Role of Breast milk in Infant Growth and Development

Majority of infants are fed human-milk substitutes by 6 months of care and they are given to promote normal growth and development of infants and balance their nutritional requirement. Manufacturers of infant formula often add new ingredients in infant formulas so that they can perform the same function as that of human milk. However, before taking the decision to include the new ingredient in infant formula, proper evaluation is needed to confirm the benefits of the ingredients for babies. The long chain polyunsaturated fatty acids (LCPs) are one such ingredient that is found naturally in breast milk (Martin, Ling and Blackburn 2016). The main purpose of this report is to consider the decision of using LCPs as a new ingredient for infant formulae as a nutrition consultant for a food company and evaluate recent evidence regarding positive and negative effects of LCPs for infant growth and development.

The growth and the development of the infants depend upon the type of nutrition it gets. Breast milk is the best choice of nutrition in the first years of infant which is rich in long chain   polyunsaturated fatty acids, specifically docosahexaenoic acid (DHA). According to Lopez-Huertas,  (2010) this component present in the breast milk plays an important role in the neuro-development of the child. The long chain polyunsaturated fatty acids (LC-PUFA) helps in the formation of the brain and the meninges, as they are found to be an important component of the phospholipids. The brain growth in the infants and the accumulation of the DHA in the neural tissues in the first two years and rapid accumulation of the DHA at the age of two are significant. DHA has been found to be the structural and the functional component of the developing brain and is generally synthesized from alpha lenoleic acid by the action of the de-saturation enzymes. Arachidonic acid (ARA) is an important component of the cell membrane and is synthesized from the lenoleic acid (Lopez-Huertas 2010). It also acts as precursors for the generation of the prostaglandins. Prostaglandin plays an important role in the maintenance of the cellular immunity, inflammation band other cellular functions.

Deficiency of PUFA in infants may cause retarded development of the brain. Since omega-3 and omega-6 fatty acids are abundantly found in the brain and the retina, the deficiency of the fatty acids may affect the cognitive development and may cause visual impairment. PUFA has also been linked with the development of immune system and hence deficiency may lead to immune disorders. Dyslexia, ADHD, dyspraxia and autism is also linked to the imbalances in omega-3 and/or omega-6 FA (Willatts et al. 2013).

Positive Effects of LCPs on Infant Growth and Development

Evidence from observational study:

There were three observation studies which discussed about the effect of LCP supplementation of infant development. El-Shobaki et al. (2011) aimed to study about  the impact of one of the precursor of LCPs, α-linolenic acid on growth and development of the body. After the preparation of the infant formula, the biological evaluation of the prepared formula was done thirty five white weanling albino rats and the main parameters evaluated after six weeks of experimentation included body weight gain, food intake and food efficiency ratio rate of rats. The data analysis of data obtained for different parameter in rats taking different infant formula showed that there was no difference in food intake between control group and other experimental group, however some changes in weight gain for group 2 was found. Hence, the evidence did not gave any satisfying results to accept LCPs as infant formula. Although the sample size for the study was adequate, however conducting research with animals reduces the reliability of the study. Therefore, research done on human subject is needed to identify positive effects of LCPs as a supplementation formula for infants.

Lapillonne et al. (2014) conducted the study with infants in multiple centers and the effect of LCP on respiratory illness and diarrhea was judged in the first year of life. The observation of infants receiving LCPUFA in the first year revealed lower incidence of respiratory illness thus suggesting the use of LCP for health growth and development of infants. The strength of this study is that it had similar concentration of LCP as per international standard for consumption. Another study that is of importance to understand the clinical benefits of LCPs for infant development is the study by Keim et al. (2012) who used observational method to collect data on impact of breastfeeding, breast milk samples and infant formula fed through four  months post-partum. The study was done with 358 women recruited from prenatal clinics and they were asked questions on cognitive development of infants due to breastfeeding in the four months and the impact of LCP concentration on development of infants. The Mullen tool was used to assess cognitive functioning in the areas of visual perception, fine motor, gross motor, expressibe language and receptive language functioning in infants. Out of 358 women, there were only 38 women who exclusively fed infants formula to their babies. Infants who were fed exclusively breast mil has advanced development in several domains compared with infants who were formula fed. The researcher also considered eliminating all confounding factors that can influence the study result. The weakness of this study is that it had very few infants who were fed infant formulas and it lacked sample group analysis of infant formula on infant development. It gave negative evidence regarding the effects of LCPUFA on cognitive development and argued that concentration in breast milk formula does not influence cognitive skills of infants. Instead it pointed out that LCP may be beneficial only for visual maturation of infants which is consistent with the research study by (Van der Merwe et al. 2012).

Observational Studies on the Effects of LCP Supplementation on Infant Development

Guxen et al. (2011) conducted a population cohort study, where 657 women were recruited at the first trimester of pregnancy. Information about the breast feeding and other parental features was obtained by using a questionnaire. The mental and the psychomotor development of the baby were assessed by the Bayley Scales of Infant Development in 504 children of 14 months age. As per the findings, a breast feeding was found to be related to higher mental development within the children of 14 months of age. LC-PUFA level was found to be playing a beneficial role in the mental development of the child. Children exposed to longer duration of breastfeeding and higher ratios of -3 and n-6 PUFAs in colostrums had higher mental scores than those with low breast feeding exposure.

A total for six RCT trials were evaluated out of which one gave negative and three gave positive results. A randomized controlled trial by Van der Merwe et al. (2012) tested the impact of n-3 long chain PUFA supplementation in rural African infants. The double-blind controlled trial was done with 172 rural infants between the age of 3-9 months and the primary outcome variable for the study included gut integrity, cognitive development at 12 months and daily morbidity of infants. The intervention group received PUFA supplementation in the form of fish oil, whereas as the control group received olive oil. The results of the study provide insufficient evidence on impact of dietary LC-PYFA supplementation on growth performance of rural African infants. This can be said because no significant difference in cognitive performance for two groups were found and morbidity rate was almost similar expect high rate of diarrhea in infants. Randomized controlled trials are the strongest piece of evidence to consider while considering use of the evidence in real setting. Although the study used randomized controlled method, however this study is not suitable to decide the suitability of LCPs as ingredients for infants because the researcher supplemented LCP in  diet of infants and not in the infant formula. Hence, from this perspective, the study gives weak evidence to support supplementations of LCPs in infant formula. This was supported by another randomized controlled trial which considered safety of supplementing infant formula with LCPs in infants. The intervention group received LCP supplemented formula and the control group received probiotic. The assessment related to weight gain and length and head circumference at 7 months of age revealed no influence of supplementation on infant growth (Gibson et al. 2009).

Randomized Controlled Trials on the Effects of LCP Supplementation on Infant Development

Lee et al. (2013) conducted a randomized control study including the Mexican pregnant women who was being supplemented with 400 mg of docosahexaenoic acid (DHA) or a placebo for about 18 to 22 weeks. DNA profiling of the DNA methylation was done. The aim was to find out the weather prenatal dietary supplementation with DHA reduces the epigenetic state in the immune system of the infants. The findings shows that maternal supplementation with PUFA at the time of pregnancy may actually modulate the DNA methylation balance in the infants, which refers to the prevention of the immune disorders and other inflammatory disorders in early child hood.

Colombo et al. (2010) used double-blind randomized controlled trial to investigate about impact of LCP supplementation on heart rate and cognitive performance of infants. The study was done with 122 term infants and they were fed one of four different infant formulas containing different concentration of total fatty acids as DHA. The control groups had infants who were formula with no DHA. The evaluation of participants were done at 4, 6 and 9 months and infant’s visual and cardiac response was assessed on visual habituation protocol. The findings showed that infants heart rate changed with age and lower HR was found for supplemented groups compared to control group. The study also showed that positive effects of supplementation were seen in infants who were given 0.20% total fatty acids. This finding gave positive evidence for the role of LCPs on neurodevelopment of infants. However, as the study showed improvement for DHA concentraton of 0.20%, the effect of large concentration of LCPs on infant concentration needs to be evaluated too.

Another research is of significance to the purpose of report as it determined the effect of dietary LC-PUFAs on cognitive function of infants at 6 years of age. The randomized controlled trial was done with intervention group receiving docosahexanoic acid and a control group receiving no LC-PUFA for four months. The follow-up study at 6 years assessed infants on intelligent quotient (IQ), attention control and speed of processing. Although no change was found in IQ scores in both group, children receiving LC-PUFA had positive outcome related to information processing. This study gave the evidence that dietary supply of LC-PUFAs can affect some cognitive functions in later childhood (Willatts et al. 2013). However, this study cannot be generalized because of the chance difference in outcome and lack of consideration about dose of supplement.

Evaluation of the Evidence

The past three RCT trial were done with pre-term infants, however research with pre-term infants were also reviewed. Omega 3 DHA is an important LCP and Baack et al. (2016) evaluated the effect of enteral DHA supplementation in alleviating deficiency in premature infants. The pre-term infants selected for the study received DHA supplementation and it had a control group receiving placebo supplementation. The findings of the study showed that blood DHA levels increased in infants with DHA supplementation and no adverse events were found in supplemented infants. The study demonstrated feasibility of daily DHA for premature infants.

Based on review of current evidence on effectiveness of LCP supplementation on infant development, it can be said that moderate evidence has been found for positive effects of LCP on infant development. Although three evidences confirmed positive effect of LCP in visual and cognitive development, however the lacked certain factor that was needed for generalizability of the study. Hence, the recommendation to the company is that they can consider the use of LCP as a new ingredient for developing infants, however they need to conduct more research in the following area before including LCP as a composition in infant formula:

• There is a need to consider the best concentration of LCPs that can give optimal results related to infant development because Colombo et al. (2010)found positive results only for 0.20 % concentration of DHA.
• The company needs to consider individual exposure using actual concentration of fatty acid in breast milk to achieve same outcome as obtained from the presence of LCP in breast milk.
• As research gave some benefits of LCP on cognitive function of infants, the company needs to conduct research with different concentration to understand the impact on development.
• While implementing new LCP as an infant formula, the company also need to consider the bioavailabaility and toxicity effect of the compound to ensure that the ingredient is safe for infants. The useful of LCP should also be observed in case of mixed feeding (Martin, Ling and Blackburn 2016).

Conclusion:

The review of evidence related to the decision for including LCPs as a new ingredient in infant formula gave the evidence that there exist few studies that gave positive impact of LCP on visual and cognitive development of infants. As cognitive factor and visual factor are also important element of infant development, it can be concluded that LCPs are beneficial for supplementation in infant formula. However, as LCPS in breast milk perform optimal growth function at different concentration, there is a need for manufacturing companies and health care professionals to consider the efficacy of LCPs at different concentration for supplementation.

References:

Baack, M.L., Puumala, S.E., Messier, S.E., Pritchett, D.K. and Harris, W.S., 2016. Daily enteral DHA supplementation alleviates deficiency in premature infants. Lipids, 51(4), pp.423-433.

Colombo, J., Carlson, S.E., Cheatham, C.L., Fitzgerald-Gustafson, K.M., Kepler, A. and Doty, T., 2011. Long-chain polyunsaturated fatty acid supplementation in infancy reduces heart rate and positively affects distribution of attention. Pediatric research, 70(4), p.406.

El-Shobaki, F.A., Attia, A.R.M., Badawy, I.H., Mahmoud, M.H. and Mohamad, S.S., 2011. Preparation of Infant Formulas Supplemented with Long Chain Polyunsaturated Fatty Acid Precursors. The Medical Journal of Cairo University, 79(2).

Gibson, R.A., Barclay, D., Marshall, H., Moulin, J., Maire, J.C. and Makrides, M., 2009. Safety of supplementing infant formula with long-chain polyunsaturated fatty acids and Bifidobacterium lactis in term infants: a randomised controlled trial. British journal of nutrition, 101(11), pp.1706-1713.

Guxens, M., Mendez, M.A., Moltó-Puigmartí, C., Julvez, J., García-Esteban, R., Forns, J., Ferrer, M., Vrijheid, M., López-Sabater, M.C. and Sunyer, J., 2011. Breastfeeding, long-chain polyunsaturated fatty acids in colostrum, and infant mental development. Pediatrics, pp.peds-2010.

Keim, S.A., Daniels, J.L., Siega?Riz, A.M., Herring, A.H., Dole, N. and Scheidt, P.C., 2012. Breastfeeding and long?chain polyunsaturated fatty acid intake in the first 4 post?natal months and infant cognitive development: an observational study. Maternal & child nutrition, 8(4), pp.471-482.

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.

Lee, H.S., Barraza-Villarreal, A., Hernandez-Vargas, H., Sly, P.D., Biessy, C., Ramakrishnan, U., Romieu, I. and Herceg, Z., 2013. Modulation of DNA methylation states and infant immune system by dietary supplementation with ω-3 PUFA during pregnancy in an intervention study–. The American journal of clinical nutrition, 98(2), pp.480-487.

Lopez-Huertas, E., 2010. Health effects of oleic acid and long chain omega-3 fatty acids (EPA and DHA) enriched milks. A review of intervention studies. Pharmacological research, 61(3), pp.200-207.

Martin, C.R., Ling, P.R. and Blackburn, G.L., 2016. Review of infant feeding: key features of breast milk and infant formula. Nutrients, 8(5), p.279.

Van der Merwe, L.F., Moore, S.E., Fulford, A.J., Halliday, K.E., Drammeh, S., Young, S. and Prentice, A.M., 2012. Long-chain PUFA supplementation in rural African infants: a randomized controlled trial of effects on gut integrity, growth, and cognitive development–. The American journal of clinical nutrition, 97(1), pp.45-57.

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.