High doses of enteral docosahexaenoic acid omega-3 supplementation for prevention of bronchopulmonary dysplasia in very preterm infants: a protocol for a systematic review and meta-analysis

Isabelle Marc, Amélie Boutin, Etienne Pronovost, Mireille Guillot, Frédéric Bergeron, Lynne Moore, Maria Makrides, Isabelle Marc, Amélie Boutin, Etienne Pronovost, Mireille Guillot, Frédéric Bergeron, Lynne Moore, Maria Makrides

Abstract

Introduction: Docosahexaenoic acid (DHA) supplementation in the neonatal period has been proposed to prevent bronchopulmonary dysplasia (BPD) in very preterm infants. We aim to determine the effects of an enteral supplementation with high doses of DHA on the risk for BPD at 36 weeks' postmenstrual age (PMA) in very preterm infants born less than 29 weeks' gestation compared with a control.

Methods and analysis: We will conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) searching PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, MedRxiv, ClinicalTrials.gov (up to 1 November 2021) as well as reference lists and citations of included articles and previous reviews. RCTs targeting infants born less than 29 weeks' gestation and evaluating the effect of high doses of DHA enteral supplementation in the neonatal period compared with a control will be eligible. Primary outcome will be BPD defined as the need for oxygen and/or ventilation at 36 weeks' PMA. Two authors will independently screen for inclusion, extract data and assess data quality using the Cochrane instrument (risk-of-bias tool 2.0). We will perform meta-analysis using random effects models. Prespecified subgroup analyses are planned for the infant gestational age and sex, the marine source of DHA, mode of administration and duration of exposure. Sensitivity analysis will be performed according to the accuracy of the BPD definition (ie, physiological definition) and according to the risk of bias of the RCTs.

Ethics and dissemination: This protocol for a systematic review and meta-analysis does not require ethics approval, as no primary data are collected. This study will assess the effectiveness of high doses of enteral DHA supplementation on BPD and provide evidence to clinicians and families for decision-making. Findings will be disseminated through conferences, media interviews and publications to peer review journals.

Prospero registration number: CRD42021286705.

Keywords: NEONATOLOGY; NUTRITION & DIETETICS; PAEDIATRICS.

Conflict of interest statement

Competing interests: IM and MM were both principal investigators of RCTs expected to be included in this review.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

References

    1. Jobe AH. The new bronchopulmonary dysplasia. Curr Opin Pediatr 2011;23:167–72. 10.1097/MOP.0b013e3283423e6b
    1. Kinsella JP, Greenough A, Abman SH. Bronchopulmonary dysplasia. Lancet 2006;367:1421–31. 10.1016/S0140-6736(06)68615-7
    1. Anderson PJ, Doyle LW. Neurodevelopmental outcome of bronchopulmonary dysplasia. Semin Perinatol 2006;30:227–32. 10.1053/j.semperi.2006.05.010
    1. Schmidt B, Asztalos EV, Roberts RS, et al. . Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA 2003;289:1124–9. 10.1001/jama.289.9.1124
    1. Martin CR, Dasilva DA, Cluette-Brown JE, et al. . Decreased postnatal docosahexaenoic and arachidonic acid blood levels in premature infants are associated with neonatal morbidities. J Pediatr 2011;159:743–9. 10.1016/j.jpeds.2011.04.039
    1. Valentine CJ. Maternal dietary DHA supplementation to improve inflammatory outcomes in the preterm infant. Adv Nutr 2012;3:370–6. 10.3945/an.111.001248
    1. Leroy S, Caumette E, Waddington C, et al. . A time-based analysis of inflammation in infants at risk of bronchopulmonary dysplasia. J Pediatr 2018;192:60–5. 10.1016/j.jpeds.2017.09.011
    1. Makrides M, Gibson RA, McPhee AJ, et al. . Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial. JAMA 2009;301:175–82. 10.1001/jama.2008.945
    1. Manley BJ, Makrides M, Collins CT, et al. . High-Dose docosahexaenoic acid supplementation of preterm infants: respiratory and allergy outcomes. Pediatrics 2011;128:e71–7. 10.1542/peds.2010-2405
    1. Lapillonne A, Groh-Wargo S, Gonzalez CHL, et al. . Lipid needs of preterm infants: updated recommendations. J Pediatr 2013;162:S37–47. 10.1016/j.jpeds.2012.11.052
    1. Calder PC. Long chain fatty acids and gene expression in inflammation and immunity. Curr Opin Clin Nutr Metab Care 2013;16:425–33. 10.1097/MCO.0b013e3283620616
    1. Tenorio-Lopes L, Baldy C, Jochmans-Lemoine A, et al. . Consequences of maternal omega-3 polyunsaturated fatty acid supplementation on respiratory function in rat pups. J Physiol 2017;595:1637–55. 10.1113/JP273471
    1. Velten M, Britt RD, Heyob KM, et al. . Maternal dietary docosahexaenoic acid supplementation attenuates fetal growth restriction and enhances pulmonary function in a newborn mouse model of perinatal inflammation. J Nutr 2014;144:258–66. 10.3945/jn.113.179259
    1. Zhang P, Lavoie PM, Lacaze-Masmonteil T, et al. . Omega-3 long-chain polyunsaturated fatty acids for extremely preterm infants: a systematic review. Pediatrics 2014;134:120–34. 10.1542/peds.2014-0459
    1. Wang Q, Zhou B, Cui Q, et al. . Omega-3 long-chain polyunsaturated fatty acids for bronchopulmonary dysplasia: a meta-analysis. Pediatrics 2019;144. 10.1542/peds.2019-0181. [Epub ahead of print: 04 06 2019].
    1. Tanaka K, Tanaka S, Shah N. Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis.. J Matern Fetal Neonatal Med 2020:1–9.
    1. Collins CT, Gibson RA, McPhee AJ, et al. . The role of long chain polyunsaturated fatty acids in perinatal nutrition. Semin Perinatol 2019;43:151156. 10.1053/j.semperi.2019.06.004
    1. Collins CT, Makrides M, McPhee AJ, et al. . Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants. N Engl J Med 2017;376:1245–55. 10.1056/NEJMoa1611942
    1. Marc I, Piedboeuf B, Lacaze-Masmonteil T, et al. . Effect of maternal docosahexaenoic acid supplementation on bronchopulmonary Dysplasia-Free survival in breastfed preterm infants: a randomized clinical trial. JAMA 2020;324:157–67. 10.1001/jama.2020.8896
    1. Moon K, Rao SC, Schulzke SM, et al. . Longchain polyunsaturated fatty acid supplementation in preterm infants. Cochrane Database Syst Rev 2016;12:CD000375. 10.1002/14651858.CD000375.pub5
    1. Tam EWY, Chau V, Barkovich AJ, et al. . Early postnatal docosahexaenoic acid levels and improved preterm brain development. Pediatr Res 2016;79:723–30. 10.1038/pr.2016.11
    1. Gould JF, Makrides M, Sullivan TR, et al. . Protocol for assessing whether cognition of preterm infants <29 weeks' gestation can be improved by an intervention with the omega-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA): a follow-up of a randomised controlled trial. BMJ Open 2021;11:e041597. 10.1136/bmjopen-2020-041597
    1. Gould JF, Roberts RM, Anderson PJ, et al. . Protocol for assessing if behavioural functioning of infants born <29 weeks' gestation is improved by omega-3 long-chain polyunsaturated fatty acids: follow-up of a randomised controlled trial. BMJ Open 2021;11:e044740. 10.1136/bmjopen-2020-044740
    1. Gould JF, Roberts RM, Makrides M. The influence of omega-3 long-chain polyunsaturated fatty acid, docosahexaenoic acid, on child behavioral functioning: a review of randomized controlled trials of DHA supplementation in pregnancy, the neonatal period and infancy. Nutrients 2021;13. 10.3390/nu13020415. [Epub ahead of print: 28 Jan 2021].
    1. Higgins JPT, Thomas J, Chandler J. Cochrane Handbook for systematic reviews of interventions version 6.2 (updated February 2021. Cochrane, 2021.
    1. Moher D, Shamseer L, Clarke M, et al. . Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015;4:1. 10.1186/2046-4053-4-1
    1. Page MJ, McKenzie JE, Bossuyt PM, et al. . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. 10.1136/bmj.n71
    1. Shamseer L, Moher D, Clarke M, et al. . Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015;350:g7647. 10.1136/bmj.g7647
    1. Page MJ, Moher D, Bossuyt PM, et al. . PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 2021;372:n160. 10.1136/bmj.n160
    1. Kapoor V, Malviya MN, Soll R. Lipid emulsions for parenterally fed term and late preterm infants. Cochrane Database Syst Rev 2019;6:CD013171. 10.1002/14651858.CD013171.pub2
    1. Brenna JT, Varamini B, Jensen RG, et al. . Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide. Am J Clin Nutr 2007;85:1457–64. 10.1093/ajcn/85.6.1457
    1. Innis SM, Elias SL. Intakes of essential n-6 and n-3 polyunsaturated fatty acids among pregnant Canadian women. Am J Clin Nutr 2003;77:473–8. 10.1093/ajcn/77.2.473
    1. Lefebvre C, Glanville J, Briscoe S. Technical Supplement to Chapter 4: Searching for and selecting studies. In: Higgins JPT, Thomas J, Chandler J, eds. Cochrane Handbook for systematic reviews of interventions version 62 (updated February 2021. Cochrane, 2021..
    1. Sterne JAC, Savović J, Page MJ, et al. . Rob 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019;366:l4898. 10.1136/bmj.l4898

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