Polyethylene bags before cord clamping in very preterm infants: a randomised controlled trial.

OBJECTIVE: Hypothermia on admission to the neonatal intensive care unit (NICU) is associated with an increased risk of death in preterm infants. There are currently no evidence-based recommendations for thermal care before cord clamping (CC). We wished to determine whether placing very preterm infants in a polyethylene bag (PB) before CC, compared with after CC, results in more infants with a temperature in the normal range on NICU admission. DESIGN: Randomised controlled trial. SETTING: Tertiary maternity hospital. PATIENTS: Inborn infants<32 weeks' gestational age (GA). INTERVENTIONS: Infants were randomly assigned to have a PB placed before or after CC. MAIN OUTCOME: Rectal temperature within the normal range (36.5°C-37.5°C) on NICU admission. RESULTS: Between July 2020 and September 2022, 198/220 (90%) eligible infants were enrolled in this study; 99 (44 (44%) girls) were randomly assigned to BEFORE and 99 (53 (54%) girls) to AFTER. Median (IQR) GA 29 (27-31) vs 29 (27-31) weeks, mean (SD) birth weight 1206 (429) vs 1138 (419) g, respectively. The proportion of infants who had normal temperature on NICU admission did not differ between the groups (BEFORE 54/99 (55%) vs AFTER 55/98 (56%), p 0.824). The proportion of infants with a temperature outside of the normal range was similar between the groups; hypothermia (BEFORE 34/99 (34%) vs AFTER 33/98 (34%), hyperthermia (BEFORE 10/99 (10%) vs AFTER 10/98 (10%)). CONCLUSIONS: Placing a PB before CC did not increase the proportion of preterm infants with normal temperature on NICU admission. A large proportion of preterm infants had abnormal temperature. Further studies on thermoregulation before CC are needed. TRIAL REGISTRATION NUMBER: NCT04463511.

Nasal interfaces for neonatal resuscitation.

BACKGROUND: The Neonatal Task Force of the International Liaison Committee on Resuscitation (ILCOR) makes practice recommendations for the care of newborn infants in the delivery room (DR). ILCOR recommends that all infants who are gasping, apnoeic, or bradycardic (heart rate < 100 per minute) should be given positive pressure ventilation (PPV) with a manual ventilation device (T-piece, self-inflating bag, or flow-inflating bag) via an interface. The most commonly used interface is a face mask that encircles the infant's nose and mouth. However, gas leak and airway obstruction are common during face mask PPV. Nasal interfaces (single and binasal prongs (long or short), or nasal masks) and laryngeal mask airways (LMAs) may also be used to deliver PPV to newborns in the DR, and may be more effective than face masks. OBJECTIVES: To determine whether newborn infants receiving PPV in the delivery room with a nasal interface compared to a face mask, laryngeal mask airway (LMA), or another type of nasal interface have reduced mortality and morbidity. To assess whether safety and efficacy of the nasal interface differs according to gestational age or ventilation device. SEARCH METHODS: Searches were conducted in September 2022 in CENTRAL, MEDLINE, Embase, Epistemonikos, and two trial registries. We searched conference abstracts and checked the reference lists of included trials and related systematic reviews identified through the search. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCT's that compared the use of nasal interfaces to other interfaces (face masks, LMAs, or one nasal interface to another) to deliver PPV to newborn infants in the DR. DATA COLLECTION AND ANALYSIS: Each review author independently evaluated the search results against the selection criteria, screened retrieved records, extracted data, and appraised the risk of bias. If they were study authors, they did not participate in the selection, risk of bias assessment, or data extraction related to the study. In such instances, the study was independently assessed by other review authors. We contacted trial investigators to obtain additional information. We completed data analysis according to the standards of Cochrane Neonatal, using risk ratio (RR) and 95% confidence Intervals (CI) to measure the effect of the different interfaces. We used fixed-effect models and the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included five trials, in which 1406 infants participated. They were conducted in 13 neonatal centres across Europe and Australia. Each of these trials compared a nasal interface to a face mask for the delivery of respiratory support to newborn infants in the DR. Potential sources of bias were a lack of blinding to treatment allocation of the caregivers and investigators in all trials. The evidence suggests that resuscitation with a nasal interface in the DR, compared with a face mask, may have little to no effect on reducing death before discharge (typical risk ratio (RR) 0.72, 95% CI 0.47 to 1.13; 3 studies, 1124 infants; low-certainty evidence). Resuscitation with a nasal interface may reduce the rate of intubation in the DR, but the evidence is very uncertain (RR 0.68, 95% CI 0.54 to 0.85; 5 studies, 1406 infants; very low-certainty evidence). The evidence is very uncertain for the rate of intubation within 24 hours of birth (RR 0.97, 95% CI 0.85 to 1.09; 3 studies, 749 infants; very low-certainty evidence), endotracheal intubation outside the DR during hospitalisation (RR 1.15, 95% CI 0.93 to 1.42; 1 study, 144 infants; very low-certainty evidence) and cranial ultrasound abnormalities (intraventricular haemorrhage (IVH) grade ≥ 3, or periventricular leukomalacia; RR 0.94, 95% CI 0.55 to 1.61; 3 studies, 749 infants; very low-certainty evidence). Resuscitation with a nasal interface in the DR, compared with a face mask, may have little to no effect on the incidence of air leaks (RR 1.09, 95% CI 0.85 to 1.09; 2 studies, 507 infants; low-certainty evidence), or the need for supplemental oxygen at 36 weeks' corrected gestational age (RR 1.06, 95% CI 0.8 to 1.40; 2 studies, 507 infants; low-certainty evidence). We identified one ongoing study, which compares a nasal mask to a face mask to deliver PPV to infants in the DR. We did not identify any completed trials that compared nasal interfaces to LMAs or one nasal interface to another. AUTHORS' CONCLUSIONS: Nasal interfaces were found to offer comparable efficacy to face masks (low- to very low-certainty evidence), supporting resuscitation guidelines that state that nasal interfaces are a comparable alternative to face masks for providing respiratory support in the DR. Resuscitation with a nasal interface may reduce the rate of intubation in the DR when compared with a face mask. However, the evidence is very uncertain. This uncertainty is attributed to the use of a new ventilation system in the nasal interface group in two of the five trials. As such, it is not possible to differentiate separate, specific effects related to the ventilation device or to the interface in these studies.

Oral stimulation for promoting oral feeding in preterm infants.

BACKGROUND: Preterm infants (< 37 weeks' post-menstrual age (PMA)) are often delayed in attaining oral feeding. Normal oral feeding is suggested as an important outcome for the timing of discharge from the hospital and can be an early indicator of neuromotor integrity and developmental outcomes. A range of oral stimulation interventions may help infants to develop sucking and oromotor co-ordination, promoting earlier oral feeding and earlier hospital discharge. This is an update of our 2016 review. OBJECTIVES: To determine the effectiveness of oral stimulation interventions for attainment of oral feeding in preterm infants born before 37 weeks' PMA. SEARCH METHODS: Searches were run in March 2022 of the following databases: CENTRAL via CRS Web; MEDLINE and Embase via Ovid. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. Searches were limited by date 2016 (the date of the search for the original review) forward. Note: Due to circumstances beyond our control (COVID and staffing shortages at the editorial base of Cochrane Neonatal), publication of this review, planned for mid 2021, was delayed. Thus, although searches were conducted in 2022 and results screened, potentially relevant studies found after September 2020 have been placed in the section, Awaiting Classification, and not incorporated into our analysis. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing a defined oral stimulation intervention with no intervention, standard care, sham treatment or non-oral intervention (e.g. body stroking protocols or gavage adjustment protocols) in preterm infants and reporting at least one of the specified outcomes. DATA COLLECTION AND ANALYSIS: Following the updated search, two review authors screened the titles and abstracts of studies and full-text copies when needed to identify trials for inclusion in the review. The primary outcomes of interest were time (days) to exclusive oral feeding, time (days) spent in NICU, total hospital stay (days), and duration (days) of parenteral nutrition. All review and support authors contributed to independent extraction of data and analysed assigned studies for risk of bias across the five domains of bias using the Cochrane Risk of Bias assessment tool. The GRADE system was used to rate the certainty of the evidence. Studies were divided into two groups for comparison: intervention versus standard care and intervention versus other non-oral or sham intervention. We performed meta-analysis using a fixed-effect model. MAIN RESULTS: We included 28 RCTs (1831 participants). Most trials had methodological weaknesses, particularly in relation to allocation concealment and masking of study personnel. Oral stimulation compared with standard care Following meta-analysis, it is uncertain whether oral stimulation reduces the time to transition to oral feeding compared with standard care (mean difference (MD) -4.07 days, 95% confidence interval (CI) -4.81 to -3.32 days, 6 studies, 292 infants; I2 =85%, very low-certainty evidence due to serious risk of bias and inconsistency). Time (days) spent in the neonatal intensive care unit (NICU) was not reported. It is uncertain whether oral stimulation reduces the duration of hospitalisation (MD -4.33, 95% CI -5.97 to -2.68 days, 5 studies, 249 infants; i2 =68%, very low-certainty evidence due to serious risk of bias and inconsistency). Duration (days) of parenteral nutrition was not reported. Oral stimulation compared with non-oral intervention Following meta-analysis, it is uncertain whether oral stimulation reduces the time to transition to exclusive oral feeding compared with a non-oral intervention (MD -7.17, 95% CI -8.04 to -6.29 days, 10 studies, 574 infants; I2 =80%, very low-certainty evidence due to serious risk of bias, inconsistency and precision). Time (days) spent in the NICU was not reported. Oral stimulation may reduce the duration of hospitalisation (MD -6.15, 95% CI -8.63 to -3.66 days, 10 studies, 591 infants; I2 =0%, low-certainty evidence due to serious risk of bias). Oral stimulation may have little or no effect on the duration (days) of parenteral nutrition exposure (MD -2.85, 95% CI -6.13 to 0.42, 3 studies, 268 infants; very low-certainty evidence due to serious risk of bias, inconsistency and imprecision). AUTHORS' CONCLUSIONS: There remains uncertainty about the effects of oral stimulation (versus either standard care or a non-oral intervention) on transition times to oral feeding, duration of intensive care stay, hospital stay, or exposure to parenteral nutrition for preterm infants. Although we identified 28 eligible trials in this review, only 18 provided data for meta-analyses. Methodological weaknesses, particularly in relation to allocation concealment and masking of study personnel and caregivers, inconsistency between trials in effect size estimates (heterogeneity), and imprecision of pooled estimates were the main reasons for assessing the evidence as low or very low certainty. More well-designed trials of oral stimulation interventions for preterm infants are warranted. Such trials should attempt to mask caregivers to treatment when possible, paying particular attention to blinding of outcome assessors. There are currently 32 ongoing trials. Outcome measures that reflect improvements in oral motor skill development as well as longer term outcome measures beyond six months of age need to be defined and used by researchers to capture the full impact of these interventions.

Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes.

BACKGROUND: At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable gas exchange. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs. OBJECTIVES: To assess the benefits and harms of an initial sustained lung inflation (SLI) (> 1 second duration) versus standard inflations (≤ 1 second) in newborn infants receiving resuscitation with intermittent PPV. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 3), MEDLINE via PubMed (1966 to 1 April 2019), Embase (1980 to 1 April 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 1 April 2019). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data; and mean standard deviation (SD), and weighted mean difference (WMD) for continuous data. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Ten trials enrolling 1467 infants met our inclusion criteria. Investigators in nine trials (1458 infants) administered sustained inflation with no chest compressions. Use of sustained inflation had no impact on the primary outcomes of this review: mortality in the delivery room (typical RR 2.66, 95% confidence interval (CI) 0.11 to 63.40 (I² not applicable); typical RD 0.00, 95% CI -0.02 to 0.02; I² = 0%; 5 studies, 479 participants); and mortality during hospitalisation (typical RR 1.09, 95% CI 0.83 to 1.43; I² = 42%; typical RD 0.01, 95% CI -0.02 to 0.04; I² = 24%; 9 studies, 1458 participants). The quality of the evidence was low for death in the delivery room because of limitations in study design and imprecision of estimates (only one death was recorded across studies). For death before discharge the quality was moderate: with longer follow-up there were more deaths (n = 143) but limitations in study design remained. Among secondary outcomes, duration of mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37 days, 95% CI -6.31 to -4.43; I² = 95%; 5 studies, 524 participants; low-quality evidence). Heterogeneity, statistical significance, and magnitude of effects of this outcome are largely influenced by a single study at high risk of bias: when this study was removed from the analysis, the size of the effect was reduced (MD -1.71 days, 95% CI -3.04 to -0.39; I² = 0%). Results revealed no differences in any of the other secondary outcomes (e.g. risk of endotracheal intubation outside the delivery room by 72 hours of age (typical RR 0.91, 95% CI 0.79 to 1.04; I² = 65%; 5 studies, 811 participants); risk of surfactant administration during hospital admission (typical RR 0.99, 95% CI 0.91 to 1.08; I² = 0%; 9 studies, 1458 participants); risk of chronic lung disease (typical RR 0.99, 95% CI 0.83 to 1.18; I² = 0%; 4 studies, 735 participants); pneumothorax (typical RR 0.89, 95% CI 0.57 to 1.40; I² = 34%; 8 studies, 1377 infants); or risk of patent ductus arteriosus requiring pharmacological treatment (typical RR 0.99, 95% CI 0.87 to 1.12; I² = 48%; 7 studies, 1127 infants). The quality of evidence for these secondary outcomes was moderate (limitations in study design ‒ GRADE) except for pneumothorax (low quality: limitations in study design and imprecision of estimates ‒ GRADE). We could not perform any meta-analysis in the comparison of the use of initial sustained inflation versus standard inflations in newborns receiving resuscitation with chest compressions because we identified only one trial for inclusion (a pilot study of nine preterm infants). AUTHORS' CONCLUSIONS: Our meta-analysis of nine studies shows that sustained lung inflation without chest compression was not better than intermittent ventilation for reducing mortality in the delivery room (low-quality evidence ‒ GRADE) or during hospitalisation (moderate-quality evidence ‒ GRADE), which were the primary outcomes of this review. However, the single largest study, which was well conducted and had the greatest number of enrolled infants, was stopped early for higher mortality rate in the sustained inflation group. When considering secondary outcomes, such as rate of intubation, rate or duration of respiratory support, or bronchopulmonary dysplasia, we found no benefit of sustained inflation over intermittent ventilation (moderate-quality evidence ‒ GRADE). Duration of mechanical ventilation was shortened in the SLI group (low-quality evidence ‒ GRADE); this result should be interpreted cautiously, however, as it might have been influenced by study characteristics other than the intervention. There is no evidence to support the use of sustained inflation based on evidence from our review.

Needle aspiration versus intercostal tube drainage for pneumothorax in the newborn.

BACKGROUND: Pneumothorax occurs more frequently in the neonatal period than at any other time of life and is associated with increased mortality and morbidity. It can be treated with either aspiration with a syringe (using a needle or an angiocatheter) or a chest tube inserted in the anterior pleural space and then connected to a Heimlich valve or an underwater seal with continuous suction. OBJECTIVES: To compare the efficacy and safety of needle aspiration (either with immediate removal of the needle or with the needle left in situ) to intercostal tube drainage in the management of neonatal pneumothorax (PTX). SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE via PubMed (1966 to 4 June 2018), Embase (1980 to 4 June 2018), and CINAHL (1982 to 4 June 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials, quasi-randomised controlled trials and cluster trials comparing needle aspiration (either with the needle or angiocatheter left in situ or removed immediately after aspiration) to intercostal tube drainage in newborn infants with pneumothorax. DATA COLLECTION AND ANALYSIS: For each of the included trials, two authors independently extracted data (e.g. number of participants, birth weight, gestational age, kind of needle and chest tube, choice of intercostal space, pressure and device for drainage) and assessed the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcomes considered in this review are mortality during the neonatal period and during hospitalisation.We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Two randomised controlled trials (142 infants) met the inclusion criteria of this review. We found no differences in the rates of mortality when the needle was removed immediately after aspiration (risk ratio (RR) 3.92, 95% confidence interval (CI) 0.88 to 17.58; participants = 70; studies = 1) or left in situ (RR 1.50, 95% CI 0.27 to 8.45; participants = 72; studies = 1) or complications related to the procedure. With immediate removal of the needle following aspiration, 30% of the newborns did not require the placement of an intercostal tube drainage. None of the 36 newborns treated with needle aspiration with the angiocatheter left in situ required the placement of an intercostal tube drainage. Overall, the quality of the evidence supporting this finding is very low. AUTHORS' CONCLUSIONS: There is insufficient evidence to establish the efficacy and safety of needle aspiration and intercostal tube drainage in the management of neonatal pneumothorax. The two included trials showed no differences in mortality; however the information size is low. Needle aspiration reduces the need for intercostal tube drainage placement. Limited or no evidence is available on other clinically relevant outcomes.

Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes.

BACKGROUND: At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable effective breathing. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs. OBJECTIVES: To assess the efficacy of an initial sustained (> 1 second duration) lung inflation versus standard inflations (≤ 1 second) in newly born infants receiving resuscitation with intermittent PPV. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1), MEDLINE via PubMed (1966 to 17 February 2017), Embase (1980 to 17 February 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 17 February 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and weighted mean difference (WMD) for continuous data. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. MAIN RESULTS: Eight trials enrolling 941 infants met our inclusion criteria. Investigators in seven trials (932 infants) administered sustained inflation with no chest compressions. Use of sustained inflation had no impact on the primary outcomes of this review - mortality in the delivery room (typical RR 2.66, 95% confidence interval (CI) 0.11 to 63.40; participants = 479; studies = 5; I² not applicable) and mortality during hospitalisation (typical RR 1.01, 95% CI 0.67 to 1.51; participants = 932; studies = 7; I² = 19%); the quality of the evidence was low for death in the delivery room (limitations in study design and imprecision of estimates) and was moderate for death before discharge (limitations in study design of most included trials). Amongst secondary outcomes, duration of mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37 days, 95% CI -6.31 to -4.43; participants = 524; studies = 5; I² = 95%; low-quality evidence). Heterogeneity, statistical significance, and magnitude of effects of this outcome are largely influenced by a single study: When this study was removed from the analysis, the effect was largely reduced (MD -1.71 days, 95% CI -3.04 to -0.39, I² = 0%). Results revealed no differences in any of the other secondary outcomes (e.g. rate of endotracheal intubation outside the delivery room by 72 hours of age (typical RR 0.93, 95% CI 0.79 to 1.09; participants = 811; studies = 5; I² = 0%); need for surfactant administration during hospital admission (typical RR 0.97, 95% CI 0.86 to 1.10; participants = 932; studies = 7; I² = 0%); rate of chronic lung disease (typical RR 0.95, 95% CI 0.74 to 1.22; participants = 683; studies = 5; I² = 47%); pneumothorax (typical RR 1.44, 95% CI 0.76 to 2.72; studies = 6, 851 infants; I² = 26%); or rate of patent ductus arteriosus requiring pharmacological treatment (typical RR 1.08, 95% CI 0.90 to 1.30; studies = 6, 745 infants; I² = 36%). The quality of evidence for these secondary outcomes was moderate (limitations in study design of most included trials - GRADE) except for pneumothorax (low quality: limitations in study design and imprecision of estimates - GRADE). AUTHORS' CONCLUSIONS: Sustained inflation was not better than intermittent ventilation for reducing mortality in the delivery room and during hospitalisation. The number of events across trials was limited, so differences cannot be excluded. When considering secondary outcomes, such as need for intubation, need for or duration of respiratory support, or bronchopulmonary dysplasia, we found no evidence of relevant benefit for sustained inflation over intermittent ventilation. The duration of mechanical ventilation was shortened in the SLI group. This result should be interpreted cautiously, as it can be influenced by study characteristics other than the intervention. Future RCTs should aim to enrol infants who are at higher risk of morbidity and mortality, should stratify participants by gestational age, and should provide more detailed monitoring of the procedure, including measurements of lung volume and presence of apnoea before or during the SLI.

Frenotomy for tongue-tie in newborn infants.

BACKGROUND: Tongue-tie, or ankyloglossia, is a condition whereby the lingual frenulum attaches near the tip of the tongue and may be short, tight and thick. Tongue-tie is present in 4% to 11% of newborns. Tongue-tie has been cited as a cause of poor breastfeeding and maternal nipple pain. Frenotomy, which is commonly performed, may correct the restriction to tongue movement and allow more effective breastfeeding with less maternal nipple pain. OBJECTIVES: To determine whether frenotomy is safe and effective in improving ability to feed orally among infants younger than three months of age with tongue-tie (and problems feeding).Also, to perform subgroup analysis to determine the following.• Severity of tongue-tie before frenotomy as measured by a validated tool (e.g. Hazelbaker Assessment Tool for Lingual Frenulum Function (ATLFF) scores < 11; scores ≥ 11) (Hazelbaker 1993).• Gestational age at birth (< 37 weeks' gestation; 37 weeks' gestation and above).• Method of feeding (breast or bottle).• Age at frenotomy (≤ 10 days of age; > 10 days to three months of age).• Severity of feeding difficulty (infants with feeding difficulty affecting weight gain (as assessed by infant's not regaining birth weight by day 14 or falling off centiles); infants with symptomatic feeding difficulty but thriving (greater than birth weight by day 14 and tracking centiles). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and CINAHL up to January 2017, as well as previous reviews including cross-references, expert informants and journal handsearching. We searched clinical trials databases for ongoing and recently completed trials. We applied no language restrictions. SELECTION CRITERIA: Randomised, quasi-randomised controlled trials or cluster-randomised trials that compared frenotomy versus no frenotomy or frenotomy versus sham procedure in newborn infants. DATA COLLECTION AND ANALYSIS: Review authors extracted from the reports of clinical trials data regarding clinical outcomes including infant feeding, maternal nipple pain, duration of breastfeeding, cessation of breastfeeding, infant pain, excessive bleeding, infection at the site of frenotomy, ulceration at the site of frenotomy, damage to the tongue and/or submandibular ducts and recurrence of tongue-tie. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Five randomised trials met our inclusion criteria (n = 302). Three studies objectively measured infant breastfeeding using standardised assessment tools. Pooled analysis of two studies (n = 155) showed no change on a 10-point feeding scale following frenotomy (mean difference (MD) -0.1, 95% confidence interval (CI) -0.6 to 0.5 units on a 10-point feeding scale). A third study (n = 58) showed objective improvement on a 12-point feeding scale (MD 3.5, 95% CI 3.1 to 4.0 units of a 12-point feeding scale). Four studies objectively assessed maternal pain. Pooled analysis of three studies (n = 212) based on a 10-point pain scale showed a reduction in maternal pain scores following frenotomy (MD -0.7, 95% CI -1.4 to -0.1 units on a 10-point pain scale). A fourth study (n = 58) also showed a reduction in pain scores on a 50-point pain scale (MD -8.6, 95% CI -9.4 to -7.8 units on a 50-point pain scale). All studies reported no adverse effects following frenotomy. These studies had serious methodological shortcomings. They included small sample sizes, and only two studies blinded both mothers and assessors; one did not attempt blinding for mothers nor for assessors. All studies offered frenotomy to controls, and most controls underwent the procedure, suggesting lack of equipoise. No study was able to report whether frenotomy led to long-term successful breastfeeding. AUTHORS' CONCLUSIONS: Frenotomy reduced breastfeeding mothers' nipple pain in the short term. Investigators did not find a consistent positive effect on infant breastfeeding. Researchers reported no serious complications, but the total number of infants studied was small. The small number of trials along with methodological shortcomings limits the certainty of these findings. Further randomised controlled trials of high methodological quality are necessary to determine the effects of frenotomy.

Oral stimulation for promoting oral feeding in preterm infants.

BACKGROUND: Preterm infants (< 37 weeks' postmenstrual age) are often delayed in attaining oral feeding. Normal oral feeding is suggested as an important outcome for the timing of discharge from the hospital and can be an early indicator of neuromotor integrity and developmental outcomes. A range of oral stimulation interventions may help infants to develop sucking and oromotor co-ordination, promoting earlier oral feeding and earlier hospital discharge. OBJECTIVES: To determine the effectiveness of oral stimulation interventions for attainment of oral feeding in preterm infants born before 37 weeks' postmenstrual age (PMA).To conduct subgroup analyses for the following prespecified subgroups.• Extremely preterm infants born at < 28 weeks' PMA.• Very preterm infants born from 28 to < 32 weeks' PMA.• Infants breast-fed exclusively.• Infants bottle-fed exclusively.• Infants who were both breast-fed and bottle-fed. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed (1966 to 25 February 2016), Embase (1980 to 25 February 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 25 February 2016). We searched clinical trials databases, conference proceedings and the reference lists of retrieved articles. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing a defined oral stimulation intervention with no intervention, standard care, sham treatment or non-oral intervention in preterm infants and reporting at least one of the specified outcomes. DATA COLLECTION AND ANALYSIS: One review author searched the databases and identified studies for screening. Two review authors screened the abstracts of these studies and full-text copies when needed to identify trials for inclusion in the review. All review authors independently extracted the data and analysed each study for risk of bias across the five domains of bias. All review authors discussed and analysed the data and used the GRADE system to rate the quality of the evidence. Review authors divided studies into two groups for comparison: intervention versus standard care and intervention versus other non-oral or sham intervention. We performed meta-analysis using a fixed-effect model. MAIN RESULTS: This review included 19 randomised trials with a total of 823 participants. Almost all included trials had several methodological weaknesses. Meta-analysis showed that oral stimulation reduced the time to transition to oral feeding compared with standard care (mean difference (MD) -4.81, 95% confidence interval (CI) -5.56 to -4.06 days) and compared with another non-oral intervention (MD -9.01, 95% CI -10.30 to -7.71 days), as well as the duration of initial hospitalisation compared with standard care (MD -5.26, 95% CI -7.34 to -3.19 days) and compared with another non-oral intervention (MD -9.01, 95% CI -10.30 to -7.71 days).Investigators reported shorter duration of parenteral nutrition for infants compared with standard care (MD -5.30, 95% CI -9.73 to -0.87 days) and compared with another non-oral intervention (MD -8.70, 95% CI -15.46 to -1.94 days). They could identify no effect on breast-feeding outcomes nor on weight gain. AUTHORS' CONCLUSIONS: Although the included studies suggest that oral stimulation shortens hospital stay, days to exclusive oral feeding and duration of parenteral nutrition, one must interpret results of these studies with caution, as risk of bias and poor methodological quality are high overall. Well-designed trials of oral stimulation interventions for preterm infants are warranted. Such trials should use reliable methods of randomisation while concealing treatment allocation, blinding caregivers to treatment when possible and paying particular attention to blinding of outcome assessors.

High flow nasal cannula for respiratory support in preterm infants.

BACKGROUND: High flow nasal cannulae (HFNC) are small, thin, tapered cannulae used to deliver oxygen or blended oxygen and air at flow rates of > 1 L/min. HFNC can be used to provide high concentrations of oxygen and may deliver positive end-expiratory pressure. OBJECTIVES: To compare the safety and efficacy of HFNC with other forms of non-invasive respiratory support in preterm infants. SEARCH STRATEGY: The strategy included searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010), MEDLINE, CINAHL, EMBASE and abstracts from conference proceedings. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing HFNC with other non-invasive forms of respiratory support in preterm infants immediately after birth or following extubation. DATA COLLECTION AND ANALYSIS: Data were extracted and analysed by the authors. Relative risk, risk difference and number needed to treat were calculated. MAIN RESULTS: Four studies were identified for inclusion in the review. The studies differed in the interventions compared (nasal continuous positive airway pressure (CPAP), humidified HFNC, non-humidified HFNC), the flow rates provided and the indications for respiratory support. Meta-analysis and subgroup analysis were not possible. When used as primary respiratory support after birth, one trial found similar rates of treatment failure in infants treated with HFNC and nasal CPAP. Following extubation, one trial found that infants treated with HFNC had a significantly higher rate of reintubation than those treated with nasal CPAP. Another trial found similar rates of reintubation for humidified and non-humidified HFNC, and the fourth trial found no difference between two different models of equipment used to deliver humidified HFNC. AUTHORS' CONCLUSIONS: There is insufficient evidence to establish the safety or effectiveness of HFNC as a form of respiratory support in preterm infants. When used following extubation, HFNC may be associated with a higher rate of reintubation than nasal CPAP. Further adequately powered randomised controlled trials should be undertaken in preterm infants comparing HFNC with nasal CPAP and with other means of respiratory support; or of support following extubation. These trials should measure clinically important outcomes.