Cost-utility analysis of Palivizumab for Respiratory Syncytial Virus infection prophylaxis in preterm infants: update based on the clinical evidence in Spain.

BACKGROUND: This study aimed at estimating the efficiency of palivizumab in the prevention of Respiratory Syncytial Virus (RSV) infection and its sequelae in preterm infants (32day 1-35day 0weeks of gestational age -wGA-) in Spain. METHODS: A decision-tree model was developed to compare health benefits (Quality Adjusted Life Years-QALYs) and costs of palivizumab versus a non-prophylaxis strategy over 6 years. A hypothetical cohort of 1,000 preterm infants, 32day 1-35day 0 wGA (4.356 kg average weight) at the beginning of the prophylaxis (15 mg/kg of palivizumab; 3.88 average number of injections per RSV season) was analysed. The model considered the most recent evidence from Spanish observational and epidemiological studies on RSV infection: the FLIP II study provided hospital admission and Intensive Care Unit (ICU) admission rates; in-hospital mortality rate was drawn from an epidemiological study from 2004 to 2012; recurrent wheezing rates associated to RSV infection from SPRING study were adjusted by the evidence on the palivizumab effect from clinical trials. Quality of life baseline value, number of hospitalized infants and the presence of recurrent wheezing over time were granted to estimate QALYs. National Health Service and societal perspective (included also recurrent wheezing indirect cost) were analysed. Total costs (€, 2016) included pharmaceutical and administration costs, hospitalization costs and recurrent wheezing management annual costs. A discount rate of 3.0% was applied annually for both costs and health outcomes. RESULTS: Over 6 years, the base case analysis showed that palivizumab was associated to an increase of 0.0731 QALYs compared to non-prophylaxis. Total costs were estimated in €2,110.71 (palivizumab) and €671.68 (non-prophylaxis) from the National Health System (NHS) perspective, resulting in an incremental cost utility ratio (ICUR) of €19,697.69/QALYs gained (prophylaxis vs non-prophylaxis). Results derived from the risk-factors population subgroups analysed were in line with the total population results. From the societal perspective, the incremental cost associated to palivizumab decreased to an €1,253.14 (ICUR = €17,153.16€/QALYs gained for palivizumab vs non-prophylaxis). One-way and probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: The prophylaxis with palivizumab is efficient for preventing from RSV infections in preterm infants 32day 1-35day 0 wGA in Spain.

[Medication errors in a neonatal unit: One of the main adverse events]. / Los errores de tratamiento en una unidad neonatal, uno de los principales acontecimientos adversos.

INTRODUCTION: Neonatal units are one of the hospital areas most exposed to the committing of treatment errors. A medication error (ME) is defined as the avoidable incident secondary to drug misuse that causes or may cause harm to the patient. The aim of this paper is to present the incidence of ME (including feeding) reported in our neonatal unit and its characteristics and possible causal factors. A list of the strategies implemented for prevention is presented. MATERIAL AND METHODS: An analysis was performed on the ME declared in a neonatal unit. RESULTS: A total of 511 MEs have been reported over a period of seven years in the neonatal unit. The incidence in the critical care unit was 32.2 per 1000 hospital days or 20 per 100 patients, of which 0.22 per 1000 days had serious repercussions. The ME reported were, 39.5% prescribing errors, 68.1% administration errors, 0.6% were adverse drug reactions. Around two-thirds (65.4%) were produced by drugs, with 17% being intercepted. The large majority (89.4%) had no impact on the patient, but 0.6% caused permanent damage or death. Nurses reported 65.4% of MEs. The most commonly implicated causal factor was distraction (59%). Simple corrective action (alerts), and intermediate (protocols, clinical sessions and courses) and complex actions (causal analysis, monograph) were performed. CONCLUSIONS: It is essential to determine the current state of ME, in order to establish preventive measures and, together with teamwork and good practices, promote a climate of safety.

[Towards a safety culture in the neonatal unit: Six years experience]. / Caminando hacia una cultura de seguridad en la unidad neonatal: experiencia de 6 años.

INTRODUCTION: A safety culture is the collective effort of an institution to direct its resources toward the goal of safety. MATERIAL AND METHODS: An analysis is performed on the six years of experience of the Committee on the Safety of Neonatal Patient. A mailbox was created for the declaration of adverse events, and measures for their correction were devised, such as case studies, continuous education, prevention of nosocomial infections, as well as information on the work done and its assessment. RESULTS: A total of 1287 reports of adverse events were received during the six years, of which 600 (50.8%) occurred in the neonatal ICU, with 15 (1.2%) contributing to death, and 1282 (99.6%) considered preventable. Simple corrective measures (notification, security alerts, etc.) were applied in 559 (43.4%), intermediate measures (protocols, monthly newsletter, etc.) in 692 (53.8%), and more complex measures (causal analysis, scripts, continuous education seminars, prospective studies, etc.) in 66 (5.1%). As regards nosocomial infections, the prevention strategies implemented (hand washing, insertion and maintenance of catheters) directly affected their improvement. Two surveys were conducted to determine the level of satisfaction with the Committee on the Safety of Neonatal Patient. A rating 7.5/10 was obtained in the local survey, while using the Spanish version of the Hospital Survey on Patient Safety Culture the rate was 7.26/10. CONCLUSIONS: A path to a culture of safety has been successfully started and carried out. Reporting the adverse events is the key to obtaining information on their nature, etiology and evolution, and to undertake possible prevention strategies.

[Underwater delivery. Consensus of the Spanish Neonatology Society and the Perinatal Section of the Spanish Obstetrics and Gynecology Society]. / Atención del parto en el agua. Consenso de la Sociedad Española de Neonatología y de la Sección de Medicina Perinatal de la Sociedad Española de Obstetricia y Ginecología.

Immersion in water during labor and delivery as an alternative to traditional delivery is a practice that has increased in many countries. This technique is effective in reducing pain and duration of labor. The American Academy of Pediatrics and The American College of Obstetricians and Gynecologists have published a clinical report which indicates the potential maternal benefits during the first stage of labor but, questions the performance of this technique during delivery and birth of the newborn. In this report, the Spanish Society of Neonatology and the Spanish Society of Obstetrics and Gynecology analyze the current scientific evidence on water immersion delivery, and the impact this practice could have in the mother and especially in the wellbeing of newborn.

[Update of recommendations on the use of palivizumab as prophylaxis in RSV infections]. / Actualización de las recomendaciones de la Sociedad Española de Neonatología para la utilización del palivizumab como profilaxis de las infecciones graves por el virus respiratorio sincitial.

The Standards Committee of the Spanish Neonatology Society (SENeo) considers that the new document from the American Academy of Pediatrics, including recommendations for palivizumab use to prevent serious infections produced by the Respiratory Syncytial Virus (RSV), provides no new scientific evidence which would justify the modification of the current recommendations of the SENeo. However, some adjustments to the criteria of the existing recommendations are proposed to reduce the cost of the drug by its correct and judicious management.

[Influence of in-home nursing care on the weight of the early discharged preterm newborn]. / Evolución del peso del prematuro con alta precoz y atención domiciliaria de enfermería.

INTRODUCTION: In-Home nursing care of the preterm newborn helps to bring the family situation to normal, promotes breastfeeding and development of the newborn, and enables the reorganization of health care resources. The purpose of this paper is to demonstrate that in-home nursing care of the preterm newborn leads to an increase in weight and a similar morbidity. PATIENTS AND METHODOLOGY: A total of 65 cases and 65 controls (matched by weight, age and sex) were studied, all of them preterm newborns born in hospital and weighing less than 2100 g at discharge. In-home nursing care was carried out by a pediatrician neonatologist, as well as two nurses specialized in neonatology who made several visits to the home. Weight gain was calculated as g/day and g/Kg/day, comparing the first week of the study with the week prior to the beginning of the study. RESULTS: The groups were comparable. Weight gain in the group with home nursing care was 38 g per day, significantly higher than the weight gain in the control group (31 g/day). The independent predictive variables of the increase in g/Kg/day during the study were in-home nursing care, male gender, breastfeeding less, and not having suffered from a peri-intraventricular hemorrhage. Neonatal morbidity was similar in both groups. CONCLUSIONS: In-home care was associated with a greater weight gain of the newborn at home than during their stay in the hospital, and can be considered safe because neonatal morbidity was not increased.

[Universal cytomegalovirus infection screening in premature newborns less than 1500 g]. / Cribado universal de infección por citomegalovirus en prematuros de menos de 1.500 g.

INTRODUCTION: Cytomegalovirus (CMV) infection is endemic, and children who attend day care are the most important source of infection. OBJECTIVE: To establish recommendations based on the medical evidence on the vertical transmission of cytomegalovirus in preterm infants weighing less than 1500g at birth. BACKGROUND: Infection in pregnant women may be primary or secondary. Although there is fetal infection, 85% of newborn infants are asymptomatic. Symptoms of infection include low birth weight, hepatosplenomegaly, thrombocytopenia, microcephaly and neurological disorders. The prognosis of symptomatic children is very poor, with high mortality and neurological disorders. The virus can be reactivated during breast feeding, and early infection is possible through breast milk, probably with little impact in term infants, although the long-term neurological outcome worsens in preterm infants. The diagnostic method of choice is the identification of CMV in urine; the determination in the first two weeks of life suggests congenital infection; later it can be acquired at birth or through breast milk or contaminated blood transfusion. CONCLUSION AND RECOMMENDATION: Determine viral DNA at 4-6 weeks of life by protease chain reaction. If it is positive, monitoring of samples from the first days of life and breast milk are mandatory. This should allow the newborn to be classified into three states: "Without CMV infection", "Congenital CMV infection", "Acquired CMV infection".

[Morbidity and mortality in newborns at the limit of viability in Spain: a population-based study]. / Morbimortalidad en recién nacidos al límite de la viabilidad en España: estudio de base poblacional.

INTRODUCTION: Perinatal care in extremely immature newborns is a clinical and ethical problem of great importance for professionals and families, and requires that the available information on the chances of child survival is of the highest quality. The aim of this study was to determine the specific rates of survival at hospital discharge, and survival without major morbidity in newborns with a gestation age (GA) ≤ 26 weeks in Spain. PATIENTS AND METHODS: We included live newborns ≤ 26 weeks admitted to the collaborating centers of the SEN1500 network (2004-2010). Out born patients, infants who died in delivery room, and those with congenital anomalies incompatible with life were excluded. RESULTS: A total of 3,236 patients were included. GA specific survival was 12.5, 13.1, 36.9, 55.7, and 71.9% at 22, 23, 24, 25, and 26 weeks of GA, respectively. Survival without severe intracranial hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, and/or retinopathy of prematurity was 1.5, 9.5, 19.0, and 29.9% at 23, 24, 25 and 26 weeks GA, respectively. CONCLUSIONS: Survival without major morbidity in infants less than 23 weeks GA is exceptional, and scarce in newborns with 23 and 24 weeks GA. Infants ≥ 25 weeks GA have reasonable chances of survival and, in the absence of major malformations or other relevant complications, should be offered active resuscitation and intensive care. The continuous updating of the results of individual centers is of utmost importance, as well as their comparison with the reference population-based results.

[New population curves in spanish extremely preterm neonates]. / Nuevas curvas poblacionales de crecimiento en recién nacidos extremadamente prematuros españoles.

INTRODUCTION: Most anthropometric reference data for extremely preterm infants used in Spain are outdated and based on non-Spanish populations, or are derived from small hospital-based samples that failed to include neonates of borderline viability. OBJECTIVES: To develop gender-specific, population-based curves for birth weight, length, and head circumference in extremely preterm Caucasian infants, using a large contemporary sample size of Spanish singletons. PATIENTS AND METHODS: Anthropometric data from neonates ≤ 28 weeks of gestational age were collected between January 2002 and December 2010 using the Spanish database SEN1500. Gestational age was estimated according to obstetric data (early pregnancy ultrasound). The data were analyzed with the SPSS.20 package, and centile tables were created for males and females using the Cole and Green LMS method. RESULTS: This study presents the first population-based growth curves for extremely preterm infants, including those of borderline viability, in Spain. A sexual dimorphism is evident for all of the studied parameters, starting at early gestation. CONCLUSIONS: These new gender-specific and population-based data could be useful for the improvement of growth assessments of extremely preterm infants in our country, for the development of epidemiological studies, for the evaluation of temporal trends, and for clinical or public health interventions seeking to optimize fetal growth.

[Screening for cytomegalovirus infection in very low birth weight infants]. / Cribado de la infección por citomegalovirus en recién nacidos de muy bajo peso.

INTRODUCTION: Cytomegalovirus (CMV) is the most common congenital and acquired vertically transmitted viral infection in humans. The aim of the study is to determine the clinical relevance of this infection in very low birth weight (VLBW) infants in our area. PATIENTS AND METHOD: Preterm infants (gestational age ≤ 31 weeks) with a birth weight ≤ 1500g treated between March 2006 and December 2010 were included. They underwent the screening protocol for diagnosing CMV infection. CMV serology was performed on the mothers. When it was positive, their breast milk was frozen at -20°C for 72hours from the 7th day of birth. At 5 weeks, the urine of the newborn was tested for CMV-DNA. In case of a positive result, CMV-DNA was performed in breast milk and in the dry blood sample from metabolic screening. RESULTS: A total of 342 preterm infants were studied, with 53 (15.5%) infected by CMV: 8 (2.3%) with congenital infection, 35 (10.2%) with acquired infection, and 10 (2.9%) in which it was impossible to determine precisely. IgM-CMV+in the mother was found in two congenital infections and two acquired infections. Newborns affected by congenital CMV infection showed a lower birth weight, more intrauterine growth restriction, thrombopenia, need for platelet transfusions, early sepsis (including clinical sepsis), and cerebral ultrasound anomalies. Late sepsis was more frequent in cases of acquired CMV infection. CONCLUSIONS: Congenital or acquired CMV infections are frequent in VLBW infants, and our protocol enables them to be diagnosed and probably prevents some acquired CMV infections by selecting which patients should freeze the breast milk.

[Recommendations for the computerisation of neonatology services]. / Recomendaciones para la informatización de los servicios de neonatología.

The aim is to provide a framework for data collection in the health area of newborn infants allowing harmonization of their care. This requires knowing the population served, and the greatest difficulty is the absence of a data collection system and standards of care for all conditions of the newborn infant. It is essential to have a single record with the main perinatal and neonatal data of all newborn infants. The Spanish Society of Neonatology (SEN) should be responsible for the database, which must meet all legal requirements of privacy and confidentiality. It is possible to determine the relative weight of the pathology treated using Diagnostic Related Groups (DRG) and the results from a quality care perspective. Guidelines for diagnosis and treatment may be established by comparative analysis (benchmarking studies…). Conclusion and Recommendation. It is necessary to know the newborn population served, and define criteria for diagnosis and treatment to improve quality of care. The SEN wishes to address those responsible for the care in hospitals, and to ask for their support and cooperation in the implementation of these recommendations.

[Erythropoietin treatment for late anaemia after haemolytic disease of the newborn]. / Tratamiento con eritropoyetina para la anemia tardía tras enfermedad hemolítica del recién nacido.

INTRODUCTION: After several years of erythropoietin (EPO) use in the prophylaxis of anaemia of prematurity, it also began to be administered to treat post-haemolytic disease anaemia of the newborn in order to avoid blood transfusions. OBJECTIVE: To show the results obtained with EPO treatment in post-haemolytic disease anemia of the newborn. PATIENTS AND METHODS: Observational study in 13 newborns with late anaemia due to an hemolytic disease caused by Rh isoimmunization (9 cases), AB0 isoimmunization (2 cases), glucose-6-P-dehydrogenase deficiency (1 case) or idiopathic (1 case). The newborns began EPO treatment when they reached the haematocrit level for a blood transfusion. RESULTS: EPO treatment was started at 26±7 days of life (15-46), with a haematocrit value of 21.7±3% (18-27) and a reticulocyte count of 3.8±2.2%. Blood transfusion was not necessary in 11 newborns (haematocrit of 30.7±4.4% and reticulocytes of 5.9±1.4%), and only 2 newborns were admitted for a blood transfusion (haematocrit 18±4.4% and reticulocytes 0.6%). Significant increases in haemoglobin and reticulocyte figures were seen after EPO treatment. CONCLUSIONS: EPO administration proved useful to avoid blood transfusion in 84% of treated newborns. No adverse events were detected which could be attributed to this treatment,.

[Early administration of erythropoietin in the extreme premature, a risk factor for retinopathy of prematurity?]. / Administración precoz de eritropoyetina en el prematuro extremo, ¿factor de riesgo de la retinopatía del prematuro?

INTRODUCTION: Erythropoietin (EPO) stimulates angiogenesis and may favour the appearance of retinopathy of prematurity (ROP). The objective was to determine if EPO+Fe administered from the 5th day of life could be an independent risk factor for ROP appearance and its severity. PATIENTS AND METHOD: The study included 718 preterm newborns with a birth weight ≤1,500g or a gestational age ≤32 weeks (and 6 days), admitted between 2001 and 2008. During these years, the target SaO2 was between 88% and 93%. EPO treatment began at 5-7 days of life, with a dose of 250 UI/Kg, 3 times a week, subcutaneously, together with Fe, 5-6mg/kg/day, both until 34 weeks of corrected age or discharge. RESULTS: A total of 493 preterms (68.7%) did not have ROP, 139 (19.4%) had a grade 1 ROP, 50 (7.0%) a grade 2 ROP and 36 (5.0%) a grade 3 ROP. Laser therapy was required by 27 severe ROP was associated with lower birth weight and gestational age, more neonatal morbidity and a more aggressive treatment (duration of oxygen supplements or mechanical ventilation, number of blood transfusions). Risk factors independently and significantly associated with any ROP grade were: lower birth weight, no caesarean section, EPO administration and need for blood transfusion. EPO administration increased the risk of ROP by 2.4, but this only happened in case of grade 1 ROP (OR: 5.50). CONCLUSIONS: EPO+Fe administration is associated and perhaps stimulates the appearance of grade 1 ROP.

[Recommendations for the use of palivizumab in the prevention of respiratory syncytial virus infection in late preterm infants (32(1) to 35(0) weeks of gestation)]. / Recomendaciones de uso de palivizumab para la prevención de la infección por virus respiratorio sincitial en prematuros de 32(1) a 35(0) semanas de gestación.

Late preterm infants (32(1) to 35(0) weeks gestation) aged less than 6 months at start of RSV station or discharged during this time may benefit from RSV monoclonal antibodies (palivizumab) administration to decrease the rates of RSV hospitalization. The Spanish Society of Neonatology considers, based on FLIP2 results in Spain, that palivizumab prophylaxis is strongly recommended if the "2 major risk factors" are present (chronological age less than 10 weeks at start of RSV season or being born during its first 10 weeks; sibling of school age or attending day-care assistance). Palivizumab is also recommended when "1 major risk factor and the 2 minor risk factors" are present. Minor risk factors are: mother smoking during pregnancy and being a male.

[Quality of life of preterm infants and admissions due to respiratory infections]. / Calidad de vida en lactantes nacidos prematuros según ingresos por infección respiratoria.

INTRODUCTION: Study of the association between lower respiratory tract infection hospitalisations and health related quality of life (HRQoL) in preterm infants of 32-35 weeks of gestational age. METHODS: Survey study nested into a prospective follow-up cohort study of preterm infants (FLIP-2). During the last FLIP-2 visit, 216 preterm-parent pairs were interviewed. The structured questionnaire included measures of HRQoL (QUALIN modified scale for the infant, and SF-12 for the parent, and Visual scales for both), caregiver overload (Zarit modified scale and indirect measurements). RESULTS: From October 2006 to March 2007 (RSV season), there were 71 respiratory hospitalisations (33%). Triplets and infants living in homes with >5 inhabitants were most likely to be hospitalised. Parents of hospitalised children were most likely, to have more and longer times off work for child care (47% vs. 18%), to have higher overload, and to obtain lower values in the physical dimension of SF-12. Multiple regression model associated infant HRQoL with higher gestational age, having 0-3 year-old siblings, being recommended palivizumab and had received it, lower caregiver overload, higher caregiver mental HRQoL and no absence from work for child care. CONCLUSIONS: Although respiratory hospitalisations were not associated with infant HRQoL, caregivers' HRQoL and overload were. Preterm infant HRQoL is associated with their caregivers' HRQoL and overload, and with receiving RSV prophylaxis when their risk profile recommends it.

[Usefulness of Clinical Risk Index for Babies based on birth weight in predicting hospital death and severe intraventicular hemorrhage in the SEN 1500 Spanish neonatal network]. / Análisis de la utilidad del Clinical Risk Index for Babies por estratos de peso como predictor de muerte hospitalaria y de hemorragia intraventricular grave en la Red Neonatal Española SEN 1500.

OBJECTIVE: To evaluate the usefulness of the Clinical Risk Index for Babies (CRIB) in predicting hospital mortality and severe intraventricular hemorrhage (IVH) in very low birth weight infants stratified by weight groups, in the Spanish neonatal network SEN 1500. PATIENTS AND METHODS: A prospective cohort study was made. Morbidity-mortality data and CRIB were collected in newborns weighing below 1500 g and admitted to 68 neonatal intensive care units between January 2002 and December 2006. Data were analyzed globally and stratified by weight groups (< 501 g, 500-750 g, 751-1000 g, 1001-1250 g, 1251-1500 g). Multivariate models were generated and ROC curves were plotted for estimating predictive values. RESULTS: A total of 10,608 patients were analyzed. The mean weight was 1116 g (SD 267), and gestational age 29.5 weeks (SD 2.9). Low birth weight for gestational age was 34.3% and the multiple birth rate 36%. Prenatal corticoids were given in 78.2%. Severe intraventricular hemorrhage was diagnosed in 8.5%. Gender, prenatal corticoids, birth weight, gestational age and CRIB proved significant for the outcomes. CRIB showed the highest predictive accuracy in all strata (P < 0.001) except in the 501-750 g group, where it was similar to gestational age. Body weight showed the lowest AUC in all groups, except in the 1251-1500 g group, where it was no different to gestational age. Gestational age and CRIB yielded greater AUC values than weight (P < 0.001) in all groups. No significant differences were found between CRIB and gestational age, except in the 751-1000 g group, where gestational age was greater (P = 0.029). CONCLUSIONS: The CRIB is the best predictor among newborns below 1500 g, except in the 501-750 g group, where CRIB is similar to gestational age. Body weight is the worst predictor, except in the group 1251-1500 g, where it is similar to gestational age. The accuracies of CRIB and gestational age in the prediction of IVH are similar, and both superior to body weight. This similarity persists in all the groups, except in the 751-1000 g interval, where gestational age is a better predictor.

[Usefulness of different risk factor associations in predicting admissions due to respiratory syncytial virus in premature newborns of 32 to 35 weeks gestation in Spain]. / Utilidad predictiva de ingreso por infección por virus respiratorio sincitial de diferentes asociaciones de factores de riesgo en prematuros de 32 a 35 semanas de gestación en España.

AIM: The aim of the study was to evaluate the risk factor associations for respiratory syncytial virus (RSV) hospitalization in preterm infants from 32 to 35 weeks gestation, treated during two consecutive RSV seasons in Spain. PATIENTS AND METHODS: A database (FLIP-2) was used after excluding the infants who received prophylactic palivizumab. A total of 193 RSV+ admissions and 4568 non-hospitalized children were studied. The risk factors analyzed were: chronological age <=10 weeks at start of RSV season or to be born during the first 10 weeks of the season; school-age siblings or daycare attendance; mother smoking during pregnancy; male gender; breastfeeding <=2 months; >=4 adults at home; history of wheezing; small for gestational age; >=2 smokers at home. RESULTS: Logistic regression model included the first four previously mentioned risk factors as independently significant variables, with R(2) of 0.062 and area under curve of 0.687 (P<0.001). Predictive values for a child with the four risk factors were: sensitivity 6.2%, specificity 98.6%, predictive positive value 16.2%, negative predictive value 96.1%, accuracy 94.9%, positive likelihood ratio 4.581, and negative likelihood ratio 0.951. Positive likelihood ratio for a child with the two major risk factors is 2.657. CONCLUSIONS: Usefulness of different risk factor associations to predict hospitalization for respiratory syncytial virus infection in preterm infants 32 to 35 weeks gestation in Spain is low, although similar to other models.