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Prenatal Drug Exposure

by Nicholas Jospe, MD

Alcohol and illicit drugs are toxic to the placenta and developing fetus and can cause congenital syndromes and withdrawal symptoms. Prescription drugs also may have adverse effects on the fetus (see Table: Some Drugs With Adverse Effects During Pregnancy). For effects of cigarette smoking, see Exposure to teratogens.

Although some toxic substances used by the mother are not illegal, many are. In any case, the home situation should be evaluated to determine whether the infant will be safely cared for after discharge. With the supportive help of relatives, friends, and visiting nurses, the mother may be able to care for her infant. If not, foster home care or an alternative care plan may be best.


Alcohol exposure in utero increases the risk of spontaneous abortion, decreases birth weight, and can cause fetal alcohol syndrome (FAS), a constellation of variable physical and cognitive abnormalities. At birth, infants with FAS can be identified by small stature and a typical set of facial traits including microcephaly, microphthalmia, short palpebral fissures, epicanthal folds, a small or flat midface, a flat elongated philtrum, a thin upper lip, and a small chin. Abnormal palmar creases, cardiac defects, and joint contractures may also be evident. After birth, cognitive deficits become apparent. The most serious manifestation is severe intellectual disability, thought to be a teratogenic effect of alcohol given the high number of intellectually disabled infants of alcoholic women; FAS may be the most common cause of noninherited intellectual disability. No single physical or cognitive finding is pathognomonic; lesser degrees of alcohol use cause less severe manifestations, and the diagnosis of mild cases can be difficult because partial expression occurs. It is often difficult to distinguish the effects of alcohol on the developing fetus from those of other exposures (eg, tobacco, other drugs) and factors (eg, poor nutrition, lack of health care, violence) that affect women who drink excessively.

Diagnosis is given to infants with characteristic findings born women who used alcohol excessively during pregnancy.

Because it is unknown when during pregnancy alcohol is most likely to harm the fetus and whether there is a lower limit of alcohol use that is completely safe, pregnant women should be advised to avoid all alcohol intake. Siblings of an infant diagnosed with FAS should be examined for subtle manifestations of the disorder.


Prenatal exposure to amphetamines has lasting subtle effects on neonatal brain structure and function. Some studies have shown decreased volume of the caudate, putamen, and globus pallidus (anatomic components of brain) in methamphetamine-exposed children, whereas other studies have not uniformly confirmed these findings. Other studies indicate that prenatal methamphetamine exposure may be associated with abnormal neurobehavioral patterns or fetal growth restriction, but these findings are not yet fully established.


Prolonged maternal abuse of barbiturates may cause neonatal drug withdrawal with jitteriness, irritability, and fussiness that often do not develop until 7 to 10 days postpartum, after the neonate has been discharged home. Sedation with phenobarbital 0.75 to 1.5 mg/kg po or IM q 6 h may be required and then tapered over a few days or weeks, depending on the duration of symptoms.


Cocaine inhibits reuptake of the neurotransmitters norepinephrine and epinephrine ; it crosses the placenta and causes vasoconstriction and hypertension in the fetus. Cocaine abuse in pregnancy is associated with a higher rate of placental abruption and spontaneous abortion, perhaps caused by reduced maternal blood flow to the placental vascular bed; abruption may also lead to intrauterine fetal death or to neurologic damage if the infant survives. Neonates born to addicted mothers have low birth weight, reduced body length and head circumference, and lower Apgar scores. Cerebral infarcts may occur, and rare anomalies associated with prenatal cocaine use include limb amputations; GU malformations, including prune-belly syndrome; and intestinal atresia or necrosis. All are caused by vascular disruption, presumably secondary to local ischemia caused by the intense vasoconstriction of fetal arteries caused by cocaine. In addition, a pattern of mild neurobehavioral effects has also been observed, including decreases in attention and alertness, lower IQ, and impaired gross and fine motor skills.

Some neonates may show withdrawal symptoms if the mother used cocaine shortly before delivery, but symptoms are less common and less severe than for opioid withdrawal, and signs and treatment are the same.


Marijuana does not consistently seem to increase risk of congenital malformations, fetal growth restriction, or postnatal neurobehavioral abnormalities. However, women who use marijuana during pregnancy often also use alcohol, cigarettes, or both, which can cause fetal problems.


Opioid exposure in utero can cause withdrawal on delivery. The neonate of a woman addicted to opioids should be observed for withdrawal symptoms, which usually occur within 72 h after delivery. Characteristic signs of withdrawal include irritability, jitteriness, hypertonicity, vomiting, diarrhea, sweating, seizures, and hyperventilation that causes respiratory alkalosis. Prenatal benzodiazepine exposure may cause similar effects.

Mild withdrawal symptoms are treated by a few days of swaddling and soothing care to alleviate the physical overarousal and giving frequent feedings to reduce restlessness. With patience, most problems resolve in no more than a week. Severe symptoms can be controlled by diluting tincture of opium (which contains 10 mg morphine/mL) 25-fold with water and giving 2 drops (0.1 mL)/kg po q 4 h. The dose can be increased by 0.1 mL/kg q 4 h as needed. Phenobarbital 0.75 to 1.5 mg/kg po q 6 h may also control withdrawal symptoms. Treatment is tapered and stopped over several days or weeks as symptoms subside.

The incidence of sudden infant death syndrome is greater among infants born to women addicted to opioids but still is < 10/1000 infants, so routine use of home cardiorespiratory monitors is not recommended for these infants.

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