Approach to prenatal teratogen exposure: Clinical sciences

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Introduction 0:00–0:36

Prenatal teratogens are substances or conditions that disrupt normal fetal growth and development. Depending on the timing, dose and duration of exposure, teratogens can increase the risk of early pregnancy loss, stillbirth, fetal growth restriction, congenital anomalies and developmental delays.
Potential teratogens include recreational substances, maternal conditions like diabetes and prescription medications. Now, if a pediatric patient presents with a chief concern, suggesting a prenatal teratogen exposure, you should first perform an ABCDE assessment to determine if the patient is stable or unstable.

Unstable patient 0:36–1:08

If unstable, stabilize their airway breathing and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring including BP, heart rate and pulse oximetry.
Finally, if needed, provide supplemental oxygen. Now that we've discussed unstable patients, let's return to the ABCD E assessment and look at stable ones first, obtain a focused history and physical examination and order A CBC and C MP history usually reveals a known prenatal exposure to recreational substances or medications or a maternal history of an underlying medical condition associated with teratogenicity.

Stable patient 1:08–2:01

The patient also might have a history of fetal growth restriction, preterm, birth, developmental delay or congenital anomalies like cardiac or neural tube defects.
Additionally, the physical exam often demonstrates poor growth and certain characteristic facial features. Occasionally with other anomalies such as cleft lip and palate or limb and digit abnormalities at this point, consider prenatal teratogen exposure.

Teratogen exposure 2:01–2:23

Now, while some substances such as alcohol are directly teratogenic other substances such as opioids, most commonly cause complications due to withdrawal.
So as a next step, assess for a maternal history of substance use during pregnancy. If a history of substance use is present, assess your patient for signs and symptoms of opioid withdrawal.

Opioid exposure 2:23–3:12

History typically reveals irritability, jitters and a high pitched cry as well as hiccups or gagging, poor feeding and poor growth.
Some patients may also have vomiting, diarrhea, tremors or seizures with these signs and symptoms of withdrawal. Expect the maternal history to include use of opioids, either recreational or therapeutic such as methadone.
As for the exam, you may see elevated temperature tachypnea or hypertonicity. These findings are highly suggestive of opioid withdrawal after prenatal exposure.
However, if you identify no signs or symptoms of opioid withdrawal, consider alcohol exposure, any alcohol use during pregnancy can adversely affect the developing fetus.

Fetal alcohol spectrum disorder 3:12–4:47

So, history frequently reveals poor pre and postnatal growth, possibly in combination with cardiac defects such as atrial or ventricular septal defect, renal anomalies like hypoplastic or horseshoe kidneys, skeletal defects like pectus carinatum or radioulnar synostosis and eye or ear anomalies.
Later, these Children often demonstrate a poor attention span, cognitive delay and behavioral problems. Exam findings typically include characteristic facial features such as short palpebral fissures, a thin vermilion border and a smooth philtrum.
You might also appreciate epicanthal folds, mid face, hypoplasia, railroad track ears or hypoplastic nails. Additionally, the head circumference length and weight are often less than the 10th percentile.
These findings are consistent with fetal alcohol spectrum disorder. Here's a clinical pearl.
Other recreational substances associated with low birth weight and developmental delay include tobacco, marijuana and cocaine.
Cocaine use can also cause problems like placental abruption and preterm, birth switching gears. Let's look at when a history of substance use is not present.

Diabetes 4:47–6:54

Here, you should assess the neonate for hypoglycemia. And if present, consider maternal diabetes affected infants may have either macrosomia or growth restriction as well as feeding difficulties and in the first days of life, they might appear jittery, hyper excitable or irritable.
Prenatal. Ultrasound might have identified a cardiac or neural tube defect or neonatal small left colon syndrome during the immediate newborn period.
The exam is likely to demonstrate tachypnea, labored breathing and even respiratory distress and you might find evidence of caudal regression like a sacral dimple.
Significant laboratory findings include an elevated hemoglobin and hematocrit indicating polycythemia and decreased serum calcium levels.
These findings suggest maternal diabetes. Remember that pregestational diabetes and poor glucose control during pregnancy significantly increase the risk of these complications.
Here's another clinical pearl, other maternal medical conditions associated with teratogenicity include cushing disease, thyroid disorders, and untreated phenylketonuria.
Let's follow that up with a high yield fact during pregnancy, some infections can cross the placenta and cause teratogenic sequelae such as intrauterine growth restriction, microcephaly, hearing loss or ocular abnormalities.
Traditionally, these congenital infections have been grouped under the pneumonic torch, which stands for toxoplasma, other rubella, cytomegalovirus and herpes simplex virus.
The category other continues to evolve and includes pathogens such as zika virus, varicella, zoster virus, syphilis and human immunodeficiency virus.
Now let's look at patients without hypoglycemia. Next, assess your patient for abnormal bleeding or bruising and if present, consider prenatal exposure to phenytoin or warfarin which antagonize Vitamin K thereby increasing a newborn's risk of Vitamin K deficiency and bleeding.

Phenytoin exposure 6:54–8:29

Here's a clinical pearl. The teratogenic effects of phenytoin and warfarin include impaired development and craniofacial abnormalities.
Although the teratogenic mechanism of phenytoin is unclear, it might be related to impaired folate absorption. On the other hand, warfarin's effects seem to be due to a deficiency of Vitamin K dependent proteins needed for bone and cartilage formation.
Next, assess your patients facial features. If you notice a wide anterior fontanelle, broad, depressed, nasal bridge, short nose and bowed upper lip, possibly with a cleft lip or palate.
Consider phenytoin exposure history often reveals congenital heart defects, developmental delay and strabismus. Other exam findings often include stiff, tapered fingers, hypoplastic digits and nails, an abnormal palmar crease and possibly hip dislocation.
These findings are consistent with prenatal phenytoin exposure previously called Fetal hydantoin syndrome. On the other hand.

Warfarin exposure 8:29–9:37

If your patient has nasal hypoplasia and a depressed nasal bridge consider warfarin exposure. In this case, the exposure likely occurred during early pregnancy at 6 to 9 weeks of gestation, affected patients often have a history of fetal growth restriction and developmental delay.
While the physical exam typically reveals hypoplastic digits. Next order a skeletal x-ray.
And if it shows punctate or stippled epiphyses, diagnose fetal warfarin syndrome. Here's a high yield fact, Thalidomide is a medication known to cause severe limb defects such as Emelia and folk Emelia.
Patients with Emelia have complete absence of a limb. While those with folk Emelia lack proximal limb segments in the hand or foot is directly attached to the torso.
Thalidomide use during pregnancy is also associated with ear and eye abnormalities, heart defects and urinary and genital malformations.
Let's go back and look at patients without abnormal bleeding or bruising. Here, assess for a neural tube defect such as myelomeningocele anencephaly or encephalocele if present, consider folate deficiency.

Valproic acid exposure 9:37–10:23

Here's a high yield fact, during the first four weeks of pregnancy, folates is essential for normal neural tube development and closure.
Folate deficiency is a leading cause of neural tube defects and the risk of these defects increases significantly when a pregnant individual takes medications that interfere with folic acid activity like anti seizure medications.
Now, once you've identified a neural tube defect, you should also assess for limb defects. If your patient has clubfoot, consider exposure to valproic acid an anti seizure medication that impairs folate transport and metabolism.

Mon (375)10:23–11:38

These patients also usually have cognitive and developmental delays and occasionally autism spectrum disorder or cardiac anomalies.
The physical exam typically reveals characteristic features including a wide skull, high forehead and broad, low nasal bridge, as well as midface hypoplasia, a smooth philtrum and a thin vermilion border.
Some patients also have cleft lip and palate or hypospadias. These findings are consistent with prenatal valproic acid exposure.
Here's another clinical pearl lithium use during pregnancy is associated with a slight increased risk of Epstein anomaly.
A cardiac defect involving the tricuspid valve and right ventricle. Likewise, some selective serotonin reuptake inhibitors like paroxetine can also cause congenital heart defects if taken during the first trimester of pregnancy.
On the flip side, if your patient has short limbs, hypodactyly or syndactyly, consider prenatal exposure to methotrexate.

Methotrexate exposure 11:38–12:41

A folate antagonist history often reveals fetal growth restriction and occasionally cardiac anomalies. Meanwhile, the exam typically demonstrates microcephaly and characteristic facial features including a broad nasal bridge, prominent eyes, low set ears and micrognathia.
You might also notice a cleft lip or palate. These findings suggest prenatal methotrexate exposure.
Here's another clinical pearl. In addition to methotrexate, several other chemotherapeutic agents have teratogenic potential.
For example, alkylating agents like cyclophosphamide are associated with growth restriction, microphthalmia, cleft palate limb reductions and genital malformations.
Ok. If you don't identify a neural tube defect, your next step is to assess for a history of oligohydramnios or evidence of renal dysfunction if either is present, consider prenatal exposure to angiotensin converting enzyme or ace inhibitors when taken during the second or third trimester of pregnancy.

ACE inhibitor exposure 12:41–13:44

These medications can cause fetal growth restriction, oligohydramnios, renal failure, and patent ductus arteriosus or PDA.
In severe cases, affected infants present with potter sequence. A combination of renal dysplasia, pulmonary hypoplasia and fetal compression.
The physical exam typically reveals abnormal positioning of the hands and feet and craniofacial abnormalities. These findings are consistent with ace inhibitor exposure.
It's worth noting that angiotensin receptor antagonists have similar effects on the fetus. Now, if there's no evidence of oligohydramnios or renal dysfunction, assess for cranial facial abnormalities.

Isotretinoin exposure 13:44–14:23

If your patient's ears are small or absent, consider ISOtretinoin exposure, affected patients often have a known history of hydrocephalus, cardiac anomalies and occasionally thymic hypoplasia or blindness.
The exam typically reveals facial nerve palsies, microcephaly and in some cases, micrognathia and cleft palate. This clinical picture is consistent with ISOtretinoin exposure.
Finally, if your patient has brown or yellow stained teeth, consider tetracycline exposure. Tetracycline can bind to calcium ions in developing teeth and bones from four months of gestation through childhood.

Tetracycline exposure 14:23–15:11

Here, history may reveal inhibited long bone growth. These findings are highly suggestive of tetracycline exposure.
Here's your last clinical pearl. Other teratogens include environmental exposures like lead or mercury, maternal hyperthermia and radiation as well as over the counter medications like nonsteroidal antiinflammatory drugs which can be associated with cardiac anomalies or fetal loss.
All right, as a quick recap. When a pediatric patient presents with a chief concern suggesting a prenatal teratogen exposure, obtain a focused history and physical exam as well as a CBC and CMP.

Review 15:11–16:13

If there is maternal history of recreational substance use, consider opioid exposure and fetal alcohol spectrum disorder.
However, if you don't suspect recreational substance use, assess for hypoglycemia and if present, consider maternal diabetes.
If your patient has abnormal bleeding and bruising, consider prenatal phenytoin or warfarin exposure. Neural tube defects are associated with folic acid deficiency caused by valproic acid or methotrexate exposure.
While renal anomalies are associated with ace inhibitor exposure. Finally, small or absent ears suggest ISOtretinoin exposure.
While brown or yellow stained teeth suggest tetracycline exposure.
Approach to prenatal teratogen exposure: Video | Osmosis