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No more infant formula advertising in The BMJ

BMJ 2019; 364 doi: https://doi.org/10.1136/bmj.l1279 (Published 21 March 2019) Cite this as: BMJ 2019;364:l1279

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Still on the superiority of breastmilk over breastmilk substitutes (including infant formula): further justification for the programmatic appropriateness of the prohibition of advertisement of beastmilk substitutes

The ‘BMJ Organizational Policy’ stopped ‘Advertisement’ of Infant Formula [1]. ‘Infant Formulas’ are ‘Breastmilk Substitutes (BMS)’ by ‘The Code’ [2] (WHA 34.22/ 1981). ‘The Code’ prohibits ‘Advertisement’ of ’BMS’. Diverse reactions re: ‘BMJ Advertisement Policy’ include the startling suggestion that no ‘Scientific Data’ confirm superiority of ‘Breastmilk’ over ‘Infant Formula’/ ‘BMS’ and hence my earlier ‘Contribution’ [3]. This further ‘Contribution’ addresses ‘Breastmilk Superiority’ over ‘BMS’!

My earlier ‘Contribution’ ventilated the tantalizing ‘8 Deficits’ in ‘BMS’ from my 2007 Presentation which make them not ‘Substitutes for Breastmilk’ and also a teaser from ‘Breastmilk is not Formula’ presented at the 2014 Academy of Breastfeeding Medicine Meeting [3]! More scientific facts are herein exposed to undergird the superiority of ‘Breastmilk’ over ‘BMS’.

‘Breastmilk’ is produced by ‘Mammals’ of different species to nurse their offspring and there are ‘Inter-Species Differences’ in the ‘Breastmilk Contents and Composition’. There are also ‘Intra-Species Differences’ in ‘Breastmilk Composition’ of different individuals. For a given individual, and in a very unique way, ‘Breastmilk Composition’ varies according to certain factors: Stage of Lactation, Phase of index Nursing, Maternal Ingestions/ Diet, Environmental Exposure, Maternal Health State, Infant Health State and Degree of Breast Fullness among several others.
‘Breastmilk Composition’ generically includes the following ‘Components’:

i. Macronutrients: Protein, Carbohydrates, Fats, Water and Energy. The ‘Whey-Casein Proportion’ is uniquely different between species and certainly between ‘Human Breastmilk’ and ‘Cow’s Milk’ and, indeed, synthetic ‘Formulas’! Taurine and Phosphoethanolamine are uniquely important for ‘Brain Development’ and are lacking in ‘Formulas’! The ‘Essential Fatty Acids’ (LCPUFAs etc) in ‘Human Breastmilk’ are uniquely important for ‘Brain Tissue Formation’ including myelination. The unique ‘Lactose Concentration’ is also important re: Renal ‘Solute Load’ and Gastro-intestinal ‘Acid-Base Status’ of the Breastfeeding Infant re: ‘Intestinal Flora’. These ‘Components’ are distinctly different in ‘Formulas’ with some resultant ‘Issues’: Bioavailability, Immunopathogenicity, etc!

ii. Micronutrients: Water-soluble and Fat-soluble Vitamins, Minerals particularly Calcium and Phosphorus with critical Hydroxyapatite for Bone/ Teeth Formation and Trace Elements especially Iron, Copper, Magnesium, Manganese, Molybdenum, etc; all these are uniquely and delicately maintained in ‘Human Breastmilk’ and clearly different from ‘Formulas’. Fortification with these ‘Micronutrients’ raises ‘Practicality-Utilization Issues’: Organoleptics, Bioavailability, Tolerability, Shelf-life, etc.

iii. Humoral and Bioactive Substances: Bombesin, Neurotensin, Immunoreactive Vasoactive Intestinal Peptides (VIPs), Insulin, Lactoferin, Bifidus Factor, Lysosomal Enzymes, Secretory IgA, IgM, IgG, etc. These cannot be synthesized for ‘Fortification’ of ‘BMS’ successfully.

iv. Living Cells: These include ‘Immune Cells’ and ‘Non-immune Cells’. The ‘Immune Cells’ include Leucocytes, Lymphocytes, Macrophages, etc. Among the ‘Non-immune Cells’ are: Luminal Cells, Myoepithelial Cells, Haematopoietic Cells among others. These are not in ‘Formulas’ and ‘Fortification’ is not possible!

Here are more facts on the ‘Breastmilk Living Cells (BLCs)’ [4]! ‘Human Breastmilk Cells (HBCs)’ were documented since the 17th Century [5]. ‘Human Breastmilk’ is populated with ‘Living Cells’ which ‘Composition’ changes dynamically. They are absent in ‘BMS’ with ‘Constant and Fixed Composition’! The ‘BLCs’ include:

1. ‘Immune Cells’: The Leucocytes account for < 2% of the ‘Living Milk Cells’ in a ‘Healthy Mother-Baby Dyad’ and this proportion changes with the ‘Health Status’ of the Dyad. Macrophages and Lymphocytes reflect the ‘Dyad Exposures’. Lysosomes (Organelles) are present.

2. ‘Non-immune Cells’: These include ‘Mammary Gland Milk Cells’ (Luminal Cells (Lactocytes), Myoepithelial Cells and Stem Cells) and ‘Extra-mammary Gland Milk Cells’ (Maternal Bone Marrow-derived Stem Cells and CD34+ Haematopoietic Cells)6. Luminal and Myoepithelial Cells account for about 98% of ‘Breastmilk Cells’ in the ‘Secretory Mammary Gland’.

Concerning the ‘Human Breastmilk Stem Cells (hBSCs)’, there is a mixed population of ‘Mature Uncommitted Cells’ and ‘Progenitor Cells’ depending on ‘Epigenetic Factors’ and are recognized with their ‘Pluripotency Genes’/ ‘Markers’ as ‘Cytokeratin (CK)18+ (Luminal Cell-destined)’, ‘CK14+ (Myoepithelial Cell-destined)’, ‘CK5+’, ‘Smooth Muscle Actin (SMA)+’ and ‘Nestin+’. Some hBSCs also have ‘Cluster Determinant (CD) Markers’: CD49f, CD24, CD29, CD34, CD73, CD90, CD105, etc. The hBSCs are ‘Pluripotent Multilineage Stem Cells’ and can be ‘Recruited and Committed’ to the ‘Tri-germinal Lineage’ in ‘Breastmilk’:

i. Ectoderm: Lactocytes, Myoepithelial Cells, Neuron- and Glial-like Cells

ii. Mesoderm: Osteoblasts, Chondroblasts, Adipocytes, Cardiomyocytes, etc

iii. Endoderm: Pancreatic β-Cells (Insulin), Hepatocyte-like Cells (Albumin), etc.

iv. Epithelial-to-Mesenchymal Transition (EMT): Some cells are in the ‘Transition Phase’ from one ‘Germinal Lineage’ to another.

The ‘Importance and Functions’ of the hBSCs is still being unearthed but some scientific facts are constantly emerging! The hBSCs have two broad functions: ‘Self-Renewal’ and ‘Differentiation through Progenitor Cells Stimulation’ into the ‘Multilineage Germinal Derivatives’ under Epigenetic ‘Pluripotency Genes’ influence. Here are ‘Tantalizers’ for ‘Starters’:

1. ‘Secretory Mammary Gland’: Under ‘Lactogenic Hormone Complex’ (Oestrogen, Progesterone, Prolactin, Human Placental Lactogen and Insulin), the Mammary Gland of the ‘Pregnant Woman’ is ‘Remodelled’ into the ‘Secretory Stage’ for ‘Breastmilk Production and Secretion’.

2. The Lactocytes and Myoepithelial Cells participate in the ‘Milk Ejection Reflex’

3. The predominant hBSCs are dictated by ‘Epigenetic Stimulation’ and produce the ‘Relevant Specific Substances’ to meet the ‘Dynamic and Changing Immunological, Nutritional and Developmental Needs’ of the ‘Growing Child’

4. ‘Mother-Child Transplant Acceptance’ through the ‘Micro-Chimerism Process’ as ‘Maternal Bone Marrow-derived Stem Cells’ are in ‘Breastmilk’, protected from Enzyme and Acid destruction in the gut and, through ‘Diapedesis’, integrate stably with the Nursling’s ‘Target Organs/ Tissues’ [7].

5. In the evolving ‘Revolutionary Therapy’ of ‘Regenerative Medicine’, hBSCs have been proposed as ‘Stable Non-Tumorigenic Teratoma-Negative’ and, therefore, superior to ‘Human Embryonic Stem Cells (hESCs)’ and ‘Induced Pluripotent Stem Cells (iPSCs)’ which are ‘Unstable Tumorigenic Teratoma-Positive’ [8,9]. ‘Teratoma-Positive Assays’ is the test for ‘Pluripotency’!

The hBSCs are currently being investigated for their importance in ‘Lactation Biology’, ‘Breastmilk Stem Cell Research’, ‘Regenerative Medicine’ and ‘Breastfeeding Medicine’. The ‘BLCs’ and other ‘Components’ in ‘Human Breastmilk’ exist/ are produced ‘Naturally’ and are absent in ‘BMS’ and largely cannot be synthesized for ‘Fortification Purposes’ and where attempted, Bioavailability, Immunopathogenicity and Organoleptic ‘Issues’ arise! Yet, there is a reason for everything in ‘Nature’!! The ‘Breastfed Child’ is the beneficiary of the illimitable benefits of these unique ‘Breastmilk Components’!!! What ‘Scientific Data’ are needed to confirm the distinct differences between ‘Human Breastmilk’ and ‘BMS’ and the unquestionable superiority of the former? ‘The Code’ prohibition of ‘BMS Advertisement’ is ‘Programmatically Apt’; Bravo BMJ on your new ‘Advertisement Policy’!

REFERENCES
1. Godlee F. No more infant formula advertising in The BMJ. BMJ 2019; 364: l1279 of 21st March 2019
2. Eregie C.O. A Major Programmatic Misstep in the 2018 Revised Ten Steps to Successful Breastfeeding. https://bmj.com/content/363/bmj.k5146/rr-7 of 16th January 2019BMJ Advert
3. Eregie C.O. There is no Breastmilk Substitute (Including Infant Formula) and Prohibition of its Advertisement is Programmatically Appropriate for Optimal Child Health. https://bmj.com/content/364/bmj.l1279/rr-4 of 28th March 2019
4. Hassiotou F and Hartmann P.E. At the Dawn of a New Discovery: The Potential of Breastmilk Stem Cells. Adv Nutr 2014; 5:770-778
5. Van Leeuwenhoek A. Epistola 106. Arcana naturae detecta delphis batavorum. Apud Henricum a Krooneveld 1695
6. Fan Y, Chong YS, Choolani MA, Cregan MD, Chan JK. Unravelling the Mystery of Stem / Progenitor Cells in Human Breastmilk. PLoS ONE 2010; 5:e14421
7. Zhou I, Yoshimura Y, Huang Y et al. Two Independent Pathways of Maternal Cell Transmission to Offspring through Placenta during Pregnancy and by Breastfeeding after Birth. Immunology 2000; 101:570-80
8. de Lazaro I, Yilmazer A, Kostarelos K. Induced Pluripotent Stem (IPS) Cells: A New Source for Cell-based Therapeutics? Journal of Controlled Release; Official Journal of the Controlled Release Society 2014; 185C:37-44
9. Lensch MW, Schlaeger TM, Zon LI, Daley GQ. Teratoma Formation Assays with Human Embryonic Stem Cells: A Rationale for One Type of Human-Animal Chimera. Cell Stem Cell 2007; 1:253-8

Professor Charles Osayande Eregie
MBBS, FWACP, FMCPaed, FRCPCH (UK), Cert. ORT (Oxford), MSc (Religious Education)
Professor of Child Health and Neonatology, University of Benin
Consultant Paediatrician and Neonatologist, University of Benin Teaching Hospital, Benin City, Nigeria
UNICEF-Trained BFHI Master Trainer
ICDC-Trained in Code Implementation
Technical Expert/ Consultant on the FMOH-UNICEF-NAFDAC Code Implementation Project in Nigeria
*No Competing Interests.

Competing interests: No competing interests

02 April 2019
CHARLES OSAYANDE EREGIE
MEDICAL DOCTOR
Professor of Child Health and Neonatology, University of Benin and Consultant Paediatrician and Neonatologist, University of Benin Teaching Hospital, Benin City, Nigeria. Also, UNICEF-Trained BFHI Master Trainer and ICDC-Trained in Code Implementaion. Also a Technical Expert/ Consultant on FMOH-UNICEF-NAFDAC Project on Code Implementation in Nigeria
Institute of Child Health, University of Benin, PMB 1154, Benin City, Nigeria