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TRANSCRIPT
4/13/14
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Caring for women for life
Hormones, birth, breastfeeding, and their
impact on perinatal mood disorders
Alison Stuebe, MD, MSc
Case CC/ID: 29 yo G2P1011 at 4 weeks postpartum presents for lactation consultation for sore nipples
HPI: Presented to LC for evaluation of sore nipples, and infant found to be at birth weight, with 4 oz gain in last 2
weeks. The LC asks her to complete an EPDS.
The EPDS Case On further discussion, she reports that immediately after the baby’s birth, the patient remembers feeling euphoric and
being unable to sleep. Now, she reports worsening
sleeplessness, tearfulness, anxiety and depression, waking
frequently to check on the baby.
She denies any personal history of anxiety or depression, but
her mother has frequent paranoid thoughts and episodes of manic behavior, to the extent that she no longer has contact
with her mother. Her maternal grandmother had similar
psychiatric symptoms, and the patient says, "I don't want to be that kind of mother for my baby.”
Today’s objectives
•�Understand the relationship
between breastfeeding and
postpartum depression
•�Discuss mechanisms linking
these two disorders
•�Apply strategies for integrated management of mood
disorders and breastfeeding
problems
Postpartum Support International / http://www.postpartum.net/ Caring for women for life
Understand the relationship between breastfeeding and
postpartum depression
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Conventional Wisdom: Breastfeeding prevents postpartum depression
“The many health benefits of breastfeeding include
less risk of postpartum depression for you.”
- The Joint Commission
Does not breastfeeding cause depression?
“At the level of a mother’s basic biology, the decision to bottle feed unwittingly mimics conditions associated with the death of
an infant. Child loss is a well documented trigger for depression particularly in mothers, and growing evidence shows that bottle
feeding is a risk factor for postpartum depression.”
1.96 2.13 2.24
0.1
1
10
First Day First Week Second Week
OR postpartum depression at 2 months, severe pain vs. no pain
Watkins, Zolnoun, Meltzer-Brody and Stuebe. Obstet Gynecol August 2011
Prospective data from 2586 women
who initiated breastfeeding in the
Infant Feeding Practices Survey II.
Or does bad breastfeeding cause depression?
Paul et al (2013) Pediatrics 131(4): e1218-24.
Higher state anxiety
during the postpartum stay was
associated with
shorter breastfeeding duration in a
prospective cohort
study.
Dennis C-L and McQueen K (2009). Pediatrics 123(4): e736-751.
Stuebe et al (2014). J Womens Health
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Stuebe, A. M., K. Grewen, et al. (2012). "Failed lactation and perinatal depression: common problems with shared neuroendocrine mechanisms?" Journal of Women's Health 21(3): 264-272. Caring for women for life
Discuss mechanisms linking these two disorders
Breastfeeding is a two-person organ system
Milk synthesis
Dopamine (-)
Prolactin
Milk secretion
Oxytocin
Anterior pituitary
Posterior pituitary
Paraventricular nucleus
(+)
Milk ejection
reflex
Placenta
Progesterone (-)
Hypothalamus
(+)
Cortisol T3, T4
Insulin Growth hormone
Breastfeeding
Success
Let Down
Latch
Moving Milk
Ejection moves milk to the areola
CNS mechanisms allow the baby to access mothers’ milk
Speroff et al. Reproductive Endocrinology and Infertility.
167
69
114 114
139
163 159
Control Ice water Math + shock Toe Pull
Distraction and Milk Volume (g)
saline oxytocin
Newton & Newton. J. Pediatr 1948; 33:698-704.
Stress and Milk Volume Latch ‘milks’ the milk
Rhythmic suckling transfers milk from breast to baby.
INCORRECT
CORRECT
Photos © Jane Morton, MD, FAAP
AAP Breastfeeding Residency Curriculum
Breastfeeding
Success
Let Down
Latch
Moving Milk
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Demand drives supply
Emptying lobules drives ongoing milk production.
Breastfeeding
Success
Let Down
Latch
Moving Milk
Mother
Baby
Breast
Communication in a two-person
organ system
Quiet, alert baby with strong suck can latch
and moves milk
Engagement triggers
oxytocin
Breast stimulation triggers oxytocin
and prolactin
Breastfeeding
Success
Let Down
Latch
Moving Milk
Depression and infant behavior
•�Exposure to depression in utero associated with differences in infant
»�Neonatal neuromuscular maturity
»�Early suckling behavior
»�Infant temperament
•�Does exposure to depression in utero affect latch, feeding
cues, and temperament, thereby latch and milk removal?
Reviewed in Stuebe, A. M., K. Grewen, et al. (2012). "Failed lactation and perinatal depression: common problems with shared neuroendocrine mechanisms?" Journal of Women's Health 21(3): 264-272.
Maternal mood affects behavior
Sensitivity Intrusiveness Withdrawal Child Engagement
Depression Anxiety Control
Feldman et al (2009) " J Am Acad Child Adolesc Psychiatry 48(9): 919-27.
Mother
Baby
Breast
Depression interferes with
breastfeeding physiology
Exposure to depression may affect
oromotor function
Mother-infant interaction
dysregulated
Stress suppresses oxytocin
Breastfeeding
Success
Let Down
Latch
Moving Milk
Stuebe, A. M., K. Grewen, et al. (2012). Journal of Women's Health 21(3): 264-272.
4/13/14
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Caring for women for life
What’s the underlying physiology?
Neurosteroids and perinatal depression
Milk synthesis
Dopamine (-)
Prolactin
Milk secretion
Oxytocin
Anterior pituitary
Posterior pituitary
Paraventricular nucleus
(+)
Milk ejection
reflex
Placenta
Progesterone (-)
Hypothalamus
(+)
Cortisol T3, T4
Insulin Growth hormone
Mean plasma concentrations of estrone (E1), estradiol (E2), estriol (E3), and progesterone (P)
during pregnancy.
Fetal and maternal neuroendocrine changes around partuition.
Peripartum neuroendocrinology
Neuropsychopharmacology (2006) 31, 1249–1263.
GABA receptors are downregulated during pregnancy, and must return to
normal levels after partuition to maintain steady level of inhibition
In a knockout mouse model, loss of the GABA(R)delta gene prevents
postpartum recruitment of GABA(R), and results in aberrant mothering
behavior and decreased pup survival.
Maguire J, & Mody I (2008). GABA(A)R plasticity during pregnancy: relevance to postpartum
depression. Neuron, 59(2), 207-213. PubmedCID
2875248
‘About two days after delivery some women become excited, sleepless, and
incoherent; they have a flushed face, a rather full
pulse and slight elevation of temperature; this is called ‘milk fever,’ and coincides
with the beginning of the flow of milk.’
- George Savage, 1875
4/13/14
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Caring for women for life
What’s the underlying physiology?
Oxytocin and the autonomic nervous system
Vagus
III. Myelinated vagus: Social communication,
self-soothing, calming, inhibits “a
I. Unmyelinated vagus: Immobilization (death
feigning, passive avoidance)
II. Sympathetadrenal syste
Mobilization (active avoida
Porges SW. Biol Psychol 74:116-143, 2007
•�What happens to lactation when you interfere with oxytocin-vagal pathways?
»�The cPAG is a brain region implicated in maternal response
to nursing in rats
»�Researchers studied the effect of lesion in cPAG region on
maternal behavior
»�Damaging this region of the brain interfered with feeding
behavior
Brain Research 804:21-35, 1998
Effect on weight gain Effect on attack behavior
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Increased vagal tone, maternal
behavior
Reduced stress reactivity, decreased depression and anxiety
Stressor
SNS PNS
Central oxytocin
pathways
-
+
CRH
ACTH
Modulation of cortisol
Hypothalamus
Pituitary
Adrenal
-
Maternal oxytocin response
to feeding at 8 weeks among women with
depression/anxiety symptoms (dashed line) or
without mood symptoms (solid line).
Stuebe, Grewen & Meltzer-Brody (2013) Journal of Women's Health 22(4): 352-361.
Oxytocin AUC during feeding and maternal mood.
Stuebe, Grewen & Meltzer-Brody, In press
Does the relationship between oxytocin and cortisol vary among individuals?
Meinlschmidt, G. and C. Heim (2007). "Sensitivity to intranasal oxytocin in adult men with early parental separation." Biological Psychiatry 61(9): 1109-1111
0
4
8
12
16
Post
feed
Res
t
0
4
8
12
16
0 100 200 300
Spee
ch
OT AUC during feeding
PA
SAT
0 100 200 300
Rec
ove
ry
OT AUC during Feeding
w/ symptoms w/o symptoms
OT AUC during feeding
and cortisol during TSST among women with and
without mood symptoms at 8 weeks postpartum.
Do postpartum mood symptoms modify the association between oxytocin and cortisol?
Oxytocin receptor polymorphisms, social support and stress response
Chen, F. S., R. Kumsta, et al. (2011). "Common oxytocin receptor gene (OXTR) polymorphism and social support interact to reduce stress in humans." Proceedings of the National Academy
of Sciences of the United States of America 108(50): 19937-19942.
4/13/14
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Oxytocin receptor polymorphisms and postpartum mood
0.9%
7.6%
GG AG/AA
rs53576
EPDS �13 at 3 months
Carriage of the A allele was associated with an
increased risk of depression symptoms
among 260 participants in the Pregnancy, Infection
and Nutrition Postpartum
Study (p=.01).
Mood, mother and infant: The psychobiology of impaired dyadic development
R01 HD073220-A1A, Stuebe (PI)
Specific Aim 1: Use lactation as a physiologic challenge to quantify the extent to which PPD reduces oxytocin, dysregulates stress
reactivity, and diminishes maternal sensitivity.
Specific Aim 2: Use standardized mother-infant interactions
to determine the extent to which PPD & reduced maternal sensitivity impair development of infant emotional regulation
and increase risk for insecure attachment.
�Specific Aim 3: Determine the extent to which diminished
maternal oxytocin and reduced sensitivity mediate associations between PPD, impaired infant emotional regulation, and
insecure attachment.
Caring for women for life
Discuss treatment plans for characteristic mood disorders
associated with the perinatal period
Case
•�CC/ID: 35 yo G2P2 at 5.5 months postpartum seen in consultation for breastfeeding associated pain.
•�She describes the pain as “consistent burning with deeper
pain on and off throughout the day. Sometimes, it feels that I cannot completely “empty” my breast� pain radiates
to my arm / armpit.”
•�EPDS: 15
Clinical Pearl: Screen early and often for postpartum depression/anxiety
•� PPD affects up to 15% of mother-infant dyads
•� Edinburgh Postnatal Depression Survey is a validated screening tool that takes <5 minutes to complete
•� Like all screening tools, interpret the EPDS in the context of the
clinical situation
»�Score �13 sensitivity 75%, specificity 84% for MDD
»�Review responses, not just the total score
•� Key questions:
»�Are you sleeping?
»�Are you having any scary thoughts?
•� Close follow-up to distinguish situational vs mood disorder
Clinical Pearl: Start with non-medical therapy
•�Are you sleeping?
»�Must balance importance of on-demand feeding with
maternal medical need for sleep
•�Are you eating?
»�Protein, regular meals
•�Are you engaged in life outside your home?
•�Offer or refer for psychotherapy
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Clinical Pearl: Sleep & breastfeeding are not mutually exclusive
•�Optimizing sleep
»�The goal for sleep is 6 hours of continuous sleep
»�Use sleep aids as needed
»�Enlist help of partner to bring baby to mom just for feeding during her 6 hours of sleep
Clinical Pearl: Sleep & breastfeeding are not mutually exclusive
•�Optimizing feeding
»�Limit feedings to 30-40 minutes total time/ feeding
»�Intense feeding plans generally only can be sustained for 3-4
days by anyone
»�Focus on what is most productive & find other ways to
accomplish the rest
»�Milk making hormones are highest level between 2-5 AM
•�Consider longer sleep interval from evening till middle of this
range, rather than across this range
•�Maximize breast emptying following this time frame
•�Mother must have time to enjoy her baby, not just feed
Clinical Pearl: Include sleep aid when starting medication
•� Trazodone
»�Start at 25mg and increase up to 200mg if needed for sleep (50mg is
usual dose)
»�Addressing sleep can vastly improve mood symptoms
•� Benzodiazepines
»�Klonopin 0.5mg at bedtime and � tab BID as needed until SSRI “kicks” in
»�Used because of its longer half life, can use smaller amounts less often
•� Sertraline
»�Best safety profile of currently available SSRIs
»�Start at 25mg QAM x 6 days, then increase to 50 mg
»�Onset of effects 2-3 weeks
•� Collaborate with pediatric provider
Maternal sertraline and infant serotonin
Epperson N et al. Maternal sertraline treatment and serotonin transport in breast-feeding mother-infant pairs. Am J Psychiatry 2001 Oct;158(10):1631-7.
Case 3
•�Presenting concern
»�Pain with breastfeeding during let-down, thus pumping and
bottle-feeding
•�History of postpartum depression
»�1st and 3rd children, hospitalization for major depressive
episode in 5 years ago
»�EPDS today 4, seen by psychiatrist this morning
•�Observed feeding
»�Infant established good latch, but pulled away and clicked
tongue during let down at time of increased maternal pain.
»�On/off latch after the let down, milk frequently spilling from
sides of mouth. Choking with second let down.
Clinical Pearl: Depression affects both mood and maternal sensitivity
•�When seeing a mom with a history of depression / anxiety, evaluate maternal symptoms and mother-infant interaction
»�This mother was unaware of infant’s response to overactive
let-down, including coughing, writhing, and clamping to control flow
»�Depression / anxiety associated with impaired maternal sensitivity and intrusive behaviors
•�Treatment requires both addressing mood symptoms and helping mom respond to infant cues while addressing
presenting symptoms
»�Review cues, work with mother to understand baby’s needs and desires
4/13/14
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Bunik et al (2014). "Trifecta Approach to Breastfeeding:
Clinical Care in the Integrated Mental Health Model." J Hum Lact.
To learn more
Academy of Breastfeeding Medicine Protocols
http://www.bfmed.org/
UNC Breastfeeding Management Algorithms
http://mombaby.org/breastfeeding
Postpartum Support International
http://www.postpartum.net/
UNC Center for Women’s Mood Disorders
http://www.med.unc.edu/psych/wmd/mood-disorders/perinatal
Today’s agenda
•�Understand the relationship between breastfeeding and postpartum depression
»�There is considerable overlap between breastfeeding difficulties
and depressive symptoms – we need to screen for and treat both
»�The evidence suggests that breastfeeding does not prevent PPD
•�Discuss mechanisms linking these two disorders
»�Shared mechanisms affect lactation and maternal mood,
suggesting that breastfeeding problems and depression may be
biologically linked
•�Apply strategies for integrated management of mood disorders and breastfeeding problems
»�Screen early and often, start with non-medical therapy, address
both sleep and feeding, and teach mothers to recognize and
respond to baby’s cues
Kim Andringa Diane Asbill
Betsy Bledsoe Martha Cox
Mala Elam Barbara Fredrickson
Susan Gaylord
Susan Girdler Karen Grewen
Karen Hardy
Samantha Meltzer-Brody Kim Newton
Chris Raines David Rubinow
Brenda Pearson
Cort Pederson Cathi Propper
Ashley Soh John Thorp
University of North Carolina
Division of Maternal-Fetal Medicine
Department of Psychiatry Center for Developmental Science
Frank Porter Graham Institute
National Institutes of Health