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Departments: Critical Reviews of Current Research

Tone Abnormalities Are Associated with Maternal Cigarette Smoking During Pregnancy in In Utero Cocaine-Exposed Infants

Kahler, Wendy M.

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Tone Abnormalities Are Associated with Maternal Cigarette Smoking During Pregnancy in In Utero Cocaine-Exposed Infants

by D.A. Dempsey, B.L. Hajnal, J.C. Partridge, et al, Pediatrics, 2000;106:79–83.

Wendy M. Kahler, Northwestern University


Significant public health problem exists as a result of cocaine use by pregnant women. It has been shown that cocaine may be detrimental to the pregnancy in general, as well as to the development of the fetus. It is difficult to isolate the specific effect that cocaine exposure has on the pregnancy because of the likelihood of multiple confounding factors including maternal cigarette smoking. It has previously been reported that maternal cigarette smoking and cocaine exposure may be responsible for causing similar neurological impairments in the child. Research has noted that hypertonia is especially common among in utero infants exposed to cocaine. The purpose of this study was to control for maternal cigarette smoking and other confounding variables while attempting to determine specific neurological conditions resulting from in utero cocaine exposure.


This study was a prospective, blinded study of infants who were healthy and exposed to cocaine and infants who were healthy and not exposed to cocaine. It was conducted at San Francisco General Hospital, which serves a low socioeconomic patient population. Mothers of infants who were at risk for in utero cocaine exposure and a comparable number of mothers who were not at risk but were of similar ethnic background were approached within 24 hours of birth to enroll in the study. Mothers were given cash and voucher incentives for agreeing to enter the study. Exclusion criteria were set as follows: infant birth weight less than 2000 g, required admission to the intensive care nursery, maternal age less than 18 years, non-English-speaking mothers, polydrug exposure with the exceptions of marijuana and ethanol. Research personnel reviewed all maternal and neonatal charts of the enrolled subjects. Included in these medical charts were smoking and alcohol intake histories, which had been previously obtained by prenatal care providers. Data regarding smoking, alcohol, and drug use history were extracted from these charts.

Urine samples from all newborns at risk were collected by hospital employees and tested for alcohol, amphetamines, barbiturates, benzodiazepines, benzoylecgonine, opiates, and phencyclidine. The urine samples were then screened for the cocaine metabolite, benzoylecgonine, with a threshold for detection of 300 ng/mL. Samples of meconium, neonatal urine, and maternal urine were also collected. Quantitative drug levels of meconium were determined through gas chromatography with the threshold for detection for cocaine and metabolites of 25 ng/g. Urine concentrations of the nicotine metabolite, cotinine, were used to determine maternal cigarette smoking. In instances when no maternal urine was available, the researchers used the neonatal level of cotinine. Based on the urine cotinine levels the mother was designated a nonsmoker if levels were less than 30 ng/mL.

Complete neurological examinations were performed on the infants at six weeks of age by a pediatric neurologist blinded to group assignment. An overall assessment of normal or abnormal neurologic findings was made at this time according to examination findings in the following areas: growth indices, adaptive capacity, mental status, presence of dysmorphism, neurocutaneous signs, cranial nerve assessment, tone, power, deep tendon reflexes, and primitive reflexes.


Of the 153 newborns who were enrolled at the beginning of the study, 96 returned at six weeks of age for the neurologic exam. There was no statistically significant difference between the infants who were cocaine-exposed who did return and those who did not with respect to race, gender, urine benzoylecgonine level, urine cotinine level, prenatal care, maternal alcohol use, head circumference, length entry into foster care, and homelessness. Statistical significance was found in birth weight between infants who were cocaine exposed who returned at six weeks as compared with those who were cocaine exposed and did not return.

Fifty-four of the infants who returned had normal neurologic examination results and 42 infants had abnormal results. The research revealed no association between cocaine exposure and an abnormal neurological exam when controlling for maternal cigarette smoking. It did show, however, that as concentration of cotinine increased so did the risk of hypertonia. Generalized hypertonia was found to be present in 50% of all infants with abnormal examinations. Appendicular hypertonia was present in 33% and hypotonia in 17% of the infants with abnormal exams. There was no statistically significant difference in urine benzozylecgonine levels between those with normal and abnormal neurological examinations among infants exposed to cocaine. Additionally, no significant difference was found between infants with abnormal examinations and those with normal exams in other variables including race, sex, prenatal care, homelessness, maternal alcohol use, parity, maternal age, growth indices, and gestational age.


The results of this research support previous findings that tone abnormalities commonly found among cocaine-exposed neonates are correlated with maternal cigarette smoking during pregnancy, but not with in utero cocaine exposure. This study used continine, a dose-dependent biomarker, as its indicator of cigarette smoking as opposed to maternal history by means of interview or chart review because continine provides a more accurate measurement. The correlation that exists between maternal cigarette smoking and an abnormal neurologic exam is dependent on the cotinine concentration. As cotinine concentration increases (≥200 ng/mL) so does the risk of hypertonia. Therefore, it is highly feasible that the adverse fetal effects thought to result from cocaine exposure may in fact occur secondary to maternal cigarette smoking.

Limitations and Implications

This study was limited by the sample size and ethnic populations. Motor development impairments resulting from cocaine exposure are reported to be more pronounced in the African American population when compared to nonblacks. The number of infants however, who were exposed to cocaine and not black was small which decreases the ability to evaluate the nonblack populations. The number of infants enrolled who did not return at six weeks for the neurologic examination also limited generalizations from this study. The infants who did not return had a mean birth weight less than those who did return, and therefore, neurologic findings of the smaller infants were underrepresented in the results. However, among those infants who did return, typical growth and demographic differences were found between infants exposed to cocaine and those who were not exposed. Additionally, no statistically significant trend was found between cocaine exposure and an abnormal neurological examination.

The methods used by researchers to determine levels of cocaine metabolite present in urine and meconium did not accurately predict in utero cocaine exposure. It is possible that the metabolite may have been passed before birth or within hours of birth before the samples had been taken. Therefore, it is not possible to compare with certainty infants exposed to different magnitudes of cocaine. Improved methods of metabolite collection such as using hair samples may be necessary in future research to gain more accurate results. A definite strength of this study was the fact that the researchers improved on past research techniques by using the biomarker to gain a more accurate account of maternal nicotine use as opposed to medical chart review or interview.

From this study, we may conclude that infant hypertonia at six weeks of age is associated with prenatal exposure to cigarette smoke. This study, however, does not address long-term cognitive or developmental outcomes for these children. It is necessary for further research to be conducted that will address long-term implications of in utero cocaine and tobacco exposure.

Copyright © 2001 Academy of Pediatric Physical Therapy of the American Physical Therapy Association