Expert consensus on palivizumab use for respiratory syncytial virus in developed countries.

Respiratory syncytial virus (RSV) infection is a leading cause of hospitalisation in early childhood and palivizumab is the only licensed intervention for prevention. Palivizumab guidelines should reflect the latest evidence, in addition to cost-effectiveness and healthcare budgetary considerations. RSV experts from Europe, Canada and Israel undertook a systematic review of the evidence over the last 5 years and developed recommendations regarding prophylaxis in industrialised countries. Almost 400 publications were reviewed. This group recommended palivizumab for: preterm infants (<29 and ≤31 weeks gestational age [wGA] and ≤9 and ≤6 months of age, respectively; high-risk 32-35wGA), former preterm children ≤24 months with chronic lung disease/bronchopulmonary dysplasia, children ≤24 months with significant congenital heart disease; and other high-risk populations, such as children ≤24 months with Down syndrome, pulmonary/neuromuscular disorders, immunocompromised, and cystic fibrosis. Up to 5 monthly doses should be administered over the RSV season. It is our impression that the adoption of these guidelines would help reduce the burden of RSV.

Extrauterine growth restriction in very preterm infant: etiology, diagnosis, and 2-year follow-up.

In very-preterm small-for-gestational-age (SGA) infants, long-term postnatal growth is confused with extrauterine growth restriction (EUGR). We aimed to document EUGR in SGA infants and in non-SGA infants ("true-EUGR") and its relationship with fetal, maternal, and neonatal etiological factors. Four hundred seventy-nine very-preterm infants (< 32 weeks) born between 2003 and 2014 and attending the follow-up clinic were included. INTERGROWTH-21st preterm postnatal growth standards in conjunction with WHO Child Growth Standards were used to judge the postnatal growth patterns. EUGR was defined as weight < 10th percentile according to the sex at 36-34 weeks postmenstrual age, usually at discharge. Catch-up was evaluated at 2-2.5 years. Low-weight-for-age (wasting), low-length-for-age (stunting), and low-head-circumference-for-age were diagnosed if the z-scores were below - 2 SD. Logistic regression analysis estimated the association between the risk factors and EUGR, according to the SGA status at birth. Overall, EUGR occurred in 51% at 36-34 postmenstrual weeks and 21% at 2-2.5 years. However, among 411 non-SGA infants, "true-EUGR" rates were 43% and 15%, respectively.Conclusion: By 2-2.5 years of age, a "true-EUGR" of 15% can be expected and only the head circumference normalizes in SGA infants. Low birth weight, hyaline membrane disease, bronchopulmonary dysplasia, and male sex were associated with "true-EUGR." What is Known: • Fetal, neonatal, or postnatal charts have been considered to monitor the postnatal growth of preterm infants. • This selection influences the diagnosis of "extrauterine growth restriction" (EUGR) and the clinical strategies used. What is New: • Extrauterine growth restriction (EUGR) in small-for-gestational-age (SGA) infants can not be considered a true EUGR but a postnatal evolution of fetal growth restriction. • Preeclampsia, low gestational age, severe neonatal morbidity and male sex are independently associated with EUGR in non-SGA infants (named "true-EUGR"), which can be expected in 15% of very preterm infants by 2-2.5 years of age.

Interaction between healthcare professionals and parents is a key determinant of parental distress during childhood hospitalisation for respiratory syncytial virus infection (European RSV Outcomes Study [EROS]).

AIM: We characterised the distress that parents experienced when their child was hospitalised for respiratory syncytial virus (RSV) infection. METHODS: This survey-based, observational study was conducted during 2014-2015. Meetings were held in Spain and Italy, with 24 parents of RSV hospitalised infants and 11 healthcare professionals experienced in RSV, which identified 110 factors related to parental distress. The resulting questionnaire was completed by another 105 Spanish and Italian parents and 56 healthcare professionals, to assess the impact these factors had on parental distress, using a scale from 0 to 10 (very unimportant to very important). RESULTS: The five most important factors for parents were: healthcare professionals' awareness of the latest developments, readmission, reinfections, painful procedures and positive experiences with healthcare professionals. Healthcare professionals associated only medical factors with a meaningful impact on parents. Half of the six medical factors were given similar importance by both groups and the overall scoring for the 110 factors was comparable, with a correlation coefficient of 0.80. A primary concern on discharge was ongoing support. CONCLUSION: The relationship between parents and healthcare professionals was a significant factor in determining parental distress. Healthcare professionals appeared to have a good understanding of the overall impact on parents, particularly the key medical factors.

Impact of using the International Risk Scoring Tool on the cost-utility of palivizumab for preventing severe respiratory syncytial virus infection in Canadian moderate-to-late preterm infants.

BACKGROUND AND OBJECTIVE: To assess the cost-utility of palivizumab versus no prophylaxis in preventing severe respiratory syncytial virus (RSV) infection in Canadian moderate-to-late preterm (32-35 weeks' gestational age) infants using an (i) International Risk Scoring Tool (IRST) and (ii) Canadian RST (CRST). METHODS: A decision tree was developed to assess cost-utility. Infants assessed at moderate- and high-risk of RSV-related hospitalization (RSVH) by the IRST or CRST received palivizumab or no prophylaxis and then progressed to either (i) RSVH; (ii) emergency room/outpatient medically attended RSV-infection (MARI) or (iii) were uninfected/non-medically attended. Infants admitted to intensive care could incur mortality (0.43%). Respiratory morbidity was accounted in all uninfected surviving infants for 6 years or 18 years (RSVH/MARI). Palivizumab efficacy (72.2% RSVH reduction) and hospital outcomes were from the Canadian CARESS, PICNIC and RSV-Quebec studies. Palivizumab costs (50 mg: CAN$752; 100 mg: $1,505) were calculated from Canadian birth statistics combined with a growth algorithm. Healthcare/payer and societal costs (May 2022; 1.5% discounting) were included. RESULTS: Cost per quality-adjusted life year (QALY) was $29,789 with the IRST (0.79 probability of being <$50,000) and $15,833 with the CRST (0.96 probability). The model was most sensitive to utility scores, long-term sequelae and palivizumab cost. Vial sharing improved the incremental cost-utility ratio (IRST: $22,319; CRST: $9,231). CONCLUSIONS: Palivizumab was highly cost-effective (vs no prophylaxis) in Canadian moderate-to-late preterm infants using either the IRST or CRST. The IRST has fewer risk factors than the CRST (3 vs 7, respectively), captures more potential RSVHs (85% vs 54%) and provides another option to guide cost-effective RSV prophylaxis in Canada.

A new cost-utility analysis assessing risk factor-guided prophylaxis with palivizumab for the prevention of severe respiratory syncytial virus infection in Italian infants born at 29-35 weeks' gestational age.

Since the last Italian cost-utility assessment of palivizumab in 2009, new data on the burden of respiratory syncytial virus (RSV) and an International Risk Scoring Tool (IRST) have become available. The objective of this study was to provide an up-to-date cost-utility assessment of palivizumab versus no prophylaxis for the prevention of severe RSV infection in otherwise healthy Italian infants born at 29-31 weeks' gestational age (wGA) infants and those 32-35wGA infants categorized as either moderate- or high-risk of RSV-hospitalization (RSVH) by the IRST. A decision tree was constructed in which infants received palivizumab or no prophylaxis and then could experience: i) RSVH; ii) emergency room medically-attended RSV-infection (MARI); or, iii) remain uninfected/non-medically attended. RSVH cases that required intensive care unit admission could die (0.43%). Respiratory morbidity was considered in all surviving infants up to 18 years of age. Hospitalization rates were derived from Italian data combined with efficacy from the IMpact-RSV trial. Palivizumab costs were calculated from vial prices (50mg: €490.37 100mg: €814.34) and Italian birth statistics combined with a growth algorithm. A lifetime horizon and healthcare and societal costs were included. The incremental cost-utility ratio (ICUR) was €14814 per quality-adjusted life year (QALY) gained in the whole population (mean: €15430; probability of ICUR being <€40000: 0.90). The equivalent ICURs were €15139 per QALY gained (€15915; 0.89) for 29-31wGA infants and €14719 per QALY gained (€15230; 0.89) for 32-35wGA infants. The model was most sensitive to rates of long-term sequelae, utility scores, palivizumab cost, and palivizumab efficacy. Palivizumab remained cost-effective in all scenario analyses, including a scenario wherein RSVH infants received palivizumab without a reduction in long-term sequelae and experienced a 6-year duration of respiratory morbidity (ICUR: €27948 per QALY gained). In conclusion, palivizumab remains cost-effective versus no prophylaxis in otherwise healthy Italian preterm infants born 29-35wGA. The IRST can help guide cost-effective use of palivizumab in 32-35wGA infants.

Trends in survival among extremely-low-birth-weight infants (less than 1000 g) without significant bronchopulmonary dysplasia.

OBJECTIVE: The aim of this study was to analyze the evolution from 1997 to 2009 of survival without significant (moderate and severe) bronchopulmonary dysplasia (SWsBPD) in extremely-low-birth-weight (ELBW) infants and to determine the influence of changes in resuscitation, nutrition and mechanical ventilation on the survival rate. STUDY DESIGN: In this study, 415 premature infants with birth weights below 1000 g (ELBW) were divided into three chronological subgroups: 1997 to 2000 (n = 65), 2001 to 2005 (n = 178) and 2006 to 2009 (n = 172).Between 1997 and 2000, respiratory resuscitation in the delivery room was performed via a bag and mask (Ambu®, Ballerup, Sweden) with 40-50% oxygen. If this procedure was not effective, oral endotracheal intubation was always performed. Pulse oximetry was never used. Starting on January 1, 2001, a change in the delivery room respiratory policy was established for ELBW infants. Oxygenation and heart rate were monitored using a pulse oximeter (Nellcor®) attached to the newborn's right hand. If resuscitation was required, ventilation was performed using a face mask, and intermittent positive pressure was controlled via a ventilator (Babylog2, Drägger). In 2001, a policy of aggressive nutrition was also initiated with the early provision of parenteral amino acids. We used standardized parenteral nutrition to feed ELBW infants during the first 12-24 hours of life. Lipids were given on the first day. The glucose concentration administered was increased by 1 mg/kg/minute each day until levels reached 8 mg/kg/minute. Enteral nutrition was started with trophic feeding of milk. In 2006, volume guarantee treatment was instituted and administered together with synchronized intermittent mandatory ventilation (SIMV + VG). The complications of prematurity were treated similarly throughout the study period. Patent ductus arteriosus was only treated when hemodynamically significant. Surgical closure of the patent ductus arteriosus was performed when two courses of indomethacin or ibuprofen were not sufficient to close it.Mild BPD were defined by a supplemental oxygen requirement at 28 days of life and moderate BPD if breathing room air or a need for <30% oxygen at 36 weeks postmenstrual age or discharge from the NICU, whichever came first. Severe BPD was defined by a supplemental oxygen requirement at 28 days of life and a need for greater than or equal to 30% oxygen use and/or positive pressure support (IPPV or nCPAP) at 36 weeks postmenstrual age or discharge, whichever came first. Moderate and severe BPD have been considered together as "significant BPD". The goal of pulse oximetry was to maintain a hemoglobin saturation of between 88% and 93%. Patients were considered to not need oxygen supplementation when it could be permanently withdrawn. The distribution of the variables was not normal based on a Kolmogorov-Smirnov test (p < 0.05 in all cases). Therefore, quantitative variables were expressed as the median and interquartile range (IQR; 25th-75th percentile). Statistical analysis of the data was performed using nonparametric techniques (Kruskal-Wallis test and Mann-Whitney U test). A chi-square analysis was used to analyze qualitative variables. Potential confounding variables were those possibly related to BPD in survivors (p between 0.05 and 0.3 in univariate analysis). Logistic regression analysis was performed with variables related to BPD in survivors (p < 0.05) and potential confounding variables. The forward stepwise method adjusted for confounding factors was used to select the variables, and the enter method using selected variables was used to obtain the odds ratios. RESULTS AND CONCLUSION: There was an increase in the rate of SWsBPD (1997 to 2000: 58.5%; 2001 to 2005: 74.2%; and 2006 to 2009: 75.0%; p = 0.032). In survivors, the occurrence of significant BPD decreased after 2001 (9.5% vs. 2.3%; p = 0.013). The factors associated with improved SWsBPD were delivery by caesarean section, a reduced endotracheal intubation rate and a reduced duration of mechanical ventilation.While the mortality of ELBW infants has not changed since 2001, the frequency of SWsBPD has significantly increased (75.0%) in association with increased caesarean sections and reductions in the endotracheal intubation rate, as well as the duration of mechanical ventilation.

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries.

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed.

The effects of varying protein and energy intakes on the growth and body composition of very low birth weight infants.

OBJECTIVE: To determine the effects of high dietary protein and energy intake on the growth and body composition of very low birth weight (VLBW) infants. STUDY DESIGN: Thirty-eight VLBW infants whose weights were appropriate for their gestational ages were assessed for when they could tolerate oral intake for all their nutritional needs. Thirty-two infants were included in a longitudinal, randomized clinical trial over an approximate 28-day period. One control diet (standard preterm formula, group A, n = 8, 3.7 g/kg/d of protein and 129 kcal/kg/d) and two high-energy and high-protein diets (group B, n = 12, 4.2 g/kg/d and 150 kcal/kg/d; group C, n = 12, 4.7 g/kg/d and 150 kcal/kg/d) were compared. Differences among groups in anthropometry and body composition (measured with bioelectrical impedance analysis) were determined. An enriched breast milk group (n = 6) served as a descriptive reference group. RESULTS: Groups B and C displayed greater weight gains and higher increases in fat-free mass than group A. CONCLUSION: An intake of 150 kcal/kg/d of energy and 4.2 g/kg/d of protein increases fat-free mass accretion in VLBW infants.

The impact of clinical maternal chorioamnionitis on neurological and psychological sequelae in very-low-birth weight infants: a case-control study.

AIMS: To assess the relationship between clinically maternal chorioamnionitis and outcome in preterm very-low-birth weight (VLBW) infants. METHODS: An observational case-control study was conducted in the neonatology departments of 12 acute care teaching hospitals in Spain. Between January 2004 and December 2006, all consecutive VLBW (≤1500 g) infants who were born to a mother with clinical chorioamnionitis were enrolled. The controls included infants who were born to mothers without chorioamnionitis, matched by gestational age, and immediately born after each index case. At a corrected age of 24 months, a neurological examination and a psychological assessment of the surviving children were performed. RESULTS: Sixty-six of the newborn infants died; therefore, 262 infants from the original sample were available for the study. Follow-up data were obtained at a corrected age of 24 months from a total of 209 children (106 cases and 103 controls, 80% of the original sample size). Seventy children (33.5%) were diagnosed with some type of sequelae. The following conditions were all more prevalent in infants born to mothers with chorioamnionitis in comparison to controls: low development quotient (98.3±12.15 vs. 95.9±15.64; P=0.497), cerebral palsy (4.9% vs. 10.4%; P=0.138), seizures (1.0% vs. 3.8%; P=0.369), and other neurological or sensorial sequelae (32.0% vs. 34.9%; P=0.611). CONCLUSIONS: After controlling for gestational age, the study population demonstrated that the neurological outcomes in infants at a corrected age of 24 months was not worsened by chorioamnionitis.

The effect of respiratory syncytial virus on subsequent recurrent wheezing in atopic and nonatopic children.

BACKGROUND: Although respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) in early life are followed by later airway hyperreactivity, it is unclear whether there is a causal relationship between this and an atopic diathesis. OBJECTIVES: To separate the effects of RSV LRTI and an atopic diathesis on subsequent recurrent wheezing, we examined the protective effect of previous palivizumab administration against subsequent recurrent wheeze in infants with and without a family history of atopy. METHODS: A prospective multicenter, matched, double cohort study was conducted in 27 centers in Europe and Canada. The rates of physician-diagnosed recurrent wheezing in premature infants <36 weeks gestation who had received palivizumab in the first year of life were compared to those of gestational age-matched controls. RESULTS: The relative protective effect of palivizumab on physician-diagnosed recurrent wheezing through the ages of 2 to 5 years was 68% in those with no family history of asthma (odds ratio, 0.32; (95% CI, 0.14-0.75; N = 146 palivizumab-treated, 171 untreated) and 80% in those with no family history of atopy or food allergies (odds ratio, 0.20; 95% CI, 0.07-0.59; N = 101 palivizumab-treated, 100 untreated). In contrast, there was no effect of palivizumab on subsequent recurrent wheezing in the 90 children with a family history of atopy or food allergies compared to 130 untreated infants with atopic families. CONCLUSION: Respiratory syncytial virus prophylaxis in nonatopic children decreases by 80% the relative risk of recurrent wheezing but does not have any effect in infants with an atopic family history. This suggests that RSV predisposes to recurrent wheezing in an atopy-independent mechanism.

Challenges in the prevention or treatment of RSV with emerging new agents in children from low- and middle-income countries.

INTRODUCTION: Respiratory syncytial virus (RSV) causes approximately 120,000 deaths annually in children <5 years, with 99% of fatalities occurring in low- and middle-income countries (LMICs). AREAS COVERED: There are numerous RSV interventions in development, including long-acting monoclonal antibodies, vaccines (maternal and child) and treatments which are expected to become available soon. We reviewed the key challenges and issues that need to be addressed to maximize the impact of these interventions in LMICs. The epidemiology of RSV in LMICs was reviewed (PubMed search to 30 June 2020 inclusive) and the need for more and better-quality data, encompassing hospital admissions, community contacts, and longer-term respiratory morbidity, emphasized. The requirement for an agreed clinical definition of RSV lower respiratory tract infection was proposed. The pros and cons of the new RSV interventions are reviewed from the perspective of LMICs. EXPERT OPINION: We believe that a vaccine (or combination of vaccines, if practicable) is the only viable solution to the burden of RSV in LMICs. A coordinated program, analogous to that with polio, involving governments, non-governmental organizations, the World Health Organization, the manufacturers and the healthcare community is required to realize the full potential of vaccine(s) and end the devastation of RSV in LMICs.

Adoption in Canada of an international risk scoring tool to predict respiratory syncytial virus hospitalization in moderate-to-late preterm infants.

OBJECTIVE: The advisory board to the Ontario Ministry of Health considered adopting the new three-variable international risk scoring tool (IRST) to guide prophylaxis against respiratory syncytial virus hospitalization (RSVH) in moderate-to-late preterm infants born 32-35 weeks' gestational age (wGA). Canada currently uses a nationally validated, seven-variable RST, to predict RSVH in 33-35 wGA infants. We explored the potential implications of switching from the Canadian to the IRST. METHODS: Predictive accuracy (area under the receiver operating characteristic curve [AUROC]) of the two RSTs and correlations (Spearman rank) and number needed to treat (NNT) between cut-off scores for low-, moderate- and high-risk subjects were assessed. RESULTS: The RSTs contain many of the same risk factors (birth proximity to the RSV season, smoking, siblings, daycare), with the Canadian RST also including sex, small for GA and familial eczema. Predictive accuracy was similar (AUROC, IRST: 0.773 [sensitivity: 68.9%; specificity: 73.0%] vs Canadian: 0.762 [68.2%; 71.9%]). Significant correlations between cut-off scores (p < .001) and risk categories (p < .001) were apparent, although the correlation coefficients were weak for both (scores: 0.217; categories: 0.055). While the proportion of high-risk infants was similar (IRST: 0.7% vs Canadian: 0.6%), the NNT was lower for the Canadian RST (7.5 vs 14.3), and more infants were assigned moderate risk by the IRST (19.9% vs 9.8%). CONCLUSIONS: The IRST can be considered simpler (fewer risk factors) than the Canadian RST and its adoption may reduce the number of RSVHs among moderate-to-late preterm infants; however, the cost-effective implications for RSV prophylaxis warrant further investigation.

Effect of maternal clinical chorioamnionitis on neonatal morbidity in very-low birthweight infants: a case-control study.

AIMS: To assess the relationship between maternal clinical chorioamnionitis and neonatal outcome in preterm very-low birthweight (VLBW) infants. METHODS: An observational case-control study was conducted in the Neonatology Services of 12 acute-care teaching hospitals in Spain. Between January 2004 and December 2006, all consecutive VLBW (< or =1500 g) infants born to a mother with clinical chorioamnionitis were enrolled. Controls were infants without chorioamnionitis matched by gestational age who were born immediately after each index case. RESULTS: There were 165 cases and 163 controls. A significantly higher percentage of cases than controls required intubation (53% vs. 35.8%), had normal intrauterine growth (98.1% vs. 84.7%), were born in a tertiary center (inborn) (95.1% vs. 89.1%), from single gestations (76.4% vs. 65.6%) and vaginal delivery (47.3% vs. 33.3%), showed a lower Apgar score at 5 min, and presented a higher rate of early-onset sepsis (10.4% vs. 1.2%). Older maternal age (32.5 vs. 30.8 years), premature labor (67.3% vs. 25.8%), premature rupture of membranes (61.3% vs. 25.8%), and antibiotic treatment (88.5% vs. 52.3%) were significantly more frequent among cases than controls. CONCLUSIONS: After controlling by gestational age, maternal chorioamnionitis was associated with neonatal depression and early sepsis but not with other prematurity-related complications.

Validation of a model to predict hospitalization due to RSV of infants born at 33-35 weeks' gestation.

BACKGROUND: A model to predict hospitalization due to respiratory syncytial virus (RSV) of infants born at 33- 35 weeks' gestation was developed using seven risk factors from the Spanish FLIP study "birth +/-10 weeks from the beginning of the RSV season", "birth weight", "breast fed or=2 years", "number of family members with atopy", "number of family members with wheezing", and "gender". The aim of this study was to validate the model using French data. METHODS: The FLIP model [predictive accuracy 71%, receiver operating characteristic (ROC) 0.791] was tested against the French data (77 hospitalized infants with RSV born at 33-35 weeks and 154 age-matched controls) using discriminatory function analysis by applying the FLIP coefficients to the French data and by generating the seven variable model from the French data. RESULTS: Applying the FLIP coefficients to the French dataset, the model correctly classified 69% of cases (ROC 0.627). The predictive power increased to 73% (ROC 0.654) when "number of siblings >or=2 years" was substituted for "number of children at school". The number needed to treat (NNT) in order to prevent 70% of hospitalizations was 18. The model derived using French data could correctly classify 62% of cases in the French data (ROC 0.658). CONCLUSIONS: The model was successfully validated and may potentially optimize immunoprophylaxis in French infants born at 33-35 week's gestation.

Health economics and RSV.

An economic analysis was performed in Spain to evaluate the efficiency (cost-effectiveness) of palivizumab in preventing severe RSV infection in premature infants with GA 32-35 and two or more risk factors (RF). The design was a decision tree model using data from the scientific literature and the FLIP I and FLIP II studies IRIS Study Group. The main effectiveness measure was quality-adjusted life years (QALY) gained from both the National Health System (NHS) and societal perspectives. Prophylaxis with palivizumab was found to produce an incremental cost-effectiveness ratio (ICER) of 13,849euro/QALY from the NHS perspective, and 4,605euro/QALY from the societal perspective. Palivizumab is a cost-effective therapy as prophylaxis against RSV in infants with GA 32-35 and two or more RF. Its use is efficient from the NHS perspective, since the cost of a QALY, even in the least favourable scenarios, is lower than the threshold of 30,000euro/QALY considered socially acceptable in Europe.

Guidelines on CMV congenital infection.

Congenital cytomegalovirus (CMV) infection occurs in 0.6-0.7% of all newborns and is the most prevalent infection-related cause of congenital neurological handicap. Vertical transmission occurs in around 30% of cases, but the fetus is not always affected. Symptomatic newborns at birth have a much higher risk of suffering severe neurological sequelae. Detection of specific IgG and IgM and IgG avidity seem to be the most reliable tests to identify a primary infection but interpretation in a clinical context may be difficult. If a seroconversion is documented or a fetal infection is suspected by ultrasound markers, an amniocentesis should be performed to confirm a vertical transmission. In the absence of a confirmed fetal infection with fetal structural anomalies, a pregnancy termination should be discouraged. Fetal prognosis is mainly correlated to the presence of brain damage. Despite promising results with the use of antiviral drugs and CMV hyperimmune globulin (HIG), results have to be interpreted with caution. Pregnant women should not be systematically tested for CMV during pregnancy. Managing CMV screening should be restricted to pregnancies where a primary infection is suspected or among women at high risk. The magnitude of congenital CMV disease and the value of interventions to prevent its transmission or to decrease the sequelae need to be established before implementing public health interventions. In this paper, aspects of CMV infection in the pregnant woman and her infant are reviewed.

Respiratory syncytial virus prophylaxis for children with chronic lung disease: have we got the criteria right?

INTRODUCTION: The use of palivizumab for the prevention of respiratory syncytial virus-related hospitalization is well-established and has been adopted universally in pediatric position statements. Areas covered: The definition of chronic lung disease (CLD, bronchopulmonary dysplasia) has evolved over time and has significantly impacted the reported incidence of the condition, and the description of mild, moderate and severe disease in published studies. We reviewed lung function in infancy, childhood and adulthood of healthy preterm infants and those with CLD and how alterations in airway function, especially following respiratory syncytial virus infection may set the stage for chronic obstructive pulmonary disease in adults. We also characterized the real-world experience of the use of palivizumab compared to the single, randomized trial and examined the socioeconomic burden of respiratory syncytial virus hospitalization, an element that is commonly overlooked, when considering the value of prevention in the extremely high-risk, CLD population. Expert opinion: Based on the current evidence, we propose that palivizumab should be offered to all children with CLD in the first two years of life, irrespective of CLD disease severity. This may positively influence pulmonary maturation and normalize the trajectory of compromised lung function in these children into adulthood.