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Longchain polyunsaturated fatty acid supplementation in preterm infants.

Abstract

BACKGROUND

Controversy exists over whether longchain polyunsaturated fatty acids (LCPUFA) are essential nutrients for preterm infants because they may not be able to synthesise sufficient amounts of LCPUFA to meet the needs of the developing brain and retina.

OBJECTIVES

To assess whether supplementation of formula milk with LCPUFA is safe and of benefit to preterm infants. The main areas of interest were the effects of supplementation on the visual function, development and growth of preterm infants.

SEARCH METHODS

Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2) in the Cochrane Library (searched 28 February 2016), MEDLINE Ovid (1966 to 28 February 2016), Embase Ovid (1980 to 28 February 2016), CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1980 to 28 February 2016), MEDLINE In Process & Other Non-indexed Citations (1966 to 28 February 2016) and by checking reference lists of articles and conference proceedings. We also searched ClinicalTrials.gov (13 April 2016). No language restrictions were applied.

SELECTION CRITERIA

All randomised trials evaluating the effect of LCPUFA-supplemented formula in enterally-fed preterm infants (compared with standard formula) on visual development, neurodevelopment and physical growth. Trials reporting only biochemical outcomes were not included.

DATA COLLECTION AND ANALYSIS

All authors assessed eligibility and trial quality, two authors extracted data separately. Study authors were contacted for additional information.

MAIN RESULTS

Seventeen trials involving 2260 preterm infants were included in the review. The risk of bias varied across the included trials with 10 studies having low risk of bias in a majority of the domains. The median gestational age (GA) in the included trials was 30 weeks and median birth weight (BW) was 1300 g. The median concentration of docosahexaenoic acid (DHA) was 0.33% (range: 0.15% to 1%) and arachidonic acid (AA) 0.37% (range: 0.02% to 0.84%). Visual acuity Visual acuity over the first year was measured by Teller or Lea acuity cards in eight studies, by visual evoked potential (VEP) in six studies and by electroretinogram (ERG) in two studies. Most studies found no significant differences in visual acuity between supplemented and control infants. The form of data presentation and the varying assessment methods precluded the use of meta-analysis. A GRADE analysis for this outcome indicated that the overall quality of evidence was low. Neurodevelopment Three out of seven studies reported some benefit of LCPUFA on neurodevelopment at different postnatal ages. Meta-analysis of four studies evaluating Bayley Scales of Infant Development at 12 months (N = 364) showed no significant effect of supplementation (Mental Development Index (MDI): MD 0.96, 95% CI -1.42 to 3.34; P = 0.43; I² = 71% - Psychomotor DeveIopment Index (PDI): MD 0.23, 95% CI -2.77 to 3.22; P = 0.88; I² = 81%). Furthermore, three studies at 18 months (N = 494) also revealed no significant effect of LCPUFA on neurodevelopment (MDI: MD 2.40, 95% CI -0.33 to 5.12; P = 0.08; I² = 0% - PDI: MD 0.74, 95% CI -1.90 to 3.37; P = 0.58; I² = 54%). A GRADE analysis for these outcomes indicated that the overall quality of evidence was low. Physical growth Four out of 15 studies reported benefits of LCPUFA on growth of supplemented infants at different postmenstrual ages (PMAs), whereas two trials suggested that LCPUFA-supplemented infants grow less well. One trial reported mild reductions in length and weight z scores at 18 months. Meta-analysis of five studies (N = 297) showed increased weight and length at two months post-term in supplemented infants (Weight: MD 0.21, 95% CI 0.08 to 0.33; P = 0.0010; I² = 69% - Length: MD 0.47, 95% CI 0.00 to 0.94; P = 0.05; I² = 0%). Meta-analysis of four studies at a corrected age of 12 months (N = 271) showed no significant effect of supplementation on growth outcomes (Weight: MD -0.10, 95% CI -0.31 to 0.12; P = 0.34; I² = 65% - Length: MD 0.25; 95% CI -0.33 to 0.84; P = 0.40; I² = 71% - Head circumference: MD -0.15, 95% CI -0.53 to 0.23; P = 0.45; I² = 0%). No significant effect of LCPUFA on weight, length or head circumference was observed on meta-analysis of two studies (n = 396 infants) at 18 months (Weight: MD -0.14, 95% CI -0.39 to 0.10; P = 0.26; I² = 66% - Length: MD -0.28, 95% CI -0.91 to 0.35; P = 0.38; I² = 90% - Head circumference: MD -0.18, 95% CI -0.53 to 0.18; P = 0.32; I² = 0%). A GRADE analysis for this outcome indicated that the overall quality of evidence was low.

AUTHORS' CONCLUSIONS

Infants enrolled in the trials were relatively mature and healthy preterm infants. Assessment schedule and methodology, dose and source of supplementation and fatty acid composition of the control formula varied between trials. On pooling of results, no clear long-term benefits or harms were demonstrated for preterm infants receiving LCPUFA-supplemented formula.

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  • Authors+Show Affiliations

    ,

    Princess Margaret Hospital for Children, Perth, Australia.

    ,

    Centre for Neonatal Research and Education, King Edward Memorial Hospital for Women and Princess Margaret Hospital for Children, Perth, Western Australia, Australia, 6008.

    ,

    Department of Neonatology, University of Basel Children's Hospital (UKBB), Spitalstrasse 21, Basel, Switzerland, 4031.

    ,

    School of Paediatrics and Child Health, School of Women's and Infants' Health, University of Western Australia, King Edward Memorial Hospital, 374 Bagot Rd, Subiaco, Perth, Western Australia, Australia, 6008.

    Neonatal Care Unit, King Edward Memorial Hospital for Women and Princess Margaret Hospital for Children, Bagot Road, Subiaco, WA, Australia, 6008.

    Source

    MeSH

    Arachidonic Acid
    Dietary Supplements
    Docosahexaenoic Acids
    Fatty Acids, Unsaturated
    Humans
    Infant Formula
    Infant Nutritional Physiological Phenomena
    Infant, Newborn
    Infant, Premature
    Intelligence
    Randomized Controlled Trials as Topic
    Vision, Ocular
    Visual Acuity

    Pub Type(s)

    Journal Article
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review
    Systematic Review

    Language

    eng

    PubMed ID

    27995607

    Citation

    Moon, Kwi, et al. "Longchain Polyunsaturated Fatty Acid Supplementation in Preterm Infants." The Cochrane Database of Systematic Reviews, vol. 12, 2016, p. CD000375.
    Moon K, Rao SC, Schulzke SM, et al. Longchain polyunsaturated fatty acid supplementation in preterm infants. Cochrane Database Syst Rev. 2016;12:CD000375.
    Moon, K., Rao, S. C., Schulzke, S. M., Patole, S. K., & Simmer, K. (2016). Longchain polyunsaturated fatty acid supplementation in preterm infants. The Cochrane Database of Systematic Reviews, 12, p. CD000375. doi:10.1002/14651858.CD000375.pub5.
    Moon K, et al. Longchain Polyunsaturated Fatty Acid Supplementation in Preterm Infants. Cochrane Database Syst Rev. 2016 12 20;12:CD000375. PubMed PMID: 27995607.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Longchain polyunsaturated fatty acid supplementation in preterm infants. AU - Moon,Kwi, AU - Rao,Shripada C, AU - Schulzke,Sven M, AU - Patole,Sanjay K, AU - Simmer,Karen, Y1 - 2016/12/20/ PY - 2016/12/21/pubmed PY - 2017/2/15/medline PY - 2016/12/21/entrez SP - CD000375 EP - CD000375 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev VL - 12 N2 - BACKGROUND: Controversy exists over whether longchain polyunsaturated fatty acids (LCPUFA) are essential nutrients for preterm infants because they may not be able to synthesise sufficient amounts of LCPUFA to meet the needs of the developing brain and retina. OBJECTIVES: To assess whether supplementation of formula milk with LCPUFA is safe and of benefit to preterm infants. The main areas of interest were the effects of supplementation on the visual function, development and growth of preterm infants. SEARCH METHODS: Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2) in the Cochrane Library (searched 28 February 2016), MEDLINE Ovid (1966 to 28 February 2016), Embase Ovid (1980 to 28 February 2016), CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1980 to 28 February 2016), MEDLINE In Process & Other Non-indexed Citations (1966 to 28 February 2016) and by checking reference lists of articles and conference proceedings. We also searched ClinicalTrials.gov (13 April 2016). No language restrictions were applied. SELECTION CRITERIA: All randomised trials evaluating the effect of LCPUFA-supplemented formula in enterally-fed preterm infants (compared with standard formula) on visual development, neurodevelopment and physical growth. Trials reporting only biochemical outcomes were not included. DATA COLLECTION AND ANALYSIS: All authors assessed eligibility and trial quality, two authors extracted data separately. Study authors were contacted for additional information. MAIN RESULTS: Seventeen trials involving 2260 preterm infants were included in the review. The risk of bias varied across the included trials with 10 studies having low risk of bias in a majority of the domains. The median gestational age (GA) in the included trials was 30 weeks and median birth weight (BW) was 1300 g. The median concentration of docosahexaenoic acid (DHA) was 0.33% (range: 0.15% to 1%) and arachidonic acid (AA) 0.37% (range: 0.02% to 0.84%). Visual acuity Visual acuity over the first year was measured by Teller or Lea acuity cards in eight studies, by visual evoked potential (VEP) in six studies and by electroretinogram (ERG) in two studies. Most studies found no significant differences in visual acuity between supplemented and control infants. The form of data presentation and the varying assessment methods precluded the use of meta-analysis. A GRADE analysis for this outcome indicated that the overall quality of evidence was low. Neurodevelopment Three out of seven studies reported some benefit of LCPUFA on neurodevelopment at different postnatal ages. Meta-analysis of four studies evaluating Bayley Scales of Infant Development at 12 months (N = 364) showed no significant effect of supplementation (Mental Development Index (MDI): MD 0.96, 95% CI -1.42 to 3.34; P = 0.43; I² = 71% - Psychomotor DeveIopment Index (PDI): MD 0.23, 95% CI -2.77 to 3.22; P = 0.88; I² = 81%). Furthermore, three studies at 18 months (N = 494) also revealed no significant effect of LCPUFA on neurodevelopment (MDI: MD 2.40, 95% CI -0.33 to 5.12; P = 0.08; I² = 0% - PDI: MD 0.74, 95% CI -1.90 to 3.37; P = 0.58; I² = 54%). A GRADE analysis for these outcomes indicated that the overall quality of evidence was low. Physical growth Four out of 15 studies reported benefits of LCPUFA on growth of supplemented infants at different postmenstrual ages (PMAs), whereas two trials suggested that LCPUFA-supplemented infants grow less well. One trial reported mild reductions in length and weight z scores at 18 months. Meta-analysis of five studies (N = 297) showed increased weight and length at two months post-term in supplemented infants (Weight: MD 0.21, 95% CI 0.08 to 0.33; P = 0.0010; I² = 69% - Length: MD 0.47, 95% CI 0.00 to 0.94; P = 0.05; I² = 0%). Meta-analysis of four studies at a corrected age of 12 months (N = 271) showed no significant effect of supplementation on growth outcomes (Weight: MD -0.10, 95% CI -0.31 to 0.12; P = 0.34; I² = 65% - Length: MD 0.25; 95% CI -0.33 to 0.84; P = 0.40; I² = 71% - Head circumference: MD -0.15, 95% CI -0.53 to 0.23; P = 0.45; I² = 0%). No significant effect of LCPUFA on weight, length or head circumference was observed on meta-analysis of two studies (n = 396 infants) at 18 months (Weight: MD -0.14, 95% CI -0.39 to 0.10; P = 0.26; I² = 66% - Length: MD -0.28, 95% CI -0.91 to 0.35; P = 0.38; I² = 90% - Head circumference: MD -0.18, 95% CI -0.53 to 0.18; P = 0.32; I² = 0%). A GRADE analysis for this outcome indicated that the overall quality of evidence was low. AUTHORS' CONCLUSIONS: Infants enrolled in the trials were relatively mature and healthy preterm infants. Assessment schedule and methodology, dose and source of supplementation and fatty acid composition of the control formula varied between trials. On pooling of results, no clear long-term benefits or harms were demonstrated for preterm infants receiving LCPUFA-supplemented formula. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/27995607/Longchain_polyunsaturated_fatty_acid_supplementation_in_preterm_infants_ L2 - https://doi.org/10.1002/14651858.CD000375.pub5 DB - PRIME DP - Unbound Medicine ER -