Drug Use in Pregnancy/Lactation: Background

What confirms pregnancy?

High levels of human chorionic gonadotropin (hCG) in the urine or blood

When is an embryo most susceptible to birth defects caused by teratogens?

First trimester (0–12 weeks), although birth defects can occur later

What must a drug do to be teratogenic?

Cross the placenta into the fetal circulation

How can pregnancy affect medication therapy?

Pharmacokinetic changes during pregnancy may require dose and regimen changes

What organization publishes guidelines for safe and effective medication use in pregnancy?

American College of Obstetricians and Gynecologists (ACOG)

What does gravida (G) represent?

Number of times a person has been pregnant

What does para (P) represent?

Number of times a person has given birth

What birth defects can folate deficiency cause?

Neural tube defects of the brain and spinal cord

How much folate should adults consume daily?

400 mcg dietary folate equivalents (DFE)/day

How much folate is recommended during pregnancy?

600 mcg DFE/day

How should females of childbearing potential increase folic acid intake?

A combination of dietary supplements, fortified foods, and diet

How much calcium is recommended during pregnancy?

1,000 mg/day

How much vitamin D is recommended during pregnancy?

15 mcg/day (600 IU/day)

How much iron is recommended during pregnancy?

27 mg/day

Why are calcium and vitamin D important during pregnancy?

They support fetal skeletal development; inadequate maternal calcium can cause the mother's bone health to be sacrificed to provide calcium for the baby

Why is iron important during pregnancy?

Ensures adequate oxygenation for fetal development

Why were the old FDA pregnancy categories replaced?

They were confusing and overly simplistic and could lead clinicians to apply pregnancy-risk information incorrectly

What did former Pregnancy Category A indicate?

Controlled studies in animals and pregnant women show no risk in the first trimester; risk of fetal harm is remote

What did former Pregnancy Category B indicate?

Animal studies have not demonstrated fetal risk, but no well-controlled studies are available in pregnant women

What did former Pregnancy Category C indicate?

Animal studies have shown fetal harm and there are no well-controlled studies in pregnant women; use only if potential benefit outweighs risk

What did former Pregnancy Category D indicate?

Positive evidence of human fetal risk exists, but benefits may outweigh risk in life-threatening or serious diseases

What did former Pregnancy Category X indicate?

Animal or human studies show fetal abnormalities and risks clearly outweigh potential benefits; use in pregnancy is contraindicated

What are the 3 updated pregnancy-related sections of prescription drug package inserts?

8.1 Pregnancy, 8.2 Lactation, and 8.3 Females & Males of Reproductive Potential

What information is included in package insert section 8.1 Pregnancy?

Pregnancy risk summary, risk of adverse developmental outcomes, clinical considerations, dose adjustments, maternal/fetal adverse reactions, disease risks, and pregnancy exposure registry information

What is a pregnancy exposure registry?

A registry that collects health information from women who take prescription drugs or vaccines while pregnant or breastfeeding and information on the newborn

What should pregnant women be encouraged to do when an applicable pregnancy exposure registry exists?

Participate in the registry

What information is included in package insert section 8.2 Lactation?

Whether the drug or metabolites are present in human milk, effects on the breastfed infant, effects on milk production, and ways to minimize exposure or monitor adverse reactions

What information is included in package insert section 8.3 Females & Males of Reproductive Potential?

Effects on fertility and requirements for pregnancy testing and contraception

Why might drugs with significant teratogenic risk have REMS requirements?

Because of the potential for fetal harm

How are teratogens classified by NIOSH?

Hazardous drugs requiring special handling to reduce risk to healthcare workers

What is an example of a resource for checking medication safety during pregnancy?

Briggs' Drugs in Pregnancy and Lactation

Which acne medications are must know teratogens?

Isotretinoin and topical retinoids

(Isotretinoin has a REMS program)

Which antibiotics are must know teratogens?

Fluoroquinolones and tetracyclines

Which anticoagulant is an must know teratogen?

Warfarin

Which dyslipidemia, heart failure, and hypertension drugs are must know teratogens?

Statins, RAAS inhibitors (ACE inhibitors, ARBs, aliskiren, sacubitril/valsartan)

Which hormone-related medications are must know teratogens?

Most hormones including estradiol, progesterone including megestrol, raloxifene, Duavee, testosterone, and contraceptives

Which migraine medications are must know teratogens?

Dihydroergotamine and ergotamine

Which other commonly tested drugs are important teratogens?

Hydroxyurea, lithium, methotrexate, misoprostol, NSAIDs, paroxetine, ribavirin, thalidomide, topiramate, weight-loss drugs, and valproate

Which influenza vaccine is recommended during pregnancy?

Inactivated influenza vaccine, not the live vaccine

When can the inactivated influenza vaccine be given during pregnancy?

Any trimester at the beginning of flu season

What is the COVID-19 vaccination recommendation during pregnancy?

Pregnant individuals are recommended to be vaccinated against COVID-19 during any trimester

What is the Tdap recommendation during pregnancy?

A single dose during each pregnancy, ideally between weeks 27–36

What is the RSV vaccine recommendation during pregnancy?

Abrysvo between weeks 32–36 during September through January

Which vaccines are contraindicated during pregnancy?

All live vaccines

What is preeclampsia?

complication involving elevated blood pressure and evidence of organ damage, most commonly affecting the kidneys or liver

When does preeclampsia typically occur?

After 20 weeks gestation

What can untreated preeclampsia progress to?

Eclampsia, which can cause seizures and death

What is the only cure for preeclampsia?

Delivery of the baby

What does ACOG recommend to help prevent preeclampsia in pregnant women at risk?

Daily low-dose aspirin starting at the end of the first trimester

What are examples of preeclampsia risk factors that may warrant low-dose aspirin?

Diabetes, renal disease, history of preeclampsia, and chronic hypertension