Critiquing the scientific methods used to collate the Academy of Breastfeeding Medicine's Clinical Protocol #36 'The mastitis spectrum'

Elements of the Academy of Breastfeeding Medicine's Clinical Protocol #36 agree with the NDC guidelines for breast inflammation

You can read the article, called Does the Academy of Breastfeeding Medicine’s Clinical Protocol #36 ‘The Mastitis Spectrum’ promote overtreatment and risk worsened outcomes for breastfeeding families? Commentary, here.[1]

The ABM Clinical Protocol #36 guidelines agree with the NDC clinical guidelines [2,3] when it proposes that breast inflammation

• Is a spectrum condition

• Is not helped by and is likely to be worsened by deep lump massage

• May elicit a systemic response that is not necessarily infective

• Mostly resolves with conservative care

• Is not the same as normal lactational glandular tissue which can feel ‘lumpy’ and tender

• Does not develop into infection in a period of hours

• Is not caused by retrograde spread of bacteria from a damaged nipple

• Is not caused by mammary candidiasis [4]

• Is not helped by

  • instructions to have baby ‘drain’ the breast
  • ‘dangle’ feeds
  • topical applications

• Does not require investigations of c-reactive protein or white blood cell count, since these are markers of inflammation not specific for infection.

Clinical Protocol #36 contains significant scientific flaws

Despite the above advances, I agree with Baeza et al’s assessment that ABM Clinical Protocol #36 contains significant scientific flaws.[5] These flaws give rise to clinical recommendations which may be either of no benefit or which may worsen outcomes for some breastfeeding pairs and their families. You can read a detailed analysis here.

To give an overview, Clinical Protocol #36 fails to comply with best practice implementation science in five ways.

1. Inaccurate representation of studies

To build theoretical frameworks and translate these into recommendations which are most likely to be efficacious, implementation science requires accurate representation of and critical analysis of existing studies. In Table 1 of my published critical analysis, here, I detail a selection of research studies which are inaccurately represented in Clinical Protocol #36.

2. Theoretical models misrepresented as fact

In 2010, a Swedish midwife and academic, Associate Professor Linda Kvist, appealed to international breastfeeding researchers to keep an open mind about mastitis, writing about the importance of theoretical framing. Mental constructs, she observed with respect to mastitis, are often assumed! [6]

Naming a theoretical model facilitates debate and is important for scientific integrity and transparency. Misrepresenting theoretical models as fact in clinical guidelines misleads clinicians.

Example A. You can read about how Clinical Protocol #36 is built upon a pathogenic model of breast inflammation, which lacks supporting evidence and yet which is presented to clinicians as fact, here.

Example B. Clinical Protocol #36 asserts that ‘hyperlactation’ is the second fundamental cause of breast inflammation. You can find a critique of this theory and the associated advice not to change feeding patterns when a mother has breast inflammation here.

3. Sources not reliably attributed

Figure 4 page 362 of Clinical Protocol #36 displays a black and white image labelled ‘mastitis’, under an arrow pointing from the word ‘dysbiosis’. Two arrows between the image labelled Mastitis and the image labelled Healthy Mammary Gland in Figure 4 point in the wrong direction. They point the right way in the original version of this, Figure 3 in 2020 Fernandez et al,[13] not attributed.) Critical details of the image entitled ‘mastitis’ such as source, anatomic site, preparation, type of organism, and magnification are missing. Images from Figure 4 are repeated in Figure 17, again with crucial explanatory details missing, other than the label ‘Mammary duct Mastitis - S. epidermidis biofilm’.

Personal communication by Professor Juan Rodriguez explained that the image shows material biopsied from advanced mastitis in a lactating breast. The extracted tissue had fixative applied, before being photographed under electron microscopy at 5000x magnification. But finding a biofilm in lactiferous ducts after biopsy from late-stage mastitis and then placed in fixative does not corroborate the hypothesis that lactiferous ducts are lined with physiological biofilm, nor that pathological Staphylococcus epidermis biofilm in lactiferous ducts causes breast inflammation. A 2022 Australian case-controlled study examined the breast milk of 20 women with mastitis and 16 women without mastitis, and did not find any clear association between Staphylococcus epidermidis and mastitis.)[7]

In another example, Figure 3 does not adequately inform about the sample.

Clinical Protocol #36’s failure to comply with scientific standards for image description and source attribution misleads clinicians.

4. Strength of Recommendation Taxonomy (SORT) not reliably or appropriately applied

Clinical Protocol #36 analyses existing research using the 2004 Strength of Recommendation Taxonomy (SORT)[23], acknowledging that many of its clinical recommendations are derived from Level C evidence, which includes being based on “consensus, usual practice … and/or opinion”.

Because SORT is based “on a body of evidence (typically more than one study)” and because the Level of Evidence is based on an assessment of study design or “quality of evidence from multiple studies about a specific question or the quality of evidence supporting a clinical intervention”, each SORT recommendation must result from a comprehensive review of all existing evaluations of that specific intervention, to be valid. [8]

• But comprehensive review of all existing evaluations has not consistently occurred in the preparation of Clinical Protocol #36.

• Also, Clinical Protocol #36 makes SORT findings by grouping studies which are highly heterogenous, and which investigate different conditions applying a wide range of measures.

Because of the very high levels of subjectivity in Clinical Protocol #36’s application of SORT, the rating of evidence in Clinical Protocol #36 is not meaningful and risks misleading clinicians.

Example A: Clinical Protocol #36 recommends use of probiotics, stating levels of evidence: 1-2, strength of recommendation: B. To reach this conclusion, Clinical Protocol #36 cites the Barker et al scoping review and Crepinsek Cochrane review, along with a cautionary narrative analysis by Amir et al and narrative review of bovine and human milk microbiomes by Oikonomou et al.[9-12]. But the Crepinsek et al review investigates the use of probiotics as prevention of mastitis after childbirth (finding very low certainty of evidence) not as intervention for breast inflammation. Table 1 in Douglas 2023 details why the Barker et al review findings do not support Clinical Protocol #36’s SORT recommendation.

You can find an update about probiotics and breast inflammation here.

Example B: Clinical Protocol #36’s recommendation to avoid nipple shields is rated Level of evidence: 3. Strength of recommendation: C.

To reach this conclusion, ABM Clinical Protocol #36 considers just one 2010 study, failing to cite more recent studies and a systematic review on this topic, also detailed in Table 1 of Douglas 2023.

5. Reliance upon single case reports

Single case reports, such as in Example 4 in Clinical Protocol #36, fail to address multiple potential confounding factors, misleading clinicians, and should not be used in clinical guidelines.

Because Clinical Protocol #36 does not conform with best scientific practice, it makes recommendations which may risk worsened outcomes for breastfeeding pairs and their families

Due to failure to adhere to scientific principles detailed above, Clinical Protocol #36 recommends, without nuance or clarification:

• Interventions which have been investigated but which lack convincing evidence of efficacy;

• Interventions which have been subject to very few evaluations and which also lack pathophysiological rationale; and

• Avoidance of an intervention (nipple shields) which has demonstrated positive effects for management of breastfeeding problems in significant research studies conducted post-2010.

As a result, multiple clinical recommendations made in Clinical Protocol #36 may have no benefit or even worsen outcomes for breastfeeding pairs and their families. Baeza et al came to a similar conclusion.[5]

Example A: Advice to reduce milk removal or to not increase milk removal may exacerbate risk.

On page 367 Clinical Protocol #36 asserts that “overfeeding from the affected breast …. is a major risk factor for worsening tissue edema and inflammation”. The belief that an infant can overfeed from the breast directly contradicts the evolutionary biology model which underpins the Neuroprotective Developmental Care concept of frequent and flexible breastfeeds, necessary for adequate milk production and infant weight gain.[5]

By foregrounding the theoretical model of ‘hyperlactation’ as a key aetiological factor for breast inflammation without clear criteria for diagnosing ‘hyperlactation’, Clinical Protocol #36 derives the clinical recommendation that milk removal should be reduced when breast inflammation presents. The recommendation that milk removal should be reduced occurs in Clinical Protocol #36 in five places, detailed in my analysis. You can read abaout why this risks worsened outcomes here.

Not increasing, or actively reducing, milk removal fails to address the most common underlying causative factor for breast inflammation from the perspective of the mechanobiological model, that is, inadequate milk removal which results in excessive intra-luminal pressures.

For this reason, Clinical Protocol #36’s key recommendation of reduced milk removal may place breastfeeding women at risk of worsening breast inflammation. Breast inflammation is already associated with an increased risk of low milk production;[20] the advice to not increase, or to reduce, milk removal when breast inflammation emerges is likely to increase the risk that breast milk production fails to meet an infant’s caloric needs, once the inflammation has resolved. You can read about this here.

Example B: Unnecessary or ineffective interventions often have unintended outcomes.

Recommendations which lack an evidence-base or credible theoretical frame, such as Clinical Protocol #36’s recommendations to use ‘lymphatic drainage’, therapeutic ultrasound, and lecithin, may appear benign. But unnecessary interventions exacerbate patient anxiety and disempowerment, increase risk of unintended outcomes, increase financial burden, and may limit access to affluent patients within advanced economies.[13-17]

Clinical Protocol #36 introduces diagnoses which are poorly defined and not clinically meaningful.

New medical terms and diagnoses for clinical presentations in breastfeeding pairs should be introduced with great caution, since overdiagnosis including over-definition and overtreatment are escalating international trends, including in breastfeeding women and their babies, driving unnecessary costs for families and health systems and risking unintended outcomes.[13-17]

Example A. Erroneous use of the diagnosis ‘lymphedema’.

On page 368 Clinical Protocol #36 states: “Lactating breasts … require support to avoid dependent lymphedema”. Clinical Protocol #36 confuses temporary breast stromal interstitial fluid, associated with inflammation, with the medical condition of lymphoedema.

Lymphoedema is a chronic and progressive disease, often resulting in fibrosis. The rare condition of primary or genetic lymphoedema is not relevant to this discussion. Although the most common cause of secondary or acquired lymphoedema world-wide is filariasis, the most common cause in advanced economies is surgical excision or irradiation of lymph nodes due to breast cancer treatment, predominantly affecting the upper limbs and occasionally the breast. Lymphoedema does not occur in the otherwise normal, if inflamed, lactating breast.

On page 363, describing Figure 5, Clinical Protocol #36 states: “Day 5 postpartum breast engorgement showing edematous nipple areolar complex and dependent lymphedema with overlying erythema”. In addition to the misdiagnosis of ‘lymphedema’, I note that lactiferous ducts are dilated and tense when milk is not adequately removed to maintain equilibrium with production volume.48 Most glandular tissue is subareolar, in a 3 cm radius from the base of nipple. Although this woman may have some increased interstitial fluid and stromal tension, her nipple areolar complex swelling is much more likely to result from high milk volumes, associated with high intraluminal pressures, in both her alveoli and lactiferous ducts.

On page 371 in Figure 21 entitled ‘Lymphatic Drainage’, Clinical Protocol #36 asserts that lymphatic drainage “reduces swelling by assisting movement of lymph fluid, decreasing edema, softening fibrosis”. However, an inflamed lactating breast is not fibrotic.

Example B. Introduction of the poorly defined diagnoses of inflammatory mastitis, bacterial mastitis, phlegmon, subacute mastitis and infected galactocoele increase risk of unnecessary antibiotic use.

Introduction of the poorly defined clinical diagnoses of ‘inflammatory mastitis’, ‘bacterial mastitis’, ‘phlegmon’, ‘subacute mastitis’, and ‘infected galactocele’ into Clinical Protocol #36 risks perpetuation of unnecessary antibiotic use, in an era when the World Health Organisation calls urgently for antimicrobial stewardship due to the potentially catastrophic consequences of antimicrobial resistances.[18,19]

You can read more about the risks of these diagnoses here and here.

Selected references

1. Douglas PS. Does the Academy of Breastfeeding Medicine Clinical Protocol #36 'The Mastitis Spectrum' promote overtreatment and risk worsened outcomes for breastfeeding families? Commentary. International Breastfeeding Journal. 2023;18:Article no. 51 https://doi.org/10.1186/s13006-13023-00588-13008.

2. Douglas PS: Re-thinking benign inflammation of the lactating breast: a mechanobiological model. Women's Health 2022, 18:https://doi.org/10.1177/17455065221075907.

3. Douglas PS: Re-thinking benign inflammation of the lactating breast: classification, prevention, and management. Women's Health 2022, 18:doi: 10.1177/17455057221091349.

4. Douglas PS: Overdiagnosis and overtreatment of nipple and breast candidiasis: a review of the relationship between the diagnosis of mammary candidiasis and Candida albicans in breastfeeding women. Women's Health 2021, 17:DOI: 10.1177/17455065211031480.

5. Baeza C, Paricio-Talayero JM, Pina M, De Alba C: Re: ‘‘Academy of Breastfeeding Medicine Clinical Protocol #36: The Mastitis Spectrum, Revised 2022’’ by Mitchell et al. 17 2022, 11:970-971.

6. Kvist LJ. Toward a clarfication of the concept of mastitis as used in empirical studies of breast inflammation during lactation. Journal of Human Lactation. 2010;26(1):doi:10.1177/0890334409349806.

7. Cullinane M, Scofield L, Murray GL, Payne MS, Bennett CM, Garland SM, Amir LH: Random amplified polymorphic DNA analysis reveals no clear link bewteen Staphylococcus epidermidis and acute mastitis. Australian and New Zealand Journal of Obstetrics and Gynaecology 2022, 62:605-609.

8. Ebell MH, Siwek J, Weiss BD, Woolfe SH: Strength of Recommendation Taxonomy (SORT): a patient-centred approach to grading evidence in the medical literature. American Family Physician 2004, 69:548-556.

9. Oikonomou G, Addis MF, Chassard C: Milk microbiota: what are we exactly talking about? Frontiers in Microbiology 2020, 11(60):doi:10.3389/fmicb.2020.00060.

10. Amir LH, Griffin L, Cullinane M, Garland SM: Probiotics and mastitis: evidence-based marketing? International Breastfeeding Journal 2016, 111(19):doi:10.1186/s13006-13016-10078-13005.

11. Barker M, Adelson P, Peters MDJ, Steen M: Probiotics and human lactational mastitis: a scoping review. Women and Birth 2020, d33:e483-e491.

12. Crepinsek MA, Taylor EA, Michener K, Stewart F: Interventions for preventing mastitis after childbirth (Review). Cochrane Database of Systematic Reviews 2020(9):Doi:10.1002/14651858.CD14007239.pub14651854.

13. Albarqouni L, Arab-Zozani M, Abukmail E: Overdiagnosis and overuse of diagnostic and screening tests in low-income and middle-income countries: a scoping review. BMJ Global Health 2022, 7:e008696. doi:008610.001136/bmjgh-002022-008696.

14. Brodersen J, Schwartz LM, Heghan C: Overdiagnosis: what it is and it isn't. BMJ Evidence-based Medicine 2018, 23:1-3.

15. Born KB, Levinson W: Choosing Wisely campaigns globally: a shared approach to tackling the problem of overuse in healthcare. Journal of General Family Medicine 2019, 20(1):9-12.

16. Brownlee S, Chalkidou K, Doust J, Elshaug AG, Glasziou P, Heath I, Nagpal S, Saini V, Srivastava D: Evidence for overuse of medical services around the world. The Lancet 2017, 390:156–168.

17. Armstrong N: Overdiagnosis and overtreatment: a sociological perspective on tackling a contemporary healthcare issue. Sociology of Health and Illness 2020, 43(1):58-64.

18. Editorial: The antimicrobial crisis: enough advocacy, more action. The Lancet 2020, 395(10220):247.

19. Lesho EP, Laguio-Vila M: The slow-motion catastrophe of antimicrobial resistance and practical interventions for all prescribers. Mayo Clinic Proceedings 2019, 94(6):1040-1047.

20. Ingman WV, Glynn DJ, Hutchinson MR: Inflammatory mediators in mastitis and lactation insufficiency. Journal of Mammary Gland Biology and Neoplasia 2014, 19:161-167.