Dose-response effect of fetal cocaine exposure on newborn neurologic function

Background. Studies of fetal cocaine exposure and newborn neurologic function have obtained conflicting results. Although some studies identify abnormalities, others find no differences between cocaine-exposed and cocaine-unexposed infants. To determine the effects of prenatal cocaine exposure on intrauterine growth and neurologic function in infants, we prospectively evaluated 253 infants shortly after birth. Methods. Women who delivered a live singleton >36 weeks by dates were eligible for enrollment. Maternal exclusionary criteria were known parenteral drug use, alcoholism, and acquired immunodeficiency syndrome; infant exclusionary criteria were Apgar scores less than or equal to 4 at 5 minutes, obvious congenital malformations, seizures, or strokes. A total of 98% of infants were evaluated between 1 to 7 days of age. Newborns were assessed with the Neurological Examination for Children (NEC) by a pediatric neurologist (C.A.C.) who was blinded to exposure status. Gestational age was determined by Ballard's examination. Cocaine exposure was determined for the last trimester by radioimmunoassay of maternal hair (RIAH). Exposure values ranged from 2 to 4457 ng/10 mg hair. Infants were excluded if a maternal hair sample was missing (N = 13). The sample comprises 240 woman and infant pairs-104 cocaine-exposed and 136 cocaine-unexposed. Results. Compared with unexposed controls, cocaine-exposed infants exhibited higher rates of intrauterine growth retardation (24% vs 8%), small head circumference ([HC] <10th% percentile) (20% vs 5%) and neurologic abnormalities: global hypertonia (32% vs 11%), coarse tremor (40% vs 15%), and extensor leg posture (20% vs 4%). We found increasing odds (odds ratio) of growth and neurologic impairment with increasing level of cocaine exposure in stratified analyses. The odds ratio associated with three levels of cocaine exposure (no exposure, low exposure = RIAH 2-66 ng/mg; and high exposure = RIAH 81-4457 ng/mg) respectively are: 1.0, 3.3, and 6.1 for small head size (chi(2) for trend); 1.0, 3.3, and 4.3 for global hypertonia (chi(2) for trend); 1.0, 3.4, and 7.4 for extensor leg posturing (chi(2) for trend); and 1.0, 3.8, and 3.8 for coarse tremor (chi(2) for trend). Significant associations between cocaine exposure and neurologic signs were found in logistic regression equations that controlled for 20 or more variables. Conclusion. We conclude that adverse neonatal effects associated with fetal cocaine exposure follow a dose-response relationship: newborns with higher levels of prenatal cocaine exposure show higher rates of impairments in fetal head growth and abnormalities of muscle tone, movements, and posture. Significant relationships between cocaine exposure and these outcomes remain in controlled analyses.