CMM 585 Teratogens Discussed in Class

What is rubella?

A highly contagious viral infection that can cause congenital rubella syndrome

What is the affect of rubella on baby/pregnancy

Can affect almost everything in developing baby’s body and cause complications after birth

What is the critical period for rubella?

7-56 days post conception

What is tetracycline

An antibiotic used to treat a wide variety of bacterial infections

What is the critical period for tetracycline

Second and third trimester

What is thalidomide

An approved treatment of type 2 leprosy. Also had potential for uses as an angiogenic, AIDS, Bechet’s syndrome. Was used as a remedy for morning sickness in the 1950-1962 

What is the critical period for thalidomide

20-36 days post conception

What is the pattern of malformation for thalidomide?

Upper limb phocomelia, facial hemangioma, esophageal and duodenal atresia, heart defects, renal and genitourinary anomalies, anomalies of the eyes and outer ears, and oral clefts

What is the malformation for 21-23 days post conception for thalidomide?

External ear

What is the malformation for 25-28 days post conception for thalidomide?

Upper limb

What is the malformation for 28-30 days post conception for thalidomide?

Uterine

What is the malformation for 32-34 days post conception for thalidomide?

Lower limb

What is the malformation for 34-36 days post conception for thalidomide?

Triphalangeal thumbs

What is lithium?

Metal used as a mood stabilizer to treat bipolar disorder 

What are the risks for lithium?

Increased risks for cardiac defects, but studies have mixed results. Particular concern for Ebstein’s anomaly

Isotertinoin (Accutane) pattern of malformation?

CNS anomaly, ear anomalies, cardiovascular defects, thymus anomalies, and increased risk for risk miscarriage

Critical period for isotretinoin (accutane)

15 days post conception through the end of the first trimester 

Radiation pattern of malformation

Microcephaly, intellectual impairment, seizures, growth restrictions, and minor anomalies of the eyes

Critical period for radiation

Exposure effects depend on the timing of exposure

Anticonvulsants pattern of malformations

Hypertelorism, broad depressed nasal bridge, short nose with anteverted nares, long well-developed philtrum, “Cupid’s bow” lip, fingernail hypoplasia, and developmental delay

Anticonvulsants major malformations

Meningomyelocele, oral cleft, congenital heart defects, and limb defects

What are the risks associated with maternal epilepsy

2-3 times higher risk for fetal malformations than general public

What is fluconazole

Anti-fungal medication used for the treatment of mycotic infections

There is concern that large doses of fluconazole may cause what?

Antley-Bixer syndrome

Critical period for ACE/ARB inhibitors?

Second and third trimesters 

ACE/ARB inhibitor pattern of malformation?

Renal tubular dysplasia, IUGR (intrauterine growth restriction), and hypocalvaria manifested by large anterior fontanel

Mechanism of action for ACE/ARB inhibitors

Reduce uterine blood flow, leading to decreased placental perfusion and severe fatal hypotension.

Warfarin pattern of malformation 

Nasal hypoplasia, stippled epiphyes, and limb hypoplasia 

Warfrin critical period

6 to 9 weeks from conception

What is the normal mercury level in circulation and in hair

8ppm in circulation and 2 ppm in hair

What hair levels of mercury do children with congenital minimata disease?

5-110 ppm

What disase is associated with mercury

Congenital minamata disease

Effects of mercury (congenital minamata disease)

Mental restriction, dysarthria, chorea, atazia, hypersalivation, abnormal reflexes and growth restriction

What is late term use of aspirin associated with?

Decreased uterine contractions, prolonged pregnancy, and premature close of ductus arteriouses → pulmonary hypertension

What are NSAIDs

non-steroidal anti inflammatory drugs

Risks associated with NSAIDs

Some show increase risk of miscarriage if used around time of conception. Associationis with cardiac defects and gastroschisis

Acetaminophen (Tylenol) 

No known increase in structural birth defects

Prescription opioids risks

Most studies have not identified increased risk for a consistent pattern of birth defects. Concerns about neurodevelopment. Significant risk for neonatal withdrawl

Pseudoephedrine use

sympathomimetic medication mostly used as decongestion. Mixed alpha and beta agonist properties

Is pseudoephedrine a teratorgen?

Many studies published but there’s not enough data to confirm or rule it out

Anesthesia safe?

No conclusive evidence for general anesthesia to be considered a teratogen. Possible increased risk of miscarriage for occupational exposure

Smoking risks

Some concerns that it can cause infertility, ectopic pregnancy, miscarriage, placental abruption, placenta previa, FGR, preterm delivery, orofacial clefts, SIDS, and low birth weight 

Statins risk?

Theoretical concerns about early need of embryo for cholesterol. Current recommendation is to stop use during pregnancy

Hyperthermia (fever) pattern of malformation

Growth deficiency, CNS defects, defects of 1st and 2nd branchial arches, open neural tube defects

Hyperthermia (fever) critical period?

General: 4-14 weeks, neural tube defects: 4-6 weeks

Poorly controlled astham risks

Increase risk of preeclampsia, prematurity, low birth weight, and c-sections

Beta agonists (for asthma)

Benefit outweighs the risk

Corticosteroids (for asthma) risks 

Human studies have not shown increased birth defect risk

Hypertension complications

Placental abruption, fetal growth restriction, prematurity, superimposed preeclampsia, higher rates of c-sections, fetal loss

Thromboembolic disease

Risk for VTE increases during pregnancy