Pregnancy & Preconception Planning

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

What is the new single cell that the sperm and egg combine to create called?

zygote

What occurs in the zygote once it is formed?

male and female chromosomes join and organize for cellular division

Where does fertilization usually occur?

in the fallopian tube

What are the cells termed 6 days after fertilization?

blastocyte

When is hCG produced in appreciable amounts?

once the blastocyte is formed

When does implantation begin?

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

What are the cells called on the first day of the third week post fertilization?

an embryo

When does the blastocyte receive nutrients by the maternal blood supply?

by day 10

What is parity?

the number of deliveries after 20 weeks’ gestation (no matter the route or outcome)

What is gravida?

the number of pregnancies regardless of outcome

What is abortus?

the number of miscarriages/abortions

What is considered a full term pregnancy?

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

What is considered day 1 of the pregnancy?

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

What is the risk of harming the fetus at 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

What is the risk of harming the fetus at weeks 5-10?

major congenital anomalies likely

What is the risk of harming the fetus at week 11 to birth?

functional defects and minor anomalies possible

What is the rate of naturally occurring congenital anomalies?

3-6%

What are the most common congenital abnormalieties?

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

What are causes of congenital anomalies?

• naturally occurring (3-6%)

• genetic/ chromosomal (15-25%)

• environmental (10%)

• unknown (65-75%)

• medications (<1%)

What is a teratogen?

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

What are examples of medications that cause structural abnormalities if exposure occurs during organogenesis (weeks 5-11)?

• methotrexate

• cyclophosphamide

• diethylstilbestrol

• lithium

• retinoids

• thalidomide

• antiepileptic drugs (AEDs)

• warfarin

What are examples of medications that can cause growth retardation, CNS, or other abnormalities or death if exposure occurs after 11 weeks?

NSAIDs and tetracyclines

What are the 3 mechanisms that a medication can harm the fetus?

1. act directly on the fetus

2. alter the function of the placenta

3. cause the muscles of the uterus to contract

How would a medication harm the fetus if it acts directly on the fetus?

can cause damage, abnormal development (leading to birth defects), or death; damaged differentiating cells more likely to result in permanent organ damage

How would a medication harm the fetus if it alters 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 mom

How would a medication harm the fetus if it causes the muscles of the usterus to contract?

indirectly injures the fetus my reducing its blood supply or triggering preterm labor and delivery

How do you prevent neural tube defects?

folic acid supplementation should be done in any pregnancy capable person

What dose of folic acid supplementation has been shown to reduce the incidence of NTDs?

0.4-0.9 mg/day

True or False: higher folate doses are recommended for patients on ASM and those having children with NTD

false

What kind of safety data is most desirable for drug safety in pregnancy?

from randomized controlled trials

True or False: extrapolation of animal studies may not be relied upon

true

What should be considered when reviewing a case study for drug safety in pregnancy?

birth defect may have developed by chance or due to the medication

What are 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 medications and discouraging self-medication

• avoiding medications known to be harmful (teratogens)

True or False: never use pregnancy categories

true

What do FDA labels contain regarding pregnancy safety since 2015?

• fetal risk summary

• clinical consideration

• data about the drug in human and animal studies

What is the fetal risk summary?

what is the risk of the medication to the fetus and is the data human or animal

What is the clinical consideration?

explains the risks to the woman who took the medication before learning she was pregnant

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?

by 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 properties that affect placental drug transfer?

lipophilicity, molecular weight, protein binding, and pH

How does lipophilicity effect placental drug transfer?

highly lipophilic medication will cross more readily due to the lipid membrane of the placenta

How does molecular weight effect placental drug transfer?

molecular weight <500Da readily cross the placenta

How does protein binding effect placental drug transfer?

unbound (low protein binding) drug crosses more early; high protein bound drugs cross more readily as pregnancy progresses due to increases in fetal albumin and decreases in maternal albumin

How does pH affect 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

What PK changes 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

• nausea and vomiting

• delayed gastric emptying

• increase in gastric pH

• increased estrogen and progesterone levels

How does increased maternal plasma volume, cardiac output, and GFR effect the PK of medications during pregnancy?

lowers concentration of renally cleared medications

How does increase in body fat effect the PK of medications during pregnancy?

increased Vd of fat soluble medications

How does decrease in plasma albumin concentration effect the PK of medications during pregnancy?

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

How does increased hepatic perfusion effect the PK of medications during pregnancy?

increased hepatic extraction of drugs

How does nausea and vomiting effect the PK of medications during pregnancy?

altered absorption

How does delayed gastric emptying effect the PK of medications during pregnancy?

altered absorption

How does increase in gastric pH effect the PK of medications during pregnancy?

absorption of weak acids and based effected

How does increased estrogen and progesterone levels effect the PK of medications during pregnancy?

altered liver enzymatic activity (increase or decrease removal)

What other considerations should there be for medication use during pregnancy?

• DOCUMENT AND COUNSEL!

• treating a fetal condition with maternal medication

True or False: if mom is healthy, the fetus will be more likely healthy

true

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 during preconception planning?

• start prenatal vitamin with folic acid

• tobacco, alcohol, cannabis, illicit drug cessation

• up to date on vaccinations

• evaluate current therapies for appropriateness during pregnancy

What vaccine considerations are there during preconception planning/pregnancy?

• administer a dose of Tdap (weeks 27-36)

• administer a dose of inactivated influenza vaccine or recombinant (any time during flu season)

• administer a dose of RSV (only between weeks 32-36 IF occurs September- January if never vaccinated before)

• administer the current COVID-19 vaccine (during any trimester)

What medications/factors have preconception risk factors?

• antiseizure medications

• isotretinoin

• alcohol use

• tobacco use

• cannabis use

• caffeine

• obesity

What are the potential adverse pregnancy outcomes for antiseizure medications?

known teratogen: causes craniofacial, cardiac, and limb defects; NTD; fetal hydantoin syndrome

How do you manage/prevent the risk of antiseizure medications?

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

What are the potential adverse pregnancy outcomes for isotretinoin?

miscarriage, known teratogen: causes CNS, craniofacial, and cardiac defects

How do you manage/prevent the risk of isotretinoin?

use effective pregnancy preventions; REMs

What are the potential adverse pregnancy outcomes of alcohol use?

fetal alcohol syndrome

How do you manage/prevent the risk of alcohol use?

cessation prior to conception

What are the potential adverse pregnancy outcomes of tobacco use?

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

How do you manage/prevent the risk of tobacco use?

cessation prior to conception; non-pharmacologic therapies; non consensus for NRT products

What are the potential adverse pregnancy outcomes of cannabis use?

spontaneous abortion, preterm birth, low birth weight, developmental delay

How do you manage/prevent the risk of cannabis use?

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

What are the potential adverse pregnancy outcomes of caffeine?

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

How do you manage/prevent the risk of caffeine?

limit to 200 mg per day or less

What are the potential adverse pregnancy outcomes of obesity?

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

How do you manage/prevent the risk of obesity?

weight loss with appropriate nutritional intake before pregnancy