A Case of Enterococcal Patent Ductus Arteriosus-associated Endarteritis in a Preterm Neonate.

INTRODUCTION: The persistent patency of the ductus arteriosus frequently occurs in premature neonates and can cause infective endocarditis (IE) or ductal endarteritis (DE) during sepsis. Even though neonatal IE and DE are believed to be a rare eventuality, their incidence has been increasing in the last decades due to the improved survival of even more preterm babies, favored by highly invasive procedures and therapies. In parallel, antimicrobial resistance is another rising problem in neonatal intensive care units, which frequently compels to treat infections with broad-spectrum or last generation antibiotics. CASE PRESENTATION: We report the case of a preterm neonate affected by patent ductus arteriosus-associated DE that followed an episode of sepsis caused by a high-level aminoglycoside-resistant enterococcus. The neonate was successfully treated with the synergistic combination of ampicillin and cefotaxime. DISCUSSION: IE and patent ductus arteriosus-associated DE are rising inside neonatal intensive care units and neonatologists should be aware of these conditions. Enterococcal IE and patent ductus arteriosus-associated DE sustained by high-level aminoglycoside-resistant strains can be successfully treated with the synergistic combination of ampicillin and cefotaxime even in preterm neonates.

A biallelic variant in COX18 cause isolated Complex IV deficiency associated with neonatal encephalo-cardio-myopathy and axonal sensory neuropathy.

Pathogenic variants impacting upon assembly of mitochondrial respiratory chain Complex IV (Cytochrome c Oxidase or COX) predominantly result in early onset mitochondrial disorders often leading to CNS, skeletal and cardiac muscle manifestations. The aim of this study is to describe a molecular defect in the COX assembly factor gene COX18 as the likely cause of a neonatal form of mitochondrial encephalo-cardio-myopathy and axonal sensory neuropathy. The proband is a 19-months old female displaying hypertrophic cardiomyopathy at birth and myopathy with axonal sensory neuropathy and failure to thrive developing in the first months of life. Serum lactate was consistently increased. Whole exome sequencing allowed the prioritization of the unreported homozygous substitution NM_001297732.2:c.667 G > C p.(Asp223His) in COX18. Patient's muscle biopsy revealed severe and diffuse COX deficiency and striking mitochondrial abnormalities. Biochemical and enzymatic studies in patient's myoblasts and in HEK293 cells after COX18 silencing showed a severe impairment of both COX activity and assembly. The biochemical defect was partially rescued by delivery of wild-type COX18 cDNA into patient's myoblasts. Our study identifies a novel defect of COX assembly and expands the number of nuclear genes involved in a mitochondrial disorder due to isolated COX deficiency.

Cor Triatriatum Dexter: Contrast Echocardiography Is Key to the Diagnosis of a Rare but Treatable Cause of Neonatal Persistent Cyanosis.

Cor triatriatum dexter (CTD) is an extremely uncommon and underreported congenital cardiac anomaly in which the persistence of the embryonic right venous valve separates the right atrium into two chambers with varying degrees of obstruction to antegrade flow and variable degree of right to left shunt at atrial level. Depending on the size of the valves, clinical manifestations vary from absence of symptoms to severe hypoxia, requiring urgent surgical correction. We herein describe the diagnostic difficulties in a case of neonatal CTD, who developed increasingly severe and unresponsive cyanosis, first interpreted as postnatal maladjustment with pulmonary hypertension. The failure to respond to oxygen and pulmonary vasodilators led us to reconsider a different diagnosis. The use of contrast echocardiography improved the diagnostic performance of transthoracic echocardiogram (TTE) and revealed a massive right-to-left shunt secondary to the presence of an atrial membrane that required urgent surgery.

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.

Association between Hemodynamically Significant Patent Ductus Arteriosus and Bronchopulmonary Dysplasia.

OBJECTIVE: To assess whether the duration and magnitude of the shunt with patent ductus arteriosus (PDA) are related to a higher incidence of bronchopulmonary dysplasia (BPD) or death. STUDY DESIGN: A total of 242 infants ≤ 28 weeks gestational age were evaluated retrospectively between 2007 and 2012; 105 (43.3%) developed BPD or died (group 1) and 137 (56.6%) did not (group 2). A review of all echocardiographic evaluations performed from birth up to 36 weeks of postconceptional age or final ductal closure was carried out, to detect the presence of PDA, and estimate the severity of ductal shunt through the "PDA staging system" proposed by McNamara and Sehgal. RESULTS: Group 1 presented with a hemodynamically significant ductus arteriosus (DA) (E3 and/or E4-PDA) for a longer period of time vs group 2: 4.8 vs 2.3 days, respectively (P < .001). Persistence of a nonsignificant DA (E2) was not associated with development of BPD (P = .16). Each week of a hemodynamically significant DA represented an added risk for BPD (OR 1.7), and the duration of a small, nonsignificant DA (E2) did not. Surgical ligation of PDA itself was not found to be an independent risk factor for BPD. In the subgroup of patients who received ligation, a later ligation (33 vs 23 days) and a prolonged PDA were the only factors associated to BPD or death. CONCLUSIONS: A shared scoring system of the severity of ductal shunt is helpful to correctly evaluate the association between PDA morbidities, to compare scientific studies, and to guide treatment.

A case report of aorto-pulmonary window in an infant born to a diabetic mother.

Several studies have described the association between pre-gestational maternal diabetes and cardiac disease in the newborn. Infants of diabetic mothers have an increased incidence of congenital heart disease, reported between 3% and 6% compared to 0.8% of the general population. A particularly high prevalence of conotruncal defects has been recently described among congenital heart diseases. This group of malformations affects ventricular outflows, aorta, and pulmonary artery and shares a common embryogenic origin. They include persistence of the truncus arteriosus, transposition of great arteries, tetralogy of Fallot, interruption of the aortic arch, and double outlet right ventricle. Aorto-pulmonary window, a rare congenital heart disease belonging to conotruncal malformations, has never been previously described in association with maternal diabetes. We describe the case of a male infant born to a mother suffering from a poorly controlled type 1 diabetes during pregnancy. In the early postnatal life the infant showed respiratory distress, tachycardia, and failure to thrive. He was found to be affected by aorto-pulmonary window that required corrective surgical intervention. .

Should corticosteroids be used in bacterial meningitis in children?

Bacterial meningitis is one of the most serious infections in infants and children, with considerable morbidity and mortality. Despite the spreading of conjugated vaccines against Haemophilus influenzae type b (Hib), the most important pneumococcal serotypes and serogroup C meningococcus has reduced the incidence of this infection in developed countries, it still remains a global public health problem and an important cause of mortality and disability. Whether corticosteroids should be used as a complementary therapy to antibacterials is still not clear because of the disparate findings from clinical trials and clinical evidence. The aim of this review is to analyze the available evidence on the impact of corticosteroid therapy in infants and children with bacterial meningitis in developed countries in order to define whether they should be added routinely in the empiric therapy of such disease. Our analysis concluded that in high-income countries dexamethasone has shown good results to prevent hearing loss in Hib meningitis if administered before or at the same time as the first dose of antibiotics. Dexamethasone should be evaluated in pneumococcal meningitis: it may be less beneficial in children with delayed presentation to medical attention and may be unfavourable in case of cephalosporin-resistant pneumococci. On the contrary, there is no evidence to recommend the use of corticosteroids in meningococcal meningitis. Further studies that take into account the epidemiologic changes of recent years, consider enrolment based on the onset of symptoms and evaluate outcomes such as hearing loss and neurologic sequelae with advanced techniques are urgently needed.

Procalcitonin measurements for guiding antibiotic treatment in pediatric pneumonia.

In order to evaluate the use of an algorithm based on a procalcitonin (PCT) cut-off value as a means of guiding antibiotic therapy, 319 hospitalised children with uncomplicated community-acquired pneumonia (CAP) were randomised 1:1 to be treated on the basis of the algorithm or in accordance with standard guidelines. The children in the PCT group did not receive antibiotics if their PCT level upon admission was <0.25 ng/mL, and those receiving antibiotics from the time of admission were treated until their PCT level was ≥ 0.25 ng/mL. The final analysis was based on 155 patients in the PCT group and 155 in the control group. In comparison with the controls, the PCT group received significantly fewer antibiotic prescriptions (85.8% vs 100%; p < 0.05), were exposed to antibiotics for a shorter time (5.37 vs 10.96 days; p < 0.05), and experienced fewer antibiotic-related adverse events (3.9% vs 25.2%; p < 0.05), regardless of CAP severity. There was no significant between-group difference in recurrence of respiratory symptoms and new antibiotic prescription in the month following enrollment. The results of this first prospective study using a PCT cut-off value to guide antibiotic therapy for pediatric CAP showed that this approach can significantly reduce antibiotic use and antibiotic-related adverse events in children with uncomplicated disease. However, because the study included mainly children with mild to moderate CAP and the risk of the use of the algorithm-based approach was not validated in a relevant number of severe cases, further studies are needed before it can be used in routine clinical practice.

Impact of pandemic A/H1N1/2009 influenza on children and their families: comparison with seasonal A/H1N1 and A/H3N2 influenza viruses.

OBJECTIVES: To make a direct comparison between the total burden of pandemic influenza and that of other seasonal influenza A viral subtypes in otherwise healthy children. METHODS: The total clinical and socioeconomic burden of pandemic A/H1N1/2009 influenza was compared with that of seasonal influenza A viral subtypes in 389 otherwise healthy children with A/H1N1/2009, 126 with seasonal A/H1N1 and 486 with seasonal A/H3N2 infection referred to the Emergency Room and hospitalised in the in-patient units of a large, university-based paediatric hospital. Influenza diagnosis was confirmed by real-time polymerase chain reaction. RESULTS: Regardless of age or gender, the variables significantly associated with pandemic A/H1N1/2009 and seasonal A/H3N2 infection were a diagnosis of lower respiratory tract infection upon clinical presentation, the need for hospitalisation, hospitalisation for ≥7 days, school absences of ≥7 days, the need for aerosol therapy, the household development of a disease similar to that of the infected child, and the need for additional household medical visits and antibiotic prescriptions (p < 0.001). A longer period of hospitalisation and lost school days seemed to be associated with pandemic A/H1N1/2009 infection (p < 0.01). CONCLUSIONS: Perceived symptom severity and the risk of serious outcomes are similar in children with influenza due to pandemic A/H1N1/2009 or seasonal A/H3N2 influenza, but both of these viruses seem to have a greater clinical and socioeconomic impact than seasonal A/H1N1 virus, regardless of the patients' age or gender.

Immunogenicity and safety of intradermal influenza vaccine in children.

In order to compare the immunogenicity and safety of different doses of trivalent influenza vaccine (TIV) administered intradermallly (ID) with those evoked by a full dose of intramuscular (IM) virosomal-adjuvanted influenza vaccine (VA-TIV), 112 previously primed healthy children aged ≥ 3 years were randomised to receive 9 µg or 15 µg of each strain of ID-TIV, or a full IM dose (15 µg of each strain) of VA-TIV. The A/H1N1 and A/H3N2 seroconversion and seroprotection rates were ≥ 90% and geometric mean titres (GMTs) increased 3.2-14.9 times without any statistically significant between-group differences; however, the seroconversion and seroprotection rates against the B strain were significantly higher in the children receiving either ID-TIV dose (p<0.05) without any differences between them. GMT against B virus was significantly higher in the children receiving the highest dose (p<0.05). Local reactions were significantly more common among the children receiving either ID-TIV dose (p<0.05), but systemic reactions were relatively uncommon in all three groups. Our findings suggest that ID-TIV with 15 µg of each viral antigen can confer a significant better protection against influenza than that obtained with the same dose of IM TIV in already primed children aged ≥ 3 years with an acceptable safety profile. The lower dose of ID-TIV needs further evaluation to analyze persistence of protection.

Pandemic influenza A/H1N1 vaccine administered sequentially or simultaneously with seasonal influenza vaccine to HIV-infected children and adolescents.

In order to evaluate the immunogenicity, safety and tolerability of the 2009 A/H1N1 MF59-adjuvanted influenza vaccine administered sequentially or simultaneously with seasonal virosomal-adjuvanted influenza vaccine to HIV-infected children and adolescents, 36 HIV-infected children and adolescents, and 36 age- and gender-matched healthy controls were randomised 1:1 to receive the pandemic vaccine upon enrollment and the seasonal vaccine one month later, or to receive the pandemic and seasonal vaccines simultaneously upon enrollment. Seroconversion and seroprotection rates against the pandemic influenza A/H1N1 virus were 100% two months after vaccine administration in both groups, regardless of the sequence of administration. Geometric mean titres against pandemic and seasonal antigens were significantly higher when the seasonal and pandemic vaccines were administered simultaneously than when the seasonal vaccine was administered alone. Local and systemic reactions were mild and not increased by simultaneous administration. In conclusion, the 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine is as immunogenic, safe and well tolerated in HIV-infected children and adolescents as in healthy controls. Its simultaneous administration with virosomal-adjuvanted seasonal antigens seems to increase immune response to both pandemic and seasonal viruses with the same safety profile as that of the pandemic vaccine alone. However, because this finding cannot be clearly explained by an immunological viewpoint, further studies are needed to clarify the reasons of its occurrence.

Antibody response of healthy children to pandemic A/H1N1/2009 influenza virus.

BACKGROUND: Little is known about the proportion of pediatric pandemic A/H1N1/2009 influenza cases who showed seroconversion, the magnitude of this seroconversion, or the factors that can affect the antibody level evoked by the pandemic A/H1N1/2009 influenza. Aims of this study were to analyse antibody responses and the factors associated with high antibody titres in a cohort of children with naturally acquired A/H1N1/2009 influenza infection confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Demographic, clinical and virologic data were collected from 69 otherwise healthy children with pandemic A/H1N1/2009 influenza (27 females, mean age ± SD: 5.01 ± 4.55 years). Their antibody levels against pandemic A/H1N1/2009 and seasonal A/H1N1 influenza viruses were evaluated by measuring hemagglutination-inhibiting antibodies using standard assays. Sixty-four patients (92.8%) with pandemic A/H1N1/2009 influenza had A/H1N1/2009 antibody levels of ≥ 40, whereas only 28/69 (40.6%) were seroprotected against seasonal A/H1N1 influenza virus. Those who were seroprotected against seasonal A/H1N1 virus were significantly older, significantly more often hospitalised, had a diagnosis of pneumonia significantly more frequently, and were significantly more often treated with oseltamivir than those who were not seroprotected (p < 0.05). The children with the most severe disease (assessed on the basis of a need for hospitalisation and a diagnosis of pneumonia) had the highest antibody response against pandemic A/H1N1/2009 influenza virus. CONCLUSIONS: Otherwise healthy children seem to show seroprotective antibody titres after natural infection with pandemic A/H1N1/2009 influenza virus. The strength of the immune response seems to be related to the severity of the disease, but not to previous seasonal A/H1N1 influenza immunity.

Knowledge of human papillomavirus infection and its prevention among adolescents and parents in the greater Milan area, Northern Italy.

BACKGROUND: In order to be widely accepted by users, the implementation of a new health intervention requires them to be adequately informed about its clinical importance, benefits and risks. The aim of this study was to provide data on the knowledge of Italian adolescents and parents concerning human papillomavirus (HPV) infection and its prevention in order to allow the development of adequate training programmes. METHODS: Between 2 May and 15 June 2008, we made a cross-sectional survey of 863 high school students and 2,331 parents of middle and high school students using two anonymously completed questionnaires covering the knowledge of HPV infection and related diseases, and attitudes to vaccinations. The approached schools were a convenience sample of the schools of the greater Milan area, Northern Italy. RESULTS: More mothers than fathers were aware that HPV infection could concern their children (58% vs 53%; p = 0.004) and were favourable towards vaccinating their children against HPV (68% vs 65%; p = 0.03); among the students, more females than males were aware that HPV infection could concern themselves (45% vs 26%; p < 0.001) and would undergo vaccination against HPV (68% vs 40%; p < 0.001). The parents' propensity to vaccinate their children against HPV was significantly associated with professing the Catholic religion (odds ratio - OR = 0.61, 95% confidence interval - CI 0.46-0.82, being atheist), the gender of the offspring (OR = 1.88, 95% CI 1.53-2.30, having at least one daughter), a propensity to vaccinations in general (OR = 23.1, 95% CI 13.7-38.8), a knowledge that HPV vaccine is aimed at preventing cervical cancer (OR = 2.31, 95% CI 1.69-3.16), and an awareness that HPV could affect their own children (OR = 3.52, 95% CI 2.89-4.29). The students who were aware that HPV infection could affect themselves were more in favour of to HPV vaccination, regardless of whether they were male (OR = 5.73, 95% CI 2.85-11.5) or female (OR = 2.39, 95% CI 1.66-3.46). CONCLUSIONS: Both students and parents seem to underestimate the likelihood of HPV infection, and this is associated with a lower propensity for vaccination. This is an important indication for future training programmes concerning HPV prevention designed to increase the acceptance of HPV vaccine in families.