Tracheal suction at birth in non‐vigorous neonates born through meconium‐stained amniotic fluid
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To evaluate the efficacy of tracheal suctioning at birth in preventing meconium aspiration syndrome and other complications among non‐vigorous neonates born through meconium‐stained amniotic fluid.
Background
Description of the condition
Meconium is found in the gastrointestinal tract of the fetus as early as 14 to 16 weeks' gestation. It is a complex substance, composed of water (nearly 75%), gastric secretions, lanugo, blood, pancreatic enzymes, free fatty acids, and squamous cells (Wiswell 1993; Wiswell 1999). It accumulates in the gastrointestinal tract of the fetus throughout pregnancy and usually is first passed within 24 hours after birth. Factors that prevent meconium passage in utero include a viscous terminal cap, a contracted anal sphincter, and absence of propulsive forces. However, meconium passage may occur in utero in post‐term pregnancies and in response to fetal hypoxia, acidemia, or infection (Miller 1981; Usher 1988).
Once passed, meconium may be aspirated from amniotic fluid into the distal airways either in utero or with the first few breaths after birth. Breathing movements are observed in utero but are shallow. Therefore, amniotic fluid is not drawn into the distal airway; rather, the net flow of alveolar lung fluid moves outward. Fetal distress due to hypoxia or ischemia may induce deep gasping efforts, resulting in aspiration of amniotic fluid containing meconium. Aspiration of meconium can cause airway obstruction, alveolar collapse, ventilation‐perfusion mismatch, and chemical pneumonitis (Tyler 1978).
Nearly 10% to 25% of births are complicated by meconium passage before birth (Wiswell 1993; Wiswell 1999). Among the total births complicated by meconium passage, 5% to 12% of neonates develop meconium aspiration syndrome (Berkus 1994; Carson 1976). Meconium aspiration syndrome (MAS) is diagnosed in a neonate who is born through meconium‐stained amniotic fluid (MSAF), who develops respiratory distress shortly after birth, and whose symptoms cannot be otherwise explained (Fanaroff 2008). Meconium aspiration syndrome can present with varying degrees of severity, from mild distress to life‐threatening respiratory failure. The incidence of MAS is lower among preterm neonates (Tybulewicz 2004). International Liaison Committee on Resuscitation (ILCOR) guidelines for treatment of neonates born through meconium‐stained amniotic fluid do not differentiate between term and preterm neonates (Wyckoff 2015).
Description of the intervention
A combined obstetric and neonatal approach that aims to clear meconium from the upper airway before it can be aspirated with the infant's first breaths has been widely adopted and became part of neonatal resuscitation guidelines after it was shown to be effective in reducing the incidence of death and MAS in a cohort study (Carson 1976). The first component of this approach ‐ intrapartum suctioning of the oropharynx and nasopharynx after delivery of the head but before delivery of the shoulders and chest (Carson 1976) ‐ was removed from the guidelines after a large randomized controlled trial (RCT) reported no reduction in the incidence of MAS (Vain 2004). The second neonatal portion of this combined approach consists of direct laryngoscopic visualization of vocal cords, intubation, and endotracheal suctioning. A large RCT (Wiswell 2000) and a subsequent systematic review (Haliday 2001) revealed that routine intubation and endotracheal suctioning are ineffective in reducing the incidence of MAS if the neonate is not depressed (or is vigorous) at birth. However, evidence is insufficient to support or refute intubation and endotracheal suctioning immediately after birth for non‐vigorous neonates (defined by ILCOR Neonatal Resuscitation Program (NRP) guidelines as the presence of any of the following at the time of birth: no or gasping breathing efforts, poor muscle tone, or bradycardia (heart rate < 100 beats per minute)) (Wyckoff 2015). For a non‐vigorous infant, the upper airways are suctioned and cleared of meconium; an endotracheal tube then is passed through the vocal cords and pulled out while the trachea is being suctioned. If meconium is aspirated from the trachea, the procedure is repeated until meconium is cleared or severe bradycardia ensues.
How the intervention might work
Neonates born through MSAF are often depressed and need prompt resuscitation. With the start of breathing efforts, meconium present in the upper airways and trachea can move into the distal airways, resulting in MAS. Clearance of meconium from the airways before the start of breathing may decrease the risk of MAS.
Why it is important to do this review
Observational studies evaluating the effectiveness of immediate tracheal suctioning have described variable results, with some studies suggesting decreased likelihood of respiratory complications (Gregory 1974; Suresh 1994) after endotracheal suctioning, and others suggesting no difference (Daga 1974) or increased risk (Linder 1988; Yoder 1994). Although a large RCT has demonstrated the futility of tracheal suctioning for preventing MAS in vigorous neonates (Wiswell 2000), no similar conclusive evidence has been found for non‐vigorous neonates. After examining the evidence for prevention of MAS, ILCOR concluded in 2010 that available evidence neither supports nor refutes endotracheal suctioning of depressed infants born through MSAF (Perlman 2010).
Clearing of the larger airways before meconium can be aspirated distally into the lungs with the first few breaths seems a logical step in neonatal resuscitation. However, this intervention would be futile if deep gasping efforts, which usually precede the apnea, have already resulted in aspiration of meconium in utero. Time taken to intubate and perform tracheal suctioning can delay resuscitation and further aggravate hypoxic‐ischemic injury. This issue is of special relevance for low‐ and middle‐income countries, where most of these births take place. The incidence of MSAF and MAS remains high, but a nurse or physician with the skills needed for endotracheal intubation and tracheal suctioning may not be available for every delivery (Chettri S 2015). A meta‐analysis of trials evaluating endotracheal intubation at birth for prevention of morbidity and mortality in vigorous neonates born through meconium‐stained amniotic fluid does not support routine use of endotracheal intubation to reduce mortality, MAS, or other respiratory symptoms or disorders (Haliday 2001). No published systematic review has evaluated trials examining endotracheal intubation at birth for prevention of morbidity and mortality among non‐vigorous neonates born through meconium‐stained amniotic fluid.
Objectives
To evaluate the efficacy of tracheal suctioning at birth in preventing meconium aspiration syndrome and other complications among non‐vigorous neonates born through meconium‐stained amniotic fluid.
Methods
Criteria for considering studies for this review
Types of studies
The review will include randomized controlled clinical trials and cluster‐randomized trials comparing tracheal suction with no tracheal suction at birth in non‐vigorous neonates born through MSAF. We will apply no language or sex restrictions. Trials reported in abstract form will be eligible for inclusion if methods are reported that allow assessment of eligibility for inclusion and risk of bias. We will exclude cross‐over trials.
Types of participants
The review will include studies enrolling neonates born at term or at late preterm gestation.
Eligible studies should enroll non‐vigorous neonates born through MSAF. Studies may show some variation in the way they define “non‐vigorous.” Most studies are likely to define non‐vigorous as per ILCOR/NRP guidelines, as "presence of any of the following at the time of birth: no or gasping breathing efforts, poor muscle tone or bradycardia" (Wyckoff 2015). During the review, we will note variations in the definition, should they occur.
Types of interventions
The intervention will consist of tracheal suction of enrolled neonates at the time of birth with intent to clear the trachea of meconium before regular breathing efforts begin. Tracheal suction can be performed with an endotracheal tube or a wide‐gauge suction catheter. We will not consider suction of the upper airway (above the vocal cords) alone as an intervention. Neonates in the control group should have been resuscitated at birth with no effort made to clear the trachea of meconium. Neonates undergoing suction of the oropharynx or the nasopharynx or both without tracheal suction will belong to the control group.
Types of outcome measures
Primary outcomes
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Incidence of meconium aspiration syndrome (proportion). Meconium aspiration syndrome is diagnosed when respiratory distress develops soon after birth in an infant born through meconium‐stained amniotic fluid with compatible radiological findings that cannot be otherwise explained
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Incidence of all‐cause neonatal mortality (proportion) defined as all‐cause neonatal death (death before 28 days)
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Incidence of hypoxic‐ischemic encephalopathy (proportion) (Sarnat 1976; Thompson 1997)
Secondary outcomes
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Need for mechanical ventilation (proportion) defined as the need for mechanical ventilation (proportion) during the first 48 hours after birth
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Duration of oxygen therapy (hours/days) defined as the number of days of oxygen supplementation during hospital stay
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Duration of mechanical ventilation (hours/days) defined as the number of days of mechanical ventilation (invasive or non‐invasive) during the hospital stay
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Need for non‐invasive ventilation (proportion)
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Incidence of pulmonary air leaks (proportion) defined as the proportion such as pulmonary interstitial emphysema, pneumothorax, pneumomediastinum, or pneumopericardium during hospital stay
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Duration of hospitalization (days)
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Incidence of neurodevelopmental delay (proportion) defined as the incidence of major neurodevelopmental disability at > 18 months (major neurodevelopmental disabilities among all participants or survivors (cerebral palsy, developmental delay (Bayley or Griffith assessment > 2 standard deviations (SD) below the mean) or intellectual impairment (IQ > 2 SD below the mean), blindness (vision < 6/ 60 in both eyes), or sensorineural deafness requiring amplification)
Search methods for identification of studies
We will use criteria and standard methods of Cochrane and the Cochrane Neonatal Review Group (see the Cochrane Neonatal search strategy for specialized register).
Electronic searches
We will conduct a comprehensive search that includes the Cochrane Central Register of Controlled Trials (CENTRAL; current issue) in the Cochrane Library; MEDLINE via PubMed (1996 to current); Embase (1980 to current); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to current) using the following search terms: (meconium OR MSAF OR MAS) AND (endotracheal OR tracheal OR suction* OR intubation), plus database‐specific limiters for RCTs and neonates (see Appendix 1 for the full search strategy for each database). We will not apply language restrictions and will search clinical trials registries for ongoing and recently completed trials (clinicaltrials.gov; the World Health Organization International Trials Registry and Platform (www.whoint/ictrp/search/en/); and the ISRCTN Registry).
Searching other resources
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Reference lists from the above sources and from review articles
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Personal communication with primary authors from the above sources to retrieve unpublished data related to published articles
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Proceedings of annual meetings of the European Society for Pediatric Research and from the Society for Pediatric Research and Pediatric Academic Societies Annual Meeting. These are available at Abstracts2view from the year 2000 onward, up to and including 2015
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Proceedings of the Perinatal Society of Australia and New Zealand (PSANZ)
Data collection and analysis
We will use the standard methods of Cochrane and its Neonatal Review Group.
Selection of studies
All three review authors will independently identify studies for inclusion.
Data extraction and management
Two review authors will independently extract data from these studies using a pretested data extraction form. These review authors will resolve disagreements by discussion and will defer to the third review author if no agreement is reached.
Assessment of risk of bias in included studies
Two review authors will independently assess the risk of bias (low, high, or unclear) of all included trials using the Cochrane "Risk of bias" tool (Higgins 2011) for the following domains.
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Sequence generation (selection bias).
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Allocation concealment (selection bias).
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Blinding of participants and personnel (performance bias).
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Blinding of outcome assessment (detection bias).
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Incomplete outcome data (attrition bias).
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Selective reporting (reporting bias).
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Any other bias.
We will resolve disagreements by discussion or will consult with a third assessor. See Appendix 2 for a more detailed description of risk of bias for each domain.
Measures of treatment effect
For dichotomous data, we will calculate relative risk (RR), risk difference (RD), number needed to treat for an additional beneficial outcome (NNTB), and number needed to treat for an additional harmful outcome (NNTH), along with 95% confidence intervals (CIs). We will analyse continuous data using the standardized mean difference (SMD).
Unit of analysis issues
We will compare non‐vigorous neonates born through meconium‐stained amniotic fluid who underwent endotracheal suction versus those who did not receive endotracheal suction. We will not include repeated measurements in a group or measurements done in a cross‐over design. The review will include randomized controlled clinical trials and cluster‐randomized trials that compare tracheal suction with no tracheal suction at birth in non‐vigorous neonates born through MSAF. We will use the inverse variance method (IVM) by analysing the effect estimate from each individual cluster trial. We will calculate standard errors. We will provide in an additional table actual data used in analysis (numerators and denominators, or means and SDs) for each treatment group. We will not perform combined meta‐analysis of cluster and non‐cluster trials.
Dealing with missing data
In cases of missing data, we will contact original investigators and will request that they provide the data if feasible.
Assessment of heterogeneity
We will examine heterogeneity between trials first by assessing differences in trial methods and clinical heterogeneity. We shall use cut‐offs and labels for results of the I2 test: < 25% none, 25% to 49% low, 50% to 74% moderate, and ≥ 75% high heterogeneity. We will inspect forest plots and will quantify the impact of heterogeneity by using the I2 statistic. If we note heterogeneity, we plan to explore possible causes of statistical heterogeneity by performing prespecified subgroup analysis (e.g. differences in study quality, participants, intervention regimens, outcome assessments). We will use a fixed‐effect model for meta‐analyses.
Assessment of reporting biases
We will use funnel plots to assess for publication bias if we can include at least ten trials in the meta‐analysis.
Data synthesis
For dichotomous outcomes, we will use relative risk (RR) and risk difference (RD) with 95% confidence intervals (CIs). If the RD is significant, we will report the typical number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH). We will use weighted mean difference with 95% CIs for continuous outcomes.
Quality of evidence
The quality of evidence reflects the extent to which we are confident that an estimate of the effect is correct.
We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, as outlined in the GRADE Handbook (Schünemann 2013), to assess the quality of evidence for the following (clinically relevant) outcomes: meconium aspiration syndrome, need for mechanical ventilation, all‐cause neonatal mortality, incidence of pulmonary air leaks, duration of hospitalization, incidence of neurodevelopmental delay, and incidence of hypoxic‐ischemic encephalopathy. We will consider any important efficacy or safety outcomes that emerge from the review post hoc.
Two review authors will independently assess the quality of the evidence for each of the outcomes above. We will consider evidence from RCTs as high quality but will downgrade the evidence one level for serious (or two levels for very serious) limitations on the basis of the following: design (risk of bias), consistency across studies, directness of the evidence, precision of estimates, and presence of publication bias. We will use the GRADEpro 2008 Guideline Development Tool to create a "Summary of findings" table to report the quality of the evidence.
The GRADE approach results in an assessment of the quality of a body of evidence according to four grades.
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High: We are very confident that the true effect lies close to the estimate of effect.
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Moderate: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of effect but may be substantially different.
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Low: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of effect.
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Very low: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
Subgroup analysis and investigation of heterogeneity
We have planned subgroup analyses to consider:
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gestational age (GA) at birth: term neonates (≥ 37 weeks' GA) and late preterm neonates (34 to 36 weeks' GA);
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meconium consistency: "thick" (if the fluid was viscous and tenacious and contained large amounts of particulate material), "moderate" (if the fluid was thicker and darker in color), or "thin" (if fluid was normal except for greenish coloring);
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setting: low‐ and middle‐income countries;
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type of suctioning: endotracheal and wide‐gauge suction catheter; and
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type of delivery: vaginal versus caesarean section.
Sensitivity analysis
We will perform sensitivity analyses to test the robustness of decisions if we identify a sufficient number of trials. We will perform a sensitivity analysis to determine if findings were affected by inclusion limited to studies using adequate methods, defined as adequate randomization and allocation concealment, blinding of intervention and measurement, and less than 10% loss to follow‐up.
