Identifying the cause of breast and nipple pain during lactationBMJ 2021; 374 doi: https://doi.org/10.1136/bmj.n1628 (Published 13 July 2021) Cite this as: BMJ 2021;374:n1628
- Lisa H Amir, medical officer, principal research fellow12,
- Carmela Baeza, family doctor and International Board Certified lactation consultant3,
- Jayne R Charlamb, clinical associate professor4,
- Wendy Jones, pharmacist with a special interest in breastfeeding and medication5
- 1Breastfeeding Service, Royal Women’s Hospital, Parkville, Australia
- 2Judith Lumley Centre, La Trobe University, Victoria, Australia
- 3Raices Family Wellness Clinic, Madrid, Spain
- 4Division of Breast Health & Breastfeeding Medicine, Department of Obstetrics & Gynecology, SUNY Upstate Medical University, Syracuse, NY, USA
- 5Portsmouth, UK
- Correspondence to L Amir
What you need to know
The most frequent cause of nipple pain in breastfeeding women is poor latch or attachment to the breast
An itchy, erythematous rash on the nipple, areola area, or breast is likely to be eczema, and should not automatically be diagnosed as nipple thrush
Persistent nipple and breast pain during lactation is usually multifactorial. Elicit factors from maternal, infant, medical, mental, and psychosocial health, as well as from mechanical trauma or infection
A first time mother developed left nipple pain 24 hours after the birth. This persisted despite trying nipple shields and topical lanolin. On day 7 she developed mastitis in her left breast and was prescribed flucloxacillin, but the nipple and breast pain continued. Her friend suggested oral probiotics, to no effect. At the breastfeeding clinic (6 weeks postpartum) the left breast pain was excruciating and a burning pain had started in her right breast. She was also concerned about her baby’s slow weight gain. On examination, her nipples were sensitive to light touch and examination of the baby indicated torticollis. When observing a feed, good positioning and attachment was seen on the right but the infant’s torticollis made it difficult for him to attach on the left side and the mother quickly took him off her breast because it was too painful. The left nipple was flattened after the feed.
More than 70% of first time mothers report nipple and/or breast pain in the first week post partum.1 This is frequently nipple pain resulting from inadequate latching; however, multiple diagnoses should be considered.2
This article helps clinicians promptly identify and resolve the underlying cause(s) of pain so that premature cessation of breastfeeding can be avoided and the breastfeeding relationship becomes enjoyable for mother and baby. We explain the three elements of assessment—the mother’s health, the infant’s health, and the dyadic interaction between the two—and hope to encourage clinicians to further their training in breastfeeding medicine. Detailed management is beyond the scope of this article but a summary table is provided, including information to guide referral.
We have used evidence from systematic reviews and large cohort studies, where available, but evidence in this field is lacking. Generally, consensus is poor on definitions and diagnoses, but we have used information from clinical guidelines, including the National Institute for Health and Care Excellence (NICE) and the Academy of Breastfeeding Medicine (ABM).3
How do you diagnose the cause of breast or nipple pain?
Use a respectful, individualised, family centred approach to address the mother’s concerns, and to assess mother and infant separately and together (fig 1).45 Formulate the likely diagnosis/diagnoses (from the causes in box 1) by obtaining a clear timeline and description of the problem.
Causes of nipple and breast pain during lactation
Can cause mechanical damage to the nipple
Infant oral anatomy
Poor milk expression technique
Breast pumps can cause nipple damage if the breast pump flange is too small, or if the pressure is too high or prolonged
Nipple bleb/white spot
A superficial, inflammatory fibrinous lesion, appearing as a white spot on the nipple tip which may block a nipple opening, causing mild to severe nipple pain (fig 2) (This can lead to a blocked duct8)
Can be a primary cause of pain. Or can be a secondary response to pain or nipple trauma (damaged nipples or thrush). Usually in individuals with poor circulation who experience cold hands/feet
May be atopic, irritant (from nipple creams (fig 3) or complementary foods remaining in infant’s mouth) or contact dermatitis (from breast pads) or psoriasis
Bacterial nipple infection
Nipple damage that is present for >24 hours is commonly colonised with Staphylococcus aureus (fig 4)
Uncommon. A nipple tip which folds in on itself can lead to ongoing pain as the skin inside the fold is fragile, and may become macerated9 (fig 5). The macerated skin fails to heal, unless the nipple tip can be kept everted after feeds
Herpes simplex infection
Occurs when infection is transferred to the nipple/areola from an infected source, eg visitor with cold sore touches mother’s hand and is transferred to nipple; or in later months the child may develop herpes stomatitis from contact at childcare, and transfer from mouth to nipple10
Causes of breast pain
Can occur at 2-10 days post partum when the milk “comes in,” or if breastfeeding is stopped abruptly, or if many hours pass without removing milk from the breast3
Blocked (or plugged) duct
May be non-infectious (eg, when the infant sleeps through the night for the first time), but can progress to infection, especially if nipple damage is present and bacteria can enter breast tissue (usually in first eight weeks post partum).
One in five breastfeeding women are diagnosed with mastitis,12 and the usual organism is S aureus.13 Signs and symptoms are similar to a blocked duct but women usually also have systemic illness (figs 6, 7). Breast cellulitis is a type of mastitis and may be caused by a Streptococcus spp infection rather than the typical S aureus.14
A collection of pus within the breast tissue, usually (but not always) occurring after mastitis. Occurs in 3% of women with mastitis15
Breast cyst or galactocele
A fluid or milk filled cyst within the breast may present as a tender swelling/lump11
External trauma to breast
Vigorous massage of the breast can cause bruising, as can a bump from toddler’s foot or similar hard knock
Non-lactation related skin conditions
Any skin condition can occur on the breast during lactation—eg, breast eczema (fig 8). Likewise exogenous effects like sunburn—just as they may at any other time
Conditions that can cause breast and/or nipple pain
Occurs when there is an overgrowth of Candida spp on nipple and or breast; may start on one side and spread to the other nipple/breast (not related to engorgement/mastitis). Antibiotics may have been used previously.16 Burning nipple pain is continuous, not just during feeds; breast pain may be described as radiating. Nipple soreness may develop after months of pain free breastfeeding in women predisposed to vaginal candidiasis.1718 Avoid diagnosing thrush solely on the mother’s description of radiating/shooting pain, ie, unless it clearly follows a course of antibiotics in a patient prone to vaginal thrush, consider all other diagnoses
May occur anywhere on the nipple/breast/chest in a dermatomal distribution. Occurs infrequently and pain may be present for several days prior to onset of rash
Breast cancer (unusual cause, doesn’t usually present as pain alone)
Inflammatory breast cancer
Mastitis symptoms which persist despite antibiotic treatment, especially with peau d’orange appearance. Occurs infrequently
Paget’s disease of the nipple
An uncommon type of breast cancer that appears similar to eczema on the breast or nipple.19 Occurs infrequently
What to cover in the mother’s history
Take a general health and medical history and, in multiparous mothers, a previous lactation history.
Pain could be from scarring following previous breast surgery, or dermatological conditions (eczema, psoriasis, or other skin issues)
Autoimmune conditions such as thyroiditis, diabetes, and other autoimmune conditions can target the mammary gland.20 Depression, fibromyalgia,21 or other chronic pain conditions can cause exacerbated perception of breast or nipple pain that may or may not be related to breastfeeding, ie, the person may experience breast fullness as severe pain
Vulvovaginal symptoms could be linked as there are similarities between the skin of the nipple and the vulva:
History of recurrent vulvovaginal candidiasis might indicate nipple or breast thrush, or vulvodynia (a chronic pain condition)
Previous lactation experiences may indicate the mother’s attitude towards breastfeeding. Were they able to breastfeed for as long as they wished to previously?
A mother who previously breastfed for more than 12 months is likely to persevere during early problems
Did the mother have similar problems previously? Was it owing to nipple anatomy (eg, flat/inverted/dimpled nipples)?
A sensitivity to cold (the woman might describe “poor circulation”) or history of Raynaud’s disease in herself or family, could suggest nipple vasospasm (Raynaud’s phenomenon of the nipple) as a primary cause or contributing factor to her pain.22
Ask about the pain
Consider nipple and breast pain separately, although patients often use the terms interchangeably.
What is the location of the pain? Is it in the nipple or the breast, deep versus superficial, unilateral- versus bilateral, non-breast structure (could it be chest wall or internal, eg, pleurisy?)
If the site of the pain is indicated by a finger pointing to the sternal edge, costochondritis (inflammation of the costochondral junction) is likely23
What is the character of the pain?
Achy pain is present with the continuum of engorgement, blocked duct, and mastitis
Other characteristics, such as shooting, burning, or needle-like pain, can indicate the source of the pain is from the breast ducts, even in a non-lactating breast.23 This type of pain may be present in breast thrush, but is not pathognomonic of this condition. If burning nipple pain occurs only on latching or only with direct breastfeeding, the diagnosis is more likely caused by attachment difficulty
When does the pain occur?
If pain is continuous it could be owing to a nipple or areolar skin condition; infection; or a severely damaged nipple
See below “Assessment of dyadic interaction” for pain during or after a feed.
Severity acknowledges the importance of mothers’ discomfort and can be useful to monitor management, but does not indicate the cause of pain.
Ask about onset and associated, exacerbating, or relieving features
Was the onset with illness (missed feed?), teething (baby feeding poorly), menses, or a new pregnancy (hormonal sensititivity)?
Itching and rash on other areas of the body is suggestive of eczema/dermatitis
Chills, flu-like aching, malaise, and systemic illness is suggestive of mastitis3
Pain exacerbated by cold surroundings (eg, freezer section of supermarket, or being exposed to cold wind), or relieved by heat (eg, heat packs, warm shower, or even warming the breast with their hand) could indicate nipple vasospasm or Raynaud’s phenomenon of the nipple
Management history—have any remedies or treatments suggested by friends, family, social media, or other healthcare professionals helped?
If the obstetric/postnatal history includes antibiotic use, consider nipple/breast thrush
If nipple creams or pads have worsened symptoms, consider irritant or contact dermatitis (fig 2)
If topical steroids have had no effect, consider the rare Paget’s disease of the nipple19
If mastitis has not responded to antibiotics in individuals with autoimmune conditions,20 consider autoimmune mastitis (uncommon).
Mothers’ concerns might offer clues to diagnosis/es
She may have been assured her that breast implants would not affect breastfeeding; however, implants can be associated with pain during lactation29
A common fear is that breast changes are cancer related; however, most commonly, new lumps are caused by a blocked duct, mastitis, or abscess
Does the mother have adequate support (physical and emotional)?
Does she feel conflicted, powerless, frightened, or depressed? Does anxiety or uncertainty related to pain cause resentment of the infant, the breastfeeding process, or motherhood itself? Consider asking about past or present physical or emotional abuse. These factors exacerbate symptoms for some25
Breastfeeding aversion can manifest as breast or nipple pain during lactation.31
What to cover in the mother’s examination
On inspection, how is the mother’s overall appearance? If she looks unwell, consider mastitis. If she looks pale, consider anaemia (which may contribute to fatigue or exhaustion, exacerbating pain). Dry skin or signs of dermatitis may be visible on face or hands.
It is common for pain to cause worry; however, consider safety, financial, and/or mental wellbeing concerns if the mother appears overly anxious.
Surgical scars or nipple piercing may be evident (and may cause localised pain)
Look for nipple damage34 and other signs that may suggest the cause of the pain (there may be none):
Both very long nipples and poorly protractile (“flat” or inverted) nipples can be painful, if mother cannot latch baby deeply onto the breast
Yellow crusting or exudate could indicate bacterial infection; there will also be evidence of nipple damage and/or eczema (fig 4)
On people with darker skin tones, nipple dermatitis tends to have a brown, violaceous or grey-coloured hue—history can help with the diagnosis if examination findings are unclear (eg, history of childhood eczema or sudden onset of itchiness)36
Post-inflammatory hypopigmentation following areolar dermatitis can be more profound in people with darker skin tones36
Herpes simplex presents as extremely painful small red or fluid-filled blisters, or open sores35; typical presentation is mother of a toddler with herpes stomatitis with lesions where the baby’s mouth comes in contact with the mother’s nipple/areola10
The nipple tip may turn white when exposed to the cold, indicating nipple vasospasm. It is more common for the vasospasm to be caused by a tendency to poor circulation22; however, Raynaud’s disease might be causing the pain
Bleeding from the nipple is usually due to nipple damage.
Look for breast signs (there may be none):
Bilateral fullness might indicate engorgement. Redness might indicate blocked duct/mastitis (figs 6, 7). If swelling and redness is marked, and spreading across the breast/chest, it is cellulitis. In darker skin tones, erythema may not be obvious (consider other markers37)
Peau d’orange appearance might indicate cellulitis, or rarely inflammatory breast cancer
Well demarcated itchy erythematous lesions extending from areola onto the breast could be breast eczema; crusty appearance suggests S aureus colonisation (fig 8)
If breasts have been exposed to the sun, painful red appearance might be caused by sunburn.
Palpation is not always necessary. Palpate the breast if the mother has reported “lumps,” nodules, or swellings in her breast/s, or if you see any bulging area. This could indicate blocked duct, mastitis, galactocele, abscess or in very rare cases, malignancy.
With engorgement, both breasts can be tender, tense, and “full.” A blocked duct or mastitis may cause localised tenderness in a section of one breast that may be swollen or hard. With mastitis, the breast might be inflamed, firm, and lumpy. Breast abscess may cause a localised, tender, and firm or fluctuant swelling or lump; but this may not be palpable if it is deep within the breast. Localised heat and tenderness are also useful indicators of mastitis, especially in darker skin tones when erythema might not be obvious.37
If the breast is red and tender, take the mother’s temperature. ABM advises considering mastitis if the woman has a fever of 38.5°C or greater (this may be affected by recent analgesia). However, women with a breast abscess may have no fever, ie, their temperature is likely to be less than 38.5°C.
Perform a full breast examination where a blocked duct or mastitis recurs in the same location, to exclude a persistent mass that might be suggestive of malignancy.
Take a history about the infant’s health
Birth history may reveal prematurity or other reasons for poor feeding
Do not miss low infant weight gain by solely focusing on maternal pain; ask about growth and weight gain
Inquire if infant tongue-tie has been suggested by other health professionals so you can address this in your examination (see ‘‘Common pitfalls’’ below)
Has the infant been vomiting fresh blood or black stools? This suggests bleeding from nipple trauma but is not harmful to the infant.
What to cover in the infant examination
Asymmetric body/neck/head posture in the infant (eg, in torticollis) makes comfortable breast attachment difficult. Facial asymmetries or fractured clavicle after a traumatic birth may also cause difficulties with latching.
Assess for “classic tongue-tie.” NICE defines this as when the lingual frenulum restricts tongue movement.38 The Tongue-tie and Breastfed Babies assessment tool is helpful in determining severity of tongue tie.39
Look for white patches inside cheeks or lips, which are suggestive of oral thrush. However, a mother can be diagnosed with nipple thrush without any signs in her infant, and white tongue alone in an infant is usually just a “coated tongue.”40
Assessment of suck can detect mechanical issues (suboptimal tongue movement, high palate, high or low intraoral muscle tone) which could be the cause of pain, but using this technique for diagnosis requires training.
How to assess the interaction between mother and baby
Ask about any pregnancy or birth complications that led to early separation of mother and baby, ie, disruption of postpartum skin-to-skin and early breastfeeding practices. For example, did maternal diabetes in pregnancy lead to infant hypoglycaemia and early supplementation with infant formula? Was admission to the neonatal/special care unit needed?
Ask about current feeding practices:
How often are breastfeeds? One or both breasts? For how long?
Are supplementary feeds given?
With expressed breast milk, infant formula, other?
Complete assessment includes observing a breastfeed—if your time or skills are restricted, refer to a local lactation consultant/breastfeeding support for this.
Does infant pathology (eg, fractured clavicle) or asymmetry affect latch and feeding position?
How to assess breastfeeding positioning and attachment
Check that the infant is being held close to the mother, facing the breast with wide open mouth so that they latch on to the breast, not the nipple41
Check for awkward positions involving mother rotating and flexing her thoracic area.42 Mother should be leaning back slightly, like on a deck chair, with her feet on the floor/supported and shoulders symmetrical and relaxed25 (fig 9)
Check that the mother is bringing the baby to the breast (not breast to baby), and that the baby’s chin is pressing into the breast with nose free. If baby’s nose is buried in the breast, bring baby’s bottom in closer
Baby’s cheeks should be round (not sucked in), and jaw opens and closes as baby swallows43
Initial sucks are quick until the milk lets down, and then sucking should be rhythmical
Assess pain during and after the feed. Pain present only at the start of a feed usually indicates nipple trauma from sub-optimal attachment, which could be related to nipple anatomy or infant anatomy. Pain after a feed could be nipple vasospasm, white spot causing blockage and local duct spasm, or breast thrush. Blocked duct pain usually lessens after a feed.
Also check for nipple colour change after a feed. If the nipple is white and malformed (flattened, creased, pointed, etc) immediately upon coming out of baby’s mouth this is owing to compression from poor attachment. In nipple vasospasm, the nipple tip, or part of the nipple tip, turns white shortly after the feed and is associated with throbbing pain; mothers who hold breast in their hand may be warming the nipple to reduce pain. In classic Raynaud’s phenomenon of the nipple, the nipple tip turns white, followed by blue or red and blue, ie, biphasic or triphasic colour changes.22
Consider primary care diagnostic tools
S aureus is usually present when the nipple/areola is damaged,2444546 therefore routine skin swabs are not usually done. However, consider skin swabs for persistent infection to rule out meticillin-resistant S aureus or an unusual organism, such as herpes simplex.35
Box 3 summarises common diagnostic pitfalls.
How to avoid common diagnostic pitfalls
Misdiagnosis and missed diagnosis occurs when clinicians have little education in breastfeeding medicine. To avoid common pitfalls:
Recognise that pain could be due to a poor latch
Acknowledge overdiagnosis of tongue-tie, ie, when normal oral anatomy is diagnosed as tongue-tie and released unnecessarily. Become familiar with infant oral anatomy and explain to parents that the presence of a lingual frenulum is not synonymous with “tongue-tie.” Be aware that in some settings posterior tongue-tie is being diagnosed and treated on the basis of “a tight, non-visible submucosal band of tissue at the very base of the ventral tongue that is palpated rather than seen”; treatment involves invasive deep submucosal dissection which is potentially harmful, and not evidence based49
Recognise there may be multiple contributing factors35
Recognise that management options may be contributing to symptoms (eg, irritant dermatitis secondary to using topical nipple agent25; trauma from too small nipple shield or pump flange; overly vigorous breast massage)
Assess infant growth and health as well as mother health
What are the primary care management options, including referral advice?
Support parents to maintain breast milk feeding, while recognising their infant feeding plans.5051 Use a respectful, individualised, family centred approach to inform and support the mother and family, empowering them to make decisions suitable for their situation and cultural preferences.5
Refer to an infant feeding expert for prompt, immediate assistance when the woman has nipple pain after the first week or so; and if a multiparous mother has a history of early breastfeeding cessation (eg, within the first month). Further primary care management options, including referral advice, are summarised in box 4.
Summary of primary care management and when to refer
Inadequate latch, nipple damage, poor milk expression technique, and/or nipple blanching and malformation immediately after feed
Refer to local infant feeding specialist for practical help, including finding comfortable feeding positions for mother and baby. Mother may consider expressing by hand or with a hospital grade breast pump until nipples heal
A simple scissor frenotomy in the early months can reduce pain if the infant frenulum is tight and impairing breastfeeding (evidence from the NICE guideline and a recent US meta-analysis).3852 No evidence suggests that infants need treatment for upper labial or “buccal” ties.64953
Apply a strong steroid ointment, sparingly, to the affected area after breastfeeding, for up to 10 days (absorption by the infant should be minimal if steroid is used as directed). Avoid soap or shampoo on breasts. An emollient can be used on nipples (eg, purified lanolin). Reassure patients that post-inflammatory nipple hypopigmentation, which is not uncommon in darker skin after areolar dermatitis, is usually temporary3554
Bacterial nipple infection or infected eczema
Consider topical antibiotic ointment, eg, mupirocin, if wound is not healing; or oral antibiotic if infection is spreading to the breast (ie, mastitis/cellulitis)
Explain the condition to the mother and suggest she keep warm, avoid airing her nipples, and regularly apply heat packs to nipples/breasts. If pain persists, consider oral nifedipine
Herpes simplex/zoster infection
Consider oral antiviral treatment, unless infection is resolving. Great care should be taken to avoid any contact between the infant and open lesions. If lesions are present on the nipple or areola, the mother should be instructed to express and discard milk from that breast until the lesions have healed.
White spot/milk bleb
May resolve spontaneously. Consider de-roofing with a sterile needle if it is thin and causing an acute blockage. Case report evidence suggests that a small amount of strong steroid ointment, applied daily and covered with clingfilm wrap between feeds to increase absorption, can be effective55
Engorgement, blocked ducts, and mastitis
Improve breast drainage with extra feeds or expressing, application of cold packs, and oral analgesia. Mother can gently massage toward the nipple when feeding/expressing; after feeds gentle light stroking from areola toward axilla can reduce swelling.56 Management of mastitis is similar, but antibiotics are added if symptoms persist after 24 hours, according to the ABM guidelines (based on a World Health Organization review in 2000).357 Anti-staphylococcal antibiotics, such as flucloxacillin, are preferred3 (cephalexin or clindamycin in cases of penicillin allergy)58
If suspected, refer for ultrasonography. Abscesses can be drained by the radiologist by needle aspiration with local anaesthetic3
Apply topical antifungal to the nipples after feeds, and treat the infant with an oral antifungal (eg, miconazole oral gel). Prescribe oral fluconazole to the mother if she has breast pain
Friction from using a breast pump
Try larger size flange; apply lubrication to areolae prior to pumping (olive oil or purified lanolin)
Breast masses that persist despite active management for longer than ~ one week (ABM protocol)11
Mastitis recurring in same part of the breast
Nipple/areolar eczema not responding to treatment (suspect Paget’s disease of the nipple)19
Refer for diagnostic ultrasound to differentiate between fluid collections (eg, galactocele or breast abscess), and solid masses.59 If cancer is suspected, a mammogram and/or biopsy may be required in consultation with specialists in radiology/surgery.11 However, reassure women that acute lumps are most likely to be blocked ducts, acute mastitis, or abscess and unlikely to be cancer related
Non-red flag associated medical conditions
Refer to rheumatology if autoimmune mastitis is suspected in patients with autoimmune conditions such as systemic lupus erythematosus20
Refer to dermatology if skin condition does not resolve with usual management, and/or if infection is present35
Consider physiotherapy referral for mother if tenderness in chest wall, pectoral muscles, or back suggest musculoskeletal strain25
Infants with torticollis or other signs of head and neck asymmetry can be referred to a physiotherapist or osteopath experienced in paediatrics
Associated psychosocial signs or symptoms
Consider referring first time mothers for parenting support and/or peer support
Refer for psychosocial support if a mother needs further help with her mental wellbeing
Resources showing positioning and attachment
Breastfeeding videos, Global Health Media. https://globalhealthmedia.org/videos/
Breastfeeding videos, Raising Children Network. https://raisingchildren.net.au/newborns/breastfeeding-bottle-feeding/breastfeeding-videos
Education into practice
What questions could you ask to understand the characteristics of breast or nipple pain during lactation and its likely cause?
How do you account for different cutaneous presentations of pain in individuals with darker skin?
How patients were involved in the creation of this article
On 16 June 2020, Wendy Jones posted three questions to breastfeeding women via her Facebook page “Breastfeeding and Medications.” The questions were: What do you want doctors to know about nipple pain? How does nipple pain make you feel? Does nipple pain affect the rest of your family too? Within 24 hours, she received 31, 15, and 13 responses, respectively. We incorporated these responses into the article, by stressing the importance of latching, that pumps can cause pain, that not all pain is due to thrush, and that it’s OK to refer if you don’t know the answer. The respondents’ comments about the effect of breast/nipple pain during lactation on the whole family motivated us to include the description of family centred assessment. We will inform the public when the paper is published on Wendy's Facebook page.
How this article was made
We bring skills from working with mothers and babies in four countries, and although the healthcare systems vary, our approach is similar. We have used research and guidelines where available, but the paper mostly comes from our clinical experience. The authors are experienced in breastfeeding medicine (or support breastfeeding women requiring medications) and based this article on questions commonly asked by breastfeeding mothers, as suggested by a BMJ appointed breastfeeding adviser and responses from women (see ‘‘How patients were involved in the creation of this article’’). We consulted Michelle Rodrigues, a dermatologist with expertise in skin of colour, to ensure accuracy about this topic. The advice given is based on our expert opinion based on clinical practice, reading, and teaching.
Contributors: LHA, CB, JC, and WJ contributed equally to this work.
Competing interests: We have read and understood the BMJ policy on declarations of interest and declare the following interests: none.
Provenance and peer review: commissioned; externally peer reviewed.