Evaluating reporting and process quality of publications on UNHS: a systematic review of programmes.

BACKGROUND: Congenital hearing loss is one of the most frequent birth defects, and Early Detection and Intervention has been found to improve language outcomes. The American Academy of Pediatrics (AAP) and the Joint Committee on Infant Hearing (JCIH) established quality of care process indicators and benchmarks for Universal Newborn Hearing Screening (UNHS). We have aggregated some of these indicators/benchmarks according to the three pillars of universality, timely detection and overreferral. When dealing with inter-comparison, relying on complete and standardised literature data becomes crucial. The purpose of this paper is to verify whether literature data on UNHS programmes have included sufficient information to allow inter-programme comparisons according to the indicators considered. METHODS: We performed a systematic search identifying UNHS studies and assessing the quality of programmes. RESULTS: The identified 12 studies demonstrated heterogeneity in criteria for referring to further examinations during the screening phase and in identifying high-risk neonates, protocols, tests, staff, and testing environments. Our systematic review also highlighted substantial variability in reported performance data. In order to optimise the reporting of screening protocols and process performance, we propose a checklist. Another result is the difficulty in guaranteeing full respect for the criteria of universality, timely detection and overreferral. CONCLUSIONS: Standardisation in reporting UNHS experiences may also have a positive impact on inter-program comparisons, hence favouring the emergence of recognised best practices.

Congenital anomalies among live births in a high environmental risk area--a case-control study in Brindisi (southern Italy).

Maternal exposure to ambient pollution has been increasingly linked to the risk of congenital anomalies (CAs) in the fetus and newborns. Recently, a descriptive study in the high environmental risk city of Brindisi (Italy) revealed an increased prevalence of total CAs, especially congenital heart disease (CHD) and ventricular septal defects (VSDs), both at the local level and in comparison with the pool of EUROCAT registries. This paper concerns a population-based case control study to investigate the association between maternal exposure to air pollutants - sulfur dioxide (SO2) and total suspended particulate (TSP) matter - and the risk of CA. Cases were newborns up to 28 days of age, born to mothers resident in Brindisi between 2001 and 2010, and discharged with a diagnosis of CA. Cases and controls were individually matched according to sex, socio-economic status of the census area of residence of the mother, and year of beginning of pregnancy. Up to four controls were extracted for each case. Concentration data from monitoring stations were used to estimate air pollution exposure. Each case and control was assigned pollutant concentration values as mean and 90th percentile of the daily average values during weeks 3-8 of pregnancy. Exposure as both continuous and categorical variables was considered and a conditional logistic regression model was constructed to quantify the odds ratios of exposure to air pollutants and the occurrence of total CAs, CHDs and VSDs. We found exposure to the 90th percentile of SO2 to be associated with CHDs (p for trend =0.01) and VSDs (p for trend <0.05). Findings for TSP were less consistent. In conclusion, in the studied area, maternal exposure to sulfur dioxide increased risk of CHD.

[SENTIERI Project on Italian polluted sites: health in Brindisi]. / Il progetto SENTIERI sui siti di interesse nazionale per le bonifiche (SIN): Brindisi alla salute?

Epidemiological data should support policy makers in their decisions. Misjudgments in data interpretation can justify the preservation of the existing situation and the lack of decision about health and environment safeguard. In the SENTIERI study on Italian polluted sites, women mortality results significantly lower than the regional mean in 11 sites in 44. The authors of this paper think that these data depend on the different impact of pollution on the population of a site, as witnessed by the cases of Brindisi and Manfredonia (Southern Italy). It is now necessary to conduct studies at suburban level integrating mortality data with other available health data.

Ultrasound mass screening for congenital anomalies of the kidney and urinary tract.

BACKGROUND: There is a high incidence of congenital anomalies of the kidneys and urinary tract (CAKUT). Early diagnosis of these defects may allow the best medical and/or surgical treatment to be implemented as rapidly as possible, preventing or at least slowing down an evolution toward chronic kidney disease. METHODS: Ultrasound mass screening for kidney and urinary tract abnormalities in infants at 2 months of age was carried out in Salento, Italy. The centers involved in the study examined a total of 17,783 infants between January 1992 and December 2010. RESULTS: A total of 171 CAKUT were identified in the course of the mass screening. The frequency of CAKUT was 0.96%. Vesicoureteral reflux (n = 39) was the most frequent renal abnormality found, followed by ureteropelvic junction obstruction (n = 33), ectopic kidney (n = 26), and renal dysplasia (n = 19). In addition, nephrogenic rests (n = 2), as well as several extra-renal pathologies, including abdominal neuroblastoma (n = 3), were diagnosed incidentally. CONCLUSION: Ultrasound has been effective for early detection of renal and urinary tract anomalies. In addition, this screening has proved to be very useful for the early identification and management of both renal and extra-renal precancerous as well as cancerous lesions. However, most patients requiring surgery in this study (0.24%) would probably have been symptomatic and come to medical attention without routine screening. On the basis of our results screening is not justified.

Congenital anomalies among live births in a polluted area. A ten-year retrospective study.

BACKGROUND: Congenital anomalies and their primary prevention are a crucial public health issue. This work aimed to estimate the prevalence of congenital anomalies in Brindisi, a city in southeastern Italy at high risk of environmental crisis. METHODS: This research concerned newborns up to 28 days of age, born between 2001 and 2010 to mothers resident in Brindisi and discharged with a diagnosis of congenital anomaly. We classified cases according to the coding system adopted by the European Network for the Surveillance of Congenital Anomalies (EUROCAT). Prevalence rates of congenital anomalies in Brindisi were compared with those reported by EUROCAT. Logistic regression models were adapted to evaluate the association between congenital anomalies and municipality of residence of the mother during pregnancy. RESULTS: Out of 8,503 newborns we recorded 194 subjects with congenital anomalies (228.2/10,000 total births), 1.2 times higher than the one reported by the EUROCAT pool of registries. We observed 83 subjects with congenital heart diseases with an excess of 49.1%. Odds Ratios for congenital heart diseases significantly increased for newborns to mothers resident in Brindisi (OR 1.75 CI 95% 1.30-2.35). CONCLUSIONS: Our findings indicated an increased prevalence of Congenital Anomalies (especially congenital heart diseases) in the city of Brindisi. More research is needed in order to analyze the role of factors potentially involved in the causation of congenital anomalies.

Lung ultrasound in bronchiolitis: comparison with chest X-ray.

The diagnosis of bronchiolitis is based mainly on the patient's medical history and physical examination. However, in severe cases, a further evaluation including chest X-ray (CXR) may be necessary. At present, lung ultrasound (LUS) is not included in the diagnostic work-up of bronchiolitis. This study aimed to compare the diagnostic accuracy of LUS and CXR in children with bronchiolitis, and to evaluate the correlation between clinical and ultrasound findings. Only patients with a diagnosis of bronchiolitis, who had undergone a CXR, were enrolled in the study. Fifty-two infants underwent LUS and CXR. LUS was also performed in 52 infants without clinical signs of bronchiolitis. LUS was positive for the diagnosis of bronchiolitis in 47/52 patients, whereas CXR was positive in 38/52. All patients with normal LUS examination had a normal CXR, whereas nine patients with normal CXR had abnormal LUS. In these patients, the clinical course was consistent with bronchiolitis. We found that LUS is a simple and reliable tool for the diagnosis and follow-up of bronchiolitis. It is more reliable than CXR, can be easily repeated at the patient's bedside, and carries no risk of irradiation. In some patients with bronchiolitis, LUS is able to identify lung abnormalities not revealed by CXR. Furthermore, there is a good correlation between clinical and ultrasound findings. Given the short time needed to get a US report, this technique could become the routine imaging modality for patients with bronchiolitis.

Topiramate: its pharmacological properties and therapeutic efficacy in epilepsy.

Since 1990 eight new antiepileptic drugs (AEDs) have been developed. Among these new drugs, Topiramate (TPM) is one of the latest AEDs available for treating drug resistant partial epilepsy both in adults and in children. The mechanisms underlying TPM antiepileptic activity are still incompletely understood. However, TPM, a sulfamate-substituted derivative of the naturally occurring monosaccharide D-fructose, has a different structure from other known AEDs. The antiepileptic activity of TPM in animal models of partial and generalized tonic-clonic seizures has been shown to be more effective as compared to other AEDs. Proposed mechanisms of action include reduction of epileptiform discharges through a voltage-dependent block of Na(+) channels, enhancement of the activity of gamma-aminobutyrate at some subtypes of gamma-aminobutyrate receptors, and antagonism of non- N-methyl-D-aspartate (NMDA) glutamate receptors. The pharmacokinetic profile of TPM, which is characterized by its rapid and almost complete absorption after oral administration, linear pharmacokinetics, minimal protein binding and predominantly renal excretion, makes the drug a good option for the treatment. TPM was found to be effective and well tolerated in many studies conducted in adults and pediatric patients suffering from epilepsy. This review, summarising the main studies in this field, provides an overview of the current knowledge about the relevant pharmacological and clinical information on the efficacy and tolerability of TPM.

Persistent pulmonary hypertension of the newborn: therapeutical approach.

Persistent pulmonary hypertension of the newborn (PPHN), is defined as a failure of the pulmonary vasculature to relax at birth and consequently of the normal adaptation to extra uterine life of the fetal heart/lung system, resulting in hypoxemia. This condition, occurs in about 1-2 newborns per 1000 live births and despite significant improvements in treatment it is associated with substantial infant mortality and morbidity. Over the years wider application of inhaled nitric oxide (iNO) therapy and improved ventilation strategies including surfactant, high-frequency oscillatory ventilation has led to a decrease in the need for invasive life-sustaining therapies such as extracorporeal membrane oxygenation (ECMO). Mortality rate varies from 10 to 20 % of affected newborns in developed countries, but it is much higher when PPHN is refractory to the above reported therapies or when they are not available. As a consequence, development of new therapeutic strategies for severe PPHN is crucial. In particular, recent studies seem to show that sildenafil, a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance may be a useful therapeutic adjunct to critically ill neonates with PPHN.

Recurrent otitis media with effusion in preterm infants with histologic chorioamnionitis--a 3 years follow-up study.

BACKGROUND: Recurrent otitis media with effusion (OME) is a leading cause of acquired hearing loss in childhood. Histological chorioamnionitis (HCA) is an important cause of preterm delivery and neonatal morbidity and mortality. Here, we tested the hypothesis of an association between recurrent OME during the first 3 years of life and HCA in very low birth weight (VLBW) infants. METHODS: A total of 110 randomly selected VLBW preterm newborns with HCA and 135 gestational age and gender-matched, HCA-negative VLBW infants were evaluated prospectively during the first 3 years of life for the presence of OME, as diagnosed on the basis of otoscopy, type B or C tympanogram, ipsilateral absence of transient evoked otoacoustic emissions responses, and ipsilaterally increased threshold at diagnostic auditory brain responses evaluation. Potential risk factors for OME were also examined in the two groups. RESULTS: The HCA-positive infants showed a approximately six times higher frequency of recurrent OME (P<0.0001), increased frequency (>5/yr) of clinical otitis media episodes (P=0.000020), approximately five times higher frequency of adenoid hypertrophy (P<0.00001), a significant seasonal pattern of birth with autumn predominance (P<0.00001), and the first OME occurred earlier (P<0.0001), as compared to the HCA-negative counterparts. Recurrent OME was significantly associated with HCA (O.R.=17.76, 95% CI: 8.98-35.13, P<0.00001), adenoid hypertrophy (O.R.=9.96, 95% CI: 5.17-19.18, P<0.00001), frequency of acute otitis episodes >5/yr (O.R.=8.91, 95% CI: 1.96-40.41, P=0.0005), and birth in autumn (O.R.=5.58, 95% CI: 2.79-11.12, P<0.00001). CONCLUSIONS: These findings indicate that HCA is a previously unrecognized risk factor for the development of recurrent bilateral OME in VLBW preterm infants during the first 3 years of life.

Maternal pulse oximetry perfusion index as a predictor of early adverse respiratory neonatal outcome after elective cesarean delivery.

OBJECTIVE: Evidence suggests increased morbidity, in particular early neonatal respiratory complications, in newborns from elective cesarean section compared with those from vaginal delivery. No reliable maternal predictors of adverse neonatal outcome at elective cesarean section are known. Here, we prospectively tested the hypothesis that a low maternal perfusion index at the baseline phase (i.e., preanesthesia) of the elective cesarean section is a predictor of early adverse neonatal respiratory outcome. DESIGN: Prospective cohort study. SETTING: Operating and delivery rooms of a public health hospital with a tertiary-level neonatal intensive care unit. PATIENTS: Forty-four healthy pregnant women with no known risk factors undergoing elective cesarean section at term gestation. INTERVENTIONS: Elective cesarean section was divided into nine phases. Analysis of pulse oximetry-derived signals (perfusion index, pulse rate, and oximetry) and systolic, diastolic, and differential blood pressure were recorded. Maternal arterial and venous newborn cord blood gas analyses and placental histology were evaluated. MEASUREMENTS AND MAIN RESULTS: Early respiratory complications (transient tachypnea of the newborn, n = 5; respiratory distress syndrome, n = 1) were observed in 13.6% (6 of 44) of the newborns. A maternal perfusion index < or = 1.9 (lower quartile) during the preanesthesia phase of the elective cesarean section was an independent predictor of early adverse neonatal respiratory outcome (odds ratio 68.0, 95% confidence interval 6.02-767.72; p < .0001). CONCLUSIONS: A decreased perfusion index value in the preanesthesia phase of elective cesarean section is a maternal predictor of increased neonatal morbidity and is significantly related to subclinical placental inflammatory disease. These observations suggest the feasibility of a noninvasive pulse oximeter prenatal screening of the high-risk fetus/newborn in elective cesarean section.

Clinical biomarkers for cancer recognition and prevention: A novel approach with optical measurements.

Cancer is the most important cause of death worldwide, and early cancer detection is the most fundamental factor for efficacy of treatment, prognosis, and increasing survival rate. Over the years great effort has been devoted to discovering and testing new biomarkers that can improve its diagnosis, especially at an early stage. Here we report the potential usefulness of new, easily applicable, non-invasive and relatively low-cost clinical biomarkers, based on abnormalities of oral mucosa spectral reflectance and fractal geometry of the vascular networks in several different tissues, for identification of hereditary non-polyposis colorectal cancer carriers as well for detection of other tumors, even at an early stage. In the near future the methodology/technology of these procedures should be improved, thus making possible their applicability worldwide as screening tools for early recognition and prevention of cancer.

Universal neonatal hearing screening: the Siena (Italy) experience on 19,700 newborns.

BACKGROUND: Hearing loss (HL) is likely to be the most common congenital abnormality in humans, with a reported prevalence of 1 to 3 per 1000 live births. Early detection and intervention is critical to prevent the adverse consequences of a delayed diagnosis on speech, language and cognitive development. As 33-50% of all congenital HLs cannot be detected in a selective hearing risk, use of universal neonatal hearing screening (UNHS) programs is expanding. AIMS: We tested the value of a UNHS protocol, based on a two-stage strategy of Transient Evoked Otoacoustic Emissions (TEOAEs) in all infants, followed by diagnostic auditory brainstem response (ABR) testing in those infants who did not meet TEOAE pass criteria and those infants at high risk for hearing loss. METHODS: TEOAES (292 DP Echoport OAE Analyzer) served as the initial screen, followed by diagnostic ABR (Amplaid MK12) in newborns that did not meet pass criteria for TEOAEs. Additionally, all infants at high audiologic risk according to the Joint Committee on Infant Hearing received a diagnostic ABR evaluation. Of 21,125 total live births, 19,700 were tested (April 1, 1998-July 31, 2006). Accuracy of the UNHS strategy in predicting congenital HL was evaluated by calculating sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: Prevalence for all HLs in the neonatal period was 1.78/1000 l.b. (35/19,700), with bilateral HL in 1.42/1000 l.b. (28/19,700) [low risk rate: 0.43/1000 l.b. (8/18,356); high risk infants rate: 14.88/1000 l.b. (20/1344)]. All the HL infants were diagnosed <3 and received intervention <6 months age. ROC curves results showed 100% sensitivity (95% C.I.: 89.0-100) and 99.3% specificity (95% C.I.: 99.2-99.4) of the two-stage strategy in detecting congenital HLs [area under the ROC curve: 0.997 (95% C.I.: 0.995-0.997)]. CONCLUSIONS: (1) The epidemiology of congenital HLs widely justifies UNHS; (2) a two-stage TEOAE and diagnostic ABR screening for congenital HL is feasible, minimally invasive and accurate in the early detection of congenital HL; and (3) a congenital HL screening strategy based exclusively on the use of TEOAEs should always consider the possibility of false negative cases.

In utero exposure to phthalates and fetal development.

The diesters of benzene-1,2-dicarboxylic (phthalic) acid, commonly known as phthalates, are a family of industrial compounds, primarily used as plasticizers in enormous quantities for a variety of industrial uses in the formulation of plastics. Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer. These plasticizers are not covalently bound to the polymer and leach out into the environment, thus becoming ubiquitous environmental contaminants. Cumulating evidence points out on the adverse effects of phthalate exposure during intrauterine life. Recently, it has been documented that in utero phthalate exposure is associated with a shorter duration of pregnancy. Phthalates induce and activate a subset of peroxisome proliferator-activated receptors (PPARs) and have an intrinsic pro-inflammatory activity, while some natural PPAR agonists induce cyclooxygenase (COX)-2 expression. To this regard, COX-2 is thought to be overexpressed in chorioamnionitis (CA), a fetal systemic inflammatory response syndrome and a leading cause of preterm birth. An adequate maternal dietary intake of essential fatty acids, well known anti-inflammatory agents, is indispensable to fetal development. Recently, it has been shown that phthalates alter the placental essential fatty acids (EFAs) homeostasis so potentially leading to abnormal fetal development. Likewise, a possible down-regulation of COX-2 by omega-3 fatty acids has been suggested. As a consequence, maternal supplementation with omega 3 during pregnancy could counteract the adverse effects of phthalates exposure in the human fetus. Here, we analyze the existing evidence on the link between antenatal phthalate exposure and abnormal fetal development, as well as on possible therapeutic tools to fight the adverse effect of this exposure.

Phthalate exposure and male infertility.

Phthalates have been used as additives in industrial products since the 1930s, and are universally considered to be ubiquitous environmental contaminants. The general population is exposed to phthalates through consumer products, as well as diet and medical treatments. Animal studies showing the existence of an association between some phthalates and testicular toxicity have generated public and scientific concern about the potential adverse effects of environmental changes on male reproductive health. In particular, prenatal exposure to phthalates seems to play a relevant role in determining these adverse effects given that human exposure has been demonstrated to begin during the intrauterine life. Unprecedented declines in fertility rates and semen quality of antenatal origin have been reported during the last half of the 20th century in developed countries and increasing interest exists on the potential relationship between exposure to environmental contaminants, including phthalates, and human male reproductive health. Here we review the data that support or discounts the evidence existing to date linking phthalate exposure and the decline of human male fertility, especially in developed countries.

Abnormal oral mucosal light reflectance in bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is an important cause of mortality and morbidity in preterm infants. A disordered vascular development and a decreased production of angiogenic factors have been recently reported in the condition. Extracellular matrix (ECM) is known to play an important role on angiogenesis and blood vessel geometry and changes in ECM components have been previously reported in experimental models and patients with BPD. Here, we aimed to assess the potential value of light reflectance on the oral mucosa in detecting infants who will develop BPD. METHODS: A total of 75 preterm newborns (gestational age: 27.7 +/- 2.8 weeks, birth weight: 870 +/- 145 g) were recruited to the study, of whom 25 developed BPD (gestational age: 26.9 +/- 3.0 weeks, birth weight: 855 +/- 150 g). Reflectance was measured on the postnatal days 1 and 28, using high-resolution photographs of the lower gingival and vestibular oral mucosa, using imaging spectrophotometry in the 400-700 nm wavelength electromagnetic spectral range. The median of artefact- and vessel-free areas was n = 78 (interquartile range: 59-88). Median range values were comparable for both groups: BPD-positive infants, median 77 (interquartile: 60-90) vs. control infants, median 74 (interquartile: 62-92). The predictive accuracy of oral spectrophotometry was calculated using receiver operating characteristic curve analysis. RESULTS: BPD patients showed significantly lower light reflectance values in the red (610-700 nm, P < 0.0001), with higher values in the violet (400 nm, P = 0.0056; 430 nm, P=0.014), and blue-green (480-500 nm, P < or = 0.024) sections of the spectrum already on the first day of life. A low reflectance value in the 640-700 nm wavelengths interval was found to identify BPD patients with 100% sensitivity and 100% specificity (640 nm: cutoff < or = 44.91%; 650 nm: < or = 45.64%; 660 nm: < or = 46.56%; 670 nm: < or = 47.14%; 680 nm: < or = 47.56%; 690 nm: < or = 48.95%; 700 nm: < or = 50.81%). CONCLUSIONS: These findings indicate the presence of previously unrecognised, early abnormalities in the average optical properties of the oral mucosa from infants developing BPD.

Early dynamic changes in pulse oximetry signals in preterm newborns with histologic chorioamnionitis.

OBJECTIVE: No reliable clinical markers of histologic chorioamnionitis (HCA), a major and often subclinical cause of prematurity leading to high neonatal morbidity and mortality, are available to date. Increasing evidence indicates myocardial dysfunctions in affected fetuses and newborns. We sought to assess the value of nonlinear dynamics from pulse oximetry signals in identifying affected newborns. DESIGN: Prospective case-control study. SETTING: Tertiary level neonatal intensive care unit, Brindisi Hospital. PATIENTS AND INTERVENTION: Pulse oximetry-derived signals (pulse rate, oxygen saturation, and perfusion index), recorded within the first 1.5 hrs of life, were analyzed for 110 very low-birth-weight infants, of whom 54 had histopathological evidence of HCA. MEASUREMENTS AND MAIN RESULTS: Four different time series parameters were determined for nonlinear dynamical (NLD) analysis. Significantly decreased Lempel-Ziv, Lyapunov largest exponent, and correlation dimension, with significantly increased Hurst values for heart rate and perfusion index (p < .00001), were observed in newborns with HCA. Heart rate Lempel-Ziv