Prediction of bronchopulmonary dysplasia in very preterm infants: competitive risk model nomogram.

Objective: To develop predictive clinical models of bronchopulmonary dysplasia (BPD) through competing risk analysis. Methods: Retrospective observational cohort study, including preterm newborns ≤32 weeks gestational age, conducted between January 1, 2013 and September 30, 2022 in a third-level Neonatal Intensive Care Unit in Spain. A prediction study was carried out using competing risk models, where the event of interest was BPD and the competing event was death. A multivariate competing risk model was developed separately for each postnatal day (days 1, 3, 7 and 14). Nomograms to predict BPD risk were developed from the coefficients of the final models and internally validated. Results: A total of 306 patients were included in the study, of which 73 (23.9%) developed BPD and 29 (9.5%) died. On day 1, the model with the greatest predictive capacity was that including birth weight, days since rupture of membranes, and surfactant requirement (area under the receiver operating characteristic (ROC) curve (AUC), 0.896; 95% CI, 0.792-0.999). On day 3, the final predictive model was based on the variables birth weight, surfactant requirement, and Fraction of Inspired Oxygen (FiO2) (AUC, 0.891; 95% CI, 0.792-0.989). Conclusions: Competing risk analysis allowed accurate prediction of BPD, avoiding the potential bias resulting from the exclusion of deceased newborns or the use of combined outcomes. The resulting models are based on clinical variables measured at bedside during the first 3 days of life, can be easily implemented in clinical practice, and can enable earlier identification of patients at high risk of BPD.

Incidence, Risk Factors and Prediction of Secondary Hyperparathyroidism in Preterm Neonates under 32 Weeks' Gestational Age.

In preterm newborns, secondary hyperparathyroidism (HPTH) is an underdiagnosed and undertreated entity. Its detection in the context of metabolic bone mineral disease (MBD) screening programs may be important to guide nutritional treatment. We designed a retrospective cohort study to determine the incidence of HPTH in very premature infants. As secondary objectives, we studied the risk factors, morbidities, and biochemical alterations associated with HPTH. A total of 154 preterm newborns ≤32 weeks gestational age (GA) were included. Of these, 40.3% (n = 62) presented with HPTH. In the multivariate analysis, independent risk factors for HPTH were cesarean section (OR: 4.00; 95% CI: 1.59-10.06), oxygen during resuscitation (OR: 3.43; 95% CI: 1.09-10.81), invasive mechanical ventilation (OR: 3.56; 95% CI: 1.63-7.77) and anemia requiring transfusion (OR: 2.37; 95% CI: 1.01-5.57). Among the analytical variables, serum calcium (OR: 0.53; 95% CI: 0.29-0.97), serum phosphate (OR: 2.01; 95% CI: 1.39-2.92), vitamin D (OR: 0.96; 95% CI: 0.93-1), and the calcium/creatinine ratio in urine (OR: 0.05; 95% CI: 0.01-0.28) were independently associated with HPTH. The simplified predictive model included GA and calcium/creatinine ratio in urine and demonstrated an AUC of 0.828. We concluded that HPTH is a frequent entity among very premature infants and that further studies are required to determine the role of HPTH in MBD and the clinical applicability of prediction models.

Epidemiology and risk factors for bronchopulmonary dysplasia in preterm infants born at or less than 32 weeks of gestation.

OBJECTIVES: To describe risk factors of bronchopulmonary dysplasia in very preterm infants in the first weeks of life. MATERIAL AND METHODS: Retrospective cohort study of preterm infants ≤ 32 weeks of gestational age and birth weight ≤ 1500 g. A multivariate logistic regression analysis was performed to identify independent risk factors for bronchopulmonary dysplasia in the first weeks of life. RESULTS: A total of 202 newborns were included in the study (mean gestational age 29.5 ± 2.1 weeks), 61.4% never received invasive mechanical ventilation. The incidence of bronchopulmonary dysplasia was 28.7%, and 10.4% of the patients were diagnosed with moderate-severe bronchopulmonary dysplasia. Bronchopulmonary dysplasia was independently associated with gestational age (P < 0.001; OR = 0.44 (95% CI = 0.30-0.65)), the need for mechanical ventilation on the first day of life (P = 0.001; OR = 8.13 ((95% CI = 2.41-27.42)), nosocomial sepsis (P < 0.001; OR = 9.51 ((95% CI = 2.99-30.28)) and FiO2 on day 14 (P < 0.001; OR = 1.39 ((95% CI = 1.16-1.66)). Receiving mechanical ventilation at the first day of life (P = 0.008; OR = 5.39 ((95% CI = 1.54-18.89)) and at the third day of life (P = 0.001; OR = 9.99 ((95% CI = 2.47-40.44)) and nosocomial sepsis (P = 0.001; OR = 9.87 ((95% CI = 2.58-37.80)) were independent risk factors for moderate-severe bronchopulmonary dysplasia. CONCLUSIONS: Gestational age, mechanical ventilation in the first days of life and nosocomial sepsis are early risk factors for bronchopulmonary dysplasia. The analysis of simple and objective clinical data, allows us to select a group of patients at high risk of bronchopulmonary dysplasia in whom it could be justified to act more aggressively, and shows areas for improvement to prevent its development or reduce its severity.

Incidence, Predictors and Outcomes of Noninvasive Ventilation Failure in Very Preterm Infants.

Non-invasive ventilation (NIV) is now considered the first-line treatment for respiratory distress syndrome in preterm infants. We aimed to evaluate the rates of non-invasive ventilation failure rate in very preterm infants, as well as to identify its predictors and associated outcomes. We designed a single-center retrospective cohort study including infants ≤32 weeks gestational age and ≤1500 g. The NIV failure was defined as the need for intubation at <72 h of life. After applying inclusion and exclusion criteria, 154 patients were included in the study, with a mean GA of 29.7 ± two weeks. The NIV failure rate was 16.2% (n = 25) and it was associated with lower bronchopulmonary dysplasia (BPD)-free survival (OR 0.08; 95% CI 0.02−0.32) and higher incidence of intraventricular hemorrhage > II (OR 6.22; 95% CI 1.36−28.3). These infants were significantly smaller in GA and weight. Higher FiO2 during resuscitation (OR 1.14; 95% CI 1.06−1.22) and after surfactant administration (OR 1.17; 95% CI 1.05−1.31) represented independent risk factors for NIV failure. In conclusion, NIV failure is frequent and it could be predicted by a higher oxygen requirement during resuscitation and a modest response to surfactant therapy. Importantly, this NIV failure is associated with worse clinical outcomes.

Epidemiología y factores de riesgo asociados a displasia broncopulmonar en prematuros menores de 32 semanas de edad gestacional / Epidemiology and risk factors for bronchopulmonary dysplasia in preterm infants born at or less than 32 weeks of gestation

Objetivos: Describir los factores de riesgo de displasia broncopulmonar en las primeras semanas de vida en grandes prematuros. Material y métodos: Estudio observacional de cohortes, retrospectivo, en recién nacidos ≤ 32 semanas y ≤ 1.500 g. Se realizó un análisis multivariante de regresión logística para identificar factores de riesgo independientes en las primeras semanas de vida. Resultados: Se incluyeron 202 recién nacidos con una edad gestacional media de 29,5 ± 2,1 semanas. El 61,4% de los pacientes no recibió ventilación mecánica invasiva. El 28,7% fue diagnosticado de displasia broncopulmonar y el 10,4% de displasia broncopulmonar moderada-grave. La edad gestacional (p < 0,001; OR = 0,44 [IC 95% = 0,30-0,65]), la ventilación mecánica en el día 1 (p = 0,001; OR = 8,13 [IC 95% = 2,41-27,42]), la sepsis nosocomial (p < 0,001; OR = 9,51 [IC 95% = 2,99-30,28]) y la FiO2 en el día 14 (p < 0,001; OR = 1,39 [IC 95% = 1,16-1,66]) fueron los factores de riesgo independientes de displasia broncopulmonar. La ventilación mecánica el día 1 (p = 0,008; OR = 5,39 [IC 95% = 1,54-18,89]) y 3 de vida (p = 0,001; OR = 9,99 [IC 95% = 2,47-40,44]) y la sepsis nosocomial (p = 0,001; OR = 9,87 [IC 95% = 2,58-37,80]) se asociaron al desarrollo de displasia broncopulmonar moderada-grave. Conclusiones: La edad gestacional, la ventilación mecánica en los primeros días de vida y la sepsis nosocomial son factores de riesgo precoces de displasia broncopulmonar. El análisis de datos clínicos sencillos y objetivos nos permite seleccionar a un grupo de pacientes con alto riesgo de desarrollar displasia broncopulmonar, en el que podría estar justificado actuar de forma más agresiva y nos muestra áreas de mejora para prevenir su desarrollo o disminuir su gravedad. (AU)

Objectives: To describe risk factors of bronchopulmonary dysplasia in very preterm infants in the first weeks of life. Material and methods: Retrospective cohort study of preterm infants ≤ 32 weeks of gestational age and birth weight ≤ 1500 g. A multivariate logistic regression analysis was performed to identify independent risk factors for bronchopulmonary dysplasia in the first weeks of life. Results: A total of 202 newborns were included in the study (mean gestational age 29.5 ± 2.1 weeks), 61.4% never received invasive mechanical ventilation. The incidence of bronchopulmonary dysplasia was 28.7%, and 10.4% of the patients were diagnosed with moderate–severe bronchopulmonary dysplasia. Bronchopulmonary dysplasia was independently associated with gestational age at birth (p < 0.001; OR = 0.44 [95% CI = 0.30–0.65]), the need for mechanical ventilation on the first day of life (p = 0.001; OR = 8.13 [95% CI = 2.41–27.42]), nosocomial sepsis (p < 0.001; OR = 9.51 [95% CI = 2.99–30.28]) and FiO2 on day 14 (p < 0.001; OR = 1.39 [95% CI = 1.16–1.66]). Receiving mechanical ventilation at the first day of life (p = 0.008; OR = 5.39 [95% CI = 1.54–18.89]) and at the third day of life (p = 0.001; OR = 9.99 [95% CI = 2.47–40.44]) and nosocomial sepsis (p = 0.001; OR = 9.87 [95% CI = 2.58–37.80]) were independent risk factors for moderate–severe bronchopulmonary dysplasia. Conclusions: Gestational age at birth, mechanical ventilation in the first days of life and nosocomial sepsis are early risk factors for bronchopulmonary dysplasia. The analysis of simple and objective clinical data, allows us to select a group of patients at high risk of bronchopulmonary dysplasia in whom it could be justified to act more aggressively, and shows areas for improvement to prevent its development or reduce its severity. (AU)

[Epidemiology and risk factors for bronchopulmonary dysplasia in prematures infants born at or less than 32 weeks of gestation]. / Epidemiología y factores de riesgo asociados a displasia broncopulmonar en prematuros menores de 32 semanas de edad gestacional.

OBJECTIVES: To describe risk factors of bronchopulmonary dysplasia in very preterm infants in the first weeks of life. MATERIAL AND METHODS: Retrospective cohort study of preterm infants ≤ 32 weeks of gestational age and birth weight ≤ 1500 g. A multivariate logistic regression analysis was performed to identify independent risk factors for bronchopulmonary dysplasia in the first weeks of life. RESULTS: A total of 202 newborns were included in the study (mean gestational age 29.5 ± 2.1 weeks), 61.4% never received invasive mechanical ventilation. The incidence of bronchopulmonary dysplasia was 28.7%, and 10.4% of the patients were diagnosed with moderate-severe bronchopulmonary dysplasia. Bronchopulmonary dysplasia was independently associated with gestational age at birth (p < 0.001; OR = 0.44 [95% CI = 0.30-0.65]), the need for mechanical ventilation on the first day of life (p = 0.001; OR = 8.13 [95% CI = 2.41-27.42]), nosocomial sepsis (p < 0.001; OR = 9.51 [95% CI = 2.99-30.28]) and FiO2 on day 14 (p < 0.001; OR = 1.39 [95% CI = 1.16-1.66]). Receiving mechanical ventilation at the first day of life (p = 0.008; OR = 5.39 [95% CI = 1.54-18.89]) and at the third day of life (p = 0.001; OR = 9.99 [95% CI = 2.47-40.44]) and nosocomial sepsis (p = 0.001; OR = 9.87 [95% CI = 2.58-37.80]) were independent risk factors for moderate-severe bronchopulmonary dysplasia. CONCLUSIONS: Gestational age at birth, mechanical ventilation in the first days of life and nosocomial sepsis are early risk factors for bronchopulmonary dysplasia. The analysis of simple and objective clinical data, allows us to select a group of patients at high risk of bronchopulmonary dysplasia in whom it could be justified to act more aggressively, and shows areas for improvement to prevent its development or reduce its severity.

Metabolic Bone Disease of Prematurity: Risk Factors and Associated Short-Term Outcomes.

Despite the importance of early recognition of metabolic bone disease (MBD) of prematurity, there is still significant variability in screening practices across institutions. We conducted an observational study of infants born at ≤32 weeks of gestation with a birth weight of ≤1500 g (n = 218) to identify clinical factors associated with biochemical indicators of MBD. Bone mineral status was assessed by measuring alkaline phosphatase and phosphate levels between weeks 3 and 5 of life. Two comparisons were performed after classifying infants as either MBD (cases) or non-MBD (controls), and as either high or low risk for MBD, as determined based on the results of MBD screening. In total, 27 infants (12.3%) were classified as cases and 96 (44%) as high-risk. Compared with controls, MBD infants had a significantly lower gestational age and birth weight, and a longer duration of parenteral nutrition and hospital stay. Respiratory outcomes were significantly poorer in high- versus low-risk infants. Multivariate logistic regression showed that birth weight was the only independent risk factor for MBD (odds ratio [OR]/100 g, 0.811; confidence interval [CI95%], 0.656-0.992; p = 0.045) and that birth weight (OR/100 g, 0.853; CI95%, 0.731-0.991; p = 0.039) and red blood cell transfusion (OR, 2.661; CI95%, 1.308-5.467; p = 0.007) were independent risk factors for high risk of MBD. Our findings provide evidence of risk factors for MBD that could help clinicians to individualize perinatal management. The association of red blood cell transfusion with MBD is a novel finding that may be related to iron overload and that merits further study.

La conductancia de la piel para evaluar el dolor y el estrés durante el cribado de la retinopatía de la prematuridad / Skin conductance to assess pain and stress during retinopathy of prematurity screening

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Pain assessment during eye examination for retinopathy of prematurity screening: Skin conductance versus PIPP-R.

AIM: To assess changes in skin conductance during retinopathy of prematurity screening and to study the correlation between the skin conductance and a validated pain scale. METHODS: Prospective observational study. Fifty-three eye examinations were performed in 32 preterm infant candidates for retinopathy of prematurity screening. Outcome measures were changes in Premature Infant Pain Profile-Revised (PIPP-R) scale and number of skin conductance fluctuations. RESULTS: There was a significant increase from baseline in the number of skin conductance fluctuations and PIPP-R during the procedure. The maximum value of number of skin conductance fluctuations was 0.64 ± 0.44 peaks/sec, and the maximum value of PIPP-R was 10.8 ± 3.3. A correlation between the skin conductance and PIPP-R was not found at any time during the eye examination. Repeated measures correlation analyses showed only a moderate positive correlation between PIPP-R and number of skin conductance fluctuation values. CONCLUSION: There were significant changes in both PIPP-R and number of skin conductance fluctuations during retinopathy of prematurity screening, reaffirming that this procedure is painful and stressful. The number of skin conductance fluctuations and PIPP-R are not significantly correlated, which likely reflects that these parameters evaluate different but complementary aspects of neonatal pain responses.

Uso de medicamentos en condiciones no aprobadas en cuidados intensivos neonatales / Use of off-label drugs in neonatal intensive care

Objetivo: Evaluar la prevalencia de prescripciones en condiciones no autorizadas (off-label y unlicensed) en una Unidad de Cuidados Intensivos Neonatales (UCIN) y definir qué características de los neonatos se asocian a un mayor uso de fármacos en estas condiciones. Material y métodos: Estudio observacional prospectivo en una UCIN nivel III-C durante un periodo de 6 meses. Se evaluó la condición de uso de cada fármaco, tomando como referencia su ficha técnica. Se utilizó un algoritmo secuencial para la clasificación de las prescripciones en: aprobadas, unlicensed u off-label (por edad, por indicación, por vía de administración, y por dosis). Resultados: Se incluyeron 84 pacientes y 564 prescripciones. Un total de 127 prescripciones fueron consideradas off-label y 45 unlicensed; lo cual supuso el 22,5% y el 8% del total, respectivamente. El 59,5% de los pacientes recibieron al menos un fármaco en una de estas condiciones, ascendiendo este porcentaje al 100% en los grandes prematuros y en los pacientes quirúrgicos (p < 0,001). Se encontró una correlación lineal positiva entre la estancia en UCIN y el número de prescripciones off-label (coeficiente de correlación 0,6 p < 0,001). Conclusiones: La prescripción de fármacos en condiciones no autorizadas es habitual en UCIN, siendo especialmente frecuente en los pacientes con mayor vulnerabilidad. Estos resultados ponen de manifiesto la necesidad de avanzar en la investigación y homogeneizar la información existente sobre los fármacos en neonatología, con el objetivo de realizar una prescripción eficaz y segura

Objective: To evaluate the prevalence of non-approved prescriptions (off-label and unlicensed) in a Neonatal Intensive Care Unit (NICU), and to describe factors of the neonate associated with its use. Materials and methods: Observational prospective study in a level III NICU during a 6-month period. Every prescription was analysed using the summary of product characteristics as a reference. A sequential algorithm was used to create a classification of prescriptions based on current status: approved, unlicensed, off-label (by age, route of administration, dosage, or indication). Results: The study included 84 patients and 564 prescriptions. A total of 127 (22.5%) prescriptions were considered off-label, and 45 (8%) were considered unlicensed. More than half (59.5%) of the patients received at least one of these drugs, and this increases to 100% among very preterm neonates and surgical patients (P < .001). A positive linear correlation was found between duration of NICU stay and the number of off-label prescriptions (correlation coefficient 0.6; P < .001). Conclusions: Non-licensed drugs are frequently prescribed in NICU, especially in the most vulnerable patients. Our results show the need to move forward on clinical research in order to homogenise the existing data about neonatology drugs, with the aim of making an efficient and safe prescription

[Use of off-label drugs in neonatal intensive care]. / Uso de medicamentos en condiciones no aprobadas en cuidados intensivos neonatales.

OBJECTIVE: To evaluate the prevalence of non-approved prescriptions (off-label and unlicensed) in a Neonatal Intensive Care Unit (NICU), and to describe factors of the neonate associated with its use. MATERIALS AND METHODS: Observational prospective study in a level III NICU during a 6-month period. Every prescription was analysed using the summary of product characteristics as a reference. A sequential algorithm was used to create a classification of prescriptions based on current status: approved, unlicensed, off-label (by age, route of administration, dosage, or indication). RESULTS: The study included 84 patients and 564 prescriptions. A total of 127 (22.5%) prescriptions were considered off-label, and 45 (8%) were considered unlicensed. More than half (59.5%) of the patients received at least one of these drugs, and this increases to 100% among very preterm neonates and surgical patients (P<.001). A positive linear correlation was found between duration of NICU stay and the number of off-label prescriptions (correlation coefficient 0.6; P<.001). CONCLUSIONS: Non-licensed drugs are frequently prescribed in NICU, especially in the most vulnerable patients. Our results show the need to move forward on clinical research in order to homogenise the existing data about neonatology drugs, with the aim of making an efficient and safe prescription.