Xavier Carbonell-Estrany

Case-control study of the risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born at a gestational age of 33-35 weeks in Spain.

Background and Objective: The aim of this study was to identify those risk factors most likely to lead to the development of RSV-related respiratory Infection and subsequent hospital admission among premature infants born at 33–35 WGA (FLIP study) Methods: This was a prospective case-control study. Cases (186) hospitalized for respiratory syncytial virus (RSV) illness were recruited from 50 participating Spanish hospitals during the 2002–2003 RSV season (October 2002–April 2003). Controls (371) were selected in June 2003 but born at same time as cases. Results: Of these cases, 20.5% were admitted to the intensive care unit intensive care unit, and 7.6% required mechanical ventilation. None of the patients died. Conditional logistic regression analysis adjusted for medical center demonstrated that the risk of RSV-related respiratory infection requiring hospital admission in preterm infants 33–35 weeks of gestation (WGA) in Spain was most often associated with absolute chronologic age at start of RSV season ≤10 weeks [ie, born between July 15 and December 15; odds ratio (OR), 3.95; 95% confidence interval (CI), 2.65–5.90], breast-feeding for ≤2 months total (OR 3.26; 95% CI 1.96–5.42), presence of ≥1 school age siblings (OR 2.85; 95% CI 1.88–4.33), ≥4 residents and visitors at home (discounting school age siblings and the case/control him/herself) (OR 1.91; 95% CI 1.19–3.07) and a family history of wheezing (OR 1.90; 95% CI 1.19–3.01). Conclusions: In premature infants born 33–35 WGA, certain underlying risk factors significantly increase the risk of RSV-related respiratory infection and hospitalization. Premature infants 33–35 WGA with additional risk factors should be considered for RSV prophylaxis with palivizumab.

Motavizumab for Prophylaxis of Respiratory Syncytial Virus in High-Risk Children: A Noninferiority Trial

OBJECTIVE: Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by ∼50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with palivizumab. METHODS: This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged ≤6 months at enrollment or children aged ≤24 months with chronic lung disease of prematurity who received 15 mg/kg palivizumab or motavizumab monthly. Secondary end points included outpatient medically attended lower respiratory tract infections (MALRIs), RSV-specific LRIs, otitis media, antibiotic use, development of antimotavizumab antibodies, and motavizumab serum concentrations. RESULTS: Motavizumab recipients had a 26% relative reduction in RSV hospitalization compared with palivizumab recipients, achieving noninferiority. Motavizumab was superior to palivizumab for reduction of RSV-specific outpatient MALRIs (50% relative reduction). Overall, adverse events (AEs) were not significantly different between groups. Cutaneous events were reported in 2 percentage points more motavizumab recipients (7.2% vs 5.1%); most were mild, but 0.3% resulted in dosing discontinuation. Antidrug antibodies (ADA) were detected in 1.8% of motavizumab recipients. Patients with anti-drug antibody reported 6 RSV events and 17 cutaneous events. CONCLUSIONS: Children receiving prophylaxis with motavizumab or palivizumab had low rates of RSV hospitalization; motavizumab recipients experienced 50% fewer RSV MALRIs than palivizumab recipients. AEs were similar in both groups, although cutaneous AEs were higher for motavizumab recipients. Motavizumab may offer an improved alternative in prophylaxis for serious RSV disease in infants and children at high risk.

Hospitalization rates for respiratory syncytial virus infection in premature infants born during two consecutive seasons.

Objective. To collect data on hospitalization rates for respiratory syncytial virus (RSV) illness during the season of 1999 to 2000 in nonprophylaxed premature infants ≤32 weeks gestational age (GA) in Spain and compare this with previously published data collected in the season of 1998 to 1999. Methods. Children born at ≤32 weeks GA between April 1, 1999, and April 31, 2000, and discharged from the hospital before April 31, 2000, were included. Neonatal and demographic data were obtained at the initial visit. Study subjects were followed at monthly intervals throughout the respiratory season. RSV status and morbidity data were collected on patients rehospitalized for respiratory illness. Results. The 999 evaluable patients in the 2000 season were comparable to the 1999 sample, except for higher rates of family allergy history and number of multiple deliveries and a lower rate of neonatal morbidity. The hospitalization rate for RSV illness was 13.4% in the 1999 season and 13.1% in the 2000 season; 10 (8%) were RSV reinfections in the 2000 season. Significant independent prognostic variables for high risk of RSV hospital admission included: lower gestational age; chronologic age <3 months at onset of the RSV season; living with school age siblings; and exposure to tobacco smoke. Conclusions. Hospitalization rates for RSV disease in nonprophylaxed preterm infants ≤32 weeks GA were high in Spain and comparable during two consecutive RSV seasons (13%). Readmission for a second RSV infection was also common.

Effect of palivizumab prophylaxis in decreasing respiratory syncytial virus hospitalizations in premature infants.

Background. Respiratory syncytial virus (RSV) is a major cause of hospitalization in preterm infants and infants with chronic lung disease (CLD). Palivizumab, a humanized monoclonal antibody, was approved in Europe in 1999 as prophylaxis against severe RSV-related respiratory illness. No multiple season data have been published on palivizumab effectiveness in European populations. Data collected during 4 years in Spain compared RSV hospitalization rates and risk factors in a cohort of palivizumab-prophylaxed and nonprophylaxed preterm infants. Methods. The first cohort was derived from 2 previous studies and included 1583 infants followed during 2 RSV seasons (1998 to 1999, 1999 to 2000) before palivizumab initiation in Spain. The second cohort included 1919 infants who received palivizumab prophylaxis for 2 subsequent respiratory seasons (2000 to 2001, 2001 to 2002). Both cohorts were preterm (≤32 weeks gestational age) and ≤6 months old at onset of RSV season. Results. The RSV hospitalization rate in the palivizumab-prophylaxed cohort was 3.95, and it was 13.25% in nonprophylaxed infants This 70% overall difference in RSV hospitalization was observed despite the palivizumab-prophylaxed group’s lower gestational ages, more severe neonatal intensive care unit respiratory courses and higher incidence of CLD. Significant risk factors for RSV hospitalization in both cohorts included: lower gestational age; chronologic age <3 months at RSV season onset; school age siblings; and lower parental education. Nonprophylaxed children had a higher risk for RSV-related hospitalization than did prophylaxed patients (odds ratio, 3.86; 95% confidence interval, 2.83 to 5.25). Conclusion. Data from this study support the effectiveness of palivizumab in significantly modifying RSV-related hospitalizations in high risk preterm infants, with and without CLD, during two respiratory seasons.

FLIP-2 Study: risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born in Spain at a gestational age of 32 to 35 weeks.

Background: Ex-premature infants are more predisposed to complicated primary respiratory syncytial virus (RSV) infection. The aim of the present study was to validate the risk factors found in a previous epidemiologic case-control study regarding hospitalization as a result of RSV infection in premature infants born at 32–35 weeks of gestational age (WGA) in Spain. Methods: A prospective 2-cohort study was conducted during the 2005–2006 (October 2005 to April 2006) and 2006–2007 (October 2006 to April 2007) RSV seasons, respectively. Cases were premature infants hospitalized for RSV infection whereas controls were premature infants of the same age who did not require any hospitalization for respiratory causes. Results: During the study period 5441 children from 37 Spanish hospitals were included in the risk factor analysis. Two hundred two (3.7%) were cases and the rest controls. Of the cases, 17.8% were admitted to the intensive care unit and 7.4% required mechanical ventilation. None of the patients died. Logistic regression analysis demonstrated that the risk of RSV-related respiratory infection requiring hospital admission in preterm infants (32–35 WGA) was associated with the following factors: absolute chronologic age of ≤10 weeks at the onset of RSV season [odds ratio (OR): 2.99; 95% confidence interval (CI): 2.23–4.01]; presence of school-age siblings or day care attendance (OR: 2.04; 95% CI: 1.53–2.74); and smoking during pregnancy (OR: 1.61; 95% CI: 1.16–2.25). Conclusions: In premature infants (32–35 WGA), only 3 independent risk factors were found to significantly increase the risk of RSV-related respiratory infection and hospitalization.

Guidelines on CMV congenital infection.

Abstract 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.

Development and Validation of a Risk Scoring Tool to Predict Respiratory Syncytial Virus Hospitalization in Premature Infants Born at 33 through 35 Completed Weeks of Gestation

Objective. The purpose of the study was to develop and validate a clinical instrument predicting the risk of respiratory syncytial virus (RSV)-associated hospitalization (RSV-H) in premature infants born at 33 through 35 completed weeks of gestation (33—35GA). Design. An RSV risk scoring tool (RSV-RS) was developed by entering risk factors for RSV-H, determined in a Canadian prospective study, into a multiple logistic regression model. The scoring tool was then validated externally with data from a Spanish case-control study (FLIP). The Canadian cohort comprised 1758 RSV-positive infants born 33—35GA, of whom 66 (3.7%) had confirmed RSV-H. The FLIP data set comprised 186 (33.4%) RSV-H cases and 371 (66.7%) controls. Method. The primary outcome measure was RSV-H. The RSV-RS score was the sum of the weighted probabilities for each included risk factor multiplied by 100 and ranged from 0 to 100. Receiver operator characteristic curve analyses determined cutoff points to predict subjects at low, moderate, or high RSV-H risk. Results. The RSV-RS included 7 risk factors and cutoff scores of 0—48, 49—64, and 65— 100 for low-, moderate-, and high-risk subjects, respectively. For the Canadian cohort, RSV-RS sensitivity in predicting RSV-H cases was 68.2%, with 71.9% specificity. With the FLIP data set, the RSV-RS had lower accuracy (61.3% sensitivity; 65.8% specificity) but showed significant positive association with increased risk for RSV-H. Conclusion. The RSV-RS accurately identified 33—35GA infants at increased risk for RSV-H in a Canadian cohort. External validation with Spanish case-control study data further confirmed that the scoring tool is appropriate for the estimation of RSV-H risk.

Identifying Risk Factors for Severe Respiratory Syncytial Virus Among Infants Born After 33 Through 35 Completed Weeks of Gestation: Different Methodologies Yield Consistent Findings

Background: Prematurity is a proven risk factor for severe respiratory syncytial virus (RSV) infection. Prematurity leads to an increased need for, and duration of, hospital admission, intensive care, mechanical ventilation and supplemental oxygen, as well as increased mortality. Methods: The Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study was a prospective, multicenter, cohort study conducted in 16 regions across Canada during 2 successive RSV seasons: November 2000–June 2001, and November 2001–June 2002. The study regions were defined to capture all births and all hospital admissions. The FLIP [identify those risk Factors that most Likely may lead to development of RSV-related respiratory Infection and subsequent hospital admission among Premature infants born 33–35 weeks gestational age (GA)] study was a prospective, case-control study comparison of premature infants hospitalized for RSV infection and infants who had not been hospitalized to identify the risk factors that most likely would lead to development of RSV infection and subsequent hospital admission in this population. Results: The overall hospitalization rate for RSV in the PICNIC study was 3.6% for infants of 33–35 weeks GA. In the FLIP study, the severity of RSV infection in the 33- to 35-week GA infants was similar to that in the younger infants of <33-week GA studied previously by the Infección Respiratoria Infantil por Virus Respiratorio Sincitial Study Group. Similar risk factors were noted in both studies. Conclusions: RSV is a major cause of hospitalization in preterm infants. There is great variability among hospital admission rates globally, despite the commonality of severe RSV in many countries. Furthermore there are numerous independent risk factors for severe RSV, including socioeconomic and environmental factors, that merit further investigation. There is likely an additive effect when multiple risk factors are present. More research is needed on the various risk factors and their significance.

Intrapartum GBS screening and antibiotic prophylaxis: a European consensus conference

Abstract Group B streptococcus (GBS) remains worldwide a leading cause of severe neonatal disease. Since the end of the 1990s, various strategies for prevention of the early onset neonatal disease have been implemented and have evolved. When a universal antenatal GBS screening-based strategy is used to identify women who are given an intrapartum antimicrobial prophylaxis, a substantial reduction of incidence up to 80% has been reported in the USA as in other countries including European countries. However recommendations are still a matter of debate due to challenges and controversies on how best to identify candidates for prophylaxis and to drawbacks of intrapartum administration of antibiotics. In Europe, some countries recommend either antenatal GBS screening or risk-based strategies, or any combination, and others do not have national or any other kind of guidelines for prevention of GBS perinatal disease. Furthermore, accurate population-based data of incidence of GBS neonatal disease are not available in some countries and hamper good effectiveness evaluation of prevention strategies. To facilitate a consensus towards European guidelines for the management of pregnant women in labor and during pregnancy for the prevention of GBS perinatal disease, a conference was organized in 2013 with a group of experts in neonatology, gynecology-obstetrics and clinical microbiology coming from European representative countries. The group reviewed available data, identified areas where results were suboptimal, where revised procedures and new technologies could improve current practices for prevention of perinatal GBS disease. The key decision issued after the conference is to recommend intrapartum antimicrobial prophylaxis based on a universal intrapartum GBS screening strategy using a rapid real time testing.

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

ObjectiveTo determine the effects of high dietary protein and energy intake on the growth and body composition of very low birth weight (VLBW) infants.Study designThirty-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.ResultsGroups B and C displayed greater weight gains and higher increases in fat-free mass than group A.ConclusionAn intake of 150 kcal/kg/d of energy and 4.2 g/kg/d of protein increases fat-free mass accretion in VLBW infants.