The effect of non-invasive high-frequency oscillatory ventilation on the duration of non-invasive respiratory support in late preterm and term infants with transient tachypnea of the newborn: a randomized controlled trial.

Nasal continuous positive airway pressure (nCPAP) is one of the most commonly used non-invasive respiratory support modes in neonates with transient tachypnea of the newborn (TTN). Non-invasive high-frequency oscillatory ventilation (nHFOV) is a non-invasive respiratory support mode that has been increasingly used in neonatal respiratory disorders. This prospective randomized controlled study compared the efficacy of nHFOV and nCPAP in reducing the duration of non-invasive respiratory support. Late preterm and term infants > 34 weeks' gestation were included in the study. The infants were randomly assigned to receive either nHFOV or nCPAP. Treatment was started with standard settings in both groups. Infants who met treatment failure criteria were switched to nasal intermittent mandatory ventilation for further positive-pressure support. A total of 60 infants were included in the study. Thirty of these infants were included in the nHFOV group and 30 were included in the nCPAP group. The median duration of non-invasive respiratory support was not significantly different between the two groups (21 h [IQR: 16-68] for nHFOV vs 15 h [IQR: 11-33] for nCPAP; p = 0.09). However, after adjusting for potential confounders, nHFOV was associated with a shorter duration of non-invasive respiratory support than nCPAP (adjusted mean difference: 16.3 h; 95% CI: 0.7 to 31.9; p = 0.04). nHFOV was well tolerated and did not increase the risk of complications.    Conclusion: Our findings suggest that nHFOV is an effective and safe ventilation mode for late preterm and term neonates with TTN.   Trial registry: Clinicaltrials.gov (NCT03006354). Date of registration: December 30, 2016. What is Known: • nHFOV is a ventilation model that has been increasingly used for the management of RDS. • TTN is one of the most common causes of neonatal respiratory distress. What is New: • nHFOV is associated with shorter duration of non-invasive respiratory support and duration of oxygen support. • nHFOV may be a safe and effective alternative to nCPAP for neonates with TTN.

Association between thiol-disulfide hemostasis and transient tachypnea of the newborn in late-preterm and term infants.

BACKGROUND: Transient tachypnea of the newborn (TTN), which is the most common respiratory disease in the neonatal period, increases respiratory workload in newborns. We purposed to evaluate the oxidative stress (OS) status and thiol disulfide hemostasis in late preterm and term newborns with TTN in this study. METHODS: The study was carried out in a single-centre neonatal intensive care unit to investigate the effect of continuous airway positive pressure (CPAP) on the oxidative system in newborns with TTN. Thiol (native and total) and disulfide levels, total antioxidant and oxidant status (TAS/TOS) and Oxidative stress index (OSI) levels were measured. RESULTS: Total thiol levels measured before treatment was 429.5 (369.5-487) µmol/L in the late preterm group and 425 (370-475) µmol/L in the term group (p = 0.741). We found significant changes in TOS, OSI and TAS levels after CPAP treatment in the late preterm group (p < 0.001, p < 0.001, p = 0.012 respectively). It was also found that the disulfide level, which was 26.2 (19.2-31.7) before the treatment, decreased to 19.5 (15.5-28.75) after the treatment (p = 0.001) in late preterms. CONCLUSION: CPAP treatment reduced the OS status burden associated with TTN in neonates. The late preterm newborns with TTN are more affected by OS and increased OS levels decrease with CPAP treatment.

New parameters on prediction of severity of transient tachypnea of the newborn.

BACKGROUND: Transient tachypnea of the newborn (TTN) is a common clinical problem that often occurs in the first hours of life. Although it is considered to be a benign clinical course, some cases may have severe symptoms and require ventilation support. In this study, we aimed to determine the association between the mean platelet volume (MPV), nucleated red blood cells (NRBCs), right ventricular systolic pressure (RVSP), and the severity of TTN. METHODS: Patients with TTN were divided into two groups according to Silverman score (<7: group 1 [n: 34] and ≥7: Group 2 [n: 30]). The groups were compared in terms of demographic characteristics, hematologic parameters, and RVSP within the first 24 hours after admission. RESULTS: Mean birth weight of the patients was 3033.4 ± 364.1 g and median gestational age was 38 weeks (min-max: 34-42). Patients in Group 2 were found to require higher nasal continuous positive airway pressure (nCPAP) support and longer duration of oxygen treatment (p: 0.001). Patients in Group 2 had significantly higher thrombocyte, absolute NRBCs count, NRBCs/100 WBCs, and RVSP levels (p < 0.05). Hemoglobin and hematocrit levels were found significantly higher in group 1(p < 0.05). In logistic regression analysis, NRBCs/100 WBCs was found to be the most important independent parameter that affects Silverman score at admission (OR: 7.065, CI: 1.258-39.670, p: 0.026). DISCUSSION: This is the first study that investigates the association between NRBCs, RVSP, and severity of TTN. We think that elevated NRBCs and RVSP values are helpful for clinicians in decision making for referral of the patients to a secondary or a tertiary level of NICU and also inform the families about prognosis.

Interventions for the management of transient tachypnoea of the newborn - an overview of systematic reviews.

BACKGROUND: Transient tachypnoea of the newborn (TTN) is characterised by tachypnoea and signs of respiratory distress. It is caused by delayed clearance of lung fluid at birth. TTN typically appears within the first two hours of life in term and late preterm newborns. Although it is usually a self-limited condition, admission to a neonatal unit is frequently required for monitoring, the provision of respiratory support, and drugs administration. These interventions might reduce respiratory distress during TTN and enhance the clearance of lung liquid. The goals are reducing the effort required to breathe, improving respiratory distress, and potentially shortening the duration of tachypnoea. However, these interventions might be associated with harm in the infant. OBJECTIVES: The aim of this overview was to evaluate the benefits and harms of different interventions used in the management of TTN. METHODS: We searched the Cochrane Database of Systematic Reviews on 14 July 2021 for ongoing and published Cochrane Reviews on the management of TTN in term (> 37 weeks' gestation) or late preterm (34 to 36 weeks' gestation) infants. We included all published Cochrane Reviews assessing the following categories of interventions administered within the first 48 hours of life: beta-agonists (e.g. salbutamol and epinephrine), corticosteroids, diuretics, fluid restriction, and non-invasive respiratory support. The reviews compared the above-mentioned interventions to placebo, no treatment, or other interventions for the management of TTN. The primary outcomes of this overview were duration of tachypnoea and the need for mechanical ventilation. Two overview authors independently checked the eligibility of the reviews retrieved by the search and extracted data from the included reviews using a predefined data extraction form. Any disagreements were resolved by discussion with a third overview author. Two overview authors independently assessed the methodological quality of the included reviews using the AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews) tool. We used the GRADE approach to assess the certainty of evidence for effects of interventions for TTN management. As all of the included reviews reported summary of findings tables, we extracted the information already available and re-graded the certainty of evidence of the two primary outcomes to ensure a homogeneous assessment. We provided a narrative summary of the methods and results of each of the included reviews and summarised this information using tables and figures. MAIN RESULTS: We included six Cochrane Reviews, corresponding to 1134 infants enrolled in 18 trials, on the management of TTN in term and late preterm infants, assessing salbutamol (seven trials), epinephrine (one trial), budesonide (one trial), diuretics (two trials), fluid restriction (four trials), and non-invasive respiratory support (three trials). The quality of the included reviews was high, with all of them fulfilling the critical domains of the AMSTAR 2. The certainty of the evidence was very low for the primary outcomes, due to the imprecision of the estimates (few, small included studies) and unclear or high risk of bias. Salbutamol may reduce the duration of tachypnoea compared to placebo (mean difference (MD) -16.83 hours, 95% confidence interval (CI) -22.42 to -11.23, 2 studies, 120 infants, low certainty evidence). We did not identify any review that compared epinephrine or corticosteroids to placebo and reported on the duration of tachypnoea. However, one review reported on "trend of normalisation of respiratory rate", a similar outcome, and found no differences between epinephrine and placebo (effect size not reported). The evidence is very uncertain regarding the effect of diuretics compared to placebo (MD -1.28 hours, 95% CI -13.0 to 10.45, 2 studies, 100 infants, very low certainty evidence). We did not identify any review that compared fluid restriction to standard fluid rates and reported on the duration of tachypnoea. The evidence is very uncertain regarding the effect of continuous positive airway pressure (CPAP) compared to free-flow oxygen therapy (MD -21.1 hours, 95% CI -22.9 to -19.3, 1 study, 64 infants, very low certainty evidence); the effect of nasal high-frequency (oscillation) ventilation (NHFV) compared to CPAP (MD -4.53 hours, 95% CI -5.64 to -3.42, 1 study, 40 infants, very low certainty evidence); and the effect of nasal intermittent positive pressure ventilation (NIPPV) compared to CPAP on duration of tachypnoea (MD 4.30 hours, 95% CI -19.14 to 27.74, 1 study, 40 infants, very low certainty evidence). Regarding the need for mechanical ventilation, the evidence is very uncertain for the effect of salbutamol compared to placebo (risk ratio (RR) 0.60, 95% CI 0.13 to 2.86, risk difference (RD) 10 fewer, 95% CI 50 fewer to 30 more per 1000, 3 studies, 254 infants, very low certainty evidence); the effect of epinephrine compared to placebo (RR 0.67, 95% CI 0.08 to 5.88, RD 70 fewer, 95% CI 460 fewer to 320 more per 1000, 1 study, 20 infants, very low certainty evidence); and the effect of corticosteroids compared to placebo (RR 0.52, 95% CI 0.05 to 5.38, RD 40 fewer, 95% CI 170 fewer to 90 more per 1000, 1 study, 49 infants, very low certainty evidence). We did not identify a review that compared diuretics to placebo and reported on the need for mechanical ventilation. The evidence is very uncertain regarding the effect of fluid restriction compared to standard fluid administration (RR 0.73, 95% CI 0.24 to 2.23, RD 20 fewer, 95% CI 70 fewer to 40 more per 1000, 3 studies, 242 infants, very low certainty evidence); the effect of CPAP compared to free-flow oxygen (RR 0.30, 95% CI 0.01 to 6.99, RD 30 fewer, 95% CI 120 fewer to 50 more per 1000, 1 study, 64 infants, very low certainty evidence); the effect of NIPPV compared to CPAP (RR 4.00, 95% CI 0.49 to 32.72, RD 150 more, 95% CI 50 fewer to 350 more per 1000, 1 study, 40 infants, very low certainty evidence); and the effect of NHFV versus CPAP (effect not estimable, 1 study, 40 infants, very low certainty evidence). Regarding our secondary outcomes, duration of hospital stay was the only outcome reported in all of the included reviews. One trial on fluid restriction reported a lower duration of hospitalisation in the restricted-fluids group, but with very low certainty of evidence. The evidence was very uncertain for the effects on secondary outcomes for the other five reviews. Data on potential harms were scarce, as all of the trials were underpowered to detect possible increases in adverse events such as pneumothorax, arrhythmias, and electrolyte imbalances. No adverse effects were reported for salbutamol; however, this medication is known to carry a risk of tachycardia, tremor, and hypokalaemia in other settings. AUTHORS' CONCLUSIONS: This overview summarises the evidence from six Cochrane Reviews of randomised trials regarding the effects of postnatal interventions in the management of TTN. Salbutamol may reduce the duration of tachypnoea slightly. We are uncertain as to whether salbutamol reduces the need for mechanical ventilation. We are uncertain whether epinephrine, corticosteroids, diuretics, fluid restriction, or non-invasive respiratory support reduces the duration of tachypnoea and the need for mechanical ventilation, due to the extremely limited evidence available. Data on harms were lacking.

The neonatal respiratory morbidity associated with early term caesarean section - an emerging pandemic.

OBJECTIVES: To examine the impact of early term caesarean section (CS) on respiratory morbidity and early neonatal outcomes when elective caesarean section was carried out before 39 completed weeks gestation in our population. METHODS: A one-year population-based retrospective cohort analysis using routinely collected hospital data. Livebirths from women who had elective lower segment cesarean section (ELSCS) for uncomplicated singleton pregnancies at early term (ET) 37+0 to 38+6 weeks were compared to full term (FT)≥39+0 weeks gestation. Exclusion criteria included diabetes, antenatal corticosteroid use, stillbirths, immediate neonatal deaths, normal vaginal deliveries and emergency caesareans sections. The outcomes were combined respiratory morbidity (tachypnea [TTN] and respiratory distress syndrome [RDS]), Apgar <7 at 5 min of age, respiratory support, duration of respiratory support and NICU admission. RESULTS: Out of a total of 1,466 elective CS with term livebirths, the timing of CS was early term (ET) n=758 (52%) and full term (FT) n=708 (48%). There was a higher incidence of respiratory morbidities and neonatal outcomes in the ET in comparison to FT newborns. In the univariable analysis, significant risks for outcomes were: the need for oxygen support OR 2.42 (95% C.I. 1.38-4.22), respiratory distress syndrome and/or transient tachypnea of newborn (RDSF/TTN) OR 2.44 (95% C.I. 1.33-4.47) and neonatal intensive care unit (NICU) admission OR 1.91 (95% C.I. 1.22-2.98). Only the need for oxygen support remained (OR 1.81, 95% C.I. 1.0-3.26) in the multivariable analysis. These results were observed within the context of a significantly higher proportion of older, multiparous, and higher number of previous caesarean sections in the early term CS group. CONCLUSIONS: There is a significant risk of respiratory morbidities in infants born by elective cesarean section prior to full term gestation. Obstetricians should aim towards reducing the high rate of women with previous multiple cesarean sections including balancing the obstetric indication of early delivery among such women with the evident risk of neonatal respiratory morbidity.

Effect of continuous positive airway pressure versus nasal cannula on late preterm and term infants with transient tachypnea of the newborn.

OBJECTIVE: To compare continuous positive airway pressure (CPAP) with nasal cannula (NC) as primary noninvasive respiratory therapy in hypoxic infants for transient tachypnea of the newborn (TTN). STUDY DESIGN: Retrospective cohort study of infants born at ≥34 weeks of gestation between January 1, 2015 and December 31, 2018. RESULT: After adjusting for gestational age and birth weight, the maximum fractional inspired oxygen (FiO2) was significantly lower in the CPAP group with an incidence rate ratio (IRR) of 0.85 (95% CI: 0.76-0.96). Although nonsignificant, the CPAP group needed 32% fewer hours on oxygen with an IRR of 0.68 (95% CI: 0.38-1.22). The duration of respiratory support and the incidence of pneumothorax were similar between both groups. CONCLUSION: Comparing CPAP with NC as initial noninvasive respiratory therapy for TTN, significantly lower maximum FiO2 was observed in the infants of CPAP group without increase in the incidence of pneumothorax.

Fluid restriction in the management of transient tachypnea of the newborn.

BACKGROUND: Transient tachypnea of the newborn (TTN) is caused by delayed clearance of lung fluid at birth. TTN typically appears within the first two hours of life in term and late preterm neonates and is characterized by tachypnea and signs of respiratory distress. Although it is usually a self-limited condition, admission to a neonatal unit is frequently required for monitoring and providing respiratory support. Restricting intake of fluids administered to these infants in the first days of life might improve clearance of lung liquid, thus reducing the effort required to breathe, improving respiratory distress, and potentially reducing the duration of tachypnea. OBJECTIVES: To evaluate the efficacy and safety of restricted fluid therapy as compared to standard fluid therapy in decreasing the duration of oxygen administration and the need for noninvasive or invasive ventilation among neonates with TTN. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 12), in the Cochrane Library; Ovid MEDLINE and electronic ahead of print publications, in-process & other non-indexed citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on December 6, 2019. We also searched clinical trial databases and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs), quasi-RCTs, and cluster trials on fluid restriction in term and preterm neonates with the diagnosis of TTN or delayed adaptation during the first week after birth. DATA COLLECTION AND ANALYSIS: For each of the included trials, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, duration of oxygen therapy, need for continuous positive airway pressure [CPAP], need for mechanical ventilation, duration of mechanical ventilation) and assessed the risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). The primary outcome considered in this review was the duration of supplemental oxygen therapy in hours or days. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Four trials enrolling 317 infants met the inclusion criteria. Three trials enrolled late preterm and term infants with TTN, and the fourth trial enrolled only term infants with TTN. Infants were on various methods of respiratory support at the time of enrollment including room air, oxygen, or nasal CPAP. Infants in the fluid-restricted group received 15 to 20 mL/kg/d less fluid than those in the control group for varying durations after enrollment. Two studies had high risk of selection bias, and three out of four had high risk of performance bias. Only one study had low risk of detection bias, with two at high risk and one at unclear risk. The certainty of evidence for all outcomes was very low due to imprecision of estimates and unclear risk of bias. Two trials reported the primary duration of supplemental oxygen therapy. We are uncertain whether fluid restriction decreases or increases the duration of supplemental oxygen therapy (mean difference [MD] -12.95 hours, 95% confidence interval [CI] -32.82 to 6.92; I² = 98%; 172 infants). Similarly, there is uncertainty for various secondary outcomes including incidence of hypernatremia (serum sodium > 145 mEq/L, risk ratio [RR] 4.0, 95% CI 0.46 to 34.54; test of heterogeneity not applicable; 1 trial, 100 infants), hypoglycemia (blood glucose < 40 mg/dL, RR 1.0, 95% CI 0.15 to 6.82; test of heterogeneity not applicable; 2 trials, 164 infants), endotracheal ventilation (RR 0.73, 95% CI 0.24 to 2.23; I² = 0%; 3 trials, 242 infants), need for noninvasive ventilation (RR 0.40, 95% CI 0.14 to 1.17; test of heterogeneity not applicable; 2 trials, 150 infants), length of hospital stay (MD -0.92 days, 95% CI -1.53 to -0.31; test of heterogeneity not applicable; 1 trial, 80 infants), and cumulative weight loss at 72 hours of age (%) (MD 0.24, 95% CI -1.60 to 2.08; I² = 89%; 2 trials, 156 infants). We did not identify any ongoing trials; however, one trial is awaiting classification. AUTHORS' CONCLUSIONS: We found limited evidence to establish the benefits and harms of fluid restriction in the management of TTN. Given the very low certainty of available evidence, it is impossible to determine whether fluid restriction is safe or effective for management of TTN. However, given the simplicity of the intervention, a well-designed trial is justified.

Comparison of Nasal CPAP versus Bi-level CPAP in Transient Tachypnea of the Newborn: A Randomized Trial.

OBJECTIVE: The optimal noninvasive ventilation (NIV) modality in the treatment of transient tachypnea of the newborn (TTN) is still unknown. The aim of this study was to compare nasal continuous positive airway pressure (NCPAP) versus bi-level CPAP in the treatment of TTN. STUDY DESIGN: This was a prospective randomized study that was conducted in a tertiary level neonatal intensive care unit of Zekai Tahir Burak Women's Health Education and Research Hospital during the 1-year period between April 2017 and March 2018. The study included infants at ≥34 gestational weeks and birth weight ≥2,000 g who were diagnosed with TTN. The patients were randomized to either NCPAP or bi-level CPAP groups as initial respiratory support. The primary outcome was the rate of NIV failure. RESULTS: A total of 151 infants were incorporated into the study. The intubation rate was significantly higher in the NCPAP group (15/75) compared with the bi-level CPAP group (6/76) (p = 0.032). There was a significant decrease in the level of pCO2 at the 12 (60.7 ± 6.7 vs. 66.3 ± 8.8, p = 0.017) and 24 (50 ± 8 vs. 53 ± 10, p = 0.028) hours of NIV in the bi-level CPAP group compared with the NCPAP group. Duration of NIV, total respiratory support, hospital stay, and the incidence of pneumothorax were similar between the groups. CONCLUSION: Bi-level CPAP reduced the rate of NIV failure and pCO2 levels at the 12 and 24 hours in late preterm and term infants with a diagnosis of TTN. KEY POINTS: · Bi-level CPAP seems to be a safe and effective method in TTN.. · Bi-level CPAP may reduce the rate of NIV failure in late preterm and term infants with TTN.. · Future studies are warranted to answer the question whether bi-level CPAP might be used as a standard treatment in babies with TTN..

Recent Advances in Pathophysiology and Management of Transient Tachypnea of Newborn.

Transient tachypnea of newborn (TTN) results from failure of the newborn to effectively clear the fetal lung fluid soon after birth. TTN represents the most common etiology of respiratory distress in term gestation newborns and sometimes requires admission to the neonatal intensive care unit. TTN can lead to maternal-infant separation, the need for respiratory support, extended unnecessary exposure to antibiotics and prolonged hospital stays. Recent evidence also suggests that TTN may be associated with wheezing syndromes later in childhood. New imaging modalities such as lung ultrasound can help in the diagnosis of TTN and early management with distending pressure using continuous positive airway pressure may prevent exacerbation of respiratory distress.

A Comparative Trial of the Effectiveness of Nasal Interfaces Used to Deliver Continuous Positive Airway Pressure for a Brief Period in Infants With Transient Tachypnea of the Newborn / Estudio comparativo sobre la eficacia de las interfaces nasales para la administración de presión positiva continua de la vía aérea durante un periodo breve de tiempo en neonatos con taquipnea transitoria del recién nacido

INTRODUCTION: There is insufficient data on the effectiveness of the interfaces used for nasal continuous airway pressure (nCPAP) in newborn infants. Transpulmonary pressure (PTP) calculated from a measured esophageal pressure (Pes) could be used as a surrogate for the pressure transmitted to the distal airways during nCPAP. We aimed to compare the effectiveness of two nasal interfaces, the nasal mask and bi-nasal short prongs, during a relatively brief period of respiratory support by calculated PTP (cPTP) in infants with transient tachypnea of the newborn (TTN). METHODS: Newborns with TTN who needed respiratory assistance with nCPAP were randomized to use either bi-nasal short prongs or a nasal mask. Esophageal pressure measurements were done in order to calculate PTP with either interface. The primary outcome was the cPTP transmitted with each nasal interface. Esophageal pressure measurements were recorded and PTP values were calculated from Pes measurements at the 1st, 6th, 12th and 24th hours in each patient as long as the respiratory support lasted. RESULTS: Sixty-two newborns with TTN and on nCPAP were randomized into two groups: Group 1 to use bi-nasal short prongs (n: 31) and Group 2 to use a nasal mask (n: 31). Inspiratory and expiratory Pes and cPTP values at the 1st, 6 th, 12 th and 24 th hours were similar with the two interfaces (P < .05). CONCLUSIONS: A nasal mask is similarly effective and safe as bi-nasal short prongs during a brief period of non-invasive respiratory support with nCPAP in late preterm and term neonates with TTN

INTRODUCCIÓN: No hay datos suficientes sobre la eficacia de las interfaces que se utilizan para la administración de presión positiva continua de la vía aérea por vía nasal (CPAPn) en neonatos. La presión transpulmonar (PL), calculada a partir de la medición de la presión esofágica (Pesof), podría utilizarse como alternativa para medir la presión transmitida a la vía aérea distal durante la CPAPn. Nuestro objetivo fue comparar la eficacia de 2 interfaces nasales, la mascarilla nasal y las cánulas binasales cortas, durante un periodo relativamente corto de soporte respiratorio mediante la PL calculada (PLc) en neonatos con taquipnea transitoria del recién nacido (TTRN). MÉTODOS: Los neonatos con TTRN que requirieron ventilación con CPAPn se aleatorizaron para el uso de cánulas binasales cortas o mascarilla nasal. Se realizaron mediciones de la presión esofágica para calcular la PL con cada interfaz. La variable de resultado fue la PLc transmitida con cada interfaz nasal. Las mediciones de presión esofágica se registraron y los valores de PL se calcularon a partir de las mediciones de la Pesof en las 1.ª, 6.a, 12.a y 24.a horas en cada paciente durante el tiempo que durara la ventilación mecánica. RESULTADOS: Se aleatorizaron 62 neonatos con TTRN y tratados con CPAPn en 2 grupos: el grupo 1 usó las cánulas binasales cortas (n = 31) y el grupo 2 usó la mascarilla nasal (n = 31). Los valores inspiratorios y espiratorios de Pesof y PLc en las 1.a, 6.a, 12.a y 24.a horas fueron similares con ambas interfaces (P < 0,05). CONCLUSIONES: La máscara nasal tiene una eficiencia similar a las cánulas binasales cortas durante la administración breve de ventilación mecánica no invasiva mediante CPAPn en neonatos prematuros tardíos y neonatos a término con TTRN

A randomized controlled trial of restricted versus standard fluid management in late preterm and term infants with transient tachypnea of the newborn.

BACKGROUND: Transient tachypnea of the newborn(TTNB) is the most common respiratory morbidity in late preterm and term babies and is pathophysiologically related to delayed lung fluid clearance after birth. Mimicking low physiological fluid intake in the initial period of life may accelerate the recovery from TTNB. In a randomized controlled trial, we compared the roles of restricted versus standard fluid management in babies with TTNB requiring respiratory support. METHODS: This parallel group,non-blinded, stratified randomized controlled trial was conducted in a level III neonatal unit of eastern India. Late preterm and term babies with TTNB requiring continuous positive airway pressure (CPAP) were randomly allocated to standard and restricted fluid arms for the first 72 hours (hrs). Primary outcome was CPAP duration. RESULTS: In total, 100 babies were enrolled in this study with 50 babies in each arm. CPAP duration was significantly less in the restricted arm (48[42, 54] hrs vs 54[48,72] hrs, p = 0.002). However, no difference was observed in the incidence of CPAP failure between the two arms. In the subgroup analysis, the benefit of reduced CPAP duration persisted in late preterm but not in term infants. However, the effect was not significant in the late preterm babies exposed to antenatal steroid. CONCLUSION: This trial demonstrated the safety and effectiveness of restrictive fluid strategy in reducing CPAP duration in late preterm and term babies with TTNB. Late preterm babies, especially those not exposed to antenatal steroid were the most benefitted by this strategy.

Non-invasive respiratory support for the management of transient tachypnea of the newborn.

BACKGROUND: Transient tachypnea of the newborn (TTN) is characterized by tachypnea and signs of respiratory distress. Transient tachypnea typically appears within the first two hours of life in term and late preterm newborns. Supportive management might be sufficient. Non-invasive (i.e. without endotracheal intubation) respiratory support may, however, be administered to reduce respiratory distress during TTN. In addition, non-invasive respiratory support might improve clearance of lung liquid thus reducing the effort required to breathe, improving respiratory distress and potentially reducing the duration of tachypnea. OBJECTIVES: To assess benefits and harms of non-invasive respiratory support for the management of transient tachypnea of the newborn. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 2), MEDLINE (1996 to 19 February 2019), Embase (1980 to 19 February 2019) and CINAHL (1982 to 19 February 2019). We applied no language restrictions. We searched clinical trial registries for ongoing studies. SELECTION CRITERIA: Randomized controlled trials, quasi-randomized controlled trials and cluster trials on non-invasive respiratory support provided to infants born at 34 weeks' gestational age or more and less than three days of age with transient tachypnea of the newborn. DATA COLLECTION AND ANALYSIS: For each of the included trials, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, duration of oxygen therapy, need for continuous positive airway pressure [CPAP] and need for mechanical ventilation, duration of mechanical ventilation, etc.) and assessed the risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). The primary outcomes considered in this review were need for mechanical ventilation and pneumothorax. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included three trials (150 infants) comparing either CPAP to free-flow oxygen, nasal intermittent mandatory ventilation to nasal CPAP, or nasal high-frequency percussive ventilation versus nasal CPAP. Due to these different comparisons and to high clinical heterogeneity in the baseline clinical characteristics, we did not pool the three studies. The use of CPAP versus free oxygen did not improve the primary outcomes of this review: need for mechanical ventilation (risk ratio [RR] 0.30, 95% confidence interval [CI] 0.01 to 6.99; 1 study, 64 participants); and pneumothorax (not estimable, no cases occurred). Among secondary outcomes, CPAP reduced the duration of tachypnea as compared to free oxygen (mean difference [MD] -21.10 hours, 95% CI -22.92 to -19.28; 1 study, 64 participants). Nasal intermittent ventilation did not reduce the need for mechanical ventilation as compared with CPAP (RR 4.00, 95% CI 0.49 to 32.72; 1 study, 40 participants) or the incidence of pneumothorax (RR 1.00, 95% CI 0.07 to 14.90; 1 study, 40 participants); duration of tachypnea did not differ (MD 4.30, 95% CI -19.14 to 27.74; 1 study, 40 participants). In the study comparing nasal high-frequency ventilation to CPAP, no cases of mechanical ventilation of pneumothorax occurred (not estimable; 1 study, 46 participants); duration of tachypnea was reduced in the nasal high-frequency ventilation group (MD -4.53, 95% CI -5.64 to -3.42; 1 study, 46 participants). The quality of the evidence was very low due to the imprecision of the estimates and unclear risk of bias for detection bias and high risk of bias for reporting bias. Tests for heterogeneity were not applicable for any of the analyses as no studies were pooled. Two trials are ongoing. AUTHORS' CONCLUSIONS: There is insufficient evidence to establish the benefit and harms of non-invasive respiratory support in the management of transient tachypnea of the newborn. Though two of the included trials showed a shorter duration of tachypnea, clinically relevant outcomes did not differ amongst the groups. Given the limited and low quality of the evidence available, it was impossible to determine whether non-invasive respiratory support was safe or effective for the treatment of transient tachypnea of the newborn.

Randomized trial of mask or prongs for nasal intermittent mandatory ventilation in term infants with transient tachypnea of the newborn.

BACKGROUND: The aim of this study was to compare nasal masks (NM) with binasal prongs (NP) for applying nasal intermittent mandatory ventilation (NIMV) by assessing the duration of respiratory distress, rate of intubation, and nasal trauma in term infants with transient tachypnea of the newborn (TTN). METHODS: Infants with a gestational age ≥37 weeks and birthweight ≥2,000 g who had NIMV administered for TTN were enrolled. We randomly allocated 80 neonates to the NM (n = 40) or NP (n = 40) group. Duration of respiratory distress was the primary outcome of this study. RESULTS: There were no statistically significant differences between the groups for the duration of tachypnea and NIMV (P = 0.94 and P = 0.13, respectively). No significant differences were observed between the two groups in terms of duration of oxygen supplementation and length of hospitalization (P = 0.72 and P = 0.70, respectively). The incidence of any grade of trauma and moderate trauma (grade II) was significantly higher in the NP group than in the NM group (P = 0.004 and P = 0.04, respectively). The rate of NIMV failure and other complications, including pneumothorax, pneumonia and feeding intolerance, was not significantly different in the groups. CONCLUSIONS: In term infants with TTN, delivering NIMV using NP in comparison to using NM appears to be similar with regard to the duration of respiratory distress and preventing intubation. However, the use of NP involves a greater risk of trauma than that of NM.

Early rescue Neopuff for infants with transient tachypnea of newborn: a randomized controlled trial.

OBJECTIVE: To examine the efficacy of early continuous positive airway pressure (CPAP), delivered using a T-piece-based infant resuscitator (Neopuff) via a face mask, in reducing the severity and duration of transient tachypnea of the newborn (TTN) as well as testing a hypothesis suggesting that rapid clearance of fetal lung fluid to the circulation via CPAP would increase plasma B-type natriuretic peptide (BNP). METHODS: A randomized controlled trial (NCT01859533) was conducted on 64 late preterm/term neonates, delivered by cesarean section and presented by respiratory distress shortly after birth. The Neopuff group included 34 neonates received 20 min of early CPAP and control group included 30 neonates received free flow O2. Plasma BNP was measured baseline and 2 h later. RESULTS: The duration of tachypnea was shorter in Neopuff group with less need of neonatal intensive care unit admission and need of mechanical support (p < .05) with no effect on duration of hospitalization (p > .05). Plasma BNP showed no significant difference between pre- and post-Neopuff levels (p > .05). A positive correlation was found between BNP and duration of tachypnea as well as the length of hospitalization (p < .05) among Neopuff group. CONCLUSION: Early rescue CPAP reduces the duration and severity of respiratory distress among infants with TTN.

Respiratory morbidity in late preterm infants.

BACKGROUND: Late preterm delivery (74% of all preterm births) increases the incidence of respiratory pathology, namely respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN) and the need of ventilator support when compared to term delivery. The aim is to evaluate the respiratory morbimortality in late preterm infants and the risk factors associated with RDS and TTN. METHODS: Descriptive retrospective study of all newborns of 34+0 to 36+6 weeks of gestational age, born at our center between September 1, 2012 and August 31, 2015. Those with major malformations, chromosomopathies, hydrops fetalis and congenital TORCH infection were excluded. RESULTS: A total of 498 newborns were studied, 44 (8.83%) of them with either RDS or TTN. Respiratory morbidity was significantly associated with lower gestational age, male gender, caesarean section, exposure to peripartum antibiotics, overweighed and nulliparous mothers. RDS newborns had a significantly higher need for resuscitation, endotracheal intubation, oxygen therapy, early invasive ventilation, parenteral nutrition and a longer NICU stay when compared to newborns with TTN. 55% of the patients with RDS had 35+0 to 36+6 weeks of gestational age, moderate or severe RDS and required mechanical ventilation; six needed surfactant. Caesarean section and resuscitation with ETT were independent risk factors for respiratory morbidity. CONCLUSIONS: Late preterm remain at risk for adverse respiratory outcomes, particularly newborns delivered after 35 weeks, whose mothers are not given ACS and still have considerable morbidity. Growing evidence supports the possibility of extending the management window further into the LPT period. Caesarean section was an independent risk factor for respiratory morbidity and efforts should be undertaken to reduce the procedure rate.

Ambulatory Treatment of Fast Breathing in Young Infants Aged <60 Days: A Double-Blind, Randomized, Placebo-Controlled Equivalence Trial in Low-Income Settlements of Karachi.

(See the Editorial Commentary by Jehan and Qazi on pages 190-1) BACKGROUND: Integrated Management of Childhood Illness recommends that young infants with isolated fast breathing be referred to a hospital for antibiotic treatment, which is often impractical in resource-limited settings. Additionally, antibiotics may be unnecessary for physiologic tachypnea in otherwise well newborns. We tested the hypothesis that ambulatory treatment with oral amoxicillin for 7 days was equivalent (similarity margin of 3%) to placebo in young infants with isolated fast breathing in primary care settings where hospital referral is often unfeasible. METHODS: This randomized equivalence trial was conducted in 4 primary health centers of Karachi, Pakistan. Infants presenting with isolated fast breathing and oxygen saturation ≥90% were randomly assigned to receive either oral amoxicillin or placebo twice daily for 7 days. Enrolled infants were followed on days 1-8, 11, and 14. The primary outcome was treatment failure by day 8, analyzed per protocol. The trial was stopped by the data safety monitoring board due to higher treatment failure rate and the occurrence of 2 deaths in the placebo arm in an interim analysis. RESULTS: Four hundred twenty-three infants fulfilled per protocol criteria in the amoxicillin arm and 426 in the placebo arm. Twelve infants (2.8%) had treatment failure in the amoxicillin arm and 25 (5.9%) in the placebo arm (risk difference, 3.1; P value .04). Two infants in the placebo arm died, whereas no deaths occurred in the amoxicillin arm. Other adverse outcomes, as well as the proportions of relapse, were evenly distributed across both study arms. CONCLUSIONS: This trial failed to show equivalence of placebo to amoxicillin in the management of isolated fast breathing without hypoxemia or other clinical signs of illness in term young infants. CLINICAL TRIALS REGISTRATION: NCT01533818.

Strategies for managing transient tachypnoea of the newborn - a systematic review.

OBJECTIVE: To conduct a systematic review of strategies for the management of transient tachypnoea of the newborn (TTN). METHODS: The Cochrane Collaboration and PRISMA guidelines were used for conducting and reporting this systematic review, respectively. The Cochrane Central Register of Controlled Trials, PubMed, CINAHL and EMBASE databases were searched in February 2016. Only randomised and quasi-randomised controlled trials (RCTs) assessing any intervention for the management of TTN in infants <7 days of age, born at 35 or more weeks with a clinical diagnosis of TTN were eligible for inclusion. Primary outcomes included the duration of respiratory support, oxygen support, tachypnoea and hospitalisation. RESULTS: Nine RCTs with moderate risk of bias were included. The interventions assessed included furosemide (2 trials, n = 100), inhaled salbutamol (2 trials, n = 94), inhaled epinephrine (1 trial, n = 20), restrictive fluids (2 trials, n = 146) and non-invasive ventilation (2 trials, n = 80). Amongst all interventions, inhaled salbutamol significantly reduced the duration of hospitalisation (2 trials, n = 94) [mean difference (MD) - 1.63 days (95% CI -2.71 to -0.55); p = 0.003] and duration of oxygen requirement (1 trial, n = 37) [MD - 43.10 h (95% CI -81.82 to -4.38; p = 0.03] without adverse effects. CONCLUSION: Limited low-quality evidence exists on the effects of different management strategies for TTN. The safety and efficacy of inhaled salbutamol in the treatment of TTN can be assessed in a large RCT.

Impact of Prophylactic Continuous Positive Airway Pressure on Transient Tachypnea of the Newborn and Neonatal Intensive Care Admission in Newborns Delivered by Elective Cesarean Section.

OBJECTIVE: This study aims to evaluate the effect of the prophylactic continuous positive airway pressure (CPAP) administration in the delivery room to newborns who were delivered by elective cesarean section (CS). STUDY DESIGN: Inborn infants with gestational age between 34(0/7) to 38(6/7) and born by elective CS were prospectively randomized to receive either prophylactic CPAP for 20 minutes via face mask or standardized care without CPAP in the delivery room. Primary outcomes were the incidence of transient tachypnea of the newborn (TTN) and neonatal intensive care unit (NICU) admission due to respiratory distress. RESULTS: A total of 259 infants with a mean gestational age of 37.7 ± 0.8 weeks and birth weight of 3,244 ± 477 g were included. A total of 134 infants received prophylactic CPAP and 125 received control standard care. The rate of NICU admission was significantly lower in prophylactic CPAP group (p = 0.045). Although the rate of TTN was lower in the prophylactic CPAP group, the difference was not statistically significant (p = 0.059). The rate of NICU admission due to respiratory distress was significantly higher in late-preterm cohort than early-term cohort (p < 0.0001). CONCLUSION: Prophylactic CPAP administration decreases the rate of NICU admission without any side effect in late-preterm and early-term infants delivered by elective CS.

Effect of Ventilation Support on Oxidative Stress and Ischemia-Modified Albumin in Neonates.

BACKGROUND AND OBJECTIVE: Mechanical ventilation (MV) can induce oxidative stress, which plays a critical role in pulmonary injury in intubated neonates. Ischemia-modified albumin (IMA)-a variant of human serum albumin-is a novel biomarker of myocardial ischemia that occurs due to reactive oxygen species during ischemic insult. This study aimed to investigate IMA production due to oxidative stress induced during MV in neonates. MATERIALS AND METHODS: This study included 17 neonates that were ventilated using synchronized intermittent mechanical ventilation (SIMV; SIMV group) and 20 neonates ventilated using continuous positive airway pressure (CPAP; CPAP group). Blood samples were collected from each neonate during ventilation support and following cessation of ventilation support. Total antioxidant capacity (TAC) and total oxidant status (TOS) were measured using the Erel method. IMA was measured via an enzyme-linked immunosorbent assay kit (Cusabio Biotech Co., Ltd., Wuhan, China). The oxidant stress index (OSI) was calculated as OSI = TOS/TAC. Statistical analysis was performed using SPSS v.18.0 (SPSS Inc., Chicago, IL) for Windows. RESULTS: Among the neonates included in the study, mean gestational age was 34.7 ± 3.8 weeks, mean birth weight was 2,553 ± 904 g, and 54% were premature. There were not any significant differences in mean gestational age or birth weight between the SIMV and CPAP groups. Among the neonates in both the groups, mean IMA, TOS, and OSI levels were significantly higher during ventilation support (102.2 ± 9.3 IU mL(-1), 15.5 ± 1.3 µmol H2O2 equivalent L(-1), and 0.85 ± 0.22 arbitrary units [ABU], respectively), as compared with following cessation of ventilation support (82.9 ± 11.9 IU mL(-1), 13.4 ± 1.3 µmol H2O2 equivalent L(-1), and 0.64 ± 0.14 ABU, respectively) (p = 0.001). Among all the neonates in the study, mean TAC was significantly lower during ventilation support than the postventilation support (1.82 ± 0.28 mmol 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid [Trolox] equivalent L(-1) vs. 2.16 ± 0.31 mmol Trolox equivalent L(-1)) (p = 0.001). There were no significant differences in mean TAC, OSI, or IMA levels between the SIMV and CPAP groups. The mean TOS level during ventilation support and the mean difference in TOS between during and postventilation support was significantly greater in the CPAP group than in the SIMV group. There were no significant relationships between the mean TOS, TAC, OSI, or IMA levels, and gestational age of the neonates. CONCLUSION: SIMV and CPAP activated the oxidative stress and increased the IMA level in neonates; therefore, measurement of IMA and oxidant markers may be useful in the follow-up of lung injury in neonates due to ventilation support. Additional prospective studies are needed to compare the effects of various ventilation methods on oxidative stress and the IMA level in neonates.