exposures to breastfeeding women; impact on the infant
TRANSCRIPT
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Exposures to Breastfeeding Women; Impact on the Infant
Beth Conover, MS, APRN, CGC
Director Nebraska Teratogen Information
Service/ NE MTB
Assistant Professor, UNMC
402-559-5071
Nebraska TIS
Service – Toll-free phone
consultation to patients or health care providers about exposures during pregnancy
Education – to public
and academic groups, including medical, nursing, genetic counseling, pharmacy and others
Research – collaborative
projects looking at outcomes of exposures to specific agents
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Thomas Hale
Philip Anderson
https://www.ncbi.nlm.nih.gov/books/NBK501922/
Breastfeeding• Nursing is good for mother and
baby, but not if it results in harm to the baby via drugs in milk or avoidance of appropriate treatment for the mother.
• Most agents ingested by the mother will be excreted in the breast milk in some quantity. Fortunately, many are present in amounts less than 2% of the maternal dose. With some agents, however, even small amounts may present a risk to the infant.
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Different Agents May Be Preferred
for Pregnancy vs Breastfeeding
Risk : Benefit Ratio• There is no one “right”
choice for every woman
• Healthy outcomes for mother and baby are the
rule rather than the
exception
• “No clinical decision is risk free.”
• Lee Cohen and
Zachary Stowe
• Always monitor the baby for
adverse effects!
Considerations
• Was agent used in
pregnancy?
• Age of infanto Medically fragile?
o Premature?
o Newborn
• 2/3 of adverse drug reactions occur
during the 1st month
• More than 3/4 occur during the first two
months
• Maternal dose/route
• Reason for use and
efficacy
• Acceptable alternatives
• Nursing or pumping?
• Totally breastfed? If
not, pattern of nursing
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Basic Concepts: Amount of agent in milk
• Maternal serum levels
• Amount of the agent that is protein bound
• Lipid solubility
• pH
• Molecular size
• Half-life of medication
• Foremilk vs hindmilk
• Length of maternal therapy
• Timing of the dosage
• Bioavailability/amount absorbed through GI tract in both mother and baby
• Age of the infant
• Exposure to the agent in pregnancy as well as lactation
• Short term vs long term exposures
• Impact on milk production
Basic Concepts
• Estimated Infant
Dosageo Drug concentration in milk
x daily volume of milk
o Maximum dosage infant exposed to
• Milk Volumeo ~150mL/kg for exclusively
breastfed infant
o Colostrum only 13-17mL/kg
• M/P ratio
• Relative Infant
Dosageo (Infant dosage/maternal
dosage) x 100
o In one evaluation by the World Health Organization
Working Group, 47% had
RID less than 1% and 87%
had a RID less than 10%
Anderson, PO. Pharm Res (2018) 35: 45 https://doi.org/10.1007/s11095-017-2287-z
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Issues in using RID or M/P ratio
to determine safety• Drugs have different
degrees of toxicity that
are difficult to quantify
• Pharmacogenetic
differences in mother
and infant
• Differences in bioavailability and liver
metabolism in the infant
• Does not take
infant’s age into
account
• Not all adverse drug reactions
related to doseo Allergic reactions
Anderson, PO. Pharm Res (2018) 35: 45 https://doi.org/10.1007/s11095-017-2287-z
Pharmacogenomics
Timing Nursing to Limit Infant Exposure
• Medications move in
and out of milk based
on maternal serum levels
• Strategy to limit amount
to baby:
o nurse first
o take medication
o defer nursing until past peak level (~2-4 hours for
short acting medications)
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Minimizing Infant Exposures:
• Use short acting medications when possible
• Beware drugs with active metabolites
• Consider an alternative route of administration (topical, inhaled)
Minimizing Infant Exposures:
Choose drugs that pass poorly into milk
• Example: beta-blockers in breast milk o High risk--avoid while nursing neonates
• acebutolol, atenolol, nadolol, sotolol
o Moderate risk--avoid while nursing preterm neonates
• metoprolol, timolol
o Lower risk--alternatives with nursing neonates
• Labetalol, propranolol
Minimizing Infant Exposures:
• As a general rule, if the
medication can be safely given
directly to the infant, it is unlikely
to present a large risk via milk
• Exceptions include medications
that reduce breastmilk supply
• If there is concern that the infant
may be receiving clinically
important doses of a drug in milk,
measure the infant's plasma
drug concentration.
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Drugs that may reduce milk supply:
o Ergotamine
o Bromocriptine
o Pseudoephedrine
o Estrogens
o Progestins (prior to
6-8 weeks postpartum)
AAP: Agents that are contraindicated
during breast-feeding
• Phenindione• Ergotamine• Drugs of abuse
(amphetamines, cocaine, heroin, marijuana, PCPlarge amts of nicotine)
• Cyclosporine
• Cytotoxic drugs (methotrexate)
• Lithium
• Radioactive compounds (I-131)
Approximate Duration for Interruption of
Breastfeeding After Drugs of Abuse
• Methamphetamine 24-36 hours
• Cocaine 24 hours
• Marijuana 24 hours
• Heroin 24 hours
• LSD 48 hours
• Phencyclidine 1-2 weeks
• Alcohol 1-2 hours per drink
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Non-Medication Strategies
• The combination of bright
light therapy plus an
antidepressant significantly improves
nonseasonal major depressive disorder, and
light therapy alone is
more effective than antidepressant
monotherapy, a randomized, placebo-
controlled trial suggestso JAMA Psychiatry. 2016;73(1):56-63.
Hot Topics
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Issues in Psychotherapeutic Drugs and
Breastfeeding• Baby may have withdrawal and other issues with
newborn adaptation due to exposure during
pregnancy.
• Reports of serious toxicities associated with some
antidepressants, anxiolytics, antipsychotics, & mood
stabilizers
• Infants metabolize and clear drugs at different rates from adults with individual babies varying widely
• Long term effects of psychotropics on
neurocognitive development are largely unknown
Psychiatric Medications in Lactation
• Anxiolytics (benzodiazepines)
o Sedating
o ??? Behavioral teratogens
o If crucial, use low dose, prn if possible
o Consider use of an antidepressant
• Antidepressants
o use lowest therapeutic dose of poorly excreted, well studied agent
o Amount in milk (largest to smallest):
Prozac>Celexa/Effexor>Zoloft/Paxil
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Lithium in Lactation
• Relative infant dose varies from 5-20% but averages 30-40%; reports of lithium toxicity
• American Academy of Pediatrics classifies lithium as not compatible with breastfeeding
• Hale (MMM) says low dose lithium is not an absolute contraindication to breastfeeding; recommends monitoring
• Serum levels at 10 days of age (sooner if symptomatic)
• Periodic thyroid studies
• Watch for signs of dehydration
Alternative Medicine
• Most herbal preparations and vitamin supplements have not been studied with regard to their effect on the fetus and breast-fed infant.
• In many cases there is no evidence they are dangerous, but they are not known to be safe, either.
• Generally, they are best avoided in pregnant and breastfeeding women.
Commercial Herbal Teas• Generally have
accurate labeling of
the product
• Avoid teas with potent
pharmacologic
preparations
• Orange, cinnamon, lemon lift, raspberry,
and rose hips teas likely to be low risk when
used in moderate
amounts
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Protein shakes• Nutritional shakes and powders
are ‘nutritional supplements’ and not regulated by the FDA
• May be contaminated with bacteria, pesticides, lead and other heavy metals
• Many additives (proprietary blends, herbal, weight loss) that have not been studied in pregnancy
• May result in vitamin overdose, or not eating a nutritionally complete diet
• https://mothertobaby.org/baby-blog/shake-it-up-baby-maybe-not-considering-nutritional-shakes-in-pregnancy/
Agents Potentially Contraindicated
• Known adult toxicity
oAlkanet, borage, coltsfoot, comfrey
• Stimulate GI motility
oAloe juice, cascara, Chinese
rhubarb, elecampane, purging buckthorn, senna
• Effect on thyroid
o Bladderwrack, bugleweek
Agents Potentially Contraindicated
• Sedatingo Valerian, Kava Kava
• Estrogenic effects/ may limit milk productiono Black cohosh, Chaste tree
• Not intended for use in infants or toddlerso Basil, ephedra
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Galactogogues
• Agents intended to increase milk
volume
• Limited data to substantiate
claims
• Anecdotal reports show widely
variable results
Galactogogues• Fenugreek
o Spice used as flavor for maple syrup
o Transfer into milk is assumed; milk smells like
maple syrup
o In one study milk production doubled
o Hypoglycemic effects; potentiates warfarin
o Reports of GI bleeding, colic, abdominal upset, and diarrhea in exposed babies
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Galactogogues
• Blessed Thistleo Antibacterial and antiinflammatory
o Low toxicity, but can cause hypersensitivity reactions and has a laxative effect
o No studies on efficacy or transfer to milk
• Fennelo Estrogenic properties
o No data on excretion or milk production, but estrogenic property may actually suppress lactation
Galactogogues• Chaste Tree
o Contains forms of progesterone and testosterone
o Used to relieve symptoms of mastodynia
o Inhibits prolactin secretion and can decrease milk production
o Generally considered contraindicated for use in nursing mothers
Vaccinations
• The CDC states that breastfeeding is not a contraindication to vaccination o Rubellao Hepatitis B
o Influenza
o Tdap
• Exception: prophylactic smallpox, Yellow fever
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https://www.cdc.gov/breastfeeding/breastfeeding-special-
circumstances/vaccinations-
medications-
drugs/vaccinations.html?CDC_AA_refVal=https%3A%2F%2Fwww.
cdc.gov%2Fbreastfeeding%2Fre
commendations%2Fvaccinations.htm
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Marijuana…legal and potent…but is it safe?
Marijuana• Marijuana contains ~400 active chemicals,
and may also contain contaminants such as
other drugs or pesticides
• Today’s marijuana up to 30x more potent than marijuana studied in the past
• Studies show pregnancy complications like
prematurity, low birth weight, and withdrawal
symptoms after birth
• Several long-term studies suggest that in-
utero marijuana can affect brain
development of the baby
• ???neuro-developmental effects of exposure through breastmilk. Most studies in the past
involved lower potency products and f/u to
only 1 year of age.
• https://mothertobaby.org/fact-
sheets/marijuana-pregnancy/
Grant KS, Conover E, Chambers CD. Update on the developmental consequences of cannabis use during
pregnancy and lactation. Birth Defects Research. 2020;1–13. https://doi.org/10.1002/bdr2.1766
Marijuana• Study Two
• 50 lactating women who
reported use of cannabis in the
previous 2 weeks provided milk samples
• In at least one sample THC was detectable 6 days after last
reported use
• Authors concluded that plasma concentrations of THC would be
several orders of magnitude
lower than maternal levels
• Study One
• 8 lactating women inhaled a
single dose of cannabis
containing 23.18% THC.
• Serial milk samples were
collected in the subsequent 4 hours
• RID 2.5% (range 0.4-8.7%)
• Infant dose not measured
directly
• Unclear as to whether there
would be accumulation of THC
in milk with chronic use
Baker, T., Datta, P., Rewers-Felkins, K., Thompson, H.,
Kallem, R. R., & Hale, T. W. (2018). Transfer of inhaled cannabisinto human breast Milk. Obstetrics and Gynecology, 131(5),
783–788. https://doi.org/10.1097/aog.0000000000002575
Bertrand, K. A., Hanan, N. J., Honerkamp-Smith, G., Best,
B. M., &Chambers, C. D. (2018). Marijuana use by breastfeeding
mothers and cannabinoid concentrations in breast Milk.
Pediatrics,
142(3), e20181076. https://doi.org/10.1542/peds.2018-
1076
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OTC Agents “Safe” to Use in Breastfeeding Women
• Analgesics: Tylenol and ibuprofen
• Guaifenesin
• GI: Tums, Metamucil, docusate
• Multivitamins
• Topical hydrocortisone, fluconazole
• Most topical agents for acne
Likely OK in breastfeeding…..
• Claritin, Allegra
• Sparing use of
pseudoephedrine, phenylephrine
• Dextromethorphan
• Pepcid , Prilosec
• Topical pyrethrins
Usually Contraindicated in Breastfeeding
• Aspirin
• Cathartics such as
casanthral
• Sedating Agents
• Older antihistamines such
as Benadryl
• Mega doses of vitamins
• Most herbal medications
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Cosmetic Preparations
• Topical (generally low
systemic levels and thus minimal fetal exposure)
• Poorly studied in
pregnant and breastfeeding women
• No proven risk, but in many cases limited
benefits
Tattoos
• No studies regarding safety of inks and other agents in
pregnancy or breastfeeding
• If you decide to get a tattoo, make sure it is a registered
practitioner who uses sterile
equipment and needles, sterile dressings, and sterile
packed/unopened inks
• If you feel febrile or there are other signs of infection,
contact your health provider
immediately
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New label
New FDA Pregnancy and Lactation Labeling Rule
• Eliminates pregnancy letter catagories (ABCDX)
• Provides narrative risk
summaries on use in pregnancy and lactation
• Offers clinical
considerations
• Explains how data can
be used to determine
human risk
• Encourages updates
• All medications
approved by the FDA
since 2001 must revise their pregnancy and
lactation section
• All medications must remove ABCDX,
regardless of when approved.
Resources
• Hale, T. Medications and
Mothers’ Milk. Amarillo, TX:
Pharmasoft; 2012.
• LactMed,
http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?LACT
• Briggs, G. et al. Drugs in Pregnancy and Lactation, 10th
edition. Philadelphia: Lippincott, Williams & Wilkins;
2014.
• TERIS and REPROTOX data
bases
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FACT SHEETS
www.mothertobaby.org
• Hyperthermia
• Ciprofloxacin
• Lithium
• Influenza Vaccine
• Toxoplasmosis
• Metformin
• Zoloft
• Tegretol
• DEET
• Hair coloring
Conundrums• Pregnant women often tend to
overestimate the magnitude of teratogenic risk.
• Health providers may also have distorted perceptions of risk, even in the presence of
evidence-based facts.
• Teratogen (and other medical) data is
often limited and contradictory.
• Situations where there is no data or
inadequate data predispose to inaccurate and extreme interpretation:
o No data…assume huge risk or
o No data…assume zero risk
Facilitating Decision Making
• Use the terms ‘chance’
(likelihood, probability…)instead of
‘risk’ because them
imply less of a value judgment of good or
bad outcome
• Provide numbers in
different formats
o Ex: use both percentage
and ratio (25% or 1 in 4)
http://www/nchpeg.org
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Non-Medication Strategies
• The combination of bright
light therapy plus an
antidepressant significantly improves
nonseasonal major depressive disorder, and
light therapy alone is
more effective than antidepressant
monotherapy, a randomized, placebo-
controlled trial suggestso JAMA Psychiatry. 2016;73(1):56-63.
Resources
• Hale, T. Medications and
Mothers’ Milk. Amarillo, TX:
Pharmasoft;
• LactMed,
http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?LACT
• Briggs, G. et al. Drugs in Pregnancy and Lactation, 11th
edition. Philadelphia: Lippincott, Williams & Wilkins.
• TERIS and REPROTOX data
bases
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New FDA Drug Label
• www.mothertobaby.org
• National Phone Number:
(866) 626-6847o option for Spanish speaking
TIS counselor
• NE-TIS
(402)-559-5071
A service of the Organization of Teratology Information Specialists
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Case Presentations