Prebiotics for the prevention of hyperbilirubinaemia in neonates
Information
- DOI:
- https://doi.org/10.1002/14651858.CD012731.pub2Copy DOI
- Database:
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- Cochrane Database of Systematic Reviews
- Version published:
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- 13 August 2019see what's new
- Type:
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- Intervention
- Stage:
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- Review
- Cochrane Editorial Group:
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Cochrane Neonatal Group
- Copyright:
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- Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Authors
Contributions of authors
Dr. Armanian initiated and designed the review. Dr. Armanian, Dr. Feizi, Dr. Sadeghi, and Dr. Salehimehr reviewed the literature and wrote the review. Dr. Molaeinezhad assisted in review of the literature and in writing process of the protocol only. All stages of design and writing of the review were performed under the guidance of Dr. Jahanfar. Dr. Jahanfar also helped with data analysis and write up of the review.
Sources of support
Internal sources
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Division of Neonatology, Child Growth and Development Research Center, Isfahan University of Medical Sciences, Iran.
External sources
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Vermont Oxford Network, USA.
Cochrane Neonatal Reviews are produced with support from Vermont Oxford Network, a worldwide collaboration of health professionals dedicated to providing evidence‐based care of the highest quality for newborn infants and their families.
Declarations of interest
None to declare.
Acknowledgements
We acknowledge the opportunities provided by our institution (Isfahan University of Medical Sciences) to write this review.
The methods section of this review is based on a standard template used by Cochrane Neonatal.
Version history
| Published | Title | Stage | Authors | Version |
| 2019 Aug 13 | Prebiotics for the prevention of hyperbilirubinaemia in neonates | Review | Amir Mohammad Armanian, Shayesteh Jahanfar, Awat Feizi, Nima Salehimehr, Mitra Molaeinezhad, Erfan Sadeghi | |
| 2017 Jul 20 | Prebiotics for the prevention of hyperbilirubinaemia in neonates | Protocol | Amir Mohammad Armanian, Shayesteh Jahanfar, Awat Feizi, Mitra Molaeinezhad, Nima Salehimehr, Erfan Sadeghi | |
Differences between protocol and review
Due to the very few articles that were found:
In protocol: Investigators must compare prebiotics with enteral supplementation of milk with distilled water, no supplementation, or both.
In review: Investigators must compare effects of feeding supplementation with prebiotics on neonatal hyperbilirubinaemia with supplementation of milk with any other placebo (particularly distilled water) or no supplementation.
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
Medical Subject Headings Check Words
Female; Humans; Infant, Newborn; Male;
PICOs
Guidelines for phototherapy in infants at ≥ 35 weeks' gestation.
(American Academy of Pediatrics Subcommittee on Hyperbilirubinaemia. Management of hyperbilirubinaemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297.)
Suggested guidelines for initiating phototherapy or exchange transfusion in preterm infants (< 35 weeks' gestation).
(Maisels MJ, Watchko JF, Bhutani VK, et al. An approach to the management of hyperbilirubinaemia in the preterm infant less than 35 weeks of gestation. Journal of Perinatology 2012;32:660‐664.)
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Comparison 1 Feeding supplementation with prebiotics versus no prebiotics, Outcome 1 Incidence of hyperbilirubinaemia.
Comparison 1 Feeding supplementation with prebiotics versus no prebiotics, Outcome 2 Maximum plasma unconjugated bilirubin levels.
Comparison 1 Feeding supplementation with prebiotics versus no prebiotics, Outcome 3 Maximum plasma unconjugated bilirubin levels.
Comparison 1 Feeding supplementation with prebiotics versus no prebiotics, Outcome 4 Treatment with phototherapy.
Comparison 1 Feeding supplementation with prebiotics versus no prebiotics, Outcome 5 Stool frequency: gestational age.
Comparison 1 Feeding supplementation with prebiotics versus no prebiotics, Outcome 6 Stool frequency: birth weight.
Comparison 1 Feeding supplementation with prebiotics versus no prebiotics, Outcome 7 Stool frequency: type of prebiotic.
Comparison 1 Feeding supplementation with prebiotics versus no prebiotics, Outcome 8 Stool frequency: type of feeding.
Comparison 1 Feeding supplementation with prebiotics versus no prebiotics, Outcome 9 Duration of phototherapy (days).
Comparison 1 Feeding supplementation with prebiotics versus no prebiotics, Outcome 10 Length of hospital stay (days).
Comparison 1 Feeding supplementation with prebiotics versus no prebiotics, Outcome 11 Length of hospital stay (days).
Comparison 1 Feeding supplementation with prebiotics versus no prebiotics, Outcome 12 Neonatal mortality.
Comparison 1 Feeding supplementation with prebiotics versus no prebiotics, Outcome 13 Neonatal mortality.
| Feeding supplementation with prebiotics compared to no prebiotics for the prevention of hyperbilirubinaemia in neonates | ||||||
| Patient or population: Neonates, including term neonates (gestational age ≥ 37 weeks), late preterm neonates (35 to 37 weeks' gestation) and preterm neonates (< 35 weeks' gestation) | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
| Risk with no prebiotics | Risk with Feeding supplementation with prebiotics | |||||
| Incidence of hyperbilirubinaemia | Study population | RR 0.75 | 50 | ⊕⊕⊝⊝ | ||
| 960 per 1,000 | 720 per 1,000 | |||||
| Maximum plasma unconjugated bilirubin levels; | The mean maximum plasma unconjugated bilirubin levels; ranged from 7.6 to 8.1 mg/dL | MD 0.14 mg/dL higher | ‐ | 78 | ⊕⊕⊝⊝ | |
| Treatment with phototherapy | Study population | RR 0.75 | 50 | ⊕⊕⊝⊝ | ||
| 960 per 1,000 | 720 per 1,000 | |||||
| Stool frequency | The mean stool frequency; ranged from 1 to 3 | MD 1.18 higher | ‐ | 154 | ⊕⊕⊕⊕ | |
| Duration of phototherapy (days) | The mean duration of phototherapy (days); ranged from 2 to 3 days | MD 0.1 days higher | ‐ | 28 | ⊕⊕⊝⊝ | |
| Length of hospital stay (days) | The mean length of hospital stay (days); ranged from 29 to 72 days | MD 10.57 days lower | ‐ | 78 | ⊕⊕⊝⊝ | |
| Neonatal mortality | Study population | RR 0.94 | 78 | ⊕⊕⊝⊝ | ||
| 26 per 1,000 | 25 per 1,000 | |||||
| Acute bilirubin encephalopathy (encephalopathy) | Study population | not estimable | (0 RCTs) | ‐ | None of the included studies showed any acute bilirubin encephalopathy. | |
| 0 per 1,000 | 0 per 1,000 | |||||
| Exchange transfusion (exchange) | Study population | not estimable | (0 RCTs) | ‐ | There were no reports of the need for exchange transfusion in included studies. | |
| 0 per 1,000 | 0 per 1,000 | |||||
| Chronic bilirubin encephalopathy or kernicterus (kernicterus) | Study population | not estimable | (0 RCTs) | ‐ | There were no reports of the incidence of chronic bilirubin encephalopathy in included studies. | |
| 0 per 1,000 | 0 per 1,000 | |||||
| Major neurodevelopmental disability | Study population | not estimable | (0 RCTs) | ‐ | Major neurodevelopmental disability was not reported in any of the included studies. | |
| 0 per 1,000 | 0 per 1,000 | |||||
| Side effects | Study population | not estimable | (0 RCTs) | ‐ | No side effects were reported in any of the included studies. | |
| 0 per 1,000 | 0 per 1,000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| a Downgraded one level due to high risk of performance bias b Downgraded one level due to uncertainty about precision (one study) c Downgraded one level due to uncertainty about precision (small study) d Downgraded one level due to unclear risk of attrition bias (incomplete outcome data) | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Incidence of hyperbilirubinaemia Show forest plot | 1 | 50 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.75 [0.58, 0.97] |
| 1.1 gestational age preterm neonates (< 35 weeks' gestation); birth weight ( < 1500 grams); type of prebiotic (oligosaccharide); type of feeding (only breast milk‐fed infants) | 1 | 50 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.75 [0.58, 0.97] |
| 2 Maximum plasma unconjugated bilirubin levels Show forest plot | 2 | 78 | Mean Difference (IV, Fixed, 95% CI) | 0.14 [‐0.91, 1.20] |
| 2.1 gestational age preterm neonates (< 35 weeks' gestation), birth weight ( < 1500 grams) | 2 | 78 | Mean Difference (IV, Fixed, 95% CI) | 0.14 [‐0.91, 1.20] |
| 3 Maximum plasma unconjugated bilirubin levels Show forest plot | 2 | 78 | Mean Difference (IV, Fixed, 95% CI) | 0.14 [‐0.91, 1.20] |
| 3.1 breastfed only infants, oligosaccharide | 1 | 50 | Mean Difference (IV, Fixed, 95% CI) | ‐0.90 [‐2.28, 0.48] |
| 3.2 given a mixed form of feeding, lactulose | 1 | 28 | Mean Difference (IV, Fixed, 95% CI) | 1.60 [‐0.03, 3.23] |
| 4 Treatment with phototherapy Show forest plot | 1 | 50 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.75 [0.58, 0.97] |
| 4.1 gestational age preterm neonates (< 35 weeks' gestation); birth weight ( < 1500 grams); type of prebiotic (oligosaccharide); type of feeding (only breast milk‐fed infants) | 1 | 50 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.75 [0.58, 0.97] |
| 5 Stool frequency: gestational age Show forest plot | 3 | 154 | Mean Difference (IV, Fixed, 95% CI) | 1.18 [0.90, 1.46] |
| 5.1 term neonates (gestational age ≥ 37 weeks) | 1 | 76 | Mean Difference (IV, Fixed, 95% CI) | 1.7 [1.34, 2.06] |
| 5.2 preterm neonates (< 35 weeks' gestation) | 2 | 78 | Mean Difference (IV, Fixed, 95% CI) | 0.4 [‐0.05, 0.85] |
| 6 Stool frequency: birth weight Show forest plot | 3 | 154 | Mean Difference (IV, Fixed, 95% CI) | 1.18 [0.90, 1.46] |
| 6.1 infants ≥ 2500 grams | 1 | 76 | Mean Difference (IV, Fixed, 95% CI) | 1.7 [1.34, 2.06] |
| 6.2 infants < 1500 grams | 2 | 78 | Mean Difference (IV, Fixed, 95% CI) | 0.4 [‐0.05, 0.85] |
| 7 Stool frequency: type of prebiotic Show forest plot | 3 | 154 | Mean Difference (IV, Fixed, 95% CI) | 1.18 [0.90, 1.46] |
| 7.1 oligosaccharide | 2 | 126 | Mean Difference (IV, Fixed, 95% CI) | 1.28 [0.98, 1.58] |
| 7.2 lactulose | 1 | 28 | Mean Difference (IV, Fixed, 95% CI) | 0.40 [‐0.44, 1.24] |
| 8 Stool frequency: type of feeding Show forest plot | 3 | 154 | Mean Difference (IV, Fixed, 95% CI) | 1.18 [0.90, 1.46] |
| 8.1 breastfed only infants | 1 | 50 | Mean Difference (IV, Fixed, 95% CI) | 0.40 [‐0.13, 0.93] |
| 8.2 formula‐fed only infants | 1 | 76 | Mean Difference (IV, Fixed, 95% CI) | 1.7 [1.34, 2.06] |
| 8.3 given a mixed form of feeding | 1 | 28 | Mean Difference (IV, Fixed, 95% CI) | 0.40 [‐0.44, 1.24] |
| 9 Duration of phototherapy (days) Show forest plot | 1 | 28 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [0.00, 2.20] |
| 9.1 gestational age preterm neonates (< 35 weeks' gestation); birth weight ( < 1500 grams); type of prebiotic (lactulose); type of feeding (infants given a mixed form of feeding) | 1 | 28 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [0.00, 2.20] |
| 10 Length of hospital stay (days) Show forest plot | 2 | 78 | Mean Difference (IV, Fixed, 95% CI) | ‐10.57 [‐17.81, ‐3.33] |
| 10.1 gestational age preterm neonates (< 35 weeks' gestation), birth weight ( < 1500 grams) | 2 | 78 | Mean Difference (IV, Fixed, 95% CI) | ‐10.57 [‐17.81, ‐3.33] |
| 11 Length of hospital stay (days) Show forest plot | 2 | 78 | Mean Difference (IV, Fixed, 95% CI) | ‐10.57 [‐17.81, ‐3.33] |
| 11.1 breastfed only infants, oligosaccharide | 1 | 50 | Mean Difference (IV, Fixed, 95% CI) | ‐10.2 [‐17.59, ‐2.81] |
| 11.2 given a mixed form of feeding, lactulose | 1 | 28 | Mean Difference (IV, Fixed, 95% CI) | ‐19.10 [‐54.58, 16.38] |
| 12 Neonatal mortality Show forest plot | 2 | 78 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.14, 6.19] |
| 12.1 gestational age preterm neonates (< 35 weeks' gestation), birth weight ( < 1500 grams) | 2 | 78 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.14, 6.19] |
| 13 Neonatal mortality Show forest plot | 2 | 78 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.14, 6.19] |
| 13.1 breastfed only infants, oligosaccharide | 1 | 50 | Risk Ratio (M‐H, Fixed, 95% CI) | 3.0 [0.13, 70.30] |
| 13.2 given a mixed form of feeding, lactulose | 1 | 28 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.29 [0.01, 6.60] |
