Article Text
Abstract
Objective To evaluate the efficacy and safety of gastric lavage (GL) in neonates born through meconium-stained liquor (MSL).
Design A systematic review of randomised controlled trials by searching databases MEDLINE (from 1966), EMBASE (from1980), CINAHL, Cochrane Central Register of Controlled Trials, Google Scholar and proceedings of Pediatric Academic Society meetings (2002–2014).
Setting Delivery room/Neonatal ward.
Patients Neonates with gestation >34 weeks and birth weight ≥1800 g born through MSL.
Interventions Prophylactic GL versus no intervention before first feed.
Main outcome measure Feeding intolerance, defined as inability to initiate/upgrade feeds due to problems such as retching, vomiting, regurgitation and gastric residuals.
Results A total of six studies (GL: 918, no GL: 966) were included in the review. Meta-analysis using fixed-effects model showed decreased incidence of feed intolerance following GL ((81/918 (8.8%) vs 114/966 (11.8%); risk ratio (RR): 0.71 (95% CI 0.55 to 0.93)). However, the results were not significant when random-effects model was used (RR: 0.78 (95% CI 0.55 to 1.09)). No significant adverse effects of GL were reported.
Conclusions Routine GL immediately after birth may improve feed tolerance in neonates born through MSL. However, the evidence is limited, with probable small-study bias and high risk of bias in a number of the included studies. Well-designed studies with adequate sample size are essential to confirm these findings.
- Neonatology
- Nursing Care
- Nutrition
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What is already known on this topic?
Gastric lavage (GL) is used in many neonatal units to prevent feed intolerance (FI) in neonates born through meconium-stained liquor (MSL).
What this study adds?
This systematic review of randomised controlled trial indicates that prophylactic GL may prevent FI in neonates born through MSL.
Further studies are needed considering the limitations of the evidence, including small sample size and high risk of bias in included studies.
Background
Meconium-stained liquor (MSL) occurs in up to 15–20% of term and over 30% of post-term pregnancies.1 ,2 The presence of meconium in the stomach has been proposed to act as a chemical irritant, causing vomiting, retching and feed intolerance (FI).3 Regardless of the consistency of meconium, FI is almost three times more frequent in neonates born through MSL than those born without it.3 FI can result in hypoglycaemia, delayed establishment of breast feeds, need for parenteral fluids and increased risk of infections. Gastric lavage (GL) may theoretically benefit these infants by removing the irritant meconium.
However, GL may not be without complications. It may result in bradycardia, apnoea, vomiting, aspiration, upper airway and oesophageal damage and elevation of blood pressure.4–7 Apart from disturbing the normal prefeeding behaviour, GL might delay the initiation of breast feeding.6 A recent randomised controlled trial (RCT) found that routine gastric aspiration in the delivery room for healthy term neonates was associated with an increase in respiratory distress and transient increase in systolic and mean blood pressure at 5 min.7 To our knowledge, there are no systematic reviews addressing the efficacy and safety of GL in neonates born through MSL. Considering the potential benefits and risks of GL in MSL, we aimed to conduct a systematic review of RCTs comparing GL versus no intervention in neonates born through MSL, but otherwise healthy.
Methods
The Cochrane Collaboration methods were used for performing,8 and PRISMA (transparent reporting of systematic reviews and meta-analyses) guidelines were used for reporting this systematic review.9 Ethics approval was not required.
Eligibility criteria
Types of studies: RCTs and quasi-RCTs were eligible for inclusion. Case–control, cohort studies, case reports/series, review articles and commentaries were excluded, but read to identify other potential studies.
Participants: Inclusion criteria: Healthy neonates >34 weeks and weight >1800 g born through MSL.
Exclusion criteria: Gestation ≤34 weeks, major chromosomal/congenital anomalies.
Types of interventions: GL (irrespective of type of fluid and volume) versus no GL (or other intervention) before the first feed.
Primary outcome: Feeding intolerance was defined as inability to initiate and upgrade feeds (breast feeds/formula) due to problems such as retching, vomiting, regurgitation or gastric residuals.
Secondary outcomes: (1) adverse effects (eg, apnoea, bradycardia), (2) secondary aspiration, (3) duration of hospital stay and (4) mortality.
Search strategy: Databases MEDLINE (from 1966), EMBASE (from1980), CINAHL and Cochrane Central Register of Controlled Trials were searched in December 2014 for published studies using the following search terms: (1) Neonate(s), newborn(s), infant, (2) Meconium (subject heading) OR meconium*, (3) Gastric lavage (subject heading) OR gastric suction and (4) Feed*, vomiting.
We restricted our search to publication type ‘Randomized controlled Trial, ‘Controlled Trial’ or ‘Clinical Trial’. Online abstracts of Pediatric Academic Society (PAS) meetings were reviewed from 2002. Abstracts of other conference proceedings such as Perinatal Society of Australia and New Zealand (PSANZ), European Academy of Paediatric Societies and the British Maternal and Fetal Medicine Society were searched in EMBASE. ‘Google Scholar’ was searched for articles that might not have been cited in the standard medical databases. The reference lists of identified studies and review articles were searched to identify additional eligible studies. We also searched http://www.clinicaltrials.gov for ongoing studies. No language restriction was applied. Reviewers MD and HB conducted the literature search independently.
Study selection: The abstracts of the citations obtained from the initial broad search were read independently by two reviewers (MD and HB) to identify potentially eligible studies. Full-text articles of these studies were obtained and assessed for eligibility by two reviewers independently (MD and HB), using the predefined eligibility criteria. Differences in opinion were resolved by group discussion among all reviewers to reach consensus. Care was taken to ensure that multiple publications of the same study were identified and excluded to avoid duplication of the data.
Data extraction: Reviewers MD and HB extracted the data independently, using a data collection form designed for this review. For dichotomous outcomes, the number of patients with the event and the number of patients analysed in each treatment group of each trial were entered into the form. For continuous outcomes, we planned to enter the mean and SDs. Information about study design and outcomes was verified by all reviewers. Discrepancies during the data extraction process were resolved by discussion and consensus among all reviewers. We contacted authors for additional information/clarifications when details were not available in published manuscripts.
Risk of bias assessment: Risk of bias (ROB) was assessed using the Cochrane ‘Risk of Bias Assessment Tool’.10 Two authors (MD and HB) independently assessed the ROB in the domains of random number generation, allocation concealment, blinding of participants and outcome assessors, completeness of follow-up, selective reporting and other biases. The ROB for each of these domains was assigned as of high, low or unclear. Differences of opinion were resolved by group discussion among all reviewers and consensus.
Data synthesis: Meta-analysis was conducted using Review Manager 5.3 (Cochrane Collaboration, Nordic Cochrane Centre), with ‘intention to treat analysis’ of the data. Fixed-effects model (Mantel–Haenszel method) was used since there was no clinical heterogeneity. However, analysis using random-effects model was also conducted to ensure that the results and conclusions were not influenced by the type of model used for the meta-analysis. Categorical measure of effect size was expressed as risk ratio (RR) and 95% CI. Statistical heterogeneity was assessed using the χ2 test, I2 statistic and by visual inspection of the forest plot (overlap of CIs). Sensitivity analysis was conducted separately for studies with low ROB for the domains of random sequence generation and allocation concealment separately. The risk of publication bias was to be assessed by visual inspection of the funnel plot.11
Summary of findings table: The key information concerning the quality of evidence, the magnitude of effect of the intervention and the sum of available data on the main outcomes are presented in the ‘summary of findings table’ as per the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) guidelines.12
Results
The literature search retrieved 307 potential relevant citations (figure 1). After carefully reviewing the abstracts, 301 studies were excluded (duplicate: 19, reviews: 5, observational study: 1, commentary: 1, GL in healthy term neonates without MSL: 1, breast milk lavage in preterm neonates: 1). Finally, six studies were included in the systematic review. The characteristics of the included studies are described in table 1. Out of the six studies, five used ‘feed intolerance’ as the primary outcome, whereas in the study by Singh et al18 FI was the secondary outcome. GL was administered within 30 min of birth in all studies. The type of fluid used for GL was specified in three studies (normal saline in two studies, 5% dextrose in one study).
Details of included studies
Ameta et al:13 This was a non-blinded, single-centre RCT done in India. Neonates born at >34 weeks of gestation and >1800 g of birth weight were randomised to receive GL at birth or no intervention. GL was given with 10 mL/kg of normal saline. All mothers were advised exclusive breast feeding soon after birth. The primary outcome was FI, defined as two episodes of vomiting within 4 h or three episodes in 24 h, and/or increase in abdominal girth by 2 cm. Secondary outcomes were side effects of GL such as apnoea, bradycardia or any local trauma due to the procedure or secondary respiratory distress due to aspiration of meconium.
Cuello-Garcia et al:14 This was a single-centre RCT done in Mexico. Healthy term neonates weighing between 2500 and 4000 g were randomised to receive GL immediately after delivery with 5% dextrose or no intervention. The primary outcome was FI, defined as vomiting, nausea and breast feed failure in the first 24 h. Secondary outcomes were successful breast feeding, duration of hospital stay and adverse effects related to GL. The authors provided additional information from their study confirming that there were no deaths in either group.
Garg et al:15 It was a single-centre RCT done in India. Neonates >34 weeks and >1800 g born through MSL were randomised to undergo GL in 30 min after delivery or no intervention. GL was done using 10 mL/kg normal saline with aliquots of 5 mL each time. Neonates in the control group were not subjected to lavage. All neonates were exclusively breast fed on demand. The primary outcome was FI, defined as two episodes of vomiting in 4 h or three vomiting in 24 h and or increase in abdominal girth by 2 cm. Secondary outcomes were adverse effects, including secondary respiratory distress, apnoea, bradycardia and any trauma of nasal or oral cavity.
Singh et al:18 This was a single-centre RCT from India. Neonates born >36 weeks gestation were randomised to receive either GL within 15 min of birth or no intervention. Primary outcome was need for subsequent GL within the first 48 h of life. The secondary outcomes were FI, defined as incidence of vomiting, regurgitation in 48 h, need for parenteral fluids in the first 2 days of life, incidence of meconium aspiration syndrome (MAS) and duration of hospital stay.
Narchi and Kulaylat:16 This was the first RCT evaluating the role of GL and was conducted in a single centre in Saudi Arabia. Neonates (>34 weeks) born on even days underwent elective GL within 1 h after birth and before the first feed, while those who were born on odd days underwent GL only when they developed feeding problems. The primary outcome was FI, defined as vomiting, retching, poor feed and slow suck. The authors responded to our request, but expressed their inability to provide additional data.
Sharma et al:17 This was a single-centre RCT from India. Neonates >34 weeks were randomised to undergo GL or no intervention immediately after delivery. GL was undertaken in the labour room after initial stabilisation using 20 mL of normal saline. An attempt was made to remove the entire amount of normal saline that was used for lavage. The primary outcome was feeding problems, defined as retching, vomiting and regurgitation. All mothers were advised to exclusively breast feed their babies. Infants were assessed for feeding difficulties (retching/vomiting) until 48 h of life or until discharge. Secondary outcomes were secondary MAS, defined as the presence of tachypnoea or respiratory distress following any episode of vomiting in a previously well infant with MSL.
ROB of included studies: Four out of the six included studies (66%) were judged to have low ROB for the domain of ‘random sequence generation’. 13 ,14 ,17 ,18 Only 2/6 (33%) were considered to have low risk of bias for ‘allocation concealment’.13 ,17 For the domain of ‘blinding of participants and personnel’, 3/6 (50%) carried low ROB. 14 ,17 ,18 Blinding of outcome assessment was adequate in 2/6 (33%). 17 ,18 All studies were judged to have low ROB for the domains of ‘incomplete outcome data’, ‘selective reporting’ and ‘other bias’. Details of ROB analysis are given in figure 2.
Primary outcomes
The pooled meta-analysis showed that GL in neonates born through MSL reduced the incidence of FI (RR: 0.71 (95% CI 0.55 to 0.93, p=0.01); heterogeneity: χ2=0.19, I2=33%) (figure 3). However, this beneficial effect was not evident on sensitivity analysis of the studies that had low ROB in random sequence generation RR: 0.81 (0.60 to 1.09) or allocation concealment RR: 0.66 (95% CI 0.43 to 1.03) (table 2).
Secondary outcomes
Adverse events related to the procedure: none of the studies found procedure-related adverse effects such as apnoea, bradycardia and injury to oral/nasal cavity.
Secondary aspiration: all six studies reported that there was no secondary aspiration in either group.
Mortality: none of the studies reported on this outcome. However, Cuello-Garcia informed us that there were no deaths in either group in their study.
Duration of hospital stay: none of the studies reported on this outcome. However, Cuello Garcia informed us that there was no difference in duration of hospital stay between the two groups (48 h in each group).
Publication bias: Visual inspection of the funnel plot suggested asymmetry. Hence, a repeat search of all databases was conducted, but did not reveal any additional studies. We did not use tests for funnel plot asymmetry since there were fewer than 10 studies in the meta-analysis because test power is usually too low to distinguish chance from real asymmetry19 (figure 4).
Grading of evidence and summary of findings: The overall evidence was deemed moderate in view of the relatively small sample size and high ROB in some of the included studies12 (table 3).
Discussion
The results of our systematic review suggest that prophylactic GL may be useful in preventing FI in neonates born through MSL. The rationale for GL in MSL is similar to lung lavage in MAS20 where the pathogenesis is chemical pneumonitis leading to alveolar oedema and tissue injury caused by inflammatory mediators.21 ,22 It is unclear whether meconium in the stomach leads to similar effects. Even after detailed literature search, we could not find any reference for pathophysiology of ‘meconium gastritis’.
The incidence of MSL is higher in developing countries probably because of the limited perinatal surveillance facilities, high rate of post-term pregnancies, fetal distress and intrauterine growth restriction in such settings.23–26 This could also be the reason for such trials being conducted in developing countries.
Visual inspection of the forest plot showed the study by Narchi and Kulaylat as an outlier because its CIs had minimal overlap with those of other studies. The reason may be because it carried a high ROB on the domains of random sequence generation (odd vs even days), allocation concealment and blinding. Studies with high ROB can exaggerate effect size estimates.27 ,28 The population, intervention and outcome measures in this trial were otherwise similar to the other studies.
The strength of our study is that it is the first comprehensive systematic review on this topic. Additionally, our meta-analysis has low statistical heterogeneity, indicating consistency of effect size. Our results need to be interpreted with caution due to the limitations of our study. These include the small sample size, inclusion of trials with high ROB, lack of a standard definition of FI, subjectivity in outcome assessment and lack of data on confounding factors (eg, sepsis, swallowed maternal blood). It is also important to note that the statistical significance is lost after using random-effects model and after sensitivity analysis excluding high ROB studies.
In summary, our systematic review suggests that GL might reduce the incidence of FI by an average of 30% in neonates born through MSL. These findings will help in designing a large definitive RCT to address this important clinical issue, at least in the developing nations. Based on our results, a total of ∼3000 neonates born through MSL need to be enrolled in such a trial to detect a 30% reduction in FI (baseline incidence 12%) with 80% power and a two-sided α of 0.05, assuming a loss to follow-up of 20%.
References
Footnotes
Contributors MD: independent literature search, interpretation of data, handling meta-analysis software, writing first and final drafts of the manuscript under the supervision of authors SR and SP and addressing the reviewer's comments. HB: independent literature search and handling meta-analysis software, helping with the final draft of the manuscript. SR: interpretation of data, supervising the first and final versions of the manuscript and addressing the reviewer's comments. SP: concept, design, rechecking and interpretation of the data and supervising the first and final versions of the manuscript.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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