Medications in Pregnancy and Lactation

What are the most common congenital malformations?

- Heart defects

- Hypospadias, neural tube defects

- Clubfoot

- Cleft palate and lip

- Down syndrome

The first trimester of pregnancy consists of weeks ________

1-13

The second trimester of pregnancy consists of weeks ________

14-27

The third trimester of pregnancy consists of weeks ________

28-40

What does teratogenic mean? Give some examples

Causes changes in the developing tissues and organs. Includes neural tube defects, congenital heart defects, cleft palate, etc.

Define fetal adverse effects

Not teratogenic, causes adverse fetal outcomes like dysfunction of an organ, AFTER formation. Outcomes include withdrawal symptoms, altered glucose metabolism, difficult postnatal adaptation

What is the teratogenic period?

2-8 weeks post conception

Later exposure past the teratogenic period can lead to what outcomes?

Growth retardation, CNS abnormalities, death

What are 7 examples of common drugs to avoid in pregnancy?

1. ACEis

2. ARBs

3. Aromatase inhibitors

4. Isotretinoin, tretinoin

5. Live vaccines

6. Methotrexate

7. Thalidomide

Exchange through the placenta from mother to baby most often occurs by...

passive diffusion

What are 4 characteristics (lipophilicity, state of ionization, molecular weight, and protein boundness) that make a medication more likely to cross the placenta?

- Lipophilic

- Unionized, weak base (fetal pH is more acidic)

- Low molecular weight (

What are the OLD pregnancy risk categories?

A - Good human studies, no risk

B - No human studies, animal studies show no risk

C - No human studies, animal studies show potential risk

D - Data from studies show potential risks, but benefits may outweigh risks

X - Studies show fetal harm, risk outweighs any benefit

The old pregnancy risk categories were replaced with...

narrative sections and subsections, including 8.1 (pregnancy), 8.2 (lactation), and 8.3 (females and males of reproductive potential)

Pregnancy lasts about ____ days

280 days (40 weeks, 9 ish months)

What is "gestational age"?

Age of the embryo/fetus

What is gravidity?

Number of times a person was pregnant

What is parity?

Number of pregnancies that resulted in the delivery at 6+ month gestation (live or stillbirth)

What are 6 physical changes that occur in the mother during pregnancy?

- Changes in fat composition, weight gain

- Uterus enlargement and shift of organs

- Larger thyroid

- Larger kidneys

- Lung size limited

- Enlargement of left ventricle in heart

What cardiovascular changes occur during pregnancy?

- Increased CO

- Increased HR

- Increased SV

- Increased plasma volume

- Decrease in diastolic BP

What respiratory changes occur during pregnancy?

- Decreased residual volume

- Increased tidal volume

- Increased ventilation

- Decreased functional residual capacity

- Increased O2 consumption

What GI changes occur during pregnancy?

- Prolonged gastric emptying

- N/V

- Decrease in gastric pH

- Decrease in esophageal sphincter tone

- Changes in liver enzyme activity

What renal changes occur during pregnancy?

- Glomerular hyperfiltration (increased plasma volume)

- Increased renal plasma flow

- Increased TBW

Absorption is often ___________ in pregnancy due to...

decreased/delayed; N/V, decreased gastric motility

Distribution is often ___________ in pregnancy due to...

Increased (Vd, lipophilic drugs, unbound drugs); increase in body fat, weight, blood plasma, and decrease in plasma albumin

Metabolism is often ___________ in pregnancy due to...

variable; changes in hepatic metabolism enzymes

Excretion is often ___________ in pregnancy due to...

Increased; increase in hepatic and renal blood flow (GFR)

What are 4 healthy preconception lifestyle modifications?

- Stop alcohol use

- Lose weight if obese

- Stop tobacco use

- Stop drug abuse

What helps prevent neural tube defects? When should this be taken and how much?

Folic acid supplementation, 0.4 mg (400 mcg)/day at least 1 month before conception, daily through first trimester

What are some foods high in folic acid?

- Beans

- Peanuts

- Dark leafy vegetables

- Fruit

- Seafood

For high risk patients, what is the recommended amount of folic acid?

4 mg/day 3 months before conception, at least through first trimester

What are some drugs that should stand out to you when reviewing a pregnant patient's profile?

- Chemotherapy

- Sex hormones

- Retinoids

- Antiepileptic drugs

- Lithium

- Warfarin

When does N/V begin and resolve during pregnancy?

Begins before 9 weeks, resolves by 14-20 typically

What is the term for excessive N/V during pregnancy?

Hyperemesis gravidarum

What helps with N/V during pregnancy?

Starting a prenatal multivitamin 1 month before conception

What are 5 non-pharmacologic options for N/V in pregnancy?

1. Switch to prenatal vitamin that is iron free

2. Dietary modification (small frequent meals)

3. Ginger capsules (250 mg QID)

4. Acupuncture, acupressure

5. Avoidance of sensory stimuli

What is first line pharmacologic treatment for N/V in pregnancy?

Vitamin B6 aka pyridoxine (10-25 mg) with/without doxylamine (10-20 mg)

What are some side effects of vitamin B6?

Sleepiness

What are 4 other pharmacologic options for N/V in pregnancy?

- dimenhydrinate (Dramamine)

- diphenhydramine (Benadryl)

- prochlorperazine (Compazine)

- promethazine (Phenergan)

What are 4 third line pharmacologic options for N/V in pregnancy? Without dehydration

- metoclopramide (Reglan) PO

- ondansetron (Zofran) PO

- promethazine (Phenergan) PR IM PO

- trimethobenzamide (Tigan) IM

What are 4 third line pharmacologic options for N/V in pregnancy? With dehydration

- dimenhydrinate (Dramamine) IV

- metoclopramide (Reglan) IV

- ondansetron (Zofran) IV

- promethazine (Phenergan) IV

If a patient still has persistent N/V symptoms, what can be given?

- Chlorpromazine IV/IM/PO

- Methylprednisolone PO/IV in severe cases, after 1st trimester, limit duration to 6 weeks

Gastrointestinal reflux disease _____ with gestational age

worsens

What are some non-pharm treatments for GERD in pregnancy?

- Eat small frequent meals

- Avoid eating meals near bedtime

- Avoid trigger foods

- Use wedge pillow to elevate upper body

- Sucralfate

What are 3 pharm treatments for GERD in pregnancy?

1. Antacids/tums

2. H2 blockers (ranitidine)

3. PPIs (omeprazole)

Which GERD pharm options should be avoided in pregnancy?

- Magnesium trisilicate based antacids (Gaviscon)

- Sodium bicarbonate based antacids (Alka-Seltzer)

What are 4 non-pharm treatment options for constipation in pregnancy?

- High dietary fiber intake

- Hydration **

- Moderate physical activity

- Probiotics

What are 3 pharm treatment options for constipation in pregnancy?

1. Bulk-forming agents (psyllium, methylcellulose, polycarbophil)

2. Osmotic laxatives (PEG)

3. Stool softeners (docusate)

4. Stimulants (senna, bisacodyl, short term use only)

What are 3 pharm treatment options for constipation that should be avoided in pregnancy?

- Castor oil

- Magnesium citrate

- Mineral oil

What 3 pharm options are there for hemorrhoids in pregnancy?

- Sitz baths

- Witch hazel

- Hydrocortisone

What are 4 non-pharm options for HA in pregnancy?

- Relaxation, exercise, cognitive therapy

- Sleep

- Hydration

- Reduce caffeine intake

What can be used for pain in pregnancy?

- Acetaminophen

- Topicals like capsaicin, lidocaine patches

What can be used for migraines in pregnancy?

Sumatriptan

What should be avoided for pain in pregnancy?

- NSAIDs

- Opioids long term

- Ergotamine, dihydroergotamine

Why does gestational diabetes develop?

- Carbohydrate intolerance leads to hyperglycemia

- Development of insulin resistance

- Various hormones secreted by placenta also inhibit insulin activity

Untreated gestational diabetes can result in...

fetal macrosomia, neonatal hypoglycemia, fetal malformations

Gestational diabetes is diagnosed after ____

1st trimester

Screening early for gestational DM is recommended if...

- overweight

- hx of GDM

- PMOS

- hx of HTN

- high LDL

- high TG

What is the preprandial and postprandial (1 and 2 hours after meal) goals for gestational diabetes?

Preprandial = ≤95 mg/dL

Postprandial 1 hr after meal = ≤140 mg/dL

Postprandial 2 hr after meal = ≤120 mg/dL

What is the A1c goal for gestational DM?

When is gestational DM typically screened for?

24-28 weeks

What is used to screen for gestational DM?

- One-step 2 hours 75 g oral glucose tolerance test

- Two-step 3 hours 50 g oral glucose tolerance test

How is gestational DM managed?

- Daily self-monitoring of blood glucose (≥4x/d fasting and after each meal)

- Dietary modifications, nutrition therapy, exercise (30 min 5x/w)

- Insulin if no control after 1-2 weeks

What is first line therapy for gestational DM? What is the dosing?

Insulin (does not cross placenta) 0.7-1.0 u/kg daily in divided doses split 50/50 short-acting at mealtime and long-acting (1st trimester = 0.7, 2nd = 0.8, 3rd = 0.9)

What can be used in gestational DM if patients do not want to use insulin? What is the dosing?

Metformin (crosses placenta but safe, effective and lowest risk of macrosomia) 500 mg nightly, then 500 mg BID, max 3,000 mg daily in 2-3 doses

If patient can not use insulin or metformin, what is a 3rd option for gestational DM?

Glyburide (limited placenta crossing, but worse outcomes) 2.5-20 mg daily BID in divided doses

What DM medications are contraindicated in pregnancy and lactation?

- SGLT-2 inhibitors (congenital anomalies and increased miscarriages)

- GLP-1 receptor agonists (reduce fetal survival and growth)

When should SGLT-2 inhibitors be D/C before conception?

2 months prior

What is one of the highest causes of maternal mortiality/morbidity?

Hypertension

What are the 4 types of HTN during pregnancy?

1. Chronic (pre-existing or before 20 weeks)

2. Gestational (HTN without proteinuria)

3. Preclampsia/eclampsia (HTN with proteinuria)

4. Chronic HTN with superimposed preclampsia

HTN is defined as...

Systolic BP >140 and diasolic >90 mmHg

Why is eclampsia bad?

Mother's high BP reduces blood supply to the fetus

What are preclampsia symptoms?

- SBP

What are 2 severe symptoms that can develop from eclampsia?

Seizures and coma

What are some risk factors for eclampsia?

- Chronic HTN

- Hx of preeclampsia

- Renal disease

- Lupus

- Age over 35

- DM

What should patients with high risk of preeclampsia/eclampsia be started on?

Start low dose aspirin before 16 weeks of gestation (continue until delivery)

What are 5 PO options for non-emergency HTN?

1. Labetalol, start at 100-200 mg BID

2. Nifedipine, start 30-60 mg QD

3. HCTZ 12.5-25 mg/day

4. Methyldopa 0.5-3 g/day in 2 doses

5. Hydralazine (last line)

Which HTN meds should be avoided in pregnancy?

ACEis and ARBs

What should be used in hypertensive emergency in pregnancy?

- IV labetalol

- IV/IM hydralazine

- IR PO nifedipine

What can be used in preeclampsia to prevent progression to eclampsia?

IV magnesium sulfate 4-6 g LD followed by 1-2g/hr

Untreated hypothyroidism can lead to what pregnancy conditions?

- Low birth weight

- Fetal death

- Impaired neurological development

- Premature birth

What is the levothyroxine starting dose in pregnancy?

1-2 mcg/kg/day

If a patient has previous hypothyroidism what should be done to their dose when they get pregnant?

Increase the dose by 25%

Untreated hyperthyroidism can lead to what pregnancy conditions?

- Spontaneous abortion

- Fetal demise

- Preterm delivery

What is used to treat hyperthyroidism in pregnancy?

1st trimester = propylthiouracil

2nd and 3rd trimester = methimazole

What can be used for treatment and prophylaxis of thromboembolic disorders in pregnancy?

LMWH (preferred over heparin) aka enoxaparin 40 mg subQ daily

What anticoagulants should be avioded in pregnancy?

Warfarin and DOACs

What is the only difference in care when it comes to UTIs in pregnant patients?

They should be screened for Asymptomatic Bacteriuria (ASB) ONCE at early prenatal care and treat if positive

What are 1st line agents to treat ASB and acute cystitis in pregnancy?

5-7 day PO course of Cephalexin (250-500 mg q6h) or nitrofurantoin (100 mg q12h, 1st trimester ONLY) and fosfomycin 3 g once

What are 4 antibiotics used to treat pyelonephritis in pregnancy?

- Ampicillin

- Ceftriaxone

- Cefepime

- Aztreonam

What antibiotics should be AVOIDED in pregnancy?

- Trimethoprim (not in 1st trimester)

- Fluoroquinolones

- Tetracyclines (not after 5 month gestation)

- Nitrofurantoin (not after 37 weeks)

- Sulfa drugs (not in 3rd trimester)

There is less than __% chance of HIV perinatal transmission when treated properly

1%

What should be done if ARV therapy was not possible and HIV RNA >1000 copies/mL near delivery?

- IV zidovudine

- Infant ARV therapy

- Scheduled C-section at 38 weeks

- Breastfeeding avoidance

What should be avoided to treat epilepsy in pregnancy?

- Valproic acid

- Phenytoin

- Carbamazepine

- Phenobarbital

- topiramate

- Zonisamide

Taking what during pregnancy can help with seziures?

Folic acid 4 mg daily before pregnancy and through first trimester

What are the epilepsy medications with the lower risk?

- Lamotrigine

- Levetiracetam

- Oxcarbazepine

- Gabapentin

Which has the lowest risk to use in pregnancy? SSRIs, SNRIs, TCAs

SSRIs (sertraline) < SNRIs < TCAs

What is NOT recommended in pregnancy?

Benzodiazepines, mood stabilizers (consider individual)

What is the general takeaway with psychiatric disorders and medications in pregnancy?

Continue the medication that provides desirable response, use lowest effective dose

What is a "preterm" birth?

Between 20-37 weeks gestation (12% of all deliveries)

What can be used to prevent preterm birth?

Vaginal progesterone 8%, 90-200 mg once daily PV to relax the uterus