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9/30/2019
1
When traditional interventions for
insufficient milk just don’t work
Hidden genetic, nutritional &
environmental culprits
Marsha Walker, RN, IBCLC
Disclosure
Sufficient Milk Production Has Always
Been Important!
• Ancient writings describe
numerous reasons for
diminished milk supply
and recommend dozens
of remedies
• Many writings show
awareness of some
causes of insufficient
milk but do not relate
remedies to causes
Incidence of Insufficient Milk
Is it real or perceived?• Most frequent reason given
for supplementing or abandoning breastfeeding
• Probably 1-2% of the general population of women are anatomically or physiologically unable to produce sufficient milk
• 3,977,745 births in 2015– 1% = 39,777 mothers primary
insufficient milk production
– 2% = 79,555 mothers with primary insufficient milk
– 5% = 198,887 mothers with primary insufficient milk
Oh no! You ran out of milk?
Milk synthesis is a
very complex process
• Estrogen, progesterone,
prolactin, placental
lactogen transition breast
from non-secreting to
secreting organ
• Alveolar cells � expression
of lactogenic genes
(secretory differentiation)
• Secretory activation with
delivery of placenta
• Tight junctions between
lactocytes close,
limiting passage of ions
like sodium and
chloride
• Important for
establishment of
lactation and facilitation
of milk secretion
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Milk secretion from lactocytes
• Regulated by complex
milieu of reproductive
and metabolic
hormones
– Prolactin
– Glucocorticoids
– Insulin
– Insulin-like growth factor 1
– Growth hormone
– Thyroid hormone
• These hormones can
act directly on the
lactocyte or
indirectly by altering
endocrine response
and nutrient delivery
to the mammary
gland for milk
production
Also need an appropriately developed
and differentiated breast
• Up to a two-fold
increase in glandular
tissue during lactation
• Disruption of
appropriately
developed and
differentiated breast
tissue
– PCOS
– Environmental
exposures
Volume of colostrum
• First 24 hours colostrum
ingested by healthy full
term 6lb 13oz (3.1 kg)
infants
– 15 + 11mL colostrum
total
• Santoro et al, 2010
– 13mL/kg/d (39mL total)
• Casey et al, 1986
– 9.6mL/kg/d (28.8mL
total)
• Dollberg et al, 2001
Milk volume• Mothers of healthy term
infants should be able to produce 500-600 mL (17.8 oz-21.4 oz) of milk by day 4-7– Hill PD et al. Journal of Perinatal and
Neonatal Nursing 19: 273-282, 2005.
• Full milk production is generally reached by 14 days
• If milk production is <440mL (15.7oz) by day 7 and birth weight not regained,
• Kent et al. Nutrients 2016; 8(12):756
Risk factors for insufficient milk
• Primip
• Cesarean
• Infertility
• Polycystic ovary syndrome
• Obesity
• Hyperandrogenism
• Insulin resistance
• Advanced maternal age
• Mammary hypoplasia
• B12 deficiency
• Endocrine disruptors exposure
• Prolactin deficiency
• Prolactin receptors
• Thyroid hormones
• Milk ejection problems
• Serotonin
• Hypertension
• Breast injury
• Placenta encapsulation
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Risk factors for insufficient milk
• Retained placenta
• Breast surgery
• Infrequent breastfeeding (FIL)
• Ineffective breastfeeding
• Preterm or late preterm birth
• Diabetes
• Infant with oral anomalies, birth defects
• Postpartum hemorrhage
• Anemia
• Certain medications
• Smoking
• Certain contraceptives
• Breast pump and pumping issues
• Genetics
• Environment
• Maternal diet
• Aripiprazole (Abilify) is an atypical antipsychotic drug that is also used with other medications to treat depression
• A common adverse effect of some antipsychotic medications is hyperprolactinemia (high prolactin levels)
• Aripiprazole can be and is given to patients to reduce prolactin levels
• Breastfeeding mothers taking aripiprazole should be monitored carefully for milk sufficiency and their infants monitored for appropriate weight gain
– Li X, Tang Y, Wang C. Adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia: metaanalysis of randomized controlled trials. PLoS One. 2013;8(8):e70179.
– Walker T, Coursey C, Duffus ALJ. Low dose of Abilify (Aripiprazole) in combination with Effexor XR (Venlafaxine HCL) resulted in cessation of lactation: A case report. Clinical Lactation 2019; 10:56-58.
Aripiprazole (Abilify)
Polycystic ovary syndrome (PCOS)
• PCOS is the leading cause of infertility
– Polycystic ovaries
– Obesity
– Hyperandrogenism
– Anovulation
• Failure to ovulate results in low progesterone which inhibits mammary tissue growth
– Insulin resistance
• Co-morbidities– Hypothyroidism
– Metabolic syndrome
– Hypertension
– Glucose intolerance
– Diabetes
Polycystic ovary syndrome (PCOS)
Hypoplastic breasts• Excess of one or more
male hormones– Ovarian theca-lutein cyst
• Estrogen and progesterone receptor deficit
• Androgens inhibit breast development and limit breast growth by opposing the stimulatory effects of estrogen– Hirsutism
– Alopecia
– Adult acne
Insulin resistance
(may go undiagnosed for years)
• Study of mammary gland RNA in samples of
breast milk (a chain of molecules that are
blueprints for making specified proteins)
• Orchestrated switching on and off of genes as
breast transitions from colostrum to copious
milk production
• Insulin important to signaling in mammary
gland
– Lemay et al. PLoS One 2013, 8:e67531
Insulin resistance• Study links insulin
resistance or inefficient glucose metabolism with insufficient milk supply
• The intracellular signals triggered by the binding of the insulin with the cellular receptors get suppressed by the expression of the PTPRF gene
• This gene was found to be over expressed in insulin resistant mothers, linking the insulin resistance with insufficient milk supply. *protein tyrosine phosphatase, receptor type F
9/30/2019
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Will improving insulin action be
effective for increasing milk supply?
• Interventions that lower maternal cortisol (a
suppressor of insulin action)
• Skin-to-skin care of the newborn
• Metformin therapy
• Fenugreek-may improve glucose tolerance
due to metformin-like biguanides
• Weight loss
• Stress reduction
Overweight/obesity
and Lactation
• Mothers with delayed lactogenesis II (>72 hours post
birth) are more likely to have high BMI
• Breastfeeding durations decrease as maternal BMI
increases
• Obesity alters the 24 hour spontaneous release of
prolactin
• Prolactin response to sucking is blunted in obese
mothers, decreasing by ~45ng/mL at 48 hours
postpartum and 100ng/mL at 7 days, during the time
period important for optimal milk production
Overweight/obese mothers experience a delayed onset of
lactogenesis II and reduced milk transfer at 60 hours
postpartum
• For each 1-unit (1 kg/m2) increase in pre-
pregnant BMI, a 0.5-hour delay in the onset of
lactogenesis II has been calculated
• Difference in onset of copious milk production
can be up to 10 hours later in a mother with a
MBI of 40 compared to a mother with a BMI
of 20
Obesity effect on lactating breast
• Mouse model showed that obesity impairs mammary gland development– Obese mice exhibited marked abnormalities in
alveolar development within the mammary gland
• Obesity also impaired lactogenesis; seen as lipid accumulation in the secretory epithelial cells, showing an absence of copious milk secretion
• Obesity-induced inflammation of the mammary gland with premature involution
• May increase local estrogen production which downregulates prolactin signaling and suppresses lactation
• Flint DJ, et al. 2005 Am J Physiol Endocrinol Metab• Lee & Kelleher 2016 AJP Endocrinol Metab
Breaking the Cycle of
Overweight/Obesity
• Breaking the cycle of overweight and obesity begins at the
beginning
– Overweight/obese mothers should breastfeed VERY frequently
during the first 7-10 days
� number of feedings critical in the first 12 hours for stimulating
lactogenesis II in mothers with IDDM
(Ferris, 1993)
– Infants need to be monitored more closely
– All of these mothers need a feeding plan before hospital
discharge and close follow-up thereafter
• May have decreased perceptions of breast fullness and
milk production
Breastfeeding Management
• Frequent feeds 10-12 times each 24 hours should continue until lactogenesis II has been confirmed and the baby is gaining weight well
• Alternate massage/breast compressions
• Large breasts should be supported with a rolled up towel or receiving blanket
• Flat nipples can be everted prior to each feeding with a modified syringe
• Nipples may flatten out due to
excess adipose tissue that stretches
the areola & flattens the nipple
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Pillows, props and
difficulty with positioning
• May need to breastfeed
in front of a mirror
• Positioning difficulties
may last longer for
obese others
• May have difficulty
finding large size bras
Problems with prolactin
• Autoantibodies that target prolactin-secreting cells
• Prolactin bioavailability, bioactivity or form
• Prolactin receptor numbers and action or inaction
• Prolactin receptor resistance
• Pituitary issues
• Prolactin replacement therapy (recombinant prolactin)
• Metoclopramide
• Domperidone
Do some mothers have
the wrong kind of prolactin?• 3 kinds of prolactin, 2 of which
are inactive
• Big prolactin and Big-Big prolactin (macroprolactin) are inactive
• All show up in normal blood prolactin test, making it look like normal levels
• Do moms with high prolactin levels and little milk have the wrong kind of prolactin?
• Rarely, autoantibodies recognize a subset of prolactin secreting cells impacting prolactin deficiency– Treated with recombinant
prolactin
Prolactin and suction/vacuum levels
• Association between suction pressure and prolactin response
• Low intraoral vacuum correlated with
– lower prolactin response to sucking
– Longer time to perceived onset of lactation
• Zhang et al. Breastfeeding Medicine 2016; 11:461-468.
• Mothers of infants with low intraoral vacuum will need increased monitoring of milk production
– Preterm, late preterm, neurological issues
• Assure proper positioning and latch, intact seal of lips, strengthening of muscles involved in sucking
Thyroid dysfunction• Hypothyroid during pregnancy may affect mammary
development
• Excessive iodine intake
• Hypothyroid– Thyroid responsible for cellular activity; decreased milk
production could result from slow down in milk-secreting cell activity (Synthroid etc)
– Fatigue, decreased energy, hair loss, weight gain, dry skin, muscle aches, constipation, poor concentration
• Hyperthyroid– Assess for suppression of milk ejection reflex
– Early, dramatic onset of lactation, painful engorgement, milk ejection problems
– Weight loss, nervousness, sweating, heart palpitations
– Prophylthiouracil; Tapazole
Impaired milk ejection
• Milk ejection issues may
contribute to
insufficient milk if
breasts are unable to
release the milk they
produce
• Thyroid dysfunction
• Stress
• Breast pump use
• Massage and hand expression
• Reverse pressure softening
• Warm compresses
• Oxytocin nasal spray
• Conditioning the milk ejection reflex
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Impaired milk ejection
• Gene mutation resulting in decreased levels of connexin43
– Gap junction protein expressed in myoepithelial cells
– Delayed development of mammary gland and impaired milk ejection
– High glucose levels alter connexin43 expression
– Does diabetes play a role here?
Prenatal SSRIsMarshall et al. J Clin Endocrinol Metab. 2010;95:837-846
•Serotonin acts as a neurotransmitter, a
type of chemical that helps relay signals
from one area of the brain to another
•Serotonin is a local regulator in the breasts
for lactation
•SSRIs like Paxil inhibit serotonin reuptake in
mammary epithelial cells and disrupt
serotonin regulation in the breasts
Serotonin
• Serotonin contributes to milk volume homeostasis
• Disruption of normal serotonin levels can lead to accelerated decreases in milk synthesis and involution of the mammary gland
• Delayed lactogenesis II
• Infant hypotonia
• Increased vigilance in infants whose mothers have taken prenatal SSRIs
• Feeding plan should include– Increased feedings during
prolonged colostral phase
– Frequent weight checks
– Documentation of milk transfer
– Pre and post feed weights if needed
– May need to pump milk to bolster production
Genetics, diet, and environment
Lee & Kelleher. 2016. Am J Physiol Endocrinol Metab 311: E405-E422
Genetic variation in genes that encode
for prolactin signaling• Mutation in prolactin and
prolactin receptors
• Prolactin signaling pathway represents a set of reactions induced by the binding of prolactin to the prolactin receptor
• Genetic variations (certain genes inactive or switched off) in prolactin signaling pathways
• Recombinant prolactin may be effective in increasing milk volume when this pathway has been affected
Cytokeratin 18 (CK18)
• CK18 is a marker for luminal epithelial cells
including lactocytes (milk making cells)
• High maternal BMI is linked with lower CK18
expression in breastmilk cells
• Suggests that women with larger body mass
index have less epithelial tissue capable of
synthesizing milk
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Zinc—who knew? Zinc transport mutations• Mutation of the protein ZnT2 which transports
zinc in specific body tissues– Low Zn in milkk
– Reduced mammary gland development
– Functional problems
• ZnT2 transports zinc by importing it into vesicles -- small organelles within the cell -- that then secrete zinc into the breast milk.
• Zinc is also necessary to trigger the growth of mammary glands, mammary epithelial cells and secretion pathways.
• Without functional ZnT2, zinc accumulates in the cytoplasm, becoming toxic to the cell.
Prolactin and ZnT2 are partners
• ZnT2 is critical for
mammary gland
expansion and
differentiation and milk
secretion
• Loss of ZnT2 results in
breast hypoplasia– Lee et al. J Biol Chem
2015;290:13064-13078
• Prolactin plays a primary
role in ZnT2 activity– Qian et al. Am J Physiol Cell
Physiol 2009; 297:C369-C377Kelleher et al. Genes & Nutrition 2009;
4:83-94
Genetic variants
• The common genetic variant S288 in ZnT2 causes
– oxidative stress in the lactocyte
– Impaired paracellularbarrier function
– Lysosomal mediated cell death
– Increased sodium content in breastmilk
• Lee et al. Scientific Reports 2018;8:3542
Looking for zinc
• It is possible to take a sample of saliva and sequence the gene for ZnT2 (SLC30A2) and see if there is a mutation directly
• Some companies can do this now
• Low zinc levels in mother’s milk would strongly suggest a defect in a zinc transporter
• The mom's serum zinc levels are not affected because low milk zinc is caused by a defect in her breast.
• However, if the mom's serum zinc levels were low, then she would likely be suffering from another issue (inflammation, diabetes, obesity, or very low dietary intake of zinc) that my also lead to low milk zinc levels.
What can we do?• Most women are marginally
low in zinc
• Adding a bit more of zinc to the diet would not be harmful but too much could be toxic
• Unknown if it would be therapeutic with the ZnT2 variants
• In some cases domperidonemay help.
• Since ZnT2 is regulated by prolactin and depending upon the defect in ZnT2, extra prolactin may help fix the problem
• Enrich the mother’s diet with antioxidants
• Most lactation defects seem to have an inflammation component
• The underlying consequence of a defect in ZnT2 may be inflammation
• So if we reduce inflammation, we can solve the problem that the defect in ZnT2 is actually causing
• Future drug that targets the particular pathway/mechanism
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Adding a little incentive to
pumping + an antioxidant!Photo courtesy of Barbara Wilson-Clay
Exposure to environmental toxins• Exposure to endocrine
disrupting compounds
during pregnancy can
affect mammary gland
development
• Exposure to chemicals
increase expression of
numerous genes, some
of which disrupt normal
differentiation and
development of the
milk production
apparatus in the breast
• Atrazine and dioxin– In herbicides
• Bisphenol A (BPA) and dibutylphthalate– In plastics
• Nonylphenol– In laundry and dish detergent
• Polybrominated diphenyl ethers– A flame retardant
• Perfluorooctanoic acid (PFOA)– In cleaning products and pesticides
• Perfluoroalkyl substances (PFAS)
• Perchlorate – Blocks iodine uptake by thyroid
causing hypothyroidism
– In fireworks, contaminated water, food from contaminated croplands (milk, spinach, lettuce, soy), food packaging
Herbal Galactogogues
• Need to understand what is contributing to insufficient milk production
• Avoid shotgun approach or simultaneous taking of numerous trial remedies at the same time
• Understand HOW a galactogogue works
– Directly
– Indirectly by addressing an inhibiting problem such as hyperandrogenism or insulin resistance
• Conflicting information, differing research methodology, and lack of standardization of herbal galactogogues makes it difficult to interpret what actually works
Improving mammary gland growth
• Fenugreek
– 2 dropperfuls tincture x2-3
– 2-4 500 mg capsules x3/d
– Tea is often not potent enough
• Goat’s rue
– 1-2mL tincture x4/d
– 1 capsule x1/d
– If >175 lbs, 2 capsules x3/d
– Lactogal Plus (Salatino 2017)
• Torbangun
• Blessed thistle
• Metformin
• Zinc supplementation
Fenugreek Cautions
• Baby may smell like maple syrup; physician should know this; Maple Syrup Urine Disease has same odor
• Not all mothers respond with �milk
• Nausea and GI distress may limit its use in some mothers; high fiber content may cause diarrhea
• Some mothers may see a drop in milk as dose is �
• May � blood glucose levels in mothers with diabetes
• Antigenic similarity to peanuts; mothers with severe peanut allergy should not take this herb
• Mothers on anticoagulant therapy should use with caution as herb has “blood thinning” capability
Herbal galactogogues• Shatavari (Asparagus racemosus)
– � prolactin production; mammary tissue growth?
• Torbangun (Indian borage; Coleus amboinicus lour)
– Proliferation of mammary secretory cells
• Milk thistle (Silybum marianum)
– Estrogenic property
• Moringa oleifera
– May increase prolactin levels
• Malunggay
– Stimulates prolactin levels
• Goat’s rue (Galega officinalis)
– Phytoestrogen content
• Fennel (Foeniculum vulgare)
– Estrogenic activity
• Anise (Pimpinella anisum)
– Estrogenic activity
• Is it the herbal or the psychological benefit?
9/30/2019
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Combination herbals
• Many preparations on the market contain varying amounts and combinations of herbal preparations
• A combination of fenugreek, ginger, and turmeric was shown to increase milk volume as measured by a hand pump
– Bumrungpert et al. Breastfeeding Medicine. December 2018. ahead of print
• Mothers had a 49% increase in milk volume at week 2 and a 103% increase at week 4
Medications• Domperidone
– Dopamine antagonist, but does not cross blood-brain barrier, � likelihood of depression
– Stimulates milk production at doses of 10-20mg, 3-4 times daily
– Compounding pharmacies can formulate domperidone
– Caution if mother is also taking antacids, antifungals, Macrolides, HIV protease inhibitors, monoamine oxidase inhibitors
– Should not be given to mothers with cardiac arrhythmia or anomaly
– Does not work for all mothers; may not work unless maternal prolactin levels are low
• Human growth hormone
• Thyrotropin releasing hormone
• Recombinant human prolactin
• Kinesio tapeR was applied to the breasts using fan cuts for relaxing the pectoralis muscles and facilitating fluid movement.
• Mothers reported doubling or tripling the amount of milk they could pump after the tape was applied
Therapeutic taping Therapeutic taping
• May improve milk circulation by lifting the skin, increasing the space below
• Also has been used for blocked milk ducts
Valdez, Jet al. (2018). Abstract 81. Effects of Kinesio Tape application on breastmilk production. Breastfeeding Medicine, 13(S2), S36.
Acupuncture for insufficient milk
• Clavey (1996) reported
90% effectiveness for
insufficient milk when
started within 20 days
of delivery
• American Journal of
Acupuncture 1996;
24:35-46
• Wei et al (2008)
described electro-
acupuncture at Shaoze
(SI 1) as effective for
insufficient milk
• Wei, et al. (2008).
Journal of Traditional
Chinese Medicine
28:168-172
AcupressureEsfahani et al. 2015. Iran J Nurs Midwifery Res, 20:7-11.
• Acupressure for
enhanced milk
production
• Can be applied by the
mother• GB20 (in a depression between the
upper portion of the
sternocleidomastoid muscle and the
trapezius on the same level with
GV16), acupoint LI4 (on the dorsum
of the hand, between 1st and
2nd metacarpal bones), and acupoint
SI1 (1 cun posterior to the corner of
the nail on the upper side of the little
finger)
9/30/2019
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http://www.newbornconcepts.com/pr
oducts#pumping_cdReflexology
• Another low tech intervention for increasing milk production
• Performed on the foot on kidney one, pituitary point on middle of toe, and points between 2, 3, and 4 metacarpals
• Showed increased milk output in preterm cesarean mothers during first 4 days
– Mohammadpour et al. Iran J NursMidwifery Res 2018;23:371-375.
Warmth
• The warming of tissues is a known therapeutic intervention that has the effect of increasing local blood flow and metabolism in tissues, facilitating excretion of tissue waste materials and phagocytosis, and enhancing tissue nutrition
• Warm compresses placed on the breasts have long been recommended to aid the let down reflex.
• Kent et al(2011) found that warmed pump flanges resulted in a larger amount of available milk removal.
Warmth• Yigit et al (2012) studied if warming the breast prior
to pumping would increase the volume of milk expressed from a warmed breast compared with the other breast which was not warmed.
• Mothers placed a warm compress (40.5C/104.9F) on one breast prior to pumping with an electric breast pump.
• The amount of milk obtained from the warmed breasts was significantly higher than that obtained from the non-warmed breasts.
• Warming probably has an enhancing effect on the milk ducts or milk flow, allowing more milk to be pumped, rather than increasing actual breastmilk production.
Music
• Keith et al (2012) found
that pump dependent
mothers who listened
to music while pumping
produced significantly
more milk with a higher
fat content
Why music?• Soothing music increases oxytocin levels
(Nilsson, 2009)
• Improved endothelial vasoreactivity
• Flute music experienced by 30 preterm
mothers during first week of lactation for 30
minutes, 15 of which during actual pumping
reduced anxiety
• Mothers who experienced music therapy had
a significantly increased amount of expressed
milk compared with mothers who did not
experience music
• Lowers stress and cortisol levels
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Hang in there Mama--
you got this!