Maternal and Neonatal Polyunsaturated Fatty Acid Intake and Risk of Neurodevelopmental Impairment in Premature Infants
Round 1
Reviewer 1 Report
In this review manuscript, the authors discussed the importance of maternal and neonatal polyunsaturated fatty acid (LCPUFA) intake and risk of neurodevelopmental impairment in premature infants. The abrupt termination of placental transfer with premature birth usually induces a deficit of LCPUFA that may impair neurodevelopment. The authors discussed whether supplementation of preterm infants with LCPUFA in the postnatal period can improve neurodevelopmental outcomes. The authors also discussed the roles of maternal LCPUFA status as a modifiable factor affecting the risk of preterm birth and infant neurodevelopmental outcomes.
Firstly, this review article presents an integrated, unbiased summary of the current understanding of the topic about the LCPUFA intake.
Secondly, this manuscript is well executed, with an appropriate literature collection, sufficient breadth and depth of literature coverage. In addition, it also describes research insights and future research directions.
Overall, this article is well structured and the writing flows very well. The interpretation of literature is accurate.
Minor point,
If the authors can discuss more about the ratio of N3:N6, emphasize its importance and provide more evidence of it, the article will be improved.
Author Response
We thank the reviewer for their positive comments. The comment about N3:N6 is appreciated, and we considered at length how we might accommodate it. However, two main issues arise:
- The N3 and N6 fats most pertinent to this question and the associated RCTs are invariably DHA and AA, respectively, and we have already discussed their relative and combined supplementation and ratios at length.
- In addition to the above, each individual N3 and N6 LCPUFA has its own physiolgical effect(s), at least partly touch upon in Klevebro et al. (Frontiers in Pediatrics 2020). As such, further generalisation about the N3:N6 ratio may not add clear guidance relevant to this clinical scenario.
Due to the above, we feel that the discussion as presented is the best balance of evidence and informed speculation that can be provided with respect to N3:N6 ratio in this population.
Reviewer 2 Report
Whether supplementation of preterm infants with LCPUFA in the postnatal period can improve neurodevelopmental outcomes is largely unknown, in the present Review the Authors considered and evaluated the strengths and weaknesses of available evidence relating LCPUFA supplementation in the pre- and postnatal periods with respect to neurological development in premature infants. Thay also discussed the roles of maternal LCPUFA status as a modifiable factor affecting the risk of preterm birth and infant neurodevelopmental outcomes.
All considered, I believe that the present Review is timely, well organized, very interesting and scientifically sound: enjoyed reading it!
I have some minor suggestions aimed to improve the high quality of the paper and these are outlined below as follow:
1) The abstract needs to be rewritten as it should be more focused on Review' findings and research methods.
2) The Introduction lacks of a clear and definite section regarding aims and scopes of the present review.
3) As well, I suggest to add a brief paragraph describing how literature searches were conducted and relevant articles included.
4) Given this very important topic, I guess why the Authors didn't conducted a systematic review rather than a narrative one.
Author Response
We are very grateful to the author for their positive comments and are glad they enjoyed reading the paper! Individual minor comments are addressed below, along with examples of changes in the text:
The abstract needs to be rewritten as it should be more focused on Review' findings and research methods.
Author's response: We agree that the abstract did not entirely reflect the article. As such, it has been completely re-written to focus on the methodology as well as the main findings.
The Introduction lacks of a clear and definite section regarding aims and scopes of the present review. As well, I suggest to add a brief paragraph describing how literature searches were conducted and relevant articles included.
Authors' response: We thank the author for these recommendations. The introduction has been expanded to include aim, scope, and methodology, including the following:
"This review aims to explore the current evidence surrounding LCPUFA supplementation to improve neurodevelopmental outcomes after preterm birth. We discuss the surrounding context of LCPUFA; how these fatty acids accrete into fetal tissues during gestation and after birth, and how the physical nature of these LCPUFA molecules and their subsequent metabolism into bioactive mediators exert their wide-ranging effects upon infant brain development. This context provides a base from which we may view the effects of changes to infant LCPUFA status through the current standard of care or through interventional trials (described in Appendix 1), and speculate upon guidance for practice and future research. Our scope extends to suggest that further clinical and research considerations may be needed to make LCPUFA provision in the preterm period more physiological for the infant, accounting for placental physiology, maternal LCPUFA status, and the wider contexts of LCPUFA availability.
This narrative review synthesises evidence from articles identified in the reference lists of key preceding narrative and systematic reviews. New articles were identified via searches using the PubMed search engine of its constituent databases MEDLINE and PubMed Central and through active work in this research field amongst the authors. Keywords searched included ‘preterm / premature infant’, ‘polyunsaturated fatty acids’, ‘docosahexaenoic acid’, ‘arachidonic acid’, ‘neurodevelopment’."
Given this very important topic, I guess why the Authors didn't conducted a systematic review rather than a narrative one.
Authors' response: This is another good point. In addition to the above we have added a short section on why a new systematic review/meta-analysis was not performed:
"A previous systematic review of the effects of LCPUFA supplementation in preterm infants has been performed by the Cochrane Collaboration in 2016. All papers analysed systematically in the Cochrane review are included herein; a new systematic review is not warranted as no new RCTs assessing the effects of LCPUFA supplementation upon neurodevelopment have been performed. Importantly, while excluded from the Cochrane systematic review due to not fulfilling RCT criteria, studies by Almaas et al., Alshweki et al., Collins et al., Makrides et al., and Smithers et al. provide valuable wider insights into the field and are included in this narrative review."
