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Prenatal Drug Exposure


Kevin C. Dysart

, MD, Perelman School of Medicine at the University of Pennsylvania

Last full review/revision Dec 2018| Content last modified Dec 2018
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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). Fetal alcohol syndrome and the effects of cigarette smoking on the fetus are discussed elsewhere.

A fetus that has been exposed to drugs in utero (termed fetuses exposed to noxious substances [FENS]) can become dependent on the drug during gestation. 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.


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 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 who used opioids chronically during pregnancy should be observed for withdrawal symptoms (narcotic abstinence syndrome [NAS]). NAS usually occurs within 72 h after delivery, although many neonatal units observe infants for 4 or 5 days to be sure there are no significant signs of withdrawal.

Characteristic signs of withdrawal include

  • Irritability

  • Jitteriness

  • Hypertonicity

  • Vomiting and/or diarrhea

  • Sweating

  • Seizures

  • Hyperventilation that causes respiratory alkalosis

Prenatal benzodiazepine exposure may cause similar effects.

There are many scoring systems to help quantify the severity of withdrawal (The Opioid Exposed Newborn: Assessment and Pharmacologic Management). Mild withdrawal symptoms are treated by a few days of swaddling and soothing care to alleviate the physical overarousal and by giving frequent feedings to reduce restlessness. With patience, some problems resolve in no more than a week. However, up to 80% of infants with NAS require drug treatment, typically using an opioid, sometimes with the addition of clonidine. Phenobarbital (0.75 to 1.5 mg/kg po q 6 h) may help but is now considered 2nd-line treatment. Treatment is tapered and stopped over several days or weeks as symptoms subside; many infants require up to 5 wk of therapy.

There is no consensus on the best drug, but most experts use methadone, morphine, or sometimes tincture of opium. Dosing is based on the weight of the infant and the severity of the symptoms. Typically, a starting dose is given and increased until symptoms are controlled and then slowly tapered (see Table: One Drug Regimen for Neonatal Opioid Withdrawal).


One Drug Regimen for Neonatal Opioid Withdrawal


Starting Dose

Incremental Increase



0.04 mg/kg po q 3–4 h

0.04 mg/kg/dose

10–20% q 2–3 days


0.05–0.1 mg/kg po q 6 h

0.05 mg/kg/dose

10–20% q wk

Adapted from Hudak ML, Tan RC, The Committee on Drugs, The Committee on Fetus and Newborn: Neonatal drug withdrawal. Pediatrics 129:E540–E560, 2012.

The addition of clonidine 1 mcg/kg po q 4 h may reduce the duration of drug treatment needed in full-term infants. However, clonidine should not be given to premature infants because of the risk of bradycardia. If clonidine is used, BP should be monitored as the clonidine dose is tapered because there can be rebound hypertension.

The incidence of SIDS 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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