Long poly unsaturated fatty acids (LCPs) such as arachidonic acid (AA) and docosahexaenoic acid (DHA) have been documented to be advantageous for the growth and development of an infant. (Scholtz, Colombo and Carlson 2013). This report focuses the weight of scientific evidence available on the benefits associated with infant formulas supplemented with LCPs, through an extensive electronic literature search using key words such as ‘infant formula’, ‘supplementation’, ‘long chain fatty acids’, ‘arachidonic acid’ and ‘docosahexaenoic acid’ along with Boolean operators and databases such as Medline, COCHRANE, BioMed and PubMed.
As researched by Bazinet and Layé (2014), long chain polyunsaturated fatty acids are essential for the growth and development of the brain and play help in the development of the cognitive functions in the infant. LCPs contribute to formulation of the meninges, due to them being important compounds of phospholipids. Phospholipids contribute to the structural health of the plasma membranes and are inflammatory precursors to the cells of the body. This makes phospholipids and indirectly LCPS, essential contributors in the improvement of the immune system of the infant. There is the presence of rapid accumulation of LCPs like DHA and AA, in the brain of the infant, AA in the overall organ systems of the overall body and DHA in the retinal compartments. As researched by Saccone and Berghella (2015), LCPs also contribute actively in the enhancement of the visual prowess of the newborn. LCPs are key precursors of components like eicosanoids, which further contribute to the formation of prostaglandins. Components such as leukotrienes, prostaglandins and thromboxanes contribute essentially to functions of the cell, regulation of immunity as well as inflammation. Hence, LCPs also play beneficial roles in improving the immunity and inflammatory mechanisms of the newborn infant.
According to Koletzko et al. (2015), LCPs enhance the infant’s immune system, through improving functions of natural killer cells, macrophages and neutrophils, as well as activating and proliferating lymphocytes. These activities are regulated by pathways of eicosanoids and lipid peroxidation, of which, LCPS act as essential contributors.
Further, according to Abedi and Sahari (2014), long chain poly unsaturated fatty acids, have also been found to improve general movements in infants and reduce motor abnormalities, which are characteristic developmental milestones during ages 3 to 4 months. DHA contributes to the formation of synapses due to the active incorporation of phospholipids in the infant’s neuronal membranes, whereas, AA delivers similar synaptic advantages by regulating the signal transductions in the nervous system of the infant. Hence LCPs play protective roles against the occurrence of developmental disorders in newborns.
According to Zárate et al. (2017), deficiency of long chain poly unsaturated fatty acids in the diets of infants leads to developmental disturbances such as attention deficit hyperactivity disorders, excessive clumsiness in movements and dysfunctions in neurological processes, dermatitis, inadequacies in growth, thrombocytopenia and increased susceptibility of the infant towards various infectious diseases.
A number of systematic reviews were obtained which aimed to assess the veracity behind the documented benefits of infant formulas supplemented with LCPs. The systematic review performed by Jasani et al. (2017), evaluated the effects of long chain polyunsaturated fatty acid supplementation of infants born at term. The authors successfully obtained 31 randomized controlled trials of which, 15 were included in the review. Nine studies observed the effects of LCPs supplemented formula on infant’s visual abilities, of which, five studies obtained inconclusive findings while four studies reported advantageous consequences. The authors discovered eleven researches which assessed the neurodevelopment effects of LCP supplemented formula consumption, during birth and before the age of two. Of these, only two studies produced results indicating the positive effect of such formulas, as screened by the Fagan Infant Test and Bayley Scales of Infant Development. Further, thirteen researches uncovered no significant distinctions in the physical growth observed between infants receiving and not receiving LCP supplemented formula.
Another systematic review performed by Delgado-Noguera et al. (2015), aimed to assess the effects of supplementation with long chain polyunsaturated fatty acids to breastfeeding mothers on the growth and development of their children. The authors obtained eight randomized controlled trials consisting of a sample size of 1567 women in countries which were of high income, with the longest follow up being that of seven years. The authors reported no statistically significant improvements in the neurodevelopment, eyesight, physical growth and symptoms of post partum depression among the infants or the mothers, upon supplementation of LCPs formulas or during lactation. The authors found only one research reporting beneficial reduction of infant allergies upon supplementation during short term studies of follow up.
The systematic review performed by Zhang et al. (2018), aimed to assess the availability of researches as well as the effects of LCP supplementation on infants who were severely preterm. The authors obtained 1876 researches of which, 6 were observational researches and 18 were randomized controlled trials. None of the randomized studies studied severely preterm populations and majorly included infants born at ≤32 weeks of gestation as the study group. None of the studies reported any symptomatic reductions of bronchopulmonary dysplasia in preterm infants receiving LCP supplementation. However, 12 studies reported reductions in necrotizing enterocolitis in preterm infants receiving such supplementation.
The meta analysis performed by Qawasmi et al. (2013), aimed to assess the effects of LCP supplemented infant formula consumption on the visual acuity of infants. A total 19 researches were included, where the authors reported statistically significant beneficial effects of supplemented formula consumption on the visual capabilities of infants at ages 2, 4 and 12 months using assessments such as visual evoked potential and behavioral procedures.
Additional systematic reviews were also obtained, a majority of which however, focused primarily focused on the effects of LCP supplemented breastfeeding and formula feeding practices on the growth and development of the concerned infants. Authors Quin et al. (2016), in the Journal of Nutrition and Intermediary Metabolism, successfully reviewed a number of semi-randomized and randomized controlled trials on the effects of LCP supplementation during the pre and post natal phases. The authors reviewed 78 researches where infants received LCP supplementation through either breastfeeding or formula feeding but reported no statistically significant advantages concerning improvements in cognition, visual abilities and linguistic capabilities. Further, the authors observed reductions in infantile immune responses upon supplementation of either formula or breast milk with LCPs. An additional systematic review by Koletzko et al. (2014), evaluated existing Asian perspectives and data concerning the effects of LCP supplementation during pregnancy, lactation and infancy. The authors reported reduced susceptibility of mothers giving birth to preterm babies upon receiving supplementation of ≥200 mg of DHA and daily. However, the authors reported observational studies which uncovered beneficial effects of pre and post natal LCP supplementation on neural development, conflicting results were reported upon reviewing 11 randomized trials on the effects of visual and cognitive abilities of infants receiving LCP supplemented formulas.
One randomized controlled trial conducted by Williats et al. (2013), was obtained, which aimed to evaluate the effectiveness of infant formulas supplemented with LCPs on the cognitive abilities of children at the age of 6 years. The authors randomly divided the participating children into two groups, 71 children received infant formulas supplemented with AA or DHA and 76 children in the control group receiving formulas devoid of such supplementation for a timeframe of 4 months. A reference group of 88 children was also formulated where children received breastfeeding measures. There were no differences in outcomes among both formula groups, upon completion of screening tools such as Full Scale Intelligence Quotient (IQ), Day Night Test evaluating control of attention and Matching Familiar Figures Test (MFFT) evaluating processing speed. However, it was observed that infants receiving LCP supplemented formulas were faster significantly, while writing correct responses in the MFFT tool. Hence, the authors implicated that further research is required for assessing the benefits of LCP supplemented infant formulas on the neural and cognitive development of infants, due to the lack of variations in IQ scores in both the above formula groups.
One cohort study conducted by Foiles et al. (2016), was obtained which aimed to assess the effect of infant formulas supplemented with long chain polyunsaturated fatty acids on the incidence of allergies in early childhood. The sample size included 91 children from the Kansas City cohort of the DHA Intake and Measurement of Neural Development (DIAMOND) Study, which contained annual medical records through four years upon the birth of child, from which the authors classified illnesses in accordance to the body system. The sample size was divided into two groups, a control group where infants received a formula devoid of LCPs and an experimental groups, where infants consumed any one out of three formulas containing LCPs such as DHA and AA. The authors found that allergies were lower in the infants who received LCP supplemented formula during the first year of their life, in comparison to the control group who did not. Hence, the authors implicated through this cohort, that consumption of formulas which had been supplemented with LCPs decreased the risk of respiratory and dermal allergies in infants, which were influenced by allergies acquired by the mother. The cohort also revealed that the infant consuming LCP supplemented formulas, had decreased onset of first allergic incidences (p = 0.04) and dermal allergies (p = 0.03) and also displayed reductions in the trends of acquiring asthmatic and wheezing symptoms (p = 0.01). In situations where maternal allergies were present, LCP supplemented formulas decreased risk of infant respiratory allergies (HR = 0.24, 95% CI = 0.1, 0.56, p = 0.0.001) and skin allergies (HR = 0.35, 95% CI = 0.13, 0.93, p =0.04). Likewise, despite the presence of maternal allergies, the incidences of asthma or wheezing or also decreased by LCP supplemented infant formulas (HR = 0.26, 95% CI = 0.07, 0.9, p = 0.02).
The observational study conducted by Lapillone et al. (2014), assessed the incidences of diarrhea and respiratory disorders among infants who were fed LCP supplemented formula during the first year of their life. The authors conducted a multicenter, observational prospective study where the chosen infants were either provided with formulas devoid of LCPs or formulas containing 34 mg of AA and 17 mg of DHA per 100 Kcal followed by observations conducted by pediatricians on the symptoms of diarrhea, respiratory disorders, eczema, diarrhea and otitis media within the first year of their life. The authors reported beneficial results indicating reductions of harmful symptoms in infants receiving LCP supplemented formulas, in terms of diarrhea (p = 0.034), bronchitis (p = 0.004), nasal congestion (p = 0.001), croup (= = 0.044) and cough (p = 0.014).
The literature search revealed a lack of sufficient scientific evidence pertaining to the benefits associated with the consumption of LCP supplemented formulas on the growth and development of the infants. While observational studies and cohorts reported beneficial effects, the results presented by the systematic reviews and randomized trials were conflicting, producing negligible results in favor of the same. Hence, it is recommended that the concerned food company postpone immediate formulations and retailing of their LCP supplemented infant formula due to the lack of sufficient supportive scientific evidence. Further, as observed by Almaas et al. (2015), it is recommended that the company conducts further research on the cognitive and neural effects of LCPs on infants by focusing on studies which utilize finer brain development assessment tools rather than screening tools used globally. The food company must also focus on researching the effects of LCP supplementation on long term children’s performance of complex motor tasks during the later stages of their life rather than merely emphasizing on studies which evaluate short term effects of the above in babies born at term. The company must also consider the lack of evidence considering the effects of LCP supplementation on preterm babies.
Abedi, E. and Sahari, M.A., 2014. Long?chain polyunsaturated fatty acid sources and evaluation of their nutritional and functional properties. Food science & nutrition, 2(5), pp.443-463.
Almaas, A.N., Tamnes, C.K., Nakstad, B., Henriksen, C., Walhovd, K.B., Fjell, A.M., Due-Tønnessen, P., Drevon, C.A. and Iversen, P.O., 2015. Long-chain polyunsaturated fatty acids and cognition in VLBW infants at 8 years: an RCT. Pediatrics, pp.peds-2014.
Bazinet, R.P. and Layé, S., 2014. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nature Reviews Neuroscience, 15(12), p.771.
Delgado?Noguera, M.F., Calvache, J.A., Bonfill Cosp, X., Kotanidou, E.P. and Galli?Tsinopoulou, A., 2015. Supplementation with long chain polyunsaturated fatty acids (LCPUFA) to breastfeeding mothers for improving child growth and development. The Cochrane Library.
Foiles, A.M., Kerling, E.H., Wick, J.A., Scalabrin, D.M., Colombo, J. and Carlson, S.E., 2016. Formula with long?chain polyunsaturated fatty acids reduces incidence of allergy in early childhood. Pediatric Allergy and Immunology, 27(2), pp.156-161.
Jasani, B., Simmer, K., Patole, S.K. and Rao, S.C., 2017. Long chain polyunsaturated fatty acid supplementation in infants born at term. Cochrane Database of Systematic Reviews, (3).
Koletzko, B., Boey, C.C., Campoy, C., Carlson, S.E., Chang, N., Guillermo-Tuazon, M.A., Joshi, S., Prell, C., Quak, S.H., Sjarif, D.R. and Su, Y., 2014. Current information and Asian perspectives on long-chain polyunsaturated fatty acids in pregnancy, lactation, and infancy: systematic review and practice recommendations from an early nutrition academy workshop. Annals of Nutrition and Metabolism, 65(1), pp.49-80.
Koletzko, B., Carlson, S.E. and Van Goudoever, J.B., 2015. Should infant formula provide both omega-3 DHA and omega-6 arachidonic acid?. Annals of Nutrition and Metabolism, 66(2-3), pp.137-138.
Lapillonne, A., Pastor, N., Zhuang, W. and Scalabrin, D.M., 2014. Infants fed formula with added long chain polyunsaturated fatty acids have reduced incidence of respiratory illnesses and diarrhea during the first year of life. BMC pediatrics, 14(1), p.168.
Qawasmi, A., Landeros-Weisenberger, A. and Bloch, M.H., 2013. Meta-analysis of LCPUFA supplementation of infant formula and visual acuity. Pediatrics, 131(1), pp.e262-e272.
Quin, C., Erland, B.M., Loeppky, J.L. and Gibson, D.L., 2016. Omega-3 polyunsaturated fatty acid supplementation during the pre and post-natal period: a meta-analysis and systematic review of randomized and semi-randomized controlled trials. Journal of Nutrition & Intermediary Metabolism, 5, pp.34-54.
Saccone, G. and Berghella, V., 2015. Omega-3 long chain polyunsaturated fatty acids to prevent preterm birth: a systematic review and meta-analysis. Obstetrics & Gynecology, 125(3), pp.663-672.
Scholtz, S.A., Colombo, J. and Carlson, S.E., 2013. Clinical overview of effects of dietary long-chain polyunsaturated fatty acids during the perinatal period. In The Importance of Immunonutrition (Vol. 77, pp. 145-154). Karger Publishers.
Willatts, P., Forsyth, S., Agostoni, C., Casaer, P., Riva, E. and Boehm, G., 2013. Effects of long-chain PUFA supplementation in infant formula on cognitive function in later childhood–. The American journal of clinical nutrition, 98(2), pp.536S-542S.
Zárate, R., el Jaber-Vazdekis, N., Tejera, N., Pérez, J.A. and Rodríguez, C., 2017. Significance of long chain polyunsaturated fatty acids in human health. Clinical and translational medicine, 6(1), p.25.
Zhang, P., Lavoie, P.M., Lacaze-Masmonteil, T., Rhainds, M. and Marc, I., 2014. Omega-3 long-chain polyunsaturated fatty acids for extremely preterm infants: a systematic review. Pediatrics, 134(1), pp.120-134.
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