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Prenatal Drug Exposure

By

Kevin C. Dysart

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

Last full review/revision Mar 2021| Content last modified Mar 2021
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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. Understanding local jurisdictions and laws is important because many countries and localities have mandatory reporting guidelines. 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.

Amphetamines

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.

Barbiturates

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 orally or IM every 6 hours may be required and then tapered over a few days or weeks, depending on the duration of symptoms.

Cocaine

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, genitourinary 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

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.

Opioids

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 hours 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 (see 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.

The Eat, Sleep, Console (ESC) approach for NAS assessment (1, 2) and care is a promising new development that is more family centered. This approach is focused on comfort care and family involvement, and in many centers includes rooming-in with the mother. Some studies have shown that the ESC approach decreases length of stay and results in less opioid exposure for the infant. However, a significant number 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 orally every 6 hours) 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 weeks 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).

Table
icon

One Drug Regimen for Neonatal Opioid Withdrawal

Drug

Starting Dose

Incremental Increase

Taper

Morphine

0.04 mg/kg orally every 3–4 hours

0.04 mg/kg/dose

10–20% every 2–3 days

Methadone

0.05–0.1 mg/kg orally every 6 hours

0.05 mg/kg/dose

10–20% every week

Adapted from Hudak ML, Tan RC, The Committee on Drugs, The Committee on Fetus and Newborn: Neonatal drug withdrawal. Pediatrics 129:E540–E560, 2012. doi: 10.1542/peds.2011-3212

The addition of clonidine 1 mcg/kg orally every 4 hours 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, blood pressure 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.

Opioids references

More Information

The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

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