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.

Clinical course in infants diagnosed with transient tachypnea of newborn: A clinical trial assessing the role of conservative versus conventional management.

BACKGROUND: Transient tachypnea of the newborn (TTN) is a respiratory disorder secondary to inadequate or delayed clearance of lung fluids. Early symptoms of the disease are indistinguishable from neonatal respiratory distress syndrome, pneumonia, and persistent pulmonary hypertension. Therefore, these newborns, in addition to receiving conservative management, receive antibiotics until blood cultures provide definite results. In this study, we assessed the clinical course of neonates diagnosed with TTN who received conventional versus conservative management. METHODS: One hundred and thirty neonates diagnosed as having TTN were randomly enrolled in two study groups. While patients belonging to one group received conservative management, those from the other group were treated with conventional medical therapy. RESULTS: Mean duration of hospitalization was 7 ± 0.2 in the conventional and 5 ± 1.5 in the conservative group. Duration of antibiotic therapy was 6.7 ± 2.47 days in the conventional group. CONCLUSION: Newborns diagnosed with TTN without prenatal risk factors and a negative C reactive protein test do not need to be administered antibiotics and hospitalized until confirmatory blood culture results are obtained.

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.

Risk factors in retained fetal lung fluid syndrome.

OBJECTIVE: Antenatal, postnatal follow-ups and laboratory findings of the cases with retained fetal lung fluid syndrome were evaluated to detect prognostic factors. STUDY DESIGN: This study was conducted at Zeynep Kamil Maternity and Children's Training and Research Hospital including infants retained fetal lung fluid syndrome. Patients were divided into 3 groups according to duration of the clinical symptoms. Cases whose clinical findings resolving within first 24 hours constituted Group 1 (n = 31), cases with clinical findings persisting between 24 and 72 hours constituted Group 2 (n = 95) and cases with symptoms persisting >72 hours constituted Group 3 (n = 10). Antenatal and postnatal clinical data and laboratory findings of the patients were evaluated retrospectively. RESULT: Pneumothorax, pulmonary hypertension, antibiotic use frequency and hospitalization periods were found to be prolonged in the patients admitted due to retained fetal lung fluid syndrome who were delivered with elective caesarean section, with low birth weight and gestational age, requiring intubation and invasive ventilation within first 12 hours, having low hemoglobin and blood chloride levels. CONCLUSIONS: Low blood chloride level can be a laboratory finding predicting whether malignant tachypnea develops or not in retained fetal lung fluid syndrome. Cut-off chloride value for malignant tachypnea can be determined with new studies which will be performed in the future.

Antibiotic use in newborns with transient tachypnea of the newborn.

BACKGROUND: Initiation of empiric antibiotic treatment for possible early-onset sepsis is recommended for late preterm and term neonates with respiratory distress. There is no evidence base to this approach. OBJECTIVES: To determine the incidence of adverse infectious events in neonates with transient tachypnea of the newborn (TTN) managed with a risk-factor-based restrictive antibiotic use policy. METHODS: This is a single institution retrospective cohort study of neonates with primary diagnosis of TTN between 2004 and 2010. The relationship between antibiotic exposure and infectious outcomes during the neonatal hospitalization was evaluated. An infectious outcome was defined as pneumonia, bacteremia, clinical sepsis, or death. Analysis included t test, χ(2) test, and analysis of variance as appropriate. RESULTS: 745 neonates with TTN met inclusion criteria. None of the 494 antibiotic-naive infants, and 212 of the 251 antibiotic-exposed infants had identifiable risk factors for sepsis. No infectious outcomes occurred in infants who did not receive antibiotics. Eight neonates with TTN received full antibiotic treatment for early-onset sepsis. Each was appropriately identified for early receipt of antibiotics based on historical or clinical risk factors for early-onset sepsis. CONCLUSIONS: This study suggests that empiric postnatal antibiotic treatment may not be warranted for late preterm and term infants with TTN in the absence of specific infectious risk factors.