LM 14.6: TORCH/Teratogens Flashcards
what are the complications associated with teratogens?
- pregnancy loss
- birth defects
- growth restriction
- impaired neurologic function
what types of exposures can women have?
- infections
- mechanical
amniotic bands, umbilical cord, uterine size
- environmental
- maternal habits
when is the most impactful weeks when it comes to teratogen effect on the embryo?
first 12 weeks
what is the all or none effect?
within the first 2 weeks after conception there is an all or none effect
so if something effects the embryo you’ll have a spontaneous abortion/miscarriage or the baby will be totally fine
what is the major effect of teratogens on a baby in the first 8 weeks of gestation?
it will effect organogenesis and lead to structural defects
neural tube, heart, limbs, facial structures etc. are all being formed at this time and if mom is effected by teratogens at this time it will effect these thigns
what is the major effect of teratogens on a baby after the first 8 weeks of gestation?
growth and CNS development are effected
this can effect the fetus into childhood and adulthood
what are the drug categories for teratogens?
A = safe; like prenatal medications
B = they’re probably fine
C = most; don’t have enough info to say they’re technically safe
D = we know can be teratogenic in fetuses and we know there’s some risk; there isn’t a good alternative to this medication though and they must be used during pregnancy; must discuss risk/benefit ration
X = absolutely contraindicated in pregnancy; usually an alternative exists or they’re not essential medications
what is the mnemonic for teratogenic pharmaceuticals
TERATOWAMM
Ⓣhalidomide
Ⓔpileptic medications (valproic acid, phenytoin, phenobarbital, carbamazepine)
Ⓡetinoids
ⒶCE inhbitors/ARBs
Ⓣhird element (lithium)
Ⓞral contraceptives/other hormones
Ⓦarfarin
Ⓐntibiotics (ahminoglycosides, tetracyclines, fluoroquinolone, trimethoprim, sulfonamides
Ⓜethimazole
Ⓜmethotrexate
how does thalidomide effect the fetus?
class X drug; orphan drug aka you have to have special permission to even use it
FDA approved for use for MM and Hansen’s disease
initially used for morning sickness and insomnia in pregnancy
- phocomelia (abnormal limbs)
- micromelia (abnormally small limbs)
- amelia (absence of limbs)
how do epileptic medications effect the fetus?
valproic acid, phenytoin, phenobarbital, carbamazepine
- neural tube defects
- cardiac defects
- cleft palate
- facial and finer abnormalities
mostly related to decreased folic acid…so high dose folic acid supplementation is indicated if use is absolutely necessary during pregnancy
how does valproic acid effect the fetus?
neural tube defects
how does phenytoin effect the fetus?
fetal hydantoin syndrome:
- cleft lip/palate
- microcephaly
- mental retardation
how does phenobarbital effect the fetus?
- IUGR (intrauterine growth restriction)
- cleft lip/palate
- facial abnormalities
how does carbamazepine effect the fetus?
neural tube defects
how do retinoids effect the fetus?
FDA approved fro acne but category X drug
20% risk of spontaneous abortion
20-30% risk of abnormal facial features, congenital heart disease, hydrocephalus in live births
there is a mandatory birth control as part of prescribing this!!
how do ACEI/ARBs effect the fetus?
commonly used for HTN but use with caution in reproductive age women
leads to decline in renal function and ultimately renal failure in the fetus….this will manifest as oligohydramnios in the 2nd/3rd trimester….this could result as pulmonary hypoplasia and limb/skeletal deformities (Potter syndrome)
why does oligohydrmanios lead to pulmonary hypoplasia and limb/skeletal defects?
amniotic fluid is needed to cushion the limbs and give room to grow so without it there could be limb hypoplasia
in tuero, the fetus drinks amniotic fluid to help them fill and grow and so without it, you’d get pulmonary hypoplasia
how does lithium effect the fetus?
category D drug
risk of Ebstein’s anomaly aka tricuspid displaced toward RV apex
how do OCPs effect the fetus?
unclear evidence showing craniofacial defects, cardiac defects, limb defects
also effects on sexual differentiation in early pregnancy….
how does warfarin effect the fetus?
fetal warfarin syndrome:
1. stippled epiphysies in bones
- nasal and limb hypoplasia
- bleeding
- optic atrophy
contraindicated in pregnancy; there are other options like heparin because this doesn’t cross the placenta
how do antibiotics effect the fetus?
- aminoglycosides = deafness
- tetracyclines = discolored teeth
- fluoroquinolone = cartilage damage
- trimethoprim = disrupts folate metabolism in 1st trimester –> can use in 3rd trimester to treat UTIs
- sulfonamides = displace bilirubin from albumin which can lead to kernicterusin 3rd trimester –> can use in the 2nd trimester though for infections
all of these effect kids too so we dont usually give them to kids unless we have to
how does methimazole effect the fetus?
used for hyperthyroidism but can cause:
- aplasia cutis = missing hair patch on scalp
dont use in the 1st trimester because high risk of this happening; lower likelihood in 2nd and 3rd trimester
- propylthiouracil (PTU) is better treatment for hyperthyroidism in pregnancy during the 1st trimester
how does methotrexate effect the fetus?
category X drug…
inhibits folate metabolism so can cause neural tube defects
used for RA and other autoimmune mechanisms
how do chemotherapeutic agents effect the fetus?
- spontaneous abortions
- missing digits
- many other defects
1st trimester chemo results in 15% fetal malformations so ideally defer till at least 2nd trimester if possible
how does diethylstilbestrol effect the fetus?
DES is a nonsteroidal estrogen prescribed to prevent miscarriage and preterm labor but it causes:
- increased breast cancer risk
- hypoplastic uterus and cervix in infants
- vaginal adenomas, vaginal clear cell adenocarcinoma, and infertility in children
this is no longer on the marker..
how do opioids effect the fetus
- poor fetal growth
- preterm birth
- stillbirth
- neonatal abstinence syndrome (neonatal withdrawal once delivered)
how does alcohol effect the fetus?
- it’s a neurotoxin so it can cause cell death or failed cell migration
- fetal alcohol syndrome
Ⓕissures (eye openings shortened)
Ⓐnatomically thin vermillion border (upper lip)
Ⓢmooth philthrum under nose
- skeletal deformities
- heart deformities (ASD, VSD, tetralogy of Fallot
- microcephaly with small corpus callous, basal ganglia, and cerebellum
- MRDD
- holoprosencephaly, hypotonia, CNS deficits if severe
when is alcohol most teratogenic to the fetus?
1st trimester
but in the 3rd trimester it can cause poor growth
no amount of alcohol is safe while pregnant!
how does nicotine effect pregnancy?
- nicotine causes vasoconstriction
- CO produced competes for oxygen binding
these two combined lead to decreased oxygen flow which can result in intrauterine growth restriction
can also cause:
1. placental abruptiosn
- placenta previa
- premature rupture of membranes
- preterm labor
- increased sudden infant death syndrome (SIDS) risk**
how does cocaine effect the fetus?
very potent vasoconstriction so can cause IUGR or placental abruptions
how does mercury effect the fetus?
present in seafood and the fetal brain is HIGHLY sensitive to this
can caused delayed milestones, cerebral palsy, blindness, and deafness
how does radiation effect the fetus?
ideally avoid any radiation during pregnancy; we are unsure about the threshold of how many rads is “safe’”
use lead shielding of abdomen if necessary
8-15 weeks is most sensitive time and can result in IUGR, MRDD and microcephaly
which infections are TORCH infections?
Ⓣoxoplasma gondii
Ⓞther: treponema pallidum, listeria, varicella zoster virus, and parvovirus B19
Ⓡubella
ⒸMV
Ⓗerpes
how does maternal DM effect the fetus?
increased fetal insulin levels
even though maternal insulin doesn’t cross the placenta, maternal glucose does which causes high fetal glucose and then the fetal pancreas makes more insulin
then since insulin is a fat storage hormone, it encourages storage of energy and fat resulting in fetal growth aka giant babies!! –> this can ultimately result in neonatal hypoglycemia since the fetus has super high levels of insulin but not as much glucose since the umbilical cord is no longer transferring maternal glucose
all of this can cause:
- caudal recession defects
- neural tube defects
- mermaid syndrome
- cardiac defects
- transposition of the great vessels**
what is maternal PKU?
high levels of PKU are teratogenic because it’s similar to alcohol
can cause:
1. IUGR
- micorcephaly
- MRDD
- cardiac defects: coarctation of the aorta*, hypo plastic left heart
