Systematic Review

The Impact of Early Enteral Nutrition on Post-operative Hospital Stay and Complications in Infants Undergoing Congenital Cardiac Surgery: A Systematic Review and Meta-analysis

Introduction

Congenital cardiac diseases (CHDs) are a common birth defect that is one of the leading causes of death in children. Globally 6% of neonates are born with a congenital anomaly, which result in 2.4 million newborn deaths. Another 1.7 million children between one month and five years succumb to birth defects,¹ of which 1.2 million children per year reported congenital cardiac malformation. However neonates who born with cardiac defects may have longer and healthy lives. Conventionally, number of death due to congenital cardiac defects drastically declined from 398 580 (268 422–506 469) to 261 247 (216 567–308 159) 34.5% between 1990 and 2017.^2,3 Incidence of CHDs in India ranged from 8-12 per 1000 live births. Approximately Every year, 0.2 million neonates are born with congenital heart disease. Of these, 20% of children required immediate interventions.^4-6

The early detection and management of CHDs increased over the period of time. The survive rate of the newborn after congenital cardiac surgery improved from 67.4% to 82.5% in 1979-2005.⁷ However, evidence based intervention and modern technologies are essential for reducing CHDs related mortality.

Patients who underwent cardiac surgery are not allowed to oral feeding until their bowel activity returned. Reestablishing feeding after surgery is a challenging and positive sign of the postoperative outcome, especially for children and those who are susceptible to nutritional deficiencies.⁸ Therefore, it is crucial for children who underwent congenital surgeries to have enough electrolytes and nutrients for post-operative recovery.⁹ Consequently, early enteral nutrition (EEN) reduced the length of hospital stay and post-operative complications following congenital cardiac surgery.¹⁰ There are number of studies available for management of congenital heart diseases. Nevertheless, only a few studies reported contradictory data regarding the use of EEN after congenital heart surgery.^11,12

Children who underwent cardiac surgery need the increased continue nutrition supplementation to meet their metabolic demands. Therefore this systematic review and meta-analysis were conducted to evaluate the efficacy of EEN on postoperative outcomes of infants undergoing congenital cardiac surgery. Authors have synthesized data from various research designs of the study attributed to scarcity of randomized controlled trials (RCTs) introducing moderate to high heterogeneity. Therefore we conducted this systematic review and meta-analysis of quantitative studies to analyze the efficacy of EEN on post-operative outcomes of children undergoing congenital cardiac surgery.

Materials and Methods

This systematic review and meta-analysis was registered in PROSPERO (National Institute for Health Research-International prospective register of systematic reviews) and is available online CRD42022329349. The aim of this systematic review and meta-analysis was to appraise the evidence on the EEN on post-operative outcome of neonates undergoing congenital cardiac surgery. This systematic review and meta-analysis was carried out based on Cochrane collaboration guidelines¹³ and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.¹⁴ The search strategy was developed using the keywords of population or patient, intervention, comparator or control, and outcome (PICO). Two authors (KH, SD) independently searched the databases; PubMed, Clinical Key, UpToDate, CINAHL (Cumulative Index to Nursing and Allied Health Literature), the Cochrane Library, and Google Scholar with filters in the study period. Present review was considered experimental and non-experimental studies for evaluating the efficacy of the EEN on postoperative outcomes among the infants undergoing congenital cardiac surgery.

MeSH (Medical Subject Headings) terms used during the online search were: (neonate or newborn or infant) and (early nutrition or enteral nutrition or nutrition supplementation or early enteral nutrition) and (hospital stay or ICU stay) and (cardiac surgery or congenital cardiac surgery or congenital cardiac repair). Further a manual search of the citations and references of the primary studies were carried out. Duplicate records were removed after screening the titles and abstracts and the remaining original full articles were screened to assess the inclusion criteria.

Along with RCTs we considered non-randomized control designs, and observational studies published in English language. All primary studies reported early enteral feed (oral or nasogastric feed) or supplementary nutrition or additional calories/energy feed given in experimental groups.

Search scheme retrieved 36 652 studies from various databases and 3 studies were retrieved from printed materials. During the initial screening, 1750 duplicate articles were removed. The remaining 34 905 articles were screened. Further 34 761 articles were removed after reading through the titles and abstract, as they didn’t meet the predetermined inclusion criteria of the review. The remaining 128 articles were read and screened for eligibility, of which 117 articles were removed. The reason for excluding the articles: articles which did not report sample size and primary outcomes, statistical information were lacking. Finally, 11 articles were selected for narrative synthesis and meta-analysis. The study selection process is depicted in .

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Figure 1. Prisma flow digram of study selection

Participants of this review were postoperative infants underwent congenital cardiac surgery.

Infants in the experimental group received the EEN, whereas those in the control group were given expressed breast milk or supplementary feed in accordance to the hospital norms.

The nature of subjects,¹⁵ authors had failed to report the specific nutritional supplementation and volume. However, non-invasive interventions like nutrition therapy are the vital elements in enhancing feeding tolerance and post-operative outcomes in growing neonates. Intervention group received enriched energy (EE) or high calories or supplementary nutrition^16-21 and Human Milk Fortifier (HMF).^22,23 Every two to three hours, a calculated postoperative protein energy feed was administered.^24-26 On the other hand, control group received the nutrient as per agency protocol (Table 1).

The authors have synthesized data from different types and designs of the study attributed to scarcity in the number of RCTs introducing moderate to high heterogeneity in certain outcomes. However, we were able to retrieve additional RCTs and bring forth highest level of evidence on the efficacy of EEN on post-surgery outcomes among children born with CHDs.

Two authors independently extracted the data from the included 10 articles and any disagreement between the first and fourth authors (KH, SD) referred to the second author (LT) and resolved the disagreement. The data extraction process was carried out based on the data extraction form: name of the authors, country, year of publication, study design, type of intervention, time of first feed, inclusion and exclusion criteria, study’s result, and outcome.

The quality of the included studies was assessed using the “Downs and Black score.” The tool contains 27 questions with three major domains namely external validity, internal validity and power. Scores of the Downs and Black scale categorized as < 14 low quality, 15-19 fair quality and 20-25 high-quality articles (Table 2).

Search keywords were “newborn” “neonates” “infant” “toddler” “early nutrition” “nutrition supplementation” “early enteral nutrition” “hospital stay” “surgery” “congenital cardiac surgery” “congenital cardiac repair”.These keywords were searched using the Boolean operator “AND” and “OR”.

The extracted data from the original studies were subjected to meta-analysis. The standardized mean difference was calculated after adjusting standard deviation. Heterogeneity of studies was reported using I²tool, low heterogeneity was considered for an I² < 25%, moderate heterogeneity for I² < 75% and high heterogeneity for I² > 75%. The effect of heterogeneity reduced using a random-effects model to compute mean differences, and standardized mean differences between experimental and control group at 95% confidence interval (CI).¹⁵ Incidence of post congenital cardiac surgical complications were reported using risk ratio (RR) at 95% CI and significance was considered at P < 0.05. The pooled data of included studies were analyzed by RevMan software version 5.3 (Cochrane collaboration, Copenhagen, Denmark).

Results

Data from orginal studies were summarised and displayed in tables and forest plots. There were 887 infants from 11 studies included, with 470 infants in intervention group and 417 in the control group. The sample size of primary studies ranged from 30 to 244, with infants age ranging from one to seven months. In five studies, participants and researchers were kept in the blind.^19-21,24,25 Three primary studies were not reported as randomized control trials, but they were well-designed^16-18 (Table 1). All included studies for this review were calculated nutrition based on body weight and total nutrition volume consumed in the last 24 hours (Table 1).

The primary outcomes were continuous variables that reported mean and standard deviation (hospital stay, ICU stay, duration of mechanical ventilation, Aortic cross clamp and cardiopulmonary bypass). Among two studies, reported median and interquartile range (IQR).^21,22 We manually calculated mean and standard deviation for these two studies using mean (SD) conversion formula. Dichotomous variables considered secondary outcomes and analyzed using RR formula.

The result of the meta-analysis of hospital stay showed that pooled standard mean differences of -0.63 were significantly lower in the intervention group compared to the control group with a considerable level of heterogeneity (I²=87%, P<0.001) (N=857) (SMD=-0.63, 95% CI: -1.04 to -0.22) ().^16-23,25,26

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Figure 2. Length of hospital stay after congenital cardiac surgery (days)

Similarly, result of the meta-analysis of ICU stay showed that pooled standard mean differences of -0.15 were significantly lower in the intervention group compared to the control group with a considerable level of heterogeneity (I²=71%, P<0.001) (N=887) (SMD = -0.15, 95% CI: -0.42 to 0.11) ().^16-23,25,26

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Figure 3. Length of ICU stay after congenital cardiac Surgery (days)

Seven studies reported duration of mechanical ventilation The result of the meta- analysis of duration of mechanical showed that pooled standard mean differences of -0.31 were significantly lower in the intervention group compared to the control group with a considerable level of heterogeneity (I²=47%, P=0.08) (N=648) (SMD=-0.31, 95% CI: -0.54 to -08) ().^17-23,25,26

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Figure 4. Duration of mechanical ventilation after congenital cardiac surgery (hours)

Five studies reported the amount of time required for Aortic cross clamp.The result of the meta- analysis of duration of mechanical showed that pooled standard mean differences of 0.92 were significantly higher in the intervention group compared to the control group with a considerable level of heterogeneity (I²=96%, P<0.001) (N=320) (SMD=-0.92, 95% CI: -0.31 to 2.14%) ().^{17,18,20,23,26}

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Figure 5. Time of Aortic cross clamp postopertively (Hours)

Similarly, the result of the meta- analysis of duration of cardiopulmonary bypass that pooled standard mean differences of 0.0 were significantly lower in the intervention group compared to the control group with a considerable level of heterogeneity (I²=71%, P=0.00) (N=21) (SMD=0.0, 95% CI: -0.42 to 43) ().^{17,18,20,23,26}

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Figure 6. Time of Cardiopulmonary bypass postoperatively (hours)

Secondary outcomes reported six studies namely post-surgery infections (n=574) (RR=0.68, 95% CI: 0.43 to 1.08, P=0.40, I²=3%),^{18,20,22,23,25,26} three studies reported vomiting (n=163) (RR=1.47, 95% CI: 0.80 to 2.69, P=0.90, I²=0%)^19,23,25 and three studies reported the mortality (n=218) [RR=0.42, 95% CI: 0.03 to 5.82, P<0.001, I²=80],^17,19,20 which was addressed by subgroup analysis of overall incidence of surgical complications [RR=0.88, 95% CI: 0.58 to 1.36, P0.08, I² = 39], subgroup analysis stated [χ²=4.22, df=2, P=0.12] ().

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Figure 7. Postoperative complications

The number of trials involved in this systematic review and meta-analysis reported publication bias using fixed effect model. In the funnel plots, each dot represents a separate study ().

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Figure 8. Publication bias

Discussion

This is the first systematic review and meta-analysis assessing the effectiveness of EEN on post-operative outcomes of congenital cardiac surgery in infants. The findings of existing review summarized that early enteral feeding or supplementary nutrition is safe and effective intervention in infants to reduce the post-operative complications, ICU stay and duration of mechanical ventilation.

Little attention is paid to the nutritional management of infants in post-operative nutritional management. There are many extrinsic factors that delay nutritional supplementation in postoperative infants.²⁷ On the other hand, well established clinical guidelines are available for adult but the same protocol does not apply to infants undergoing cardiac surgery.^28-30

Nutrition plays a pivotal role in critically ill patients, especially in post-operative patients.³¹ Other important factors for postoperative management are the timing, type and amount of nutritional supplementation. Parenteral nutrition is a favorable route after surgery, however, because it prevents the aspiration, resulting in vasopressor support in postoperative infants. In this issue, recent studies have suggested that enteral nutrition is the most favorable and immediate replacement of nutrients (24-72 hours) following congenital cardiac surgery.^24,32 Nevertheless, It hasn’t been specified how quickly EEN supplementation will progress to postoperative children. Hence this systematic review and meta-analysis was carried out to yield sound evidence that early nutrition feed reduced the post-operative complication following congenital cardiac surgery.

There is evidence available that EEN reduces the length of ICU stays, lessens mechanical ventilation, and decreases hospital expenditure. The findings of our systematic review and meta-analysis are in consensus with previous systematic reviews, which inferred that EEN has positive benefits in comparison to late nutrition administration. Critical illness brings forth numerous hormonal and metabolic derangements, leading to grave micronutrient and macronutrient deficiencies.³³ In recent meta-analysis reported that EEN within 48 hours post gastro intestine anastomosis significantly reduced ICU stay, mechanical ventilation supports and reduced the post-operative complications in infants.²⁸ However, the findings of our review, similar to previous systematic review and meta-analysis, have reported on pyloromyotomy³⁴ and abdominal surgery in children,³⁵ with EEN declined hospital stay, ICU stay and postoperative complications in infants.

The key finding of our review is that the total time required for aortic cross clamping is favorable in the intervention group. Similarly, the need for cardio pulmonary support was lower in the intervention group compared to the control group. Apart from this the pooled incidence of the post-operative infections and mortality rates reduced in the intervention group. Although, active involvement of primary caregivers potential impact on post-operative outcome in children.^36,37 All primary studies of this review reported that EEN continued to be small, increasing gradually to the target volume within 48-72 hours.

Enteral nutrition is a simple and often substitute marker for post-operative recovery in routine clinical practice.³⁸

However, there is high prevalence of nutritional deficits among neonates especially in pre term and small for gestational babies after congenital cardiac surgery.³⁹ Therefore there is an urgent need for an evidence-based guideline on the specific timing and nutrients to be adopted to decrease post-operative complication following congenital cardiac surgery.

This study has some limitations. Due to the scarcity of RCTs on this topic, we included non-experimental studies, however it was challenging that acceptance level is not normally distributed, and reliability cannot be collected without introducing bias, especially when using meta-analysis methods that rely on mean and standard deviation. Second, the early enteral nutrient was administered with different composition. Hence, there may be bias in the study outcomes.

The main strength of our study that all included studies were sound research design registered with clinical trials. All primary studies conducted from various parts of world and approved from institution’s review board or clinical registry. This review only included the infants undergoing congenital cardiac surgery therefore findings can replicable and provide highest evidence in hierarchy triangle

Authors recommended further RCTs with large sample sizes among infants undergoing congenital cardiac surgery. Additionally, all infants in the intervention groups received the same nutrition composition at the same time.

Conclusion

Enteral nutrition is a simple and often a substitute marker for post-operative recovery in routine clinical practice. However, there is a high prevalence of nutritional deficits among children, especially in post-operative patients. Nutrition therapy is an easy-to-administrator and can be administered based on postoperative records. EEN is a non-invasive, cost-effective, non-pharmacological intervention that can be implemented in clinical practice to improve patient well-being within adverse reactions. The efficacy of early nutrition has been published on cardiac disease in adults. However, some studies published on efficacy of early nutrition on gastrointestinal surgery in children. No systematic reviews have assessed the efficacy of EEN on post-operative outcome among infants undergoing congenital cardiac surgery. Therefore, it is an important to discuss which type of nutrition and time of first administration need to address. Therefore, it is crucial to discuss which type of nutrition and when the first administration should be addressed among infants after congenital heart surgery.

Acknowledgments

We are extremely thankful to Ms. Reetika Williams & Mrs.Sudha Janganure for editing English language and proof reading of our article.

Authors’ Contribution

Conceptualization: Kurvatteppa Halemani, Sanjay Dhiraaj, Latha Thimmappa, Alwin Issac.

Data curation: Kurvatteppa Halemani, Latha Thimmappa, Sanjay Dhiraaj.

Formal Analysis: Prabhaker Mishra, Sanjay Dhiraaj, Latha Thimmappa.

Methodology: Kurvatteppa Halemani, Sanjay Dhiraaj, Latha Thimmappa.

Project administration: Sanjay Dhiraaj.

Supervision: Prabhaker Mishra.

Validation: Sanjay Dhiraaj, Latha Thimmappa, Anu Mavinatop.

Visualization: Prabhaker Mishra, Latha Thimmappa.

Writing – original draft: Kurvatteppa Halemani, Sanjay Dhiraaj, Latha Thimmappa.

Writing – review & editing: Alwin Issac, Sanjay Dhiraaj.

COI-statement

The authors declare no conflict of interest in this study.

Ethical Approval

This project was a PROSPERO-registered systematic review and meta-analysis. Hence didn’t require ethical approval as no direct information or interventions were collected/performed on humans.

Funding

This systematic review and meta-analysis has not received financial support from any monetary resources.

Research Highlights

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