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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

bconover@unmc.edu

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