Urogenital Anomalies in the Offspring of Women Using Cocaine during Early Pregnancy -- Atlanta, 1968-1980

Recent clinical and animal studies have suggested a possible association between maternal cocaine use early in pregnancy and the occurrence of congenital urogenital anomalies. To study that association, CDC analyzed data obtained in 1982-1983 from the population-based Atlanta Birth Defects Case-Control Study (ABDCCS). The results suggest that mothers who reported cocaine use early in pregnancy had a nearly fivefold higher risk of having babies with urinary tract anomalies than mothers who reported no cocaine use (1).

The ABDCCS collected information from parents of babies with major congenital anomalies who were born in the metropolitan Atlanta area from 1968 through 1980 and who were identified through the Metropolitan Atlanta Congenital Defects Program. Of 7133 eligible case-babies, interviews were completed by 4929 (69%) of case-mothers. Birth certificates were used to identify babies without birth defects born in the same area. Controls were matched with case-babies by race, hospital of birth, and calendar quarter of birth. Of 4246 control-babies, 3029 (71%) of control-mothers completed interviews. Data on maternal cocaine use and other maternal exposures were obtained through telephone interviews (2,3). Maternal cocaine use during early pregnancy was defined as reported cocaine use at any time from 1 month before pregnancy through the first 3 months of pregnancy.

Urinary tract anomalies* occurred in 276 babies and genital organ anomalies in 79; frequency-matched controls numbered 2837 and 2973, respectively. To assess the potential contribution of maternal recall bias, a second control group comprising all babies born with other major congenital anomalies was selected for each defect category. Conditional logistic regression was used to control for sampling design and potentially confounding variables.

Cocaine use early in pregnancy was reported by 1.4% of mothers of babies with urinary tract anomalies and by 0.5% of their controls, and 0.8% of mothers of babies with genital organ anomalies and 0.5% of their controls.

The risk for urinary tract anomalies was greater in infants born to mothers who reported using cocaine early in pregnancy (adjusted odds ratio=4.8, 95% CI=1.2-20.1). For genital organ defects, the adjusted odds ratio for self-reported cocaine users compared with nonusers was 2.3 (95% CI=0.7-7.9). The urogenital anomalies observed in infants of mothers exposed to cocaine were congenital hydronephrosis, the prune belly sequence, renal and ureteral agenesis, ambiguous genitalia, hypospadias with and without congenital chordee, and bifid scrotum.

Comparisons of exposure histories for mothers of babies with urogenital anomalies and babies with all other major birth defects also produced statistically significant odds ratios. Reported by: Birth Defects and Genetic Diseases Br, Div of Birth Defects and Developmental Disabilities, Center for Environmental Health and Injury Control, CDC.

Editorial Note

Editorial Note: Cocaine use in the United States has increased substantially during the past decade (4-6). Between 1979 and 1984, the number of women admitted to drug abuse treatment programs increased 378% (6). In 1985, an estimated 4.4 million women, most of whom were of childbearing age, had used cocaine at least once during the previous year, and an estimated 1.1 million women were regular users (7). In addition, in some areas of the country the number of babies exposed to cocaine before birth has dramatically increased in the past few years (8-10).

Although understanding of the adverse effects of cocaine use by pregnant women is limited, several studies suggest an association between cocaine use and abruptio placentae, spontaneous abortions, prematurity, impaired fetal growth, congenital urogenital anomalies, and neurobehavioral deficits (9-12). The ABDCCS is the first population-based case-control study to examine the association of maternal cocaine use with congenital urogenital anomalies. The findings are consistent with previous animal and clinical studies and suggest that women who report cocaine use early in pregnancy are at increased risk for bearing infants with urinary tract anomalies.

The pharmacokinetic effects of cocaine use could account for some of the congenital urinary tract anomalies among the infants of mothers reporting cocaine use early in pregnancy. Cocaine, which readily crosses the placenta, increases the circulating levels of norepinephrine and dopamine, thereby causing reduced blood flow to the fetus and systemic vasoconstriction. As a result, fetal hypoxia, inf arction of specific organ/systems, and subsequent vascular disruption of morphogenesis are possible. Cocaine use during gestation could also be associated with other defects caused by fetal vascular disruptions (e.g., gastroschisis).

Potential methodologic concerns must be considered when this study is interpreted. Self-reports of cocaine use underestimate the number of users when compared with urine tests (10); thus, reliance on self-reports in the ABDCCS may have underestimated the true risk of urogenital anomalies associated with cocaine use. In addition, this study encompassed a period when cocaine was used less frequently than it is currently. Although confounding is a potential problem, adjusting the data for factors (such as maternal age, alcohol use, and use of illicit drugs other than cocaine) known to be associated with cocaine use and birth defects did not alter the study results. Finally, use of control-babies with other major birth defects to assess recall bias found no evidence of differential recall.

Because of the small number of babies with urogenital anomalies identified among mothers reporting cocaine use, the results of this study should be confirmed by larger studies in areas where current data can be obtained. In addition, prospective epidemiologic studies using a biologic marker of cocaine use may assist in determining the specific spectrum of malformations associated with maternal cocaine use. This study further emphasizes the need for pregnant women and women at risk for pregnancy to avoid substances that may harm the mother and/or the fetus.

References

1. Chavez GF, Mulinare J, Cordero JF. Maternal cocaine use during early pregnancy as a risk factor for congenital urogenital anomalies. JAMA 1989;262:795-8.

2. Erickson JD, Mulinare J, McClain PW, et al. Vietnam veterans' risks for fathering babies with birth defects. JAMA 1984;252:903-12.

3. CDC. Vietnam veterans' risks for fathering babies with birth defects. Atlanta: US Department of Health and Human Services, Public Health Service, 1984.

4. National Institute on Drug Abuse. National Survey on Drug Abuse: main findings, 1982. Rockville, Maryland: US Department of Health and Human Services, Public Health Service, 1983; DHHS publication no. (ADM)83-1263.

5. National Institute on Drug Abuse. National trends in drug use and related factors among American high school students and young adults, 1975-1986. Rockville, Maryland: US Department of Health and Human Services, Public Health Service, 1987; DHHS publication no. (ADM)87-1535.

6. National Institute on Drug Abuse. Trends in demographic characteristics and patterns of drug use of clients admitted to drug abuse treatment programs for cocaine abuse in selected states: cocaine client admissions 1979-1984. Rockville, Maryland: US Department of Health and Human Services, Public Health Service, 1987; DHHS publication no. (ADM)87-1528.

7. National Institute on Drug Abuse. National Household Survey on Drug Abuse: population estimates, 1985. Rockville, Maryland: US Department of Health and Human Services, Public Health Service, 1987; DHHS publication no. (ADM)87-1539.

8. Silverman S. Scope, specifics of maternal drug use, effects on fetus are beginning to emerge from studies. JAMA 1989;261:1688-9.

9. Chasnoff IJ, Griffith DR, MacGregor S, Dirkes K, Burns KA. Temporal patterns of cocaine use in pregnancy: perinatal outcome. JAMA 1989;261:1741-4.

10. Zuckerman B, Frank DA, Hingson R, et al. Effects of maternal marijuana and cocaine use on fetal growth. N Engl J Med 1989;320:762-8.

11. Mahalik MP, Gautieri RF, Mann DE Jr. Teratogenic potential of cocaine hydrochloride in CF-1 mice. J Pharm Sci 1980;69:703-6.

12. Silverman S. Interaction of drug-abusing mother, fetus, types of drugs examined in numerous studies. JAMA 1989;261:1689,1693. *Include malformations of the kidney (such as renal agenesis) and malformations of the collecting system.

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