Universal Newborn Screening for Congenital Cytomegalovirus Infection - From Infant to Maternal Infection: A Prospective Multicenter Study.

Introduction: Most infants at risk for cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) are unrecognized because of the absence of a universal neonatal CMV screening. The search of CMV-DNA by molecular methods in salivary swabs was demonstrated to be a reliable approach. This study describes the results obtained by carrying out a universal screening for congenital CMV (cCMV) infection including all live-born newborns in three Italian sites, as well as the therapeutic interventions and clinical outcome of the CMV-infected neonates. Moreover, CMV maternal infection's characteristics were evaluated. Methods: To confirm or exclude cCMV infection, a CMV-DNA-positive result on a first salivary swab was followed by repeated saliva and urine samples collected within 21 days of age. Breast milk samples were also collected. The search of CMV-DNA was performed with a single automated quantitative commercial real-time PCR assay, regardless of the type of samples used. Results: A total of 3,151 newborns were enrolled; 21 (0.66%) of them were congenitally infected (median saliva viral load at screening, 6.65 [range, 5.03-7.17] log10 IU/ml). Very low/low viral load in screening saliva samples (median value, 1.87 [range, 1.14-2.59] log10 IU/ml) was associated with false-positive results (n = 54; 1.7%). CMV-DNA was detected in almost half of the breast milk samples of mother-infant pairs with a false-positive result, suggesting that contamination from breast milk may not be the only explanation in the study population. cCMV infection confirmation with the search of CMV-DNA in a urine sample proved to be the gold standard strategy, since false-positive results were observed in 4/54 (7.5%) of the repeated saliva samples. Symptomatic cCMV infection was observed in 3/21 (14.3%) infants; notably, one (4.7%) developed moderate unilateral SNHL at 5 months after birth. Finally, two symptomatic cCMV infections were associated with primary maternal infection acquired in the first trimester of gestation; one newborn with severe cCMV symptoms was born to a mother with no CMV checkups in pregnancy. Conclusion: Without universal neonatal CMV screening, some infected infants who develop late neurological sequelae may not be recognized and, consequently, they are not able to benefit early from instrumental and therapeutic interventions to limit and/or treat CMV disease.

Prevalence of anti-parvovirus B19 IgG and IgM and parvovirus B19 viremia in pregnant women in an urban area of Northern Italy.

Parvovirus B19 (B19V) infection in pregnancy is mostly asymptomatic, but can cause complications including abortion and fetal hydrops. Although its infection is ubiquitous, seroprevalence among pregnant women varies according to different geographical areas. Since seroprevalence data in Italy are limited, the prevalence of antibodies and DNA in pregnant women was evaluated retrospectively, correlating the clinical situation of mothers and newborns. One thousand eight hundred and ninety-three sequential sera were examined from pregnant women (60.8% in the first trimester, 16.6% in the second one, and 22.6% in the third one, respectively) for anti-B19V IgG and IgM (confirmed by immunoblot); 1402 (74.1%) were of Italian origin and 491 (25.9%) non-Italian women. Molecular tests were used to search for viral genome. One thousand three hundred and fifteen (69.5%) samples were IgG-positive, 21 (1.1%) IgM-positive, and 578 (30.5%) nonimmune. The difference in IgG seroprevalence between Italian (71.1%) and non-Italian women (64.8%) was statistically significant. Of the 21 IgM-positive women, 16 were confirmed positive also by immunoblot (prevalence: 0.8%), of which 11 were viraemic (prevalence: 0.6%; mean 1.3 × 104 geq/ml). Mothers were asymptomatic, and the newborns had no clinical signs of congenital infection. IgG seroprevalence in Italy is high, with differences between Italian women and non-Italian women from geographic areas with lower endemic levels of B19V. The consistent migratory flows in place could lead to an increase in the number of susceptible women. The prevalence of viremia is low, and has not been associated with evident fetal damage at birth.

Extreme anemia (Hb 33 g/L) in a 13-year-old girl: Is the transfusion always mandatory?

Iron-deficiency anemia is a frequent condition in women and adolescent girls often caused by heavy menstrual bleeding. Sometimes the level of chronic anemia, although well tolerated, can be very severe. The recently introduced Patient Blood Management guidelines and the availability of effective and safe intravenous iron preparations may question transfusion as the traditional option. We describe here the case of a 13 years old girl with extreme iron-deficiency chronic anemia (Hb 33 g/L) that was successfully treated with i.v. Ferric Carboxymaltose (FCM). After the administration of 2 g of FCM in three refracted doses, in association with folic acid 5 mg/day for two weeks, the hemoglobin raised to 79 g/L in 12 days and to 144 g/L after about 7 months without any undesired effect recorded. Intravenous FCM can be an effective and safe alternative to blood transfusion also in selected cases of severe iron-deficiency anemia in children.

Perfusion Index and Pulse Oximetry Screening for Congenital Heart Defects.

OBJECTIVE: To evaluate the efficacy of combined pulse oximetry (POX) and perfusion index (PI) neonatal screening for severe congenital heart defects (sCHD) and assess different impacts of screening in tertiary and nontertiary hospitals. STUDY DESIGN: A multicenter, prospective study in 10 tertiary and 6 nontertiary maternity hospitals. A total of 42 169 asymptomatic newborns from among 50 244 neonates were screened; exclusion criteria were antenatal sCHD diagnosis, postnatal clinically suspected sCHD, and neonatal intensive care unit admission. Eligible infants underwent pre- and postductal POX and PI screening after routine discharge examination. Targeted sCHD were anatomically defined. Positivity was defined as postductal oxygen saturation (SpO2) ≤95%, prepostductal SpO2 gradient >3%, or PI <0.90. Confirmed positive cases underwent echocardiography for definitive diagnosis. Missed cases were identified by consulting clinical registries at 6 regional pediatric heart centers. Main outcomes were incidence of unexpected sCHD; proportion of undetected sCHD after discharge in tertiary and nontertiary hospitals; and specificity, sensitivity, positive predictive value, and negative predictive value of combined screening. RESULTS: One hundred forty-two sCHD were detected prenatally. Prevalence of unexpected sCHD was 1 in 1115 live births, similar in tertiary and nontertiary hospitals. Screening identified 3 sCHD (low SpO2, 2; coarctation for low PI, 1). Four cases were missed. In tertiary hospitals, 95% of unsuspected sCHDs were identified clinically, whereas only 28% in nontertiary units; in nontertiary units PI-POX screening increased the detection rate to 71%. CONCLUSIONS: PI-POX predischarge screening provided benefits in nontertiary units, where clinical recognition rate was low. PI can help identify coarctation cases missed by POX but requires further evaluation in populations with higher rates of missed cases.

Neonatal gastrointestinal involvement and congenital cytomegalovirus.

Cytomegalovirus (CMV) is the most common cause of congenital viral infection, affecting 0.2 to 2.3% of all live births in developed countries. Very low birth weight and extremely low birth weight newborns are at higher risk of symptomatic CMV infection, most commonly secondary and acquired through breast milk. Gastrointestinal involvement is rare in acquired CMV infections, but it could be an important manifestation of postnatal infection in preterm infants admitted to neonatal intensive care units. Early onset of CMV gastrointestinal signs/symptoms is very rare. In a review of the literature it is described in 5 newborns in the first 24 hours of life, and 6 considering the onset in the first week of life. This review describes also a case report of congenital CMV in an immunocompetent newborn with onset of gastrointestinal signs immediately after birth: a possible association between viral infection and enteric manifestations was considered in the differential diagnosis. A review of the literature of the different case reports found has done, with description and comparison of the different patients and clinical presentations.

Epidemiology of haemolytic uremic syndrome in children. Data from the North Italian HUS network.

UNLABELLED: Despite the severity of HUS and the fact that it represents a leading cause of acute kidney injury in children, the general epidemiology of HUS is all but well documented. The present study provides updated, population-based, purely epidemiological information on HUS in childhood from a large and densely populated area of northern Italy (9.6 million inhabitants, 1.6 million children). We systematically reviewed the files concerning patients with STEC-HUS and atypical HUS (aHUS) over a 10-year observation period (January 2003-December 2012). We included all incident cases with a documented first episode of HUS before the age of 18 years. We identified 101 cases of HUS during the 10 years. The overall mean annual incidence was 6.3 cases/million children aged <18 years (range 1.9-11.9), and 15.7/million of age-related population (MARP) among subjects aged <5 years; aHUS accounted for 11.9 % of the cases (mean incidence 0.75/MARP). The overall case fatality rate was 4.0 % (3.4 % STEC-HUS, 8.3 % aHUS). CONCLUSION: Given the public health impact of HUS, this study provides recent, population-based epidemiological data useful for healthcare planning and particularly for estimating the financial burden that healthcare providers might have to face in treating HUS, whose incidence rate seems to increase in Northern Italy. WHAT IS KNOWN: • HUS is a rare disease, but it represents the leading cause of acute kidney injury in children worldwide. • STEC-HUS (also called typical, D + HUS) is more common compared to atypical HUS, but recent, population-based epidemiological data (incidence) are scanty. What is New: • Comprehensive, population-based epidemiological data concerning both typical and atypical HUS based on a long observational period.

Adherence to guidelines for management of children hospitalized for acute diarrhea.

BACKGROUND: The major burden of acute gastroenteritis (AGE) in childhood is related to its high frequency and the large number of hospitalizations, medical consultations, tests and drug prescriptions. The adherence to evidence-based recommendations for AGE management in European countries is unknown. The purpose of the study was to compare hospital medical interventions for children admitted for AGE with recommendations reported in the European Societies of Pediatric Gastroenterology, Hepatology and Nutrition and Pediatric Infectious Diseases guidelines. METHODS: A multicenter prospective study was conducted in 31 Italian hospitals. Data on children were collected through an online clinical reporting form and compared with European Societies of Pediatric Gastroenterology, Hepatology and Nutrition and Pediatric Infectious Diseases guidelines for AGE. The main outcomes were the inappropriate hospital admissions and the percentage of compliance to the guidelines (full >90%, partial >80% compliance) based on the number and type of violations to evidence-based recommendations. RESULTS: Six-hundred and twelve children (53.6% male, mean age 22.8 ± 15.4 months) hospitalized for AGE were enrolled. Many hospital admissions (346/602, 57.5%) were inappropriate. Once admitted, 20.6% (126/612) of children were managed in full compliance with the guidelines and 44.7% (274/612) were managed in partial compliance. The most common violations were requests for microbiologic tests (404; 35.8%), diet changes (310; 27.6%) and the prescription of non-recommended probiotics (161; 14.2%), antibiotics (103; 9.2%) and antidiarrheal drugs (7; 0.6%). CONCLUSIONS: Inappropriate hospital admissions and medical interventions are still common in the management of children with AGE in Italy. Implementation of guidelines recommendations is needed to improve quality of care.

In-hospital management of children with bacterial meningitis in Italy.

BACKGROUND: Over the years 2009-2013, we conducted a prospective study within a network established by the Italian Society of Pediatrics to describe the in-hospital management of children hospitalized for acute bacterial meningitis in 19 Italian hospitals with pediatric wards. METHODS: Hospital adherence to the study was voluntary; data were derived from clinical records. Information included demographic data, dates of onset of first symptoms, hospitalization and discharge; diagnostic evaluation; etiology; antimicrobial treatment; treatment with dexamethasone; in-hospital complications; neurological sequelae and status at hospital discharge. Characteristics of in-hospital management of patients were described by causative agent. RESULTS: Eighty-five patients were identified; 49.4% had received an antimicrobial treatment prior to admission. Forty percent of patients were transferred from other Centers; the indication to seek for hospital care was given by the primary care pediatrician in 80% of other children. Etiological agent was confirmed in 65.9% of cases; the most common infectious organism was Neisseria meningitidis (34.1%), followed by Streptococcus pneumoniae (20%). Patients with pneumococcal meningitis had a significant longer interval between onset of first symptoms and hospital admission. Median interval between the physician suspicion of meningitis and in-hospital first antimicrobial dose was 1 hour (interquartile range [IQR]: 1-2 hours). Corticosteroids were given to 63.5% of cases independently of etiology; 63.0% of treated patients received dexamethasone within 1 hour of antibiotic treatment, and 41.2% were treated for ≤4 days. Twenty-nine patients reported at least one in-hospital complication (34.1%). Six patients had neurological sequelae at discharge (7.1%). No deaths were observed. CONCLUSIONS: We observed a rate of meningitis sequelae at discharge similar to that reported by other western countries. Timely assistance and early treatment could have contributed to the favorable outcome that was observed in the majority of cases. Adherence to recommendation for corticosteroid adjunctive therapy seems suboptimal, and should be investigated in further studies. Most meningitis cases were due to N. meningitidis and S. pneumoniae. Reaching and maintaining adequate vaccination coverage against pneumococcal and meningococcal invasive infections remains a priority to prevent bacterial meningitis cases.

Evaluation of the quality of guidelines for acute gastroenteritis in children with the AGREE instrument.

AIM: The aim of the study was to assess the quality of clinical practice guidelines (CPGs) using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument, a validated international tool. MATERIALS AND METHODS: CPGs were identified by searching MEDLINE (1966-January 2009) and Embase (1988-January 2009), CPG databases, and relevant Web sites of agencies and organizations that produce and/or endorse guidelines. Included in the study were CPGs in English that addressed the management of acute gastroenteritis in children. Retrieved CPGs were evaluated with the AGREE instrument for quality assessment by 6 independent reviewers. AGREE consists of 6 domains for a total of 23 items. RESULTS: Nine CPGs were identified. Four were evidence based (EB) and 2 of these included tables of evidence. Eight CPGs (88%) scored <50% for "applicability," 7 (77%) for "stakeholder involvement," and 6 (66%) for "editorial independence." Compared with non-EB CPGs, EB CPGs had higher quality scores for all AGREE domains, with a better score for "rigor of development" (P < 0.001), "stakeholder involvement" and "clarity of presentation" (P < 0.01), and applicability (P < 0.05). Over time, the quality of guidelines tended to improve. The main recommendations of CPGs were similar. However, there were differences in the treatment of diarrhea, namely based on the settings and circumstances in which CPGs were produced. CONCLUSIONS: The overall quality of CPGs on acute gastroenteritis management in children is fair. Aims, target population, synthesis of evidence, formulation of recommendations, and clarity of presentation are points of strength. Weak issues are applicability, including identification of organizational barriers and adherence parameters, and cost/efficacy analysis.