Teratogens Flashcards
What is the background risk for birth defects during pregnancy?
3-5%
What percentage of birth defects are caused by teratogenic exposure?
~10%
What are some characteristics of a teratogen?
- Increased occurence of an abnormal effect
- dose-response relationship (often w/threshold effect)
- period of greatest sensitivity
- established mechanism of action
- plausible biological explanation
- genetic basis of susceptibililty
When is the “all or none” period?
0-2 weeks conceptual age
When is the period of greatest sensitivity for NTD’s? (when is the neural tube closing?)
2-4 weeks conceptual age (beware of fever/high temps, hot tubs, folic acid antagonists)
When is the period of greatest sensitivity for organogenesis?
3-8 weeks conceptual age (exposures potentially result in major malformations, growth retardation, IQ deficits)
In what trimester does the fetus grow most in length? (crown-rump)
2nd trimester (growth, maturation, and neural development of the fetus)
In what trimester does the fetus gain most weight?
3rd trimester (21-38 weeks conceptual age–> growth maturation, and neural development)
When is the “embryonic period”?
Weeks 3-8 conceptual age
(also the period of organogenesis)
(Weeks 3/4 are when gastrulation, neurulation, and development of the embryonic axis occur)
What happens during the 1st week post-conception? (CA 0-7 days)
Initial cleavage of the zygote, transport to oviduct, implantation
What happens during the 2nd week post-conception (CA 8-14 days)
Proliferation of the trophoblast, placental development
When does cardiac formation occur?
Weeks 3-8 conceptual age
When does limb development occur?
Weeks 4-9
True or False: “No teratogen causes birth defects in 100% of exposed fetuses”
True– example of the “genetic basis of susceptibility” characteristic of teratogens
Name the teratogen:
An antihistamine found to be an excellent sedative; used to treat nausea in pregnancy; later used in treatment of leprosy (Brazil); most recently shown to be effective in treating specific cancers (ex: melanoma).
Thalidomide
Name some of the characteristics of Thalidomide embryopathy
inhibits normal function of CRBN protein in limb development–> results in limb malformations (79-89%), may also see absent ears, microtia, defects of the genitals, kidneys, gut, neurological manifestations. Period of greatest sensitivity: days 20-34 conceptual age (~3-5 weeks)
Is an FDA pregnancy category A drug okay to take during pregnancy?
Apparently yes “Adequate, well-controlled human studies have shown no risk to the fetus.”
What does it mean if the FDA has placed a drug in pregnancy category X?
“Studies in animals or humans show risk AND the risks clearly outweigh the potential benefits” This drug is clearly contraindicated in pregnancy.
Where can you find MSDS sheets available to gather information about potential teratogenic effects of chemicals encountered in a lab setting?
OSHA
Are babies exposed to a higher concentration of maternal medications during pregnancy or during lactation?
Pregnancy
True or false: Medications have a shorter half-life in infants than they do in mothers.
False– half-lives of medications are longer in infants, because their livers metabolize more slowly
What does TORCH stand for?
T- Toxoplasmosis O- Other (Syphillis, Varicella) R- Rubella C- CMV H- Herpes
What percentage of maternal toxoplasmosis infections result in congenital toxoplasmosis cases?
30%
Risks associated with congenital toxoplasmosis?
Chorioretinitis, hydrocephalus, intracranial calcifications.
85% of infected infants are asymptomatic at birth, but 90% will develop symptoms later which may include:
ocular lesions, jaundice, HSM, lymphadenopathy, microcephaly, HL, ID, cerebral palsy, seizures…
Only 10% are totally asymptomatic.
Can women with toxoplasmosis safely breastfeed?
Why yes; yes they can.
Risks associated with untreated maternal syphilis?
2/3 of exposed fetuses will be affected.
-Death, stillbirth, or miscarriage risks are very significant if untreated.
-Most that are liveborn are asymptomatic, 66% symptomatic by 8 weeks, almost 100% symptomatic by 3 months with: bony abnormalities (ex: saber shins), HSM, petechiae, skin lesions, anemia, jaundice, pseudoparalysis, persistent rhinitis (irritation of mucous membrane inside nose).
Later on (>2 years) may see: frontal bossing, palate deformation, dental abnormalities, saddle nose, sensorineural deafness, DD
Can women with syphilis safely breastfeed?
Yep– as long as there are no lesions on the breast or nipple. Also delay BF until 24 hours post initiation of treatment.
What is assocaited with congenital rubella syndrome?
60% deafness, ~50% cataracts, congenital heart defects (VSDs, PDA, PS, CoA), microcephaly and MR (10-20%), encephalitis, HSM, thrombocytopenia
(most women were vaccinated in childhood)
What is associated with congenital CMV?
microcephaly, ID, sensorineural HL, chorioretinitis, seizures, intracranial calcifications, HSM, thrombocytopenia, petechiae, IUGR, dental defects, motor defects
What percentage of adults in the US have been infected with CMV?
50-80% (mostly asymptomatic)
but the risk for congenital CMV is only if it is a primary or recurrent infection
What percentage of live born babies have congenital CMV?
1-3% (it is more common than FAS, Down syndrome, and spina bifida… however:)
90% born asymptomatic– and only 20% of that 90% develop symptoms later; 80% remain asymptomatic
Can women with CMV safely breastfeed?
Yep, but safest if the baby is full term!
may cause late-onset sepsis like syndrome in premature infants, but benefits still thought to outweigh risks
What is herpes simplex virus II (HSV II)?
Genital herpes
When might HSV II (herpes simplex virus II) be transmitted to an infected fetus/infant?
5% transmitted in utero
85-90% cases transmitted intrapartum (during birth)
5-10% transmitted postnatally
What is the risk of neonatal HSV infection after vaginal delivery?
33-50%
What are the findings associated with a congenital, INTRAUTERINE HSV II infection?
skin vesicles/scarring, chorioretinitis, micropthalmia, cataracts, microcephaly, intracranial calcifications, seizures, encephalomalacia, encephalitis, growth retardation, psychomotor development delays
What are the findings associated with an intrapartum or postnatal HSV II infection?
skin, eye, mouth lesions and/or HSV encphalitis
OR
disseminated HSV which manifests as severe multi-organ dysfunction (CNS, liver, lung, brain, adrenals) + skin, eye, mouth lesions
Can a mother with HSV II breastfeed?
YES- as long as she does not have an active HSV lesion on her breast.
How can TORCH testing be done?
Can do TORCH titers on Mom’s blood.. if positive, can do PCR on AF to look for transmission to fetus.
What are the risks associated with maternal PKU?
"phenocopy of FAS" DD- 92% microcephaly- 72% IUGR- 40% cardiac defect- 12-15% postnatal growth retardation- 51% SAB: 24%
Can a mother with PKU breastfeed an unaffected (carrier) child?
Yes. (but a child with PKY may not be able to breastfeed)
What are the risks associated with diabetic embryopathy?
LOTS- preterm birth, macrosomia, congenital anomalies, cardiovascular defects (ex: hypoplastic left heart), organomegaly, skeletal defects, NTD’s, caudal regression, respiratory, hematologic, metabolic, GI, and renal problems… VACTERL
What does VACTERL stand for and what maternal condition is it associated with?
Associated with uncontrolled maternal diabetes: V-Vertebral abnormalities A-Anal atresia C-Cardiac abnormalities T- Tracheo-esophageal fistula R- Renal abnormalities L- Limb defects
Can a mother with diabetes breast feed?
Sure can.
What are the risks associated with maternal alcohol use?
FAS- a spectrum that may include– low birth weight, CL +/- CP, ID, short palpebral fissures, microcephaly, long smooth philtrum, growth deficiencies, pectus ex/cari, contractures, hypospadias, renal defects ear abnormalities, congenital heart disease (ex: ASD, VSD, TOF)
Is there a known safe amount of alcohol during pregnancy?
NO- but there is a known association between increased exposure=increased likelihood and severity affected
Can you drink and breastfeed?
Not recommended– milk alcohol level is similar to blood alcohol level. Wait until you are no longer ‘drunk’ or 8-16 hours after rinking– consider formula feeding if you will be drinking moderately-regularly.
What percentage of pregnancy women report using street drugs?
4%!
What percentage of women report using cocaine in pregnancy?
.4-31% depending on region and study.. Detroit was 31%.
What are the risks of cocaine use during pregnancy?
premature delivery (50%) with increased risks for miscarriage and placental abruption
withdrawal in the fetus/infant (50%)
cerebrovascular events in fetus resulting in brain damage (30%)– may include seizures, apnea, tachycardia,etc.
growth restriction- (18%)
congenital anomalies- (7-26%)- may include limb amputation defects (vasoconstriction), CHD, intestinal defects, CL+/-CP
Can you do cocaine and breastfeed?
Nope.
What are the risks of taking isoretinoin (ex: accutane) during pregnancy?
CNS defects (ex:hydrocephalus), microtia, CP, hypertelorism, conotruncal cardiac malformations, TOF, thymic ectopia or hypo/aplasia, spina bifida, hypotonia, liver issues, anotia, triangular skull, micrognathia and small mouth, limb reduction defects….
**Category X- 10x risk of birth defects at 30-50%, critical period of exposure is 5-7 weeks!
Has the iPLEDGE system (mandates 2 forms of birth control and monthly pregnancy tests for isoretinoin users) decreased adverse pregnancy outcomes associated with isoretinoin use?
Nope.
What are some common AEDs?
Valproic acid, lithium, carbamazepine, phenobarbital, phenytoin, lamotrigine
Which AEDs are associated with the greatest risks of birth defects?
Valproic acid and lithium (2-3x increased risk for birth defects…
2x increase for others like phenytoin, phenobarb, carbamazepine, etc.)
When is the most critical period for adverse effects associated with AEDs in pregnancy?
1st trimester exposure
What is the risk for NTD for woman taking AED?
1-2%
Because AED’s are folate antagonists (lamotrigine is the most associated)
What AED is most associated with Ebstein’s anomaly (heart defect of the tricuspid valve)?
Lithium- 1/1000 risk for Ebstein’s anomaly.
What are the features associated with “AED embryopathy”?
CL +/- CP, CHD, hypoplasia of midface and fingers, microcephaly, small body size, “doll like” facies with full cheeks.
Valproic acid carries the greatest risk for AED embryopathy at 5-9%
How should a woman who takes AEDs be ideally managed before/during pregnancy?
DON’T STOP MEDS–> control of seizures and mood disorders is most important
- use lowest effective dose
- use only one drug if possible (rather than combos)
- avoid valproic acid if possible (may need to switch meds)
- Take increased folic acid (1-4 mg vs. general pop. .4 mg) prior to pregnancy and during the 1st trimester to decrease risk of NTD’s
Can you take accutane and breastfeed?
Not recommended, because no studies exist.
Can you take AEDs and breastfeed?
Yep– however, note that the AEDs ARE transmitted into milk– but no contraindication known.
Is it okay to take antihypertensives in pregnancy?
Trick question- depends on the antihypertensive! (ACE inhhibitors are clearly contraindicated–>take a different one!)
What risks are associated with maternal ACE inhibitor use?
In the 1st trimester:
2.7x increase for birth defects, especially CNS and cardiac anomalies
In the 2nd trimester:
affects KIDNEY development and fxn leading to characteristics similar to bilateral renal agenesis (BAD!)–> oligohydramnios, Potter facies/sequence, calvarial hypoplasia, IUGR, renal failure leading to fetal demise or neonatal death,
Can you take ACE inhibitors and breastfeed?
You betcha. (does transmit to breast milk, but okay/not contraindicated).
What are the risks associated with radiation exposure during pregnancy?
None associated with <1 rad
350-500 rad would be ex: targeted cancer treatment
What is the risk for major congenital anomalies with maternal diabetes?
6-12% overall
*If glycosylated Hgb9.5%, 22% risk!**
–> VERY IMPORTANT TO CONTROL DM DURING PREGNANCY
What does failure of the neural tube to close on the rostral end lead to?
Anencephaly
How common is Rh incompatability in Caucasians?
10-15% incidence (most common)
For African Americans, 5-8%
For Asians, 1-2%
If all else is unknown, what is the likelihood of a an Rh negative woman having an Rh positive fetus?
60%
What are the risks associated with Rh incompatability?
If mom is negative and fetus is positive, risk for sensitization– mom produces D antibody that crosses placenta and causes erythoblastosis fetalis:
fetal red blood cell hemolysis leading to severe anemia–> fetal heart has to work harder to circulate oxygen to the fetus w/less RBC’s–> heart failure–> fetal hydrops–> demise
How can you treat fetal anemia and hydrops resultant from Rh incompatability?
Can perform intrauterine fetal transfusion–> blood (RBCs) into umbilical cord of fetus will resolve fetal hydrops if caught early enough (has its own risks obviously)
Must repeat the IUT every few weeks until 34-36 weeks gestation. May also require transfusion at birth
Once it occurs once–> all future pregnancies will be affected by Rh isoimmunization
What are some risks of neonatal lupus syndrome?
Maternal SLE antibodies cross placenta and attack fetus–> result in:
hematologic complications (ex: hemolytic anemia, leukopenia, thrombocytopenia) skin lesions (gone at ~1 year of life) heart defects (ex: congenital heart block- fibrosis of the AV node--> 1/3 children die in first 3 years of life, survivors require pacemakers)
What is the recurrence risk for congenital heart block for a woman with SLE who has had a previous child with congenital heart block?
15%
