Approach to prenatal teratogen exposure: Clinical sciences

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.

If unstable, stabilize their airway, breathing and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry. Finally, if needed, provide supplemental oxygen.

Now that we've discussed unstable patients, let’s return to the ABCDE assessment and look at stable ones.

First, obtain a focused history and physical examination, and order a CBC and CMP.

History usually reveals a known prenatal exposure to recreational substances or medications, or a maternal history of an underlying medical condition associated with teratogenicity. 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. 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.

History typically reveals irritability, jitters, and high-pitched cry; as well as hiccups or gagging; poor feeding, and poor growth. Some patients might 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, 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; midface hypoplasia; railroad track ears; or hypoplastic nails. Additionally, the head circumference, length, and weight are often less than the tenth 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.

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, hyperexcitable, 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 mnemonic 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.

Here’s a clinical pearl! The teratogenic effects of phenytoin and warfarin include impaired development and craniofacial abnormalities. Although teratogenic the 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 patient’s 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 palater; 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.