nurses (17.2%) and other professional categories (9.8%). Low VC was generally recorded. Higher VC was found with regard to polio, hepatitis B, tetanus and diphtheria, while coverage was very low for measles, mumps, rubella, pertussis, chickenpox and influenza (20-30%). CONCLUSIONS: This study revealed low VC rates among HCWs for all the vaccinations. Measures to increase VC are therefore necessary in order to prevent HCWs from becoming a source of transmission of infections with high morbidity and/or mortality both within hospitals and outside.

Pharmacokinetic/pharmacodynamic model for unfractionated heparin dosing during cardiopulmonary bypass.

BACKGROUND: High-dose heparin is used during cardiopulmonary bypass (CPB) to prevent thrombosis in the circuits used for extracorporeal circulation. The aim of this study was, initially, to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model to assess the variability of PK/PD parameters and their correlation with the results of the routine haemostatic test activated clotting time (ACT) and thereafter to develop a Bayesian estimator enabling an individualized dosing strategy. METHODS: Fifty consecutive patients undergoing cardiac surgery with CPB were included in the study. Heparin was administered as an initial bolus of 300 IU kg -1 followed by additional boluses of 5000 IU to maintain ACT <400 s. In total, 361 blood samples were collected. The PK and PD data were analysed using a non-linear mixed effect model. RESULTS: A two-compartment model with a linear elimination link to an E max model best described heparin anti-factor Xa activities and ACT. Covariate analysis showed that body weight was positively correlated with clearance and central compartment volume. Inclusion of body weight with these parameters decreased their variability by 11 and 15%, respectively. The Bayesian estimator performed well in predicting individual parameters in an independent group of patients. CONCLUSIONS: A population PK/PD analysis of heparin during CPB, using a routine haemostatic test, shows that Bayesian estimation might help to predict ACT on the basis of only one or two blood samples.

Accurate neurosonographic prediction of brain injury in the surviving fetus after the death of a monochorionic cotwin.

OBJECTIVE: To assess the feasibility of the prenatal diagnosis using fetal neurosonography of brain injuries in the surviving fetus after the demise of a monochorionic cotwin. METHODS: This was a retrospective observational study in the period 1990-2004 of monochorionic twin pregnancies with a single fetal demise. A detailed sonographic evaluation of the intracranial anatomy of the surviving twin had been performed whenever possible using a multiplanar approach and from 1999, fetal magnetic resonance imaging was offered as well. Postnatal follow-up was obtained in all cases. RESULTS: In six of nine cases, abnormal neurosonographic findings were identified including intracranial hemorrhage, brain atrophy, porencephaly and periventricular echogenicities evolving into polymicrogyria. Prenatal diagnosis of brain lesions was confirmed postnatally and all affected infants who survived had severe neurological sequelae. Two fetuses had normal cerebral structures both on the prenatal neurosonogram and on postnatal imaging and were following normal developmental milestones, one at 1 and the other at 5 years of age. In one case the neurosonographic examination was suboptimal and the infant was found at birth to have a porencephalic cyst. Fetal magnetic resonance imaging was performed in two cases and confirmed the ultrasound diagnosis. CONCLUSIONS: Prenatal neurosonography is a valuable tool for the prediction of neurological outcome in fetuses surviving after the intrauterine death of a monochorionic cotwin. Although our experience is limited, we suggest that magnetic resonance imaging should also be offered.

Prophylactic nasal continuous positive airways pressure in newborns of 28-31 weeks gestation: multicentre randomised controlled clinical trial.

BACKGROUND: The role of nasal continuous positive airways pressure (nCPAP) in the management of respiratory distress syndrome in preterm infants is not completely defined. OBJECTIVE: To evaluate the benefits and risks of prophylactic nCPAP in infants of 28-31 weeks gestation. DESIGN: Multicentre randomised controlled clinical trial. SETTING: Seventeen Italian neonatal intensive care units. PATIENTS: A total of 230 newborns of 28-31 weeks gestation, not intubated in the delivery room and without major malformations, were randomly assigned to prophylactic or rescue nCPAP. INTERVENTIONS: Prophylactic nCPAP was started within 30 minutes of birth, irrespective of oxygen requirement and clinical status. Rescue nCPAP was started when Fio2 requirement was > 0.4, for more than 30 minutes, to maintain transcutaneous oxygen saturation between 93% and 96%. Exogenous surfactant was given when Fio2 requirement was > 0.4 in nCPAP in the presence of radiological signs of respiratory distress syndrome. MAIN OUTCOME MEASURES: Primary end point: need for exogenous surfactant. Secondary end points: need for mechanical ventilation and incidence of air leaks. RESULTS: Surfactant was needed by 22.6% in the prophylaxis group and 21.7% in the rescue group. Mechanical ventilation was required by 12.2% in both the prophylaxis and rescue group. The incidence of air leaks was 2.6% in both groups. More than 80% of both groups had received prenatal steroids. CONCLUSIONS: In newborns of 28-31 weeks gestation, there is no greater benefit in giving prophylactic nCPAP than in starting nCPAP when the oxygen requirement increases to a Fio2 > 0.4.

Sonographic demonstration of brain injury in fetuses with severe red blood cell alloimmunization undergoing intrauterine transfusions.

OBJECTIVE: To assess sonographically brain anatomy in fetuses with severe anemia due to red blood cell alloimmunization undergoing intrauterine intravascular transfusions. METHODS: Multiplanar neurosonography was performed in seven consecutive hydropic fetuses undergoing intrauterine transfusions (mean gestational age 22 +/- 2.5 weeks; mean hemoglobin concentration at the first transfusion 2.3 +/- 1.0 g/dL). RESULTS: Abnormal cerebral findings were identified in four out of seven fetuses. An intracerebellar hemorrhage developed in two fetuses after the first transfusion and one fetus that had severe brain edema before the first transfusion was later found to have cystic periventricular leukomalacia. In one fetus unilateral ventriculomegaly was noted after the first transfusion. Two fetuses were terminated. The remaining pregnancies had an uneventful course, the infants were delivered between 34 and 36 gestational weeks and were alive and well at the time of writing. Prenatal diagnosis of brain injury was always confirmed except for the case with ventriculomegaly that underwent spontaneous intrauterine resolution. CONCLUSIONS: Fetuses with extreme anemia due to red blood cell alloimmunization can be salvaged by intrauterine transfusion. In some of these cases brain injury may occur prenatally, and the risk seems to be particularly high when the hemoglobin concentration at the time of the first transfusion is

Outcome of antenatally diagnosed intracranial hemorrhage: case series and review of the literature.

OBJECTIVES: Prenatal diagnosis of intracranial hemorrhage (ICH) has been widely reported. Hemorrhages may occur either within the cerebral ventricles, subdural space or infratentorial fossa. The aim of this study was to determine the sonographic criteria for the diagnosis of fetal ICH, the role of in utero magnetic resonance imaging (MRI) and the outcome of this condition. METHODS: The archives of our ultrasound laboratory and the literature were searched for all cases of antenatally diagnosed ICH. A grading system was used to classify the intraventricular lesions as suggested in postnatal sonographic studies. RESULTS: Adding our series of 16 fetuses to the 93 cases identified in the literature, a group of 109 fetal ICHs was obtained: 89 were intracerebral (79 intraventricular and 10 infratentorial) and 20 were subdural hemorrhages. Intraventricular lesions were mostly classified as severe (32 each for Grades III and IV). In 27 cases antenatal MRI was performed additionally to ultrasound and confirmed the sonographic findings. Of the entire group, 65 infants (59%) were reported to be alive 1 month after birth (51 intraventricular hemorrhages, three infratentorial hemorrhages, 11 subdural hematomas). At 12 months, of the 48 infants whose follow-up was available, 25 or 52% were judged neurologically normal (17/36 or 47% among the intraventricular hemorrhages, 6/9 or 66% among the hematomas, and 2/3 or 66% among the infratentorial hemorrhages). CONCLUSIONS: Fetal ICH may be accurately identified and categorized by antenatal sonography. The outcome is usually poor, especially for those fetuses affected by higher-grade intraventricular hemorrhages.

Infants of immigrant parents in Italy. A national multicentre case control study.

BACKGROUND: The aim of this study was to evaluate health state of newborns of immigrated parents from developing countries. METHODS: Hospital records of 69,605 infants born during 1996/1997 in Italy were reviewed comparing, in a case-control study, each infant of immigrated parents to two infants born immediately before and after to Italian parents. RESULTS: Of the 69,605 newborns 3906 (5.6%) were born to immigrated parents. This prevalence prolongs the increasing trend observed during the last 10 years of infants born to immigrated parents and reduces the fall of the birth rate linked to the few infants born to Italian parents. It was influenced by geographical factors, being higher in Northern-Central Italy (7%) than in Southern and Insular Italy (2.8%), as consequence of more elevated incomes in these Italian regions. The origin countries of immigrated parents were mainly Northern Africa (31.7%), Eastern Europe (18%) and Sub Saharan Africa (11.6%). Infants of immigrated parents showed higher incidences of prematurity, low birth weight, asphyxia and neonatal mortality rate than newborns with Italian parents. These higher incidences appeared related to some risk factors such as higher parity, short gestational age, some maternal infections, maternal drug dependence, maternal age less than 18 years, low familiar income, inadequate obstetric cares, difficulty to accessing the public health services. CONCLUSIONS: The health problems of infants with immigrated parents are mainly related to social disadvantage and can be overcome improving the social state, the lifestyles and the obstetric cares of the immigrated women, so as monitoring their risk pregnancies.

The clinical significance of fetal isolated cerebral borderline ventriculomegaly: report of 31 cases and review of the literature.

OBJECTIVE: To assess the clinical significance of fetal isolated borderline cerebral lateral ventriculomegaly defined as a width of the atrium of the lateral cerebral ventricles of 10-15 mm in the absence of other sonographically demonstrable malformations. DESIGN: Retrospective study of the outcome of fetuses with a sonographic diagnosis of isolated borderline cerebral lateral ventriculomegaly and review of the English-language literature. RESULTS: Of 31 fetuses, two had chromosomal aberrations (trisomy 21 and trisomy 13) and three had neurological complications (one infant developed shunt-dependent hydrocephalus, one lissencephaly and one cerebral hemorrhage and periventricular leukomalacia). The literature search revealed eight independent studies. Including the present series, 234 cases were available for analysis. An abnormal outcome was documented in 22.8% of cases. Perinatal death occurred in 3.7%. Chromosomal aberrations, mostly trisomy 21, were present in 3.8%, malformations undetected at a second-trimester sonogram in 8.6% and neurological sequelae, mostly a mild to moderate delay in cognitive and/or motor development, were present in 11.5%. The risk of an abnormal neurological outcome was increased in females versus males (22.6% versus 4.6%, relative risk 4.892; 95% confidence interval 1.356-17.656), when the atrial width was 12 mm or more (13.9% versus 3.8%, relative risk 3.6, 95% confidence interval 1.035-12.846) and when the diagnosis was made in the second trimester versus later in gestation. CONCLUSIONS: In most cases, isolated borderline cerebral lateral ventriculomegaly has no consequence. However, this finding carries an increased risk of cerebral maldevelopment, delayed neurological development and, possibly, chromosomal aberrations. The optimal management of these cases remains uncertain.

Sonographic demonstration of nuchal cord and abnormal umbilical artery waveform heralding fetal distress.

Ultrasound examination of a 30-week fetus, appropriate for gestational age, revealed a nuchal cord and absence of end-diastolic velocities in the Doppler waveforms of the umbilical artery. Cardiotocography suggested impending fetal distress, clinically confirmed following expedient abdominal delivery. We suggest that Doppler velocimetry of the umbilical vessels may be useful in the assessment of viable fetuses with a sonographic diagnosis of a nuchal cord. Conversely, a nuchal cord should be considered as part of the differential diagnosis of abnormal Doppler velocimetry of the umbilical vessels.

Antigen retrieval techniques in immunohistochemistry: comparison of different methods.

Routine sections of normal and pathological samples fixed in 10 per cent buffered formalin or B5, including EDTA-decalcified bone-marrow biopsies, were tested with 61 antibodies following heating in three different fluids: 0.01 M citrate buffer (pH 6.0), 0.1 M Tris-HCl (pH 8.0), and 1 mM EDTA-NaOH solution (pH 8.0). The sections underwent either three cycles of microwave treatment (5 min each) or pressure cooking for 1-2 min. The alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique was used as the standard detection method; with 16 antibodies a slightly modified streptavidin-biotin complex (SABC)-immunoperoxidase technique was applied in parallel. The results obtained were compared with those observed without any antigen retrieval (AR), or following section digestion with 0.05 per cent protease XIV at 37 degrees C for 5 min. Chess-board titration tests showed that all antibodies but one profited by AR. Protease XIV digestion represented the gold standard for five antibodies, while 55 produced optimal results following the application of heat-based AR. By comparison with the other fluids, EDTA appeared to be superior in terms of both staining intensity and the number of marked cells. These results were independent of tissue processing, immunohistochemical approach, and heating device. Pressure cooking was found to be more convenient on practical grounds, as it allowed the simultaneous handling of a large number of slides and a time saving of 1 min 30 s, representing the proper time for the treatment.

Differential diagnosis and outcome of fetal intracranial hypoechoic lesions: report of 21 cases.

Our objective was to evaluate the diagnostic and prognostic value of sonography hypoechoic lesions. A retrospective study revealed revealed a total of 21 cases diagnosed over a period of 10 years. Most of the diagnosis were made in the third trimester. The presence fluid-filled lesions within the brain matter always predicted porencephaly and a poor outcome. In most of these cases (nine out of ten), the lesions were seen to communicate with the cavity of the lateral ventricles. Among the 11 cases of hypoechoic lesions that were external to the brain matter, Doppler ultrasound was always able to distinguish between arachnoid cysts (seven cases) and vein of Galen aneurysms (four cases). Arachnoid cysts were associated with a good outcome in four out of the five pregnancies that delivered at term. Three of the four cases of vein of Galen aneurysm were associated with distortion of the cerebral architecture and/or hydrops: one pregnancy was terminated and two resulted in early postnatal death. One pregnancy with vein of Galen aneurysm and normal cerebral structures, without signs of hydrops, had a good outcome. It is concluded that current antenatal ultrasound has the capability of accurate differentiation between different clinical entities resulting in fetal intracranial hypoechoic lesions, and that the sonographic findings have practical clinical implications.

Cerebrospinal fluid shunt infections in infants.

Infection remains a major cause of morbidity and mortality following CSF shunt procedures. In this study 191 shunt procedures carried out from January 1981 to December 1992 in a series of 81 infants (less than 6 months old) were retrospectively analyzed for possible risk factors. The overall surgical infection rate was 7.8%, with 15 infections occurring in 14 patients (17.2%). No significant difference in the rate of infections was found in relation to sex, birth weight, gestational age, and type of shunt procedure (primary insertion/revision). The occurrence of other infections during the period of shunt surgery did not influence the infection risk either. Intraventricular hemorrhage and central nervous system infections as causes of the hydrocephalus were found to correlate with septic risk. Young age (less than 6 months) seems to represent the main risk factor, and this is related both to the immunologic deficiency and to the particular features of residential bacterial flora in this age group.

Intraventricular fused fornices: a specific sign of fetal lobar holoprosencephaly.

Lobar holoprosencephaly can be recognized in utero with sonography. However, a specific diagnosis is difficult and thus far has relied upon a qualitative evaluation of the morphology of the cerebral ventricles. In infants with this condition, magnetic resonance imaging demonstrates at times an abnormal appearance of the fornices, which are rudimentary and fused in to a single fascicle running within the third ventricle. In a 30-weeks' fetus affected by lobar holoprosencephaly, this finding could be well demonstrated by sonography and was confirmed after birth by both transfontanellar ultrasound and magnetic resonance imaging. It is proposed that the antenatal demonstration of an echogenic linear structure running within the third ventricle is a specific sign of lobar holoprosencephaly, and can assist this difficult diagnosis.

Sonography of fetal agenesis of the corpus callosum: a survey of 35 cases.

Agenesis of the corpus callosum was identified by ultrasound examination in 35 fetuses between 19 and 37 weeks' gestation. The ultrasound findings included absence of the corpus callosum and cavum septum pellucidum (hypoplasia in one case of partial agenesis of the corpus callosum), a typical 'teardrop' configuration of the lateral ventricles, distension of the interhemispheric fissure, upward displacement of the third ventricle, radiate arrangement of the medial cerebral gyri, and abnormal branching of the anterior cerebral artery. Associated anomalies were identified in 20 fetuses, including heterogeneous malformations and chromosomal aberrations (mosaic-trisomy 8 in three, trisomy 18 in two and partial duplication 8p in one). Five cases of agenesis of the corpus callosum were identified in a population of pregnant patients prospectively investigated because of genetic risk for agenesis of the corpus callosum or related syndromes. In this group, no diagnostic errors were made. Long-term neurological follow-up (6 months to 11 years) was available in 11 infants with antenatal diagnosis of isolated agenesis of the corpus callosum. Normal intellectual development was present in nine, and a low intellect (developmental quotient between 70 and 85) was found in two. It is concluded that fetal agencies of the corpus callosum is associated with elusive sonographic findings that can, however, be accurately identified by targeted examinations. In routine sonograms, an increased atrial width and/or failure to visualize the cavum septum pellucidum should arise the suspicion of fetal agencies of the corpus callosum. Given the high frequency of associated anomalies, prenatal diagnosis of agencies of the corpus callosum dictates the need for a careful survey of fetal anatomy and karyotyping. The prognosis is isolated agencies of the corpus callosum remains uncertain, although it is expected that a normal or boarderline intellectual development will occur in many cases.

Prenatal diagnosis of lobar holoprosencephaly.

Lobar holoprosencephaly was identified with sonography in 12 fetuses between 21 and 35 weeks' gestation. A confident diagnosis was made in each case by a mid-coronal view of the brain demonstrating absence of the cavum septum pellucidum with fusion and squaring of the frontal horns. The only associated anomaly was Dandy-Walker malformation that occurred in three cases. All fetuses had mild to severe ventriculomegaly. Five pregnancies were terminated; there was one spontaneous abortion and six fetuses were delivered at term. A ventriculo-peritoneal shunt was implanted in four. Follow-up was available for five and revealed severe mental retardation in each case. Lobar holoprosencephaly is amenable to prenatal ultrasound diagnosis, although a differentiation with other cerebral malformations may be difficult at times. The outcome of affected infants remains uncertain, but neurological impairment occurs frequently.

Sonography of unilateral megalencephaly in the fetus and newborn infant.

A 27-year-old primigravida women was referred for ultrasound studies at 32 weeks' gestation because of the suspicion of fetal ventriculomegaly. Sonographic examination of the fetal brain found a marked shift of the midline, with enlarged left hemisphere and ipsilateral occipital horn, and abnormal convolutions. A 3500 gm male infant was delivered by cesarean section at 39 weeks' gestation because of worsening macrocrania after which the diagnosis of unilateral megalencephaly was confirmed by computed tomography.