A Comparative Analyses of Lipid Ratios Representing Desaturase Enzyme Activity between Preterm and Term Infants Within the First Ten Weeks of Life

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In preterm infants, desaturase enzyme activity (DA) may be a rate-limiting step in maintaining PUFAs levels during this critical developmental window and impact on long term metabolic health. The study tested the hypothesis that desaturase enzyme activity is altered in preterm infants compared to term infants in early life. Methods Lipidomic analyses were conducted using blood samples from two established UK-based cohorts, involving very preterm (n = 105) and term (n = 259) infants. Blood samples were taken from term infants at birth, two and six weeks and from preterm infants when established on enteral feeds and at term corrected age. DA of the 2 groups of infants were estimated from product/precursor lipids ratios of phosphatidylcholine (PC) and triglycerides (TG) species and reported according to their postmenstrual and postnatal ages. Results There were changes in lipid ratios representing desaturase enzyme activity in preterm infants in the first weeks of life with increasing activity of fatty acid desaturase 2 (FADS2) TG but a significant reducing activity of stearoyl-COA desaturase (SCD1) and FADS2(PC). In comparison to term infants, preterm have lower FADS1 but higher FADS2 at all postnatal ages. Although point levels of DA were different, trajectories of changes in DA over time were similar in preterm and term infants. Conclusions This study findings suggest the patterns of DA in preterm infants differ from that of term infants but their trajectories of change in the first 10 weeks of life were similar. These differences of desaturases activity if they persist in later life could contribute to the mechanism of diseases in preterm adulthood and warrant further investigations. Desaturase enzyme preterm infants LCPUFAs metabolism Figures Figure 1 Figure 2 Background Desaturase enzymes play a key role in a number of biochemical pathways including biosynthesis of long chain poly unsaturated fatty acids (LCPUFAs). Altered desaturase activity has been associated with increased risks for metabolic derangements including type 2 diabetes and cardiovascular disease, as well as pro-inflammatory processes. In preterm infants desaturase enzyme activity (DA) may be a rate-limiting step in maintaining PUFA levels during this critical developmental window. LCPUFAs are essential for the structure and function of cell membranes and for growth, with impacts on body composition immunity, and neurocognition( 1 ). Humans are unable to synthesise LCPUFAs de novo and need to obtain these, and their precursors from the diet. Desaturase and elongases enzymes play a critical role in the conversion of saturated fatty acids in the diet to LCPUFAs. Recent studies in term infants have shown that DA in the first months of life are associated with subsequent body size increase, providing a potential tool to predict early life weight gain ( 2 ), while low levels of DA has been associated with insulin resistance, diabetes, and obesity ( 3 ) , ( 4 ). Preterm infants born before 32 weeks gestation miss out on the transfer of LCPUFAs and are known to be at risk of deficiency of docosahexaenoic acid (DHA) and/or arachidonic acid (ARA) that can result in impaired growth and development, ( 5 ) , ( 6 ) as well as increased risk of cardiovascular disease and metabolic syndrome in later life. ( 7 ) , ( 8 ) These deficiencies may not only be caused by DHA availability, DA due to or in combination with precursor deficiency can also limit the availability of DHA and ARA for healthy development in preterm infants. There are three main desaturase enzymes identified in human: fatty acid desaturase 1 and 2 (FADS1, FADS2) and stearoyl-COA desaturase 1 (SCD1). There are more desaturase enzymes like FADS3, but their exact functions remain unclear, likely to be specific to certain lipid types. While FADS1 or delta 5 desaturase (D5D) and FADS2 or delta 6 desaturase (D6D) are important in PUFA synthesis, SCD1 or delta 9 desaturase (D9D) plays a key role in the synthesis of monounsaturated fatty acids (MUFAs) ( 9 ). There are limited data on DA in preterm infants, in part due to the challenges of blood sampling in these very small infants. We have developed an innovative methodology that allows detailed lipidomic analyses from the small volumes of blood that can be collected onto filter paper as dried blood spots. To observe the evidence of DA alterations in preterm infants, we aimed to explore changes in DA activity in very preterm (VPT) infants in the first weeks of life after they established feedings and after they reached term corrected age and compare that to the healthy term infants. Methods This is comparative analyses of data from two cohorts. Preterm infants were part of a single centre study of preterm lipid metabolism. Infants were prospectively recruited from the neonatal intensive care unit (NICU) from July 2016 - June 2019 at Rosie Birth Centre, Cambridge University Hospitals NHS Foundation Trust (CUH). Inclusion criteria were gestational age at birth < 32 completed weeks and parental consent with exclusion factors including serious congenital defects, life threatening illness, treatment with antibiotics, necrotizing enterocolitis or serious gastrointestinal abnormalities. The term infants were participants from the Cambridge Baby Growth Breastfeeding (CBGS-BF) study, enrolled in the study between 2001–2019. The cohort profile has been described previously ( 10 ) , ( 11 ). Sample collection In the preterm cohort samples were collected at two time points: i. within 48 hours of establishing full enteral feeds (preterm established enteral feeding, PEF), ii. at term corrected age (preterm at term, PAT). Term was defined as > 37 weeks postmenstrual age. For the term cohort, samples were taken at birth, two weeks, and six weeks postnatal age. Heel prick blood samples were collected onto untreated filter paper cards (Guthrie cards, Ahlstrom 226; ID Biological Systems, Greenville, South Carolina) as single drops of blood on defined circles (x5). The cards were left to dry naturally for 24 hours then stored at -80°C until batch analyses. Clinical data including antenatal history, clinical course, and feeding history were collected prospectively from the hospital medical records, and from validated parental questionnaires. Sample Processing Dried blood spot (DBS) samples were first extracted for determination of lipid species and their relative abundances, using mass spectrometry, as described previously ( 12 ). Product-to-precursor ratio of fatty acids was measured as a surrogate marker for DA, as reported in previous studies ( 2 ) , ( 13 ) , ( 14 ). For this study, SCD-1 was estimated by PC(32:1)/PC(32:0) ratio, whereas PC(38:4)/(38:3) and TG(54:4)/(54:3) ratios represented FADS1 enzyme activity. FADS 2 activity was approximated by the PC(36:3)/(36:2) and TG(50:3)/(50:2) ratios ( 15 ) , ( 2 ) , ( 14 ). Analyses Demographic data were analysed using SPSS version 23.0 for windows 10 (IBM Corp Released 2012.Armonk, NY). Weight data was converted to sex and age-adjusted standard deviation scores (SDS) using the British 1990 growth reference and the WHO 2006 growth standard. The LMS growth was used to calculate standard deviation scores (SDS) in Microsoft Excel ( 16 ) , ( 17 ). Demographic data are presented as mean standard deviation (SD) and frequencies. The raw lipid data were initially normalized through log transformation in Metaboanalyst 5.0 and SPSS ( 18 ). Respective lipid values then were calculated into five lipid ratios, as described previously. These lipids ratio which represents SCD1, FADS1 and FADS2 were checked for normality test. One preterm subject (in PEF group) was identified as an outlier and was therefore removed from further analyses. The data then were tested with T-Test/Mann-Whitney or ANOVA/Kruskal Wallis in SPSS to get further details on mean/median differences (+/- SD) between the cohort. The trajectories of lipid ratios were explored through Metaboanalyst 5.0. Bonferroni correction for multiple testing was also applied as lipidome analysis consist of large numbers of variables and comparisons. Bonferroni corrected p -value was used based on dividing the significance threshold of 0.05 by the number of lipids analysed. DA activity at specific time points and trajectories over time were compared between cohorts by plotting activity with respect to both gestational age and postnatal age. Post hoc analyses were undertaken to explore the effect of extreme prematurity with preterm infants divided further into very preterm and extremely preterm. Results Data were available for a total of 78 preterm infants and 256 term infants. Preterm infants were born at mean (SD) of 28(2.2) weeks gestational age and term infants had a mean (SD) gestational age of 39 (2.2) weeks, with the preterm infants being statistically smaller than the term infants at all study assessments. The majority of all infants in all groups received breast milk. Further demographic details are provided in Table 1. Table 1: Clinical Characteristics. Characteristics Preterm Cohort Term Cohort PEF (n=67) PAT (n=38) Birth (n= 82) 2 weeks post delivery (n=93) 6 weeks post delivery (n=81) Gestational Age at Birth (weeks) 28.00 (2.2) 28.00 (2.3) 39.77 (1.2) 39.77 (1.2) 39.88 (1.1) Age at assessment 4 (2) weeks 10 (3) weeks 5 (2) days 2 (1) weeks 6 (0) weeks Sex ♂: 28 (40%) ♀: 42 (60%) ♂:20 (53%) ♀:18 (47%) ♂:39 (47%) ♀:43 (53%) ♂:39 (42%) ♀:54 (58%) ♂:33 (41%) ♀:48 (59%) Weight at birth (g) 1117 (407) 1125 (389) 3605 (505) 3657 (487) 3680 (537) Weight SDS at birth -0.34 (1.25) -0.37 (1.31) 0.41 (0.92) 0.51 (0.89) 0.50 (1.08) Weight at assessment (g) 1456 (422) 2488 (555) 3593 (492) 3981 (612) 4866 (115) Weight SDS at assessment -1.81 (2.16) -1.61 (1.39) 0.046 (0.87) 0.13 (0.99) 0.57 (1.18) Feeding type BM 42 (60%) FM 7 (10%) MF 18 (27%) BM 22 (58%) FM 10 (26%) MF 6 (16%) BM 71 (87%) FM 4 (5%) MF 6 (7%) NA 1(1%) BM 81 (87%) FM 2 (2%) MF 10 (11%) BM 64 (79%) FM 4 (5%) MF 13 (16%) Abbreviation: PEF –Preterm established on enteral feeding, PAT – Preterm at Term, BM – Breast milk, FM – Formula Milk, MF – Mixed Feeding. Data is given as n (%) or mean (SD) NA – not available Desaturase Activity in Preterm Infants As shown in Figure 1 there were significant differences in specific DA between the two study time points. FADS1(TG), FADS2(PC) and SCD1 levels were lower at term corrected age, compared to when preterm infants were first established on enteral feeds. In contrast FADS1(PC) and FADS2(TG) levels were higher at term corrected age. Figure 1 Box plots of the lipid ratios, represent desaturase enzyme activity in preterm infants at two time points; preterm on establishment of enteral feeding (PEF) and preterm at term corrected age (PAT). The boxes indicate 25 th -75 th percentile and a median line. Values are in mean (SD). Abbreviation: PEF-Preterm on established enteral feeding, PAT – preterm at Term, SCD 1- stearoyl-COA desaturase, FADS 1- fatty acid desaturases 1, FADS 2- fatty acid desaturases 1, PC-phosphatidylcholine, TG-triglyceride. P values were obtained by the Mann-Whitney U test. * p < .05, ** p < .001 Comparison of DA between preterm and term infants Table 2a show that PEF infants had similar SCD1 with term infants at birth, but significantly different from term infants at 2- and 6-weeks postnatal age (p=0.001). At term corrected age (>37 weeks PMA), SCD1 was statistically lower than term infants at birth (Table 2b). FADS1 activity was consistently lower in preterm infants at both time points compared to term infants from birth to 6 weeks of age. Table 2a: Lipid ratios among preterm infants on establishment of enteral feeds (PEF) and term infants VARIABLES PEF TAB Z score p T2W Z score p T6W Z score p SCD1 0.43 (0.21) 0.43 (0.17) -0.92 0.36 0.27 (0.11) -5.88 ** 0.24 (0.13) -6.59 ** FADS1 (PC) 3.08 (1.22) 6.05 (3.87) -7.11 ** 3.88 (3.36) -3.21 * 3.59 (1.05) -3.98 ** FADS1 (TG) 1.23 (0.32) 2.21 (1.06) -7.64 ** 1.39 (0.34) -3.09 * 1.28 (0.26) -1.37 0.17 FADS2 (PC) 0.53 (0.12) 0.59 (0.13) -4.11 ** 0.46 (0.07) -4.36 ** 0.39 (0.05) -8.81 ** FADS2 (TG) 0.72 (0.16) 0.33 (0.25) -9.04 ** 0.39 (0.21) -8.66 ** 0.52 (0.24) -6.13 ** Table 2a The comparison of lipid ratios among PEF and term infants at birth, 2 weeks, and 6 weeks. Lipid ratios were presented as mean (SD), but for statistical significance, the mean ranks among the groups were compared. Abbreviation: PEF – preterm after establishing enteral feeding, SCD 1- stearoyl-COA desaturase, FADS 1- fatty acid desaturases 1, FADS 2- fatty acid desaturases 1, PC-phosphatidylcholine, TG-triglyceride. P values were obtained by Kruskal Wallis Test and Post Hoc by Mann Whitney U-Test with Bonferroni adjustment at p <.0001, * p <.05, * p <.001 Table 2b: Lipid ratios among preterm at term (PAT) and term infants VARIABLES PAT TAB Z score p T2W Z score p T6W Z score p SCD1 0.32 (0.16) 0.43 (0.17) -3.84 ** 0.27 (0.11) -1.05 0.296 0.24 (0.13) -2.71 * FADS1 (PC) 3.15 (0.94) 6.05 (3.87) -5.40 ** 3.88 (3.36) -1.75 0.081 3.59 (1.05) -2.22 * FADS1 (TG) 1.13 (0.43) 2.21 (1.06) -7.08 ** 1.39 (0.34) -4.74 ** 1.28 (0.26) -3.80 ** FADS2 (PC) 0.46 (0.15) 0.59 (0.13) -5.86 ** 0.46 (0.07) -1.93 0.054 0.39 (0.05) -3.19 * FADS2 (TG) 0.83 (0.20) 0.33 (0.25) -8.03 ** 0.39 (0.21) -8.01 ** 0.52 (0.24) -6.57 ** Table 2b Comparison of lipid ratios among PAT and term infants at birth, 2 weeks, and 6 weeks. Lipid ratios were presented as mean (SD), but for statistical significance, the mean ranks among the groups were compared. Abbreviation: PAT – preterm at term, SCD 1- stearoyl-COA desaturase, FADS 1- fatty acid desaturases 1, FADS 2- fatty acid desaturases 1, PC-phosphatidylcholine, TG-triglyceride. P values were obtained by Kruskal Wallis Test, and Post Hoc by Mann Whitney U-Test with Bonferroni adjustment at p <.0001, * p <.05, * p <.001. FADS2 in preterm infants was generally higher than term infants at 2 and 6 weeks and especially FADS2(TG) was significantly higher than term infants, at all time points. Similarly in PEF infants’ FADS2(PC) activity was higher than that of term infants at 2 and 6 weeks (p<0.001). Although FADS2(PC) activity was lower in PAT compared to term infants at birth, it was higher than term infants at 6 weeks (p<0.03). Desaturase enzyme activity in the cohorts over time is shown in Figure 2, with preterm infant results plotted in duplicate to show levels in relation to postmenstrual (32 and 38 weeks) and postnatal age (4 and 10 weeks). This shows that although there were significant differences in DA levels at specific time points for most of the DA, the trajectories of activity over time were similar in the two cohorts. The exception to this was the contradict trajectory in FADS1(PC) between the cohorts and a rapid fall in FADS1 activity from birth to 2 weeks postnatal age in the term cohort. Discussion These results are the first to show the significant differences in DA in a cohort of very preterm infants compared to term controls over the first weeks of life. They also show that although there were significant differences in DA levels at specific time points the trajectory of changes in activity over time were similar in the two cohorts, although offset in terms of absolute levels of activity. As desaturase enzymes play a key role in a number of biochemical pathways including potentially being a rate-limiting step in maintaining LCPUFA levels, altered activity may impact on both short-term metabolism and long-term health. Desaturase activity can be affected by many factors including diet with altered gene expression(19) . To avoid the confounding impact of parenteral nutrition we only sampled preterm infants when established on full enteral feeds. In this cohort more preterm infants were receiving formula than term infants, and both volume and composition of breast milk and formula will have varied between the two cohorts. In this study design, we are unable to determine the causal factors for the differences shown. Larger studies would be needed to further investigate the impact of different dietary intakes on desaturase activity. There is a lack of validated biochemical reference ranges specific for the neonatal population which is a time of significant metabolic adaptation. For preterm infants postmenstrual age may provide a more developmentally appropriate reference compared to postnatal age although nutritional advice for preterm infants is guided both by gestation at birth and postnatal age. Our results suggest that changes of DA in preterm infants are in keeping with the changes seen in term infants from birth to 2-and-6 weeks postnatal age, suggesting reducing trends of MUFAs and LCPUFAs endogenous biosynthesis as infants reach 6 - 10 weeks postnatal age. Regardless of feeding type, this finding supports that preterm infants have the capacity to convert precursors fatty acids to LCPUFAs as expected for their postnatal age. Further studies would help to determine what changes in activity happen in utero at a comparable gestational age. These changes in DA over time from birth and interaction with gestational age warrant further studies to determine if the differences in activity persist into childhood. Preterm infants in our study demonstrated lower FADS1 and higher FADS2 activity relative to term cohorts, could be considered as a sign of alterations in DA. A series of transition periods, from intrauterine to extrauterine, from parenteral to enteral feeding and apparent growth changes at term corrected age are potentially demanding for metabolic adaptation, but the exact mechanism is indeterminate. It is known that FADS1 and FADS2 activity effect the balance of omega-3 and omega-6 synthesis, and that imbalance of omega 3-and-6 can be harmful to human health (8). In two childhood studies, low FADS1 and high FADS2 activity is associated with increased abdominal obesity and correlated to HOMA-IR values (20) , (21). This study did not explore the relationship between DA and either fat mass or insulin resistance but the potential increased risk of altered adiposity in preterm infants in childhood makes this an interesting area of future research as potential biomarker of later metabolism. These findings are in contrast to a previous study of moderate-to-late preterm infants, which found no difference in FADS1 and FADS2 activity compared to term infants. The differences in our findings may be due to the difference in the gestational age of the infants studied. We selected infants who were very preterm (mean GA 28 weeks) and at most risk of long term cardiovascular risk compared to the previous study which focused on moderate-to-late preterm infants born between 32 to 36 weeks gestation (mean: 34 +/- 1.7). The infants in our study, who had a mean gestational age at birth of 28 weeks would also have missed the normal in utero placental transfer of DHA and ARA that occurs between 24- and 34-weeks gestation. A further difference was in methodology using total fatty acid ratios as surrogate markers to represent FADS1 and FADS2, rather than specific lipids. This study has a number of limitations including the differences in specific postnatal time points in the two cohorts. This was the due to the proactive decision to ensure all infants were fully enterally fed prior to samples being taken to avoid the potential confounding effect of parenteral nutrition. Our methodology which estimates DA from product/precursor ratios of plasma phosphatidylcholine (PC) and triglyceride (TG) may be affected by differences in dietary intake but we were unable to control for this in the clinical setting where preterm and term feeds whether formula or breast milk will vary in composition. Given the size of the study we have not explored the impact of other confounders such as maternal characteristics, gestational age or size. Conclusion In preterm infants DA changes significantly over the first few weeks of life with activity levels differing from those of term infants at both comparable postmenstrual and postnatal ages. Trajectories of changes in enzyme activity suggest these differences may persist over time but require further studies to explore this and the impact on childhood growth and metabolism. Abbreviations ARA Arachidonic acid CUH Cambridge University Hospital CBGS-BF Cambridge Baby Growth Study - Breastfeeding DA Desaturase enzyme activity DBS Dried blood spot DHA Docosahexaenoic acid D5D Delta 5 esaturase D6D Delta 6 desaturase D9D Delta 9 desaturase FADS1 Fatty acids desaturase 1 FADS2 Fatty acids desaturase 2 LCPUFAs Long chain polyunsaturated fatty acids MUFAs Monounsaturated fatty acids NICU Neonatal intensive care unit PAT Preterm at term PEF Preterm established enteral feeding PC Phosphatidylcholine PMA Post-menstrual age PUFAs Polyunsaturated fatty acids SCD1 stearoyl-COA desaturase SDS Standard deviation score SD Standard deviation TG Triglyceride VPT Very preterm Declarations Ethics approval and consent to participate Ethical and regulatory authority approvals were obtained prior to recruitment, from the National Research Ethics Service Cambridgeshire 2 Research Ethics Committee (IRAS No 67546, REC No 11/EE/0068 and Preterm Lipids study IRAS No 67546, REC No 11/EE/0068). Written informed Consent from parents for all participants were obtained prior to all data collection for both cohorts, preterm and term infants. Consent for publication All authors have approved the final manuscript prior to submission and are accountable for the integrity of the study. For the purpose of open access, the authors have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. Availability of data and materials The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors state that they have no conflicts of interest in relation to the data presented in this paper. Funding Hanis Kasim is funded by the Cambridge Trust, Jardine Foundation and Universiti Sains Islam Malaysia for her PhD. The CBGS has been funded by the Medical Research Council [7500001180, G1001995], European Union Framework 5 [QLK4- 1999?01422], the Mothercare Charitable Foundation [RG54608], Newlife Foundation for Disabled Children (07/20), and the World Cancer Research Fund International (2004/03). The authors acknowledge the support of The National Institute for Health Research Cambridge Biomedical Research Centre. Authors' contributions Kathryn Beardsall was the Principal Investigator and Albert Koulman was Co-Investigator who had the original idea for the clinical study design and data analyses respectively. They provided resources for data acquisition and analyses. Albert Koulman and Stuart Snowden undertook sample processing and analysis, Hanis Kasim and Albert Koulman undertook analysis of the data and proceed to drafting the initial manuscript and subsequent critical revisions. Kathryn Beardsall and Albert Koulman undertook critical review and revision of the manuscript. Laurentya Olga coordinated the collection of the control cohorts’ data and Eliza Cropp coordinated the collection of the preterm cohorts’ data. Acknowledgements We wish to thank the research nurses, Lynn Thomson, Ann-Marie Wardell, Suzanne Smith and Karen Forbes for recruitment and sample collection. The families of all those who participated in the studies and the clinical teams in the antenatal clinics, postnatal wards and neonatal unit at Cambridge University Hospital NHS Trust for all their support with the study. We want to thank the financial support of the Biotechnology and Biological Sciences Research Council (BB/P028195/1) for SGS and the NIHR Cambridge Biomedical Research Centre (146281) for Albert Koulman. References Carlson SJ, Fallon EM, Kalish BT, Gura KM, Puder M. The role of the ω-3 Fatty acid DHA in the human life cycle. J Parenter Enter Nutr. 2013;37(1):15–22. Olga L, van Diepen JA, Bobeldijk-Pastorova I, Gross G, Prentice PM, Snowden SG, et al. 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Cite Share Download PDF Status: Published Journal Publication published 23 Aug, 2023 Read the published version in Lipids in Health and Disease → Version 1 posted Editorial decision: Major revision 09 Apr, 2023 Reviews received at journal 17 Mar, 2023 Reviewers agreed at journal 09 Mar, 2023 Reviewers invited by journal 09 Mar, 2023 Editor assigned by journal 09 Mar, 2023 Submission checks completed at journal 09 Mar, 2023 First submitted to journal 08 Mar, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2669031","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":182031644,"identity":"dcd6c268-328a-49d5-a638-db55ca1ee90f","order_by":0,"name":"Hanis Hidayu Kasim","email":"","orcid":"","institution":"Department of Paediatrics, University of Cambridge","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hanis","middleName":"Hidayu","lastName":"Kasim","suffix":""},{"id":182031647,"identity":"827b34ad-ee65-4945-a077-dfa805e65d0f","order_by":1,"name":"Laurentya Olga","email":"","orcid":"","institution":"Department of Paediatrics, University of Cambridge","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Laurentya","middleName":"","lastName":"Olga","suffix":""},{"id":182031649,"identity":"0249e91f-64a8-4485-9898-d8df1fa91a6b","order_by":2,"name":"Stuart Snowden","email":"","orcid":"","institution":"Medical Research Council Human Nutrition Research Cambridge","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Stuart","middleName":"","lastName":"Snowden","suffix":""},{"id":182031652,"identity":"0eabaf51-5741-42b9-9c0a-ccb2783709df","order_by":3,"name":"Eliza Cropp","email":"","orcid":"","institution":"Department of Paediatrics, University of Cambridge","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Eliza","middleName":"","lastName":"Cropp","suffix":""},{"id":182031656,"identity":"2f050632-24bb-40ea-a2b1-7e787f96ccaf","order_by":4,"name":"Albert Koulman","email":"","orcid":"","institution":"Medical Research Council Human Nutrition Research Cambridge","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Albert","middleName":"","lastName":"Koulman","suffix":""},{"id":182031660,"identity":"0b5e1e85-8af4-487b-80c3-3d250e319ecb","order_by":5,"name":"Kathrynn Beardsall","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIie3RPUsDMRjA8ec4iMvh/IRK+wmElEJ1sX6V5wjc1E2QEwSvCOfoXCx+hrpkfuCgXYpdT7LUxfmm4iL0BUEREnRzyB8CB8mPvBxAKPQPQ4zn75hvvxgErL4myEME4enik3xb5yOJwqvyL0Q+FEq9PJr24bJ6WxEMOsdF/NpEZeYkrSOmdGxsT9bZiSLQXcOih1E5dJI2ElfS2HRaJwIJODIMfYjK3EPS0e3HxN5Ml4s9OTd8sPaSFuoYZGFJ8XBPUsPJbhf3weRkJgBntjuusz6S0tpUyQXSs/v6aO/XgNe2s3sxbPLBmZnfPTXNpXaSH6ntiMH3V0KhUCj0mzZE6VZKRtjzSgAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Paediatrics, University of Cambridge","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Kathrynn","middleName":"","lastName":"Beardsall","suffix":""}],"badges":[],"createdAt":"2023-03-08 10:29:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2669031/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2669031/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12944-023-01862-8","type":"published","date":"2023-08-23T15:02:09+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":34235800,"identity":"bf2db764-3617-4353-9010-c6d609623912","added_by":"auto","created_at":"2023-03-14 14:41:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":154027,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDesaturase Activity in preterm infants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBox plots of the lipid ratios, represent desaturase enzyme activity in preterm infants at two time points; preterm on establishment of enteral feeding (PEF) and preterm at term corrected age (PAT). The boxes indicate 25\u003csup\u003eth\u003c/sup\u003e -75\u003csup\u003eth\u003c/sup\u003e percentile and a median line.\u003c/p\u003e\n\u003cp\u003eValues are in mean (SD). Abbreviation: PEF-Preterm on established enteral feeding, PAT – preterm at Term, SCD 1- stearoyl-COA desaturase, FADS 1- fatty acid desaturases 1, FADS 2- fatty acid desaturases 1, PC-phosphatidylcholine, TG-triglyceride. \u003cem\u003eP\u003c/em\u003e values were obtained by the Mann-Whitney U test. *\u003cem\u003ep\u003c/em\u003e\u0026lt; .05, **\u003cem\u003ep\u003c/em\u003e\u0026lt; .001\u003c/p\u003e","description":"","filename":"F1.png","url":"https://assets-eu.researchsquare.com/files/rs-2669031/v1/564078c9d98cef3c77dde5e5.png"},{"id":34235799,"identity":"a367c802-5239-4ce1-8ec9-5904538e5a85","added_by":"auto","created_at":"2023-03-14 14:41:40","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":386174,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDesaturase Enzyme Activity Trajectories in Preterm and Term Infants.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDesaturase enzyme activity over time comparing preterm infants with term infants in relation to postmenstrual (32 and 38 gestational age) and postnatal age (4 and 10 weeks).\u003c/p\u003e\n\u003cp\u003eAbbreviations: SCD 1- stearoyl-COA desaturase, FADS1- fatty acid desaturases 1, FADS2- fatty acid desaturases 1, PC-phosphatidylcholine, TG-triglyceride, PMA – postmenstrual age, PNA – postnatal age, W – weeks.\u003c/p\u003e","description":"","filename":"DesaturaseEnzymeActivityinPretermInfantsFIGURESCopy.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2669031/v1/638dc60a084397af68c7f688.jpg"},{"id":42781267,"identity":"b888172a-9556-4eb3-b408-b4edfc8b642e","added_by":"auto","created_at":"2023-09-07 15:09:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":532215,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2669031/v1/7d9c792c-6f8b-4096-88f9-28302d67a8c3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Comparative Analyses of Lipid Ratios Representing Desaturase Enzyme Activity between Preterm and Term Infants Within the First Ten Weeks of Life","fulltext":[{"header":"Background","content":"\u003cp\u003eDesaturase enzymes play a key role in a number of biochemical pathways including biosynthesis of long chain poly unsaturated fatty acids (LCPUFAs). Altered desaturase activity has been associated with increased risks for metabolic derangements including type 2 diabetes and cardiovascular disease, as well as pro-inflammatory processes. In preterm infants desaturase enzyme activity (DA) may be a rate-limiting step in maintaining PUFA levels during this critical developmental window. LCPUFAs are essential for the structure and function of cell membranes and for growth, with impacts on body composition immunity, and neurocognition(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Humans are unable to synthesise LCPUFAs de novo and need to obtain these, and their precursors from the diet. Desaturase and elongases enzymes play a critical role in the conversion of saturated fatty acids in the diet to LCPUFAs.\u003c/p\u003e \u003cp\u003eRecent studies in term infants have shown that DA in the first months of life are associated with subsequent body size increase, providing a potential tool to predict early life weight gain (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), while low levels of DA has been associated with insulin resistance, diabetes, and obesity (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003csup\u003e,\u003c/sup\u003e(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Preterm infants born before 32 weeks gestation miss out on the transfer of LCPUFAs and are known to be at risk of deficiency of docosahexaenoic acid (DHA) and/or arachidonic acid (ARA) that can result in impaired growth and development, (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003csup\u003e,\u003c/sup\u003e(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) as well as increased risk of cardiovascular disease and metabolic syndrome in later life. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003csup\u003e,\u003c/sup\u003e(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) These deficiencies may not only be caused by DHA availability, DA due to or in combination with precursor deficiency can also limit the availability of DHA and ARA for healthy development in preterm infants.\u003c/p\u003e \u003cp\u003eThere are three main desaturase enzymes identified in human: fatty acid desaturase 1 and 2 (FADS1, FADS2) and stearoyl-COA desaturase 1 (SCD1). There are more desaturase enzymes like FADS3, but their exact functions remain unclear, likely to be specific to certain lipid types. While FADS1 or delta 5 desaturase (D5D) and FADS2 or delta 6 desaturase (D6D) are important in PUFA synthesis, SCD1 or delta 9 desaturase (D9D) plays a key role in the synthesis of monounsaturated fatty acids (MUFAs) (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). There are limited data on DA in preterm infants, in part due to the challenges of blood sampling in these very small infants. We have developed an innovative methodology that allows detailed lipidomic analyses from the small volumes of blood that can be collected onto filter paper as dried blood spots. To observe the evidence of DA alterations in preterm infants, we aimed to explore changes in DA activity in very preterm (VPT) infants in the first weeks of life after they established feedings and after they reached term corrected age and compare that to the healthy term infants.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis is comparative analyses of data from two cohorts. Preterm infants were part of a single centre study of preterm lipid metabolism. Infants were prospectively recruited from the neonatal intensive care unit (NICU) from July 2016 - June 2019 at Rosie Birth Centre, Cambridge University Hospitals NHS Foundation Trust (CUH). Inclusion criteria were gestational age at birth\u0026thinsp;\u0026lt;\u0026thinsp;32 completed weeks and parental consent with exclusion factors including serious congenital defects, life threatening illness, treatment with antibiotics, necrotizing enterocolitis or serious gastrointestinal abnormalities. The term infants were participants from the Cambridge Baby Growth Breastfeeding (CBGS-BF) study, enrolled in the study between 2001\u0026ndash;2019. The cohort profile has been described previously (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003csup\u003e,\u003c/sup\u003e(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSample collection\u003c/p\u003e \u003cp\u003eIn the preterm cohort samples were collected at two time points: i. within 48 hours of establishing full enteral feeds (preterm established enteral feeding, PEF), ii. at term corrected age (preterm at term, PAT). Term was defined as \u0026gt;\u0026thinsp;37 weeks postmenstrual age. For the term cohort, samples were taken at birth, two weeks, and six weeks postnatal age. Heel prick blood samples were collected onto untreated filter paper cards (Guthrie cards, Ahlstrom 226; ID Biological Systems, Greenville, South Carolina) as single drops of blood on defined circles (x5). The cards were left to dry naturally for 24 hours then stored at -80\u0026deg;C until batch analyses. Clinical data including antenatal history, clinical course, and feeding history were collected prospectively from the hospital medical records, and from validated parental questionnaires.\u003c/p\u003e \u003cp\u003eSample Processing\u003c/p\u003e \u003cp\u003eDried blood spot (DBS) samples were first extracted for determination of lipid species and their relative abundances, using mass spectrometry, as described previously (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Product-to-precursor ratio of fatty acids was measured as a surrogate marker for DA, as reported in previous studies (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003csup\u003e,\u003c/sup\u003e(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003csup\u003e,\u003c/sup\u003e(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). For this study, SCD-1 was estimated by PC(32:1)/PC(32:0) ratio, whereas PC(38:4)/(38:3) and TG(54:4)/(54:3) ratios represented FADS1 enzyme activity. FADS 2 activity was approximated by the PC(36:3)/(36:2) and TG(50:3)/(50:2) ratios (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003csup\u003e,\u003c/sup\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003csup\u003e,\u003c/sup\u003e(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAnalyses\u003c/p\u003e \u003cp\u003eDemographic data were analysed using SPSS version 23.0 for windows 10 (IBM Corp Released 2012.Armonk, NY). Weight data was converted to sex and age-adjusted standard deviation scores (SDS) using the British 1990 growth reference and the WHO 2006 growth standard. The LMS growth was used to calculate standard deviation scores (SDS) in Microsoft Excel (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003csup\u003e,\u003c/sup\u003e(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Demographic data are presented as mean standard deviation (SD) and frequencies.\u003c/p\u003e \u003cp\u003eThe raw lipid data were initially normalized through log transformation in Metaboanalyst 5.0 and SPSS (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Respective lipid values then were calculated into five lipid ratios, as described previously. These lipids ratio which represents SCD1, FADS1 and FADS2 were checked for normality test. One preterm subject (in PEF group) was identified as an outlier and was therefore removed from further analyses. The data then were tested with T-Test/Mann-Whitney or ANOVA/Kruskal Wallis in SPSS to get further details on mean/median differences (+/- SD) between the cohort.\u003c/p\u003e \u003cp\u003eThe trajectories of lipid ratios were explored through Metaboanalyst 5.0. Bonferroni correction for multiple testing was also applied as lipidome analysis consist of large numbers of variables and comparisons. Bonferroni corrected \u003cem\u003ep\u003c/em\u003e-value was used based on dividing the significance threshold of 0.05 by the number of lipids analysed. DA activity at specific time points and trajectories over time were compared between cohorts by plotting activity with respect to both gestational age and postnatal age. Post hoc analyses were undertaken to explore the effect of extreme prematurity with preterm infants divided further into very preterm and extremely preterm.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eData were available for a total of 78 preterm infants and 256 term infants. Preterm infants were born at mean (SD) of 28(2.2) weeks gestational age and term infants had a mean (SD) gestational age of 39 (2.2) weeks, with the preterm infants being statistically smaller than the term infants at all study assessments. The majority of all infants in all groups received breast milk. Further demographic details are provided in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: Clinical Characteristics.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"665\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"34.08408408408408%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreterm Cohort\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"47.447447447447445%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTerm Cohort\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"22.65193370165746%\"\u003e\n \u003cp\u003ePEF\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(n=67)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.152854511970535%\"\u003e\n \u003cp\u003ePAT\u003c/p\u003e\n \u003cp\u003e(n=38)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.152854511970535%\"\u003e\n \u003cp\u003eBirth\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(n= 82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.152854511970535%\"\u003e\n \u003cp\u003e2 weeks\u0026nbsp;\u003c/p\u003e\n \u003cp\u003epost delivery\u003c/p\u003e\n \u003cp\u003e(n=93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.88950276243094%\"\u003e\n \u003cp\u003e6 weeks\u003c/p\u003e\n \u003cp\u003epost delivery\u003c/p\u003e\n \u003cp\u003e(n=81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGestational Age at Birth\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(weeks)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e28.00\u003c/p\u003e\n \u003cp\u003e(2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e28.00\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e39.77\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e39.77\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.216216216216218%\"\u003e\n \u003cp\u003e39.88\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at assessment\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e4 (2)\u003c/p\u003e\n \u003cp\u003eweeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e10 (3)\u003c/p\u003e\n \u003cp\u003eweeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e5 (2)\u003c/p\u003e\n \u003cp\u003edays\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e2 (1)\u003c/p\u003e\n \u003cp\u003eweeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.216216216216218%\"\u003e\n \u003cp\u003e6 (0)\u003c/p\u003e\n \u003cp\u003eweeks\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e♂: 28 (40%)\u003c/p\u003e\n \u003cp\u003e♀: 42 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e♂:20 (53%)\u003c/p\u003e\n \u003cp\u003e♀:18 (47%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e♂:39 (47%)\u003c/p\u003e\n \u003cp\u003e♀:43 (53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e♂:39 (42%)\u003c/p\u003e\n \u003cp\u003e♀:54 (58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.216216216216218%\"\u003e\n \u003cp\u003e♂:33 (41%)\u003c/p\u003e\n \u003cp\u003e♀:48 (59%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeight at birth (g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e1117 (407)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e1125 (389)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e3605 (505)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e3657 (487)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.216216216216218%\"\u003e\n \u003cp\u003e3680 (537)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeight SDS at birth\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e-0.34 (1.25)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e-0.37 (1.31)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e0.41 (0.92)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e0.51 (0.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.216216216216218%\"\u003e\n \u003cp\u003e0.50 (1.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeight at assessment (g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e1456 (422)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e2488 (555)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e3593 (492)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e3981 (612)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.216216216216218%\"\u003e\n \u003cp\u003e4866 (115)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeight SDS at assessment\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e-1.81 (2.16)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e-1.61 (1.39)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e0.046 (0.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003e0.13 (0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.216216216216218%\"\u003e\n \u003cp\u003e0.57 (1.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFeeding type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.46846846846847%\"\u003e\n \u003cp\u003eBM 42 (60%)\u003c/p\u003e\n \u003cp\u003eFM 7 (10%)\u003c/p\u003e\n \u003cp\u003eMF 18 (27%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003eBM 22 (58%)\u003c/p\u003e\n \u003cp\u003eFM 10 (26%)\u003c/p\u003e\n \u003cp\u003eMF 6 (16%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003eBM 71 (87%)\u003c/p\u003e\n \u003cp\u003eFM 4 (5%)\u003c/p\u003e\n \u003cp\u003eMF 6 (7%)\u003c/p\u003e\n \u003cp\u003eNA 1(1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.615615615615615%\"\u003e\n \u003cp\u003eBM 81 (87%)\u003c/p\u003e\n \u003cp\u003eFM 2 (2%)\u003c/p\u003e\n \u003cp\u003eMF 10 (11%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.216216216216218%\"\u003e\n \u003cp\u003eBM 64 (79%)\u003c/p\u003e\n \u003cp\u003eFM 4 (5%)\u003c/p\u003e\n \u003cp\u003eMF 13 (16%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviation: PEF \u0026ndash;Preterm established on enteral feeding, PAT \u0026ndash; Preterm at Term, BM \u0026ndash; Breast milk, FM \u0026ndash; Formula Milk, MF \u0026ndash; Mixed Feeding. Data is given as n (%) or mean (SD) NA \u0026ndash; not available\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eDesaturase Activity in Preterm Infants\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eAs shown in Figure 1 there were significant differences in specific DA between the two study time points. \u0026nbsp;FADS1(TG), FADS2(PC) and SCD1 levels were lower at term corrected age, compared to when preterm infants were first established on enteral feeds. In contrast FADS1(PC) and FADS2(TG) levels were higher at term corrected age.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 1\u003c/strong\u003e Box plots of the lipid ratios, represent desaturase enzyme activity in preterm infants at two time points; preterm on establishment of enteral feeding (PEF) and preterm at term corrected age (PAT). The boxes indicate 25\u003csup\u003eth\u003c/sup\u003e -75\u003csup\u003eth\u003c/sup\u003e percentile and a median line.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eValues are in mean (SD). Abbreviation: PEF-Preterm on established enteral feeding, PAT \u0026ndash; preterm at Term, SCD 1- stearoyl-COA desaturase, FADS 1- fatty acid desaturases 1, FADS 2- fatty acid desaturases 1, PC-phosphatidylcholine, TG-triglyceride. \u003cem\u003eP\u003c/em\u003e values were obtained by the Mann-Whitney U test. *\u003cem\u003ep\u003c/em\u003e\u0026lt; .05, **\u003cem\u003ep\u003c/em\u003e\u0026lt; .001\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eComparison of DA between preterm and term infants\u0026nbsp;\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eTable 2a show that PEF infants had similar SCD1 with term infants at birth, but significantly different from term infants at 2- and 6-weeks postnatal age (p=0.001). At term corrected age (\u0026gt;37 weeks PMA), SCD1 was statistically lower than term infants at birth (Table 2b). FADS1 activity was consistently lower in preterm infants at both time points compared to term infants from birth to 6 weeks of age.\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2a: Lipid ratios among preterm infants on establishment of enteral feeds (PEF) \u0026nbsp;and term infants\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.18864774624374%\"\u003e\n \u003cp\u003eVARIABLES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.681135225375627%\"\u003e\n \u003cp\u003ePEF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003eTAB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.181969949916528%\"\u003e\n \u003cp\u003eZ score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.181969949916528%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003eT2W\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.679465776293823%\"\u003e\n \u003cp\u003eZ score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.515859766277128%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003eT6W\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.347245409015025%\"\u003e\n \u003cp\u003eZ score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.68280467445743%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.18864774624374%\"\u003e\n \u003cp\u003eSCD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.681135225375627%\"\u003e\n \u003cp\u003e0.43 (0.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003cp\u003e(0.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.181969949916528%\"\u003e\n \u003cp\u003e-0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.181969949916528%\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003cp\u003e(0.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.679465776293823%\"\u003e\n \u003cp\u003e-5.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.515859766277128%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003cp\u003e(0.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.347245409015025%\"\u003e\n \u003cp\u003e-6.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.68280467445743%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.18864774624374%\"\u003e\n \u003cp\u003eFADS1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(PC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.681135225375627%\"\u003e\n \u003cp\u003e3.08 (1.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e6.05\u003c/p\u003e\n \u003cp\u003e(3.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.181969949916528%\"\u003e\n \u003cp\u003e-7.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.181969949916528%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e3.88\u003c/p\u003e\n \u003cp\u003e(3.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.679465776293823%\"\u003e\n \u003cp\u003e-3.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.515859766277128%\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e3.59\u003c/p\u003e\n \u003cp\u003e(1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.347245409015025%\"\u003e\n \u003cp\u003e-3.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.68280467445743%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.18864774624374%\"\u003e\n \u003cp\u003eFADS1\u003c/p\u003e\n \u003cp\u003e(TG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.681135225375627%\"\u003e\n \u003cp\u003e1.23 (0.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e2.21\u003c/p\u003e\n \u003cp\u003e(1.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.181969949916528%\"\u003e\n \u003cp\u003e-7.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.181969949916528%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e1.39\u003c/p\u003e\n \u003cp\u003e(0.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.679465776293823%\"\u003e\n \u003cp\u003e-3.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.515859766277128%\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e1.28\u003c/p\u003e\n \u003cp\u003e(0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.347245409015025%\"\u003e\n \u003cp\u003e-1.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.68280467445743%\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.18864774624374%\"\u003e\n \u003cp\u003eFADS2\u003c/p\u003e\n \u003cp\u003e(PC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.681135225375627%\"\u003e\n \u003cp\u003e0.53 (0.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003cp\u003e(0.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.181969949916528%\"\u003e\n \u003cp\u003e-4.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.181969949916528%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003cp\u003e(0.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.679465776293823%\"\u003e\n \u003cp\u003e-4.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.515859766277128%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003cp\u003e(0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.347245409015025%\"\u003e\n \u003cp\u003e-8.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.68280467445743%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.18864774624374%\"\u003e\n \u003cp\u003eFADS2\u003c/p\u003e\n \u003cp\u003e(TG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.681135225375627%\"\u003e\n \u003cp\u003e0.72 (0.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003cp\u003e(0.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.181969949916528%\"\u003e\n \u003cp\u003e-9.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.181969949916528%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003cp\u003e(0.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.679465776293823%\"\u003e\n \u003cp\u003e-8.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.515859766277128%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.180300500834724%\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003cp\u003e(0.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.347245409015025%\"\u003e\n \u003cp\u003e-6.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.68280467445743%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2a\u003c/strong\u003e The comparison of lipid ratios among PEF and term infants at birth, 2 weeks, and 6 weeks. Lipid ratios were presented as mean (SD), but for statistical significance, the mean ranks among the groups were compared. Abbreviation: PEF \u0026ndash; preterm after establishing enteral feeding, SCD 1- stearoyl-COA desaturase, FADS 1- fatty acid desaturases 1, FADS 2- fatty acid desaturases 1, PC-phosphatidylcholine, TG-triglyceride. P values were obtained by Kruskal Wallis Test and Post Hoc by Mann Whitney U-Test with Bonferroni adjustment at \u003cem\u003ep\u003c/em\u003e\u0026lt;.0001, *\u003cem\u003ep\u003c/em\u003e\u0026lt;.05, *\u003cem\u003ep\u003c/em\u003e\u0026lt;.001\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2b: Lipid ratios among preterm at term (PAT) and term infants\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"602\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.086235489220563%\"\u003e\n \u003cp\u003eVARIABLES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.457711442786069%\"\u003e\n \u003cp\u003ePAT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.291873963515755%\"\u003e\n \u003cp\u003eTAB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"7.960199004975125%\"\u003e\n \u003cp\u003eZ score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.457711442786069%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.291873963515755%\"\u003e\n \u003cp\u003eT2W\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.628524046434494%\"\u003e\n \u003cp\u003eZ score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.12106135986733%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"9.286898839137645%\"\u003e\n \u003cp\u003eT6W\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.628524046434494%\"\u003e\n \u003cp\u003eZ score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.7893864013267%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.11295681063123%\"\u003e\n \u003cp\u003eSCD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e0.32 (0.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003cp\u003e(0.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"7.641196013289036%\"\u003e\n \u003cp\u003e-3.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.637873754152825%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003cp\u003e(0.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"7.807308970099668%\"\u003e\n \u003cp\u003e-1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.136212624584717%\"\u003e\n \u003cp\u003e0.296\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003cp\u003e(0.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"8.803986710963455%\"\u003e\n \u003cp\u003e-2.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.637873754152825%\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.11295681063123%\"\u003e\n \u003cp\u003eFADS1\u003c/p\u003e\n \u003cp\u003e(PC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e3.15 (0.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e6.05\u003c/p\u003e\n \u003cp\u003e(3.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"7.641196013289036%\"\u003e\n \u003cp\u003e-5.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.637873754152825%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e3.88\u003c/p\u003e\n \u003cp\u003e(3.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"7.807308970099668%\"\u003e\n \u003cp\u003e-1.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.136212624584717%\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e3.59\u003c/p\u003e\n \u003cp\u003e(1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"8.803986710963455%\"\u003e\n \u003cp\u003e-2.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.637873754152825%\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.11295681063123%\"\u003e\n \u003cp\u003eFADS1\u003c/p\u003e\n \u003cp\u003e(TG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e1.13 (0.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e2.21\u003c/p\u003e\n \u003cp\u003e(1.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"7.641196013289036%\"\u003e\n \u003cp\u003e-7.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.637873754152825%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e1.39\u003c/p\u003e\n \u003cp\u003e(0.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"7.807308970099668%\"\u003e\n \u003cp\u003e-4.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.136212624584717%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e1.28\u003c/p\u003e\n \u003cp\u003e(0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"8.803986710963455%\"\u003e\n \u003cp\u003e-3.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.637873754152825%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.11295681063123%\"\u003e\n \u003cp\u003eFADS2\u003c/p\u003e\n \u003cp\u003e(PC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e0.46 (0.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003cp\u003e(0.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"7.641196013289036%\"\u003e\n \u003cp\u003e-5.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.637873754152825%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003cp\u003e(0.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"7.807308970099668%\"\u003e\n \u003cp\u003e-1.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.136212624584717%\"\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003cp\u003e(0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"8.803986710963455%\"\u003e\n \u003cp\u003e-3.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.637873754152825%\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.11295681063123%\"\u003e\n \u003cp\u003eFADS2\u003c/p\u003e\n \u003cp\u003e(TG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e0.83 (0.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003cp\u003e(0.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"7.641196013289036%\"\u003e\n \u003cp\u003e-8.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.637873754152825%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003cp\u003e(0.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"7.807308970099668%\"\u003e\n \u003cp\u003e-8.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.136212624584717%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.305647840531561%\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003cp\u003e(0.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"8.803986710963455%\"\u003e\n \u003cp\u003e-6.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.637873754152825%\"\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2b\u003c/strong\u003e Comparison of lipid ratios among PAT and term infants at birth, 2 weeks, and 6 weeks. Lipid ratios were presented as mean (SD), but for statistical significance, the mean ranks among the groups were compared. \u0026nbsp;Abbreviation: PAT \u0026ndash; preterm at term, SCD 1- stearoyl-COA desaturase, FADS 1- fatty acid desaturases 1, FADS 2- fatty acid desaturases 1, PC-phosphatidylcholine, TG-triglyceride. P values were obtained by Kruskal Wallis Test, and Post Hoc by Mann Whitney U-Test with Bonferroni adjustment at \u003cem\u003ep\u003c/em\u003e\u0026lt;.0001, *\u003cem\u003ep\u003c/em\u003e\u0026lt;.05, *\u003cem\u003ep\u003c/em\u003e\u0026lt;.001.\u003c/p\u003e\n\u003cp\u003eFADS2 in preterm infants was generally higher than term infants at 2 and 6 weeks and especially FADS2(TG) was significantly higher than term infants, at all time points. Similarly in PEF infants\u0026rsquo; FADS2(PC) activity was higher than that of term infants at 2 and 6 weeks (p\u0026lt;0.001). Although FADS2(PC) activity was lower in PAT compared to term infants at birth, it was higher than term infants at 6 weeks (p\u0026lt;0.03).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDesaturase enzyme activity in the cohorts over time is shown in Figure 2, with preterm infant results plotted in duplicate to show levels in relation to postmenstrual (32 and 38 weeks) and postnatal age (4 and 10 weeks).\u0026nbsp;This shows that although there were significant differences in DA levels at specific time points for most of the DA, the trajectories of activity over time were similar in the two cohorts. The exception to this was the contradict trajectory in FADS1(PC) between the cohorts and a rapid fall in FADS1 activity from birth to 2 weeks postnatal age in the term cohort.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThese results are the first to show the significant differences in DA in a cohort of very preterm infants compared to term controls over the first weeks of life. \u0026nbsp;They also show that although there were significant differences in DA levels at specific time points the trajectory of changes in activity over time were similar in the two cohorts, although offset in terms of absolute levels of activity. As desaturase enzymes play a key role in a number of biochemical pathways including potentially being a\u0026nbsp;rate-limiting step in maintaining LCPUFA levels, altered activity may impact on both short-term metabolism and long-term health.\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDesaturase activity can be affected by many factors including diet with altered gene expression(19)\u0026nbsp;. To avoid the confounding impact of parenteral nutrition we only sampled preterm infants when established on full enteral feeds. In this cohort more preterm infants were receiving formula than term infants, and both volume and composition of breast milk and formula will have varied between the two cohorts. In this study design, we are unable to determine the causal factors for the differences shown. Larger studies would be needed to further investigate the impact of different dietary intakes on desaturase activity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere is a lack of validated biochemical reference ranges specific for the neonatal population which is a time of significant metabolic adaptation. For preterm infants postmenstrual age may provide a more developmentally appropriate reference compared to postnatal age although nutritional advice for preterm infants is guided both by gestation at birth and postnatal age. Our results suggest that changes of DA in preterm infants are in keeping with the changes seen in term infants from birth to 2-and-6 weeks postnatal age, suggesting reducing trends of MUFAs and LCPUFAs endogenous biosynthesis as infants reach 6 - 10 weeks postnatal age. Regardless of feeding type, this finding supports that preterm infants have the capacity to convert precursors fatty acids to LCPUFAs as expected for their postnatal age. Further studies would help to determine what changes in activity happen in utero at a comparable gestational age.\u0026nbsp;These changes in DA over time from birth and interaction with gestational age warrant further studies to determine if the differences in activity persist into childhood.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePreterm infants in our study demonstrated lower FADS1 and higher FADS2 activity relative to term cohorts,\u0026nbsp;could be considered as a sign of alterations in DA. A series of transition periods, from intrauterine to extrauterine, from parenteral to enteral feeding and apparent growth changes at term corrected age are potentially demanding for metabolic adaptation, but the exact mechanism is indeterminate.\u0026nbsp;It is known that FADS1 and FADS2 activity effect the balance of omega-3 and omega-6 synthesis, and that imbalance of omega 3-and-6 can be harmful to human health\u0026nbsp;(8). In two childhood studies, low FADS1 and high FADS2 activity is associated with increased abdominal obesity and correlated to HOMA-IR values\u0026nbsp;(20)\u003csup\u003e,\u003c/sup\u003e(21).\u0026nbsp;This study did not explore the relationship between DA and either fat mass or insulin resistance but the potential increased risk of altered adiposity in preterm infants in childhood makes this an interesting area of future research as potential biomarker of later metabolism.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThese findings are in contrast to a previous study of moderate-to-late preterm infants, which found no difference in FADS1 and FADS2 activity compared to term infants. The differences in our findings may be due to the difference in the gestational age of the infants studied. We selected infants who were very preterm (mean GA 28 weeks) and at most risk of long term cardiovascular risk compared to the previous study which focused on moderate-to-late preterm infants born between 32 to 36 weeks gestation (mean: 34 +/- 1.7). The infants in our study, who had a mean gestational age at birth of 28 weeks would also have missed the normal in utero placental transfer of DHA and ARA that occurs between 24- and 34-weeks gestation. A further difference was in methodology using total fatty acid ratios as surrogate markers to represent FADS1 and FADS2, rather than specific lipids.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study has a number of limitations including the differences in specific postnatal time points in the two cohorts. This was the due to the proactive decision to ensure all infants were fully enterally fed prior to samples being taken to avoid the potential confounding effect of parenteral nutrition. Our methodology which estimates DA from product/precursor ratios of plasma phosphatidylcholine (PC) and triglyceride (TG) may be affected by differences in dietary intake but we were unable to control for this in the clinical setting where preterm and term feeds whether formula or breast milk will vary in composition. Given the size of the study we have not explored the impact of other confounders such as maternal characteristics, gestational age or size. \u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn preterm infants\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eDA changes significantly over the first few weeks of life with activity levels differing from those of term infants at both comparable postmenstrual and postnatal ages. Trajectories of changes in enzyme activity suggest these differences may persist over time but require further studies to explore this and the impact on childhood growth and metabolism.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eARA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eArachidonic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eCUH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eCambridge University Hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eCBGS-BF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eCambridge Baby Growth Study - Breastfeeding\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eDA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eDesaturase enzyme activity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eDBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eDried blood spot\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eDHA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eDocosahexaenoic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eD5D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eDelta 5 esaturase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eD6D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eDelta 6 desaturase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eD9D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eDelta 9 desaturase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eFADS1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eFatty acids desaturase 1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eFADS2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eFatty acids desaturase 2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eLCPUFAs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eLong chain polyunsaturated fatty acids\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eMUFAs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eMonounsaturated fatty acids\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eNICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eNeonatal intensive care unit\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003ePAT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003ePreterm at term\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003ePEF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003ePreterm established enteral feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003ePC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003ePhosphatidylcholine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003ePMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003ePost-menstrual age\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003ePUFAs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003ePolyunsaturated fatty acids\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eSCD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003estearoyl-COA desaturase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eSDS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eStandard deviation score\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eStandard deviation\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eTriglyceride\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.96339434276206%\"\u003e\n \u003cp\u003eVPT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"78.03660565723794%\"\u003e\n \u003cp\u003eVery preterm\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical and regulatory authority approvals were obtained prior to recruitment, from the National Research Ethics Service Cambridgeshire 2 Research Ethics Committee (IRAS No 67546, REC No 11/EE/0068 and Preterm Lipids study IRAS No 67546, REC No 11/EE/0068).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWritten informed Consent from parents for all participants were obtained prior to all data collection for both cohorts, preterm and term infants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have approved the final manuscript prior to submission and are accountable for the integrity of the study.\u0026nbsp;For the purpose of open access, the authors have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors state that they have no conflicts of interest in relation to the data presented in this paper.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHanis Kasim is funded by the Cambridge Trust, Jardine Foundation and Universiti Sains Islam Malaysia for her PhD. \u0026nbsp;The CBGS has been funded by the Medical Research Council [7500001180, G1001995], European Union Framework 5 [QLK4- 1999?01422], the Mothercare Charitable Foundation [RG54608], Newlife Foundation for Disabled Children (07/20), and the World Cancer Research Fund International (2004/03).\u0026nbsp;The authors acknowledge the support of The National Institute\u0026nbsp;for Health Research Cambridge Biomedical Research Centre.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKathryn Beardsall was the Principal Investigator and Albert Koulman was Co-Investigator who had the original idea for the clinical study design and data analyses respectively. They provided resources for data acquisition and analyses. Albert Koulman and Stuart Snowden undertook sample processing and analysis, Hanis Kasim and Albert Koulman undertook analysis of the data and proceed to drafting the initial manuscript and subsequent critical revisions. Kathryn Beardsall and Albert Koulman undertook critical review and revision of the manuscript. Laurentya Olga coordinated the collection of the control cohorts\u0026rsquo; data and Eliza Cropp coordinated the collection of the preterm cohorts\u0026rsquo; data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe wish to thank the research nurses, Lynn Thomson, Ann-Marie Wardell, Suzanne Smith and Karen Forbes for recruitment and sample collection. The families of all those who participated in the studies and the clinical teams in the antenatal clinics, postnatal wards and neonatal unit at Cambridge University Hospital NHS Trust for all their support with the study. We want to thank the financial support of the Biotechnology and Biological Sciences Research Council (BB/P028195/1) for SGS and the NIHR Cambridge Biomedical Research Centre (146281) for Albert Koulman.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCarlson SJ, Fallon EM, Kalish BT, Gura KM, Puder M. The role of the ω-3 Fatty acid DHA in the human life cycle. J Parenter Enter Nutr. 2013;37(1):15\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlga L, van Diepen JA, Bobeldijk-Pastorova I, Gross G, Prentice PM, Snowden SG, et al. Lipid ratios representing SCD1, FADS1, and FADS2 activities as candidate biomarkers of early growth and adiposity. EBioMedicine. 2021;63:1\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmstrong D. Lipidomics. Volume 1: Methods and protocols. Springer New York Dordrecht Heidelberg London. 2009.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWolters M, Schlenz H, B\u0026ouml;rnhorst C, Ris\u0026eacute; P, Galli C, Moreno LA, et al. Desaturase activity is associated with weight status and metabolic risk markers in young children. J Clin Endocrinol Metab. 2015;100(10):3760\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarris WS, Baack ML. Beyond building better brains: bridging the docosahexaenoic acid (DHA) gap of prematurity. J Perinatol. 2015;35(1):1\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUthaya S, Liu X, Babalis D, Dore C, Warwick J, Bell J, et al. 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Nutrients. 2016;8(1):1\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrentice P, Acerini CL, Eleftheriou A, Hughes IA, Ong KK, Dunger DB. Cohort profile: The Cambridge Baby Growth Study (CBGS). Int J Epidemiol. 2016;45(1):35\u0026ndash;35g.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlga L, Petry CJ, van Diepen JA, Prentice PM, Hughes IA, Vervoort J et al. Extensive study of breast milk and infant growth: Protocol of the Cambridge baby growth and breastfeeding study (CBGS-BF).Nutrients. 2021;13(8).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoulman A, Prentice P, Wong MCY, Matthews L, Bond NJ, Eiden M, et al. The development and validation of a fast and robust dried blood spot based lipid profiling method to study infant metabolism. Metabolomics. 2014;10(5):1018\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNagano N, Okada T, Kayama K, Hosono S, Kitamura Y, Takahashi S. 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Biological role of unsaturated fatty acid desaturases in health and disease.Nutrients. 2020;12(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaito E, Okada T, Abe Y, Odaka M, Kuromori Y, Iwata F et al. Abdominal adiposity is associated with fatty acid desaturase activity in boys: Implications for C-reactive protein and insulin resistance. Vol. 88, Prostaglandins Leukotrienes and Essential Fatty Acids. 2013. p.307\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeccarelli LM, Scherr RE, Newman JW, Borkowska AG, Gray IJ, Linnell JD, et al. Associations Among Fatty Acids, Desaturase and Elongase, and Insulin Resistance in Children. J Am Coll Nutr. 2018;37(1):44\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"lipids-in-health-and-disease","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lhad","sideBox":"Learn more about [Lipids in Health and Disease](http://lipidworld.biomedcentral.com/)","snPcode":"12944","submissionUrl":"https://submission.nature.com/new-submission/12944/3","title":"Lipids in Health and Disease","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Desaturase enzyme, preterm infants, LCPUFAs, metabolism","lastPublishedDoi":"10.21203/rs.3.rs-2669031/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2669031/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDesaturase enzymes play a key role in several pathways including biosynthesis of poly unsaturated fatty acids (PUFAs). In preterm infants, desaturase enzyme activity (DA) may be a rate-limiting step in maintaining PUFAs levels during this critical developmental window and impact on long term metabolic health. The study tested the hypothesis that desaturase enzyme activity is altered in preterm infants compared to term infants in early life.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eLipidomic analyses were conducted using blood samples from two established UK-based cohorts, involving very preterm (n\u0026thinsp;=\u0026thinsp;105) and term (n\u0026thinsp;=\u0026thinsp;259) infants. Blood samples were taken from term infants at birth, two and six weeks and from preterm infants when established on enteral feeds and at term corrected age. DA of the 2 groups of infants were estimated from product/precursor lipids ratios of phosphatidylcholine (PC) and triglycerides (TG) species and reported according to their postmenstrual and postnatal ages.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThere were changes in lipid ratios representing desaturase enzyme activity in preterm infants in the first weeks of life with increasing activity of fatty acid desaturase 2 (FADS2) TG but a significant reducing activity of stearoyl-COA desaturase (SCD1) and FADS2(PC). In comparison to term infants, preterm have lower FADS1 but higher FADS2 at all postnatal ages. Although point levels of DA were different, trajectories of changes in DA over time were similar in preterm and term infants.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis study findings suggest the patterns of DA in preterm infants differ from that of term infants but their trajectories of change in the first 10 weeks of life were similar. These differences of desaturases activity if they persist in later life could contribute to the mechanism of diseases in preterm adulthood and warrant further investigations.\u003c/p\u003e","manuscriptTitle":"A Comparative Analyses of Lipid Ratios Representing Desaturase Enzyme Activity between Preterm and Term Infants Within the First Ten Weeks of Life","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-03-14 14:41:35","doi":"10.21203/rs.3.rs-2669031/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-04-09T06:22:41+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-03-17T18:15:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"112bf66f-3cbe-4951-8b95-577c821eca80","date":"2023-03-09T08:47:27+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-03-09T08:25:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-03-09T07:34:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-03-09T07:34:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"Lipids in Health and Disease","date":"2023-03-08T10:17:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"lipids-in-health-and-disease","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lhad","sideBox":"Learn more about [Lipids in Health and Disease](http://lipidworld.biomedcentral.com/)","snPcode":"12944","submissionUrl":"https://submission.nature.com/new-submission/12944/3","title":"Lipids in Health and Disease","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a61032f0-114c-4f40-8517-63a165cc60da","owner":[],"postedDate":"March 14th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-09-07T15:07:18+00:00","versionOfRecord":{"articleIdentity":"rs-2669031","link":"https://doi.org/10.1186/s12944-023-01862-8","journal":{"identity":"lipids-in-health-and-disease","isVorOnly":false,"title":"Lipids in Health and Disease"},"publishedOn":"2023-08-23 15:02:09","publishedOnDateReadable":"August 23rd, 2023"},"versionCreatedAt":"2023-03-14 14:41:35","video":"","vorDoi":"10.1186/s12944-023-01862-8","vorDoiUrl":"https://doi.org/10.1186/s12944-023-01862-8","workflowStages":[]},"version":"v1","identity":"rs-2669031","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2669031","identity":"rs-2669031","version":["v1"]},"buildId":"re_ckhLnmML6MCF96OHNJ","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}