Nasal intermittent positive pressure ventilation during less invasive surfactant administration in preterm infants: An open-label randomized controlled study.

INTRODUCTION: Approximately half of very preterm infants with respiratory distress syndrome (RDS) fail treatment with nasal continuous positive airway pressure (NCPAP) and need mechanical ventilation (MV). OBJECTIVES: Our aim with this study was to evaluate if nasal intermittent positive pressure ventilation (NIPPV) during less invasive surfactant treatment (LISA) can improve respiratory outcome compared with NCPAP. MATERIALS AND METHODS: We carried out an open-label randomized controlled trial at tertiary neonatal intensive care units in which infants with RDS born at 25+0-31+6 weeks of gestation between December 1, 2020 and October 31, 2022 were supported with NCPAP before and after surfactant administration and received NIPPV or NCPAP during LISA. The primary endpoint was the need for a second dose of surfactant or MV in the first 72 h of life. Other endpoints were need and duration of invasive and noninvasive respiratory supports, changes in SpO2/FiO2 ratio after LISA, and adverse effect rate. RESULTS: We enrolled 101 infants in the NIPPV group and 99 in the NCPAP group. The unadjusted odds ratio for the composite primary outcome was 0.873 (95% confidence interval: 0.456-1.671; p = .681). We found that the SpO2/FiO2 ratio was transiently higher in the LISA plus NIPPV than in the LISA plus NCPAP group, while adverse effects of LISA had similar occurrence in the two arms. CONCLUSIONS: The application of NIPPV or NCPAP during LISA in very preterm infants supported with NCPAP before and after surfactant administration had similar effects on the short-term respiratory outcome and are both safe. Our study does not support the use of NIPPV during LISA.

Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study).

BACKGROUND: The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group. METHODS/DESIGN: In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks' gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group. DISCUSSION: Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.

Different Settings of Nonsynchronized Bilevel Nasal Continuous Positive Airway Pressure and Respiratory Function in Preterm Infants: A Pilot Study.

OBJECTIVE: With this study, we evaluated the short-term effects of different modes and settings of noninvasive respiratory support on gas exchange, breathing parameters, and thoracoabdominal synchrony in preterm infants in the acute phase of moderate respiratory distress syndrome. STUDY DESIGN: A feasibility crossover trial was conducted in neonates < 32 weeks' gestation on nasal continuous positive airway pressure (n-CPAP) or bilevel n-CPAP. Infants were delivered the following settings in consecutive order for 10 minutes each: • n-CPAP (5 cm H2O) • bilevel n-CPAP 1 (Pres low = 5 cm H2O, Pres high = 7 cm H2O, T-high = 1 second, rate = 30/min) • n-CPAP (5 cm H2O) • bilevel n-CPAP 2 (Pres low = 5 cm H2O, Pres high = 7 cm H2O, T-high = 2 second, rate = 15/min) • n-CPAP (5 cm H2O). During each phase, physiologic parameters were recorded; the thoracoabdominal synchrony expressed by the phase angle (Φ) and other respiratory patterns were monitored by noncalibrated respiratory inductance plethysmography. RESULTS: Fourteen preterm infants were analyzed. The mean CPAP level was significantly lower in the n-CPAP period compared with bilevel n-CPAP 1 and 2 (p = 0.03). Higher values were achieved with bilevel n-CPAP 2 (6.2 ± 0.6 vs. 5.7 ± 0.5 cm H2O, respectively; p < 0.05). No statistical difference in the Φ was detected, nor between the three settings. CONCLUSION: Our study did not show any superiority of bilevel n-CPAP over n-CPAP. However, nonsynchronized bilevel n-CPAP might be helpful when additional pressure is needed. KEY POINTS: · There is currently a high degree of uncertainty about the superiority of one modality and setting of noninvasive respiratory over another.. · Our study confirmed that non-synchronized bilevel n-CPAP might be helpful when additional pressure is needed for recruitment.. · A T-high of 1 second could possibly be better tolerated in this population, but further research is needed..

Neonatal Lung Ultrasound and Surfactant Administration: A Pragmatic, Multicenter Study.

BACKGROUND: Previous research shows that a lung ultrasound score (LUS) can anticipate CPAP failure in neonatal respiratory distress syndrome. RESEARCH QUESTION: Can LUS also predict the need for surfactant replacement? STUDY DESIGN AND METHODS: Multicenter, pragmatic study of preterm neonates who underwent lung ultrasound at birth and those given surfactant by masked physicians, who also were scanned within 24 h from administration. Clinical data and respiratory support variables were recorded. Accuracy of LUS, oxygen saturation to Fio2 ratio, Fio2, and Silverman score for surfactant administration were evaluated using receiver operating characteristic curves. The simultaneous prognostic values of LUS and oxygen saturation to Fio2 ratio for surfactant administration, adjusting for gestational age (GA), were analyzed through a logistic regression model. RESULTS: Two hundred forty infants were enrolled. One hundred eight received at least one dose of surfactant. LUS predicted the first surfactant administration with an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI, 0.81-0.91), cut off of 9, sensitivity of 0.79 (95% CI, 0.70-0.86), specificity of 0.83 (95% CI, 0.76-0.89), positive predictive value of 0.79 (95% CI, 0.71-0.87), negative predictive value of 0.82 (95% CI, 0.75-0.89), positive likelihood ratio of 4.65 (95% CI, 3.14-6.89), and negative likelihood ratio of 0.26 (95% CI, 0.18-0.37). No significant difference was shown among different GA groups: 25 to 27 weeks' GA (AUC, 0.91; 95% CI, 0.84-0.99), 28 to 30 weeks' GA (AUC, 0.81; 95% CI, 0.72-0.91), and 31 to 33 weeks' GA (AUC, 0.88; 95% CI, 0.79-0.95), respectively. LUS declined significantly within 24 h in infants receiving one surfactant dose. When comparing Fio2, oxygen saturation to Fio2 ratio, LUS, and Silverman scores as criteria for surfactant administration, only the latter showed a significantly poorer performance. The combination of oxygen saturation to Fio2 ratio and LUS showed the highest predictive power, with an AUC of 0.93 (95% CI, 0.89-0.97), regardless of the GA interval. INTERPRETATION: LUS is a reliable criterion to administer the first surfactant dose regardless of GA. Its association with oxygen saturation to Fio2 ratio significantly improves the prediction power for surfactant need.

Neonatal Dyshormonogenetic Goiter with Hypothyroidism Associated with Novel Mutations in Thyroglobulin and SLC26A4 Gene.

Congenital goiter is an uncommon cause of neck swelling and it can be associated with hypothyroidism. We discuss a case of primary hypothyroidism with goiter presenting at birth. Ultrasound showed the enlargement of the gland and thyroid function tests detected marked hypothyroidism. Genetic analysis via next generation sequencing (NGS) was performed finding two mutations associated with thyroid dyshormonogenesis: c.7813 C > T, homozygous in the exon 45 of the thyroglobulin gene (TG) and c.1682 G > A heterozygous in exon 15 of the SLC26A4 gene (pendrin). Sanger sequencing of parents' DNA samples revealed that the first mutation (c.7813 C > T) was inherited from both of them, while the second one (c.1682 G > A) was inherited from the mother. Hormone replacement therapy was started, following which a gradual decrease in the size of the goiter was seen with the normalization of hormonal levels. Normal infant growth status and neurological development were recorded during follow-up. Neonatal dyshormonogenetic goiter with hypothyroidism may represent an unusual cause of neonatal neck mass. Early identification and hormone replacement therapy are crucial for a better neurodevelopmental outcome. Genetic analysis is mandatory in order to reach a specific diagnosis and to elucidate new patterns of thyroid disorder.

Lung Ultrasound Score Progress in Neonatal Respiratory Distress Syndrome.

BACKGROUND AND OBJECTIVES: The utility of a lung ultrasound score (LUS) has been described in the early phases of neonatal respiratory distress syndrome (RDS). We investigated lung ultrasound as a tool to monitor respiratory status in preterm neonates throughout the course of RDS. METHODS: Preterm neonates, stratified in 3 gestational age cohorts (25-27, 28-30, and 31-33 weeks), underwent lung ultrasound at weekly intervals from birth. Clinical data, respiratory support variables, and major complications (sepsis, patent ductus arteriosus, pneumothorax, and persistent pulmonary hypertension of the neonate) were also recorded. RESULTS: We enrolled 240 infants in total. The 3 gestational age intervals had significantly different LUS patterns. There was a significant correlation between LUS and the ratio of oxygen saturation to inspired oxygen throughout the admission, increasing with gestational age (b = -0.002 [P < .001] at 25-27 weeks; b = -0.006 [P < .001] at 28-30 weeks; b = -0.012 [P < .001] at 31-33 weeks). Infants with complications had a higher LUS already at birth (12 interquartile range 13-8 vs 8 interquartile range 12-4 control group; P = .001). In infants 25 to 30 weeks' gestation, the LUS at 7 days of life predicted bronchopulmonary dysplasia with an area under the curve of 0.82 (95% confidence interval 0.71 to 93). CONCLUSIONS: In preterm neonates affected by RDS, the LUS trajectory is gestational age dependent, significantly correlates with the oxygenation status, and predicts bronchopulmonary dysplasia. In this population, LUS is a useful, bedside, noninvasive tool to monitor the respiratory status.

Aspectos clínicos da fenilcetonúria em serviço de referência em triagem neonatal da Bahia / Clinical aspects of phenylketonuria in a reference service for neonatal screening in Bahia

OBJETIVOS: descrever as características clínicas dos pacientes com hiperfenilalaninemia acompanhados no Serviço de Referência em Triagem Neonatal (SRTN) do estado da Bahia. MÉTODOS: estudo descritivo transversal, tendo como amostra todos os pacientes com diagnóstico conhecido de Hiperfenilalaninemia residentes no estado da Bahia e acompanhados no SRTN até setembro de 2005. Tal população é composta de 46 famílias, num total de 51 pacientes. A análise dos dados foi descritiva, incluindo medidas de tendência central e dispersão. RESULTADOS: houve discreto predomínio do gênero feminino (52,9 por cento). A maioria dos pacientes (78,4 por cento) teve seu diagnóstico estabelecido através da triagem neonatal, tendo, portanto, tratamento precoce. Consangüinidade foi registrada em 32,6 por cento das famílias. A média de início do tratamento entre os pacientes diagnosticados pela triagem neonatal foi de 56,6 37,8 dias, enquanto que entre os pacientes com diagnóstico tardio, foi de 7,1 anos. CONCLUSÕES: o estudo descreve um grupo de pacientes representativo de uma patologia incluída no Programa Nacional de Triagem Neonatal (PNTN), sendo, portanto, de relevância para a saúde pública. Entre os dados clínicos, chama a atenção a média de idade do início do tratamento, superior ao recomendado na literatura, alertando para a necessidade de um maior enfoque no diagnóstico precoce.