Pregnancy and Preconception

when does fertilization occur?

when sperm attaches to the outer layer of the egg, penetrates, and the sperm and egg combine to create a new single cell known as a zygote

where do male and female chromosomes join and organize for cellular division?

in the zygote

where does fertilization usually occur?

in the fallopian tube

6 days after fertilization the cells are termed a __________

blastocyte

which hormone is produced in appreciable amounts after fertilization?

hCG

what does implantation begin with?

with the blastocyte resting on and beginning growth into the endometrial wall

by day _______ the blastocyte is implanted under the endometrial surface and receives nutrients by the maternal blood supply

10

on the first day of the third week post fertilization, the cells are known as an _________

embryo

what does parity mean?

The number of deliveries after 20 weeks’ gestation

what does gravida mean?

The number of pregnancies regardless of outcome

what does abortus mean?

the number of miscarriages/abortions

what is full-term?

40-weeks’ gestation

what is considered the 1st trimester?

week 1 to end of week 13

what is considered the 2nd trimester?

week 14 to end of week 26

what is considered the 3rd trimester?

week 27 until birth

T/F: trimester is not as useful for helping assess medication use, actual weeks should be used instead

true

T/F: a medication ‘safe’ in one trimester may not be safe in another

true

when does day 1 of pregnancy start?

from the first day of menses even though conception has not taken place yet

T/F: a patient missing their period will already be 4 weeks pregnant

true

describe the risks of harming the fetus at gestational age weeks 3&4

Fetal exposure may be all or none effect (destroy the embryo or have no ill effects) — death of the embryo and spontaneous abortion most common during this time frame

how can a fetus be harmed at gestational age weeks 5-10?

major congenital anomalies likely

how can a fetus be harmed at gestational age weeks 11 to birth?

functional defects and minor anomalies possible

what is the rate of “naturally occurring” congenital anomalies?

3-6% with 3% considered severe

what are the most common congenital abnormalities?

neural tube defects (NTD), cleft palate/lip, and cardiac anomalies

what are some of the causes of congenital anomalies?

Genetic/chromosomal 15-25%

Environmental 10%

Unknown 65-75%

Medications <1%

what are teratogens?

exposure to an agent of factor that causes malformation of an embryo

which medications can result in structural abnormalities if exposure occurs during organogenesis (weeks 5-11)?

methotrexate, cyclophosphamide, diethylstilbestrol, lithium, retinoids, thalidomide, antiepileptic drugs (AEDs), warfarin

which medications can result in growth retardations, CNS or other abnormalities, or death, if exposure occurs after 11 weeks gestation?

NSAIDs, tetracycline

what are the 3 mechanisms that medications can harm a fetus by?

Act directly on the fetus, causing damage, abnormal development (leading to birth defects), or death — damaged differentiating cells more likely to result in permanent organ damage

Alter the function of the placenta, usually by causing blood vessels to narrow (constrict) and thus reducing the supply of oxygen and nutrients to the fetus from the pregnant person

Cause the muscles of the uterus to contract forcefully, indirectly injuring the fetus by reducing its blood supply or triggering preterm labor and delivery.

how can we prevent neural tube defects (NTD)?

Folic acid supplementation in pregnancy capable people substantially reduces the incidence of NTDs in offspring

Folic acid 0.4-0.9mg/day for any pregnancy capable person during reproductive years —to 4 mg/day for patients who have had babies with NTD such as spina bifida

Folic acid especially important for those taking antiseizure medications 

T/F: Higher folate doses previously recommended for patient on ASM and those having children with NTD, are no longer supported

true

what are the principles for drug use during pregnancy?

Selecting drugs that have been used safely for a long time

Prescribing doses at the lower end of the dosing range

Eliminating nonessential medication and discouraging self-medication

Avoiding medications known to be harmful (teratogens)

which medication was found to be safe in animal models but was teratogenic in humans?

thalidomide

what is now included in medication/drug labels regarding pregnancy?

Fetal Risk Summary: What is the risk of the medication to the fetus and is the data human or animal?

Clinical Consideration: Explains the risks to the woman who took the medication before learning she was pregnant

Data: Available about the drug in human and animal studies

T/F: you should never use pregnancy categories to determine if a medication is safe

true

what is the placenta?

An organ of exchange for a number of substances including medications between pregnant person and fetus

how do most drugs move from maternal to fetal circulation?

diffusion

what are the functions of the placenta?

Transfers oxygen and nutrients from pregnant person to fetus

Permits release of carbon dioxide and waste from the fetus

what are the four drug properties that play a role in placental drug transer?

lipophilicity, molecular weight, protein binding, and pH

describe lipophilicity and its effects on placental drug transfer

Highly lipophilic medications will cross more readily due to the lipid membrane of the placenta

describe molecular weight and its effects on placental drug transfer

Molecular weight <500Da readily cross the placenta

describe protein binding and its effects on placental drug transfer

Unbound (low protein binding) drug crosses more easily.

Highly protein bound drugs cross more easily as pregnancy progresses due to increases in fetal albumin and decreases in maternal albumin.

describe pH and its effects on placental drug transfer

Fetal pH is slightly more acidic than maternal pH

Weak bases more easily cross, once in fetal circulation the drug becomes ionized and less likely to diffuse back into maternal circulation

T/F: medications may transfer to fetus at varying degrees

true

what else needs to be considered after assessing safety of the medication to the fetus?

Are there alternatives? Assess the alternatives as above

What is the overall RISK VS BENEFIT (disease and medication): What if the disease is left untreated? If mom is healthy, the fetus will be more likely healthy

what are the PK changes that occur during pregnancy?

Maternal plasma volume, cardiac output and GFR increase by ≥30-50%

increase in body fat

decrease in plasma albumin concentration

hepatic perfusion increases

N/V, delayed gastric emptying

increase in gastric pH

increased estrogen and progesterone levels

how do changes to maternal plasma volume, CO, and GFR effect medications?

lowers concentration of renally cleared medications

how does increased maternal body fat effect medications?

increased Vd of fat soluble medications

how does decrease in maternal plasma albumin concentration effect medications?

Increased Vd of highly protein bound medications; unbound drugs cleared more rapidly by the liver and kidney so little effect on concentration

how does increased hepatic perfusion effect medications?

increased hepatic extraction of drugs

how does N/V and delayed gastric emptying effect medications?

altered absorption

how does increased gastric pH effect medication?

absorption of weak acids and bases affected

how do increased estrogen and progesterone levels effect medications?

altered liver enzymatic activity (increase or decrease removal)

what are the other considerations for medication use during pregnancy?

document and counsel, treating a fetal condition with maternal medication

what is the goal of preconception planning?

health promotion through modification of behavioral, biological, and social risk in all pregnancy-capable people (prior to conception)

what should be done prior to conception?

Start prenatal vitamin with folic acid

Tobacco, alcohol, cannabis, illicit drug cessation

Up-to-date vaccinations

Evaluate current therapies for appropriateness during pregnancy

which vaccines should be given prior to conception?

A dose of Tdap, preferably during the early part of gestational weeks 27 through 36, during each pregnancy irrespective of the patient’s prior Tdap vaccination history.

A dose of inactivated influenza vaccine (IIV) or recombinant influenza vaccine (RIV) to women who are pregnant during any trimester or will be pregnant during influenza season

A dose of RSV vaccine (Abrysvo, Pfizer) only between 32 through 36 weeks of gestation during September through January if the patient was not previously vaccinated. 

Administer the current COVID-19 vaccine as indicated based on the patient’s health and vaccination history. Administer vaccine during any trimester, including the 1^st trimester.

T/F: Live vaccines are usually CI during pregnancy

true

what are the potential adverse pregnancy outcomes with antiseizure medications?

Known teratogen — causes craniofacial, cardiac, and limb defects; NTD; Fetal hydantoin syndrome

what are the potential adverse pregnancy outcomes with isotretinoin?

miscarriage

known teratogen — causes CNS, craniofacial, and cardiac effects

what are the potential adverse pregnancy outcomes with alcohol use?

fetal alcohol syndrome

what are the potential adverse pregnancy outcomes with tobacco use?

preterm birth, low birth weight, spontaneous abortion, increased prenatal mortality

what are the potential adverse pregnancy outcomes with cannabis use?

Spontaneous preterm birth, low birth weight, developmental delay

what are the potential adverse pregnancy outcomes with caffeine use?

Higher intake potentially linked to miscarriage, preterm birth, fetal growth restriction, although unclear data at this time

what are the potential adverse pregnancy outcomes with obesity?

NTD, preterm delivery, diabetes, HTN, VTE, cesarean section

what are the management or prevention options for antiseizure medication use during preconception?

use lowest possible ASM dose to maintain control, folic acid supplementation, use effective pregnancy prevention

what are the management or prevention options for isotretinoin use during preconception?

use effective pregnancy prevention, REMs program

what are the management or prevention options for alcohol use during preconception?

cessation prior to conception

what are the management or prevention options for tobacco use during preconception?

Cessation prior to conception, non-pharmacologic therapies, non-consensus for NRT products, dosing or frequency, intermittent forms (gum), TD patch (limit to 16h/day), bupropion may be less risk than smoking, varenicline safety unknown

what are the management or prevention options for cannabis use during preconception?

cessation advised (not a contraindication to breastfeeding), psychobehavioral strategies, electronic or text message interventions

what are the management or prevention options for caffeine use during preconception?

limit to 200 mg per day or less

what are the management or prevention options for obesity during preconception?

weight loss with appropriate nutritional intake before pregnancy