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Existing studies on the neonatal effects of drug exposure in utero are subject to many confounding factors. Many studies have relied on the history obtained from the mother, which is notoriously inaccurate. In addition to recall bias, there is a considerable incentive to withhold information. Testing of urine for drugs of abuse does not reflect drug exposure throughout pregnancy and does not provide quantitative information. Many women who abuse drugs are multiple drug abusers and also drink alcohol and smoke cigarettes. It is thus difficult to isolate the effects of any 1 drug. Social and economic deprivation is common among drug abusers, and this factor not only confounds perinatal data but also has a major effect on long-term studies of infant outcome.


An infant of mother with substance use disorder (formerly referred to as infant of substance-abusing mother) is one whose mother has taken drugs that may potentially cause neonatal withdrawal symptoms. The constellation of signs and symptoms associated with withdrawal, often polysubstance exposure that includes opioids, is called the neonatal abstinence syndrome (NAS). Table 102–1 lists the drugs associated with this syndrome.


Maternal substance abuse has increased over the past decade. In the United States, the incidence of NAS increased nearly 5-fold between 2000 and 2012 and is continuing to increase, with the incidence of NAS being approximately 6 per 1000 hospital births. The incidence is subject to wide geographic variation.


Drugs of abuse are of low molecular weight and usually water soluble and lipophilic. These features facilitate their transfer across the placenta and accumulation in the fetus and amniotic fluid. The half-life of drugs is usually prolonged in the fetus compared with an adult. Most drugs of abuse either bind to various central nervous system (CNS) receptors or affect the release and reuptake of various neurotransmitters. This may have a long-lasting trophic effect on developing dendritic structures. Drugs of abuse have also been suggested to alter in utero or perinatal programming through either epigenetic or other factors. In addition, some drugs are directly toxic to fetal cells. The developing fetus may also be affected by the direct physiologic effects of a drug. Many of the fetal effects of cocaine, including its putative teratogenic effects, are thought to be due to its potent vasoconstrictive property.

Some drugs appear to have a partially beneficial effect. The incidence of respiratory distress syndrome (RDS) is decreased after maternal use of heroin and possibly also with cocaine use. These effects are probably a reflection of fetal stress rather than a direct maturational effect of these drugs. Particularly in the case of cocaine, the decreased incidence of RDS is more than offset by the considerable increase in preterm deliveries after its use. The major concern in these drug-exposed infants is the ...

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